WHO Expert Committee on Specifications for Pharmaceutical Preparations.

PubMed

2005-01-01

This report presents the recommendations of an international group of experts convened by the World Health Organization to consider matters concerning the quality assurance of pharmaceuticals and specifications for drug substances and dosage forms. Of particular relevance to drug regulatory authorities and pharmaceutical manufacturers, this report discusses the monographs on antiretrovirals proposed for inclusion in The International Pharmacopoeia and specifications for radiopharmaceuticals, quality specifications for antituberculosis drugs and the revision of the monograph on artemisinin derivatives, as well as quality control of reference materials, good manufacturing practices (GMP), inspection, distribution and trade and other aspects of quality assurance of pharmaceuticals, and regulatory issues. The report is complemented by a number of annexes, including an amendment to good manufacturing practices: main principles regarding the requirement for the sampling of starting materials, guidelines on good manufacturing practices regarding water for pharmaceutical use, guidelines on the sampling of pharmaceutical products and related materials and draft guidelines for registration of fixed-dose combination medicinal products.

Recent advances in the application of transmission Raman spectroscopy to pharmaceutical analysis.

PubMed

Buckley, Kevin; Matousek, Pavel

2011-06-25

This article reviews recent advances in transmission Raman spectroscopy and its applications, from the perspective of pharmaceutical analysis. The emerging concepts enable rapid non-invasive volumetric analysis of pharmaceutical formulations and could lead to many important applications in pharmaceutical settings, including quantitative bulk analysis of intact pharmaceutical tablets and capsules in quality and process control. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

Use of near-infrared spectroscopy and multipoint measurements for quality control of pharmaceutical drug products.

PubMed

Boiret, Mathieu; Chauchard, Fabien

2017-01-01

Near-infrared (NIR) spectroscopy is a non-destructive analytical technique that enables better-understanding and optimization of pharmaceutical processes and final drug products. The use in line is often limited by acquisition speed and sampling area. This work focuses on performing a multipoint measurement at high acquisition speed at the end of the manufacturing process on a conveyor belt system to control both the distribution and the content of active pharmaceutical ingredient within final drug products, i.e., tablets. A specially designed probe with several collection fibers was developed for this study. By measuring spectral and spatial information, it provides physical and chemical knowledge on the final drug product. The NIR probe was installed on a conveyor belt system that enables the analysis of a lot of tablets. The use of these NIR multipoint measurement probes on a conveyor belt system provided an innovative method that has the potential to be used as a new paradigm to ensure the drug product quality at the end of the manufacturing process and as a new analytical method for the real-time release control strategy. Graphical abstract Use of near-infrared spectroscopy and multipoint measurements for quality control of pharmaceutical drug products.

Process monitoring and visualization solutions for hot-melt extrusion: a review.

PubMed

Saerens, Lien; Vervaet, Chris; Remon, Jean Paul; De Beer, Thomas

2014-02-01

Hot-melt extrusion (HME) is applied as a continuous pharmaceutical manufacturing process for the production of a variety of dosage forms and formulations. To ensure the continuity of this process, the quality of the extrudates must be assessed continuously during manufacturing. The objective of this review is to provide an overview and evaluation of the available process analytical techniques which can be applied in hot-melt extrusion. Pharmaceutical extruders are equipped with traditional (univariate) process monitoring tools, observing barrel and die temperatures, throughput, screw speed, torque, drive amperage, melt pressure and melt temperature. The relevance of several spectroscopic process analytical techniques for monitoring and control of pharmaceutical HME has been explored recently. Nevertheless, many other sensors visualizing HME and measuring diverse critical product and process parameters with potential use in pharmaceutical extrusion are available, and were thoroughly studied in polymer extrusion. The implementation of process analytical tools in HME serves two purposes: (1) improving process understanding by monitoring and visualizing the material behaviour and (2) monitoring and analysing critical product and process parameters for process control, allowing to maintain a desired process state and guaranteeing the quality of the end product. This review is the first to provide an evaluation of the process analytical tools applied for pharmaceutical HME monitoring and control, and discusses techniques that have been used in polymer extrusion having potential for monitoring and control of pharmaceutical HME. © 2013 Royal Pharmaceutical Society.

Main Reasons for Registration Application Refusal of Generic and Similar Pharmaceutical Drug Products by the Brazilian Health Regulatory Agency (ANVISA).

PubMed

do Carmo, Ana Cerúlia Moraes; Piras, Stefânia Schimaneski; Rocha, Nayrton Flávio Moura; Gratieri, Tais

2017-01-01

Objective . The marketing authorization of generic and similar pharmaceutical drug products involves the analysis of proposing company's administrative aspects as well as drug product technical description and scientific evaluations. This study evaluated the main reasons for registration refusal of generic and similar pharmaceutical drug products in Brazil. The aim is to help future applicants to better organize the proposal. Methods . A retrospective search of drug products registration processes was performed on the Brazilian Government Official Gazette from January 1, 2015, and December 31, 2015. Results . Drug product quality control, drug product stability study, deadline accomplishment, API quality control made by drug manufacturer, active pharmaceutical ingredient (API), and production report were the main reasons for marketing authorization application refusal of generic and similar pharmaceutical drug products in 2015. Conclusion . Disclosure of the reasons behind failed applications is a step forward on regulatory transparency. Sharing of experiences is essential to international regulatory authorities and organizations to improve legislation requirements for the marketing authorization of generic and similar pharmaceutical drug products.

Main Reasons for Registration Application Refusal of Generic and Similar Pharmaceutical Drug Products by the Brazilian Health Regulatory Agency (ANVISA)

PubMed Central

do Carmo, Ana Cerúlia Moraes; Piras, Stefânia Schimaneski; Rocha, Nayrton Flávio Moura

2017-01-01

Objective. The marketing authorization of generic and similar pharmaceutical drug products involves the analysis of proposing company's administrative aspects as well as drug product technical description and scientific evaluations. This study evaluated the main reasons for registration refusal of generic and similar pharmaceutical drug products in Brazil. The aim is to help future applicants to better organize the proposal. Methods. A retrospective search of drug products registration processes was performed on the Brazilian Government Official Gazette from January 1, 2015, and December 31, 2015. Results. Drug product quality control, drug product stability study, deadline accomplishment, API quality control made by drug manufacturer, active pharmaceutical ingredient (API), and production report were the main reasons for marketing authorization application refusal of generic and similar pharmaceutical drug products in 2015. Conclusion. Disclosure of the reasons behind failed applications is a step forward on regulatory transparency. Sharing of experiences is essential to international regulatory authorities and organizations to improve legislation requirements for the marketing authorization of generic and similar pharmaceutical drug products. PMID:28280742

Unlicensed pharmaceutical preparations for clinical patient care: Ensuring safety.

PubMed

de Wilde, Sofieke; de Jong, Maria G H; Le Brun, Paul P H; Guchelaar, Henk-Jan; Schimmel, Kirsten J M

2018-01-01

Most medicinal products dispensed to patients have marketing authorization (MA) to ensure high quality of the product, safety, and efficacy. However, in daily practice, to treat patients adequately, there is a medical need for drugs that do not hold MA. To meet this medical need, medicinal products are used in clinical care without MA (unlicensed), such as products prepared by (local) pharmacies: the pharmaceutical preparations. Three types of pharmaceutical preparations are distinguished: (i) reconstitution in excess of summary of product characteristics; (ii) adaptation of a licensed medicinal product (outside its official labeling); (iii) medicinal products from an active pharmaceutical ingredient. Although unlicensed, patients may expect the same quality for these unlicensed pharmaceutical preparations as for the licensed medicinal products. To assure this quality, a proper risk-benefit assessment and proper documentation in (centralized) patient registries and linking to a national pharmacovigilance database should be in place. Based on a risk assessment matrix, requirements for quality assurance can be determined, which has impact on the level of documentation of a pharmaceutical preparation. In this paper, the approach for good documentation including quality assurance and benefit-risk assessment will be discussed and possibilities for patient registries are described to make these crucial preparations available for regular patient care. KEY POINTS Ensuring pharmaceutical quality and performing a proper benefit-risk assessment will guarantee safe use of pharmaceutical preparations. Good documentation of (ultra-)orphan treatments can be collected in centralized patient registries and should be combined with existing information in (inter)national databases and self-reflection of patients. Linking patient registries to a centralized database for adverse drug events is highly recommended as it increases safety control of the (ultra) orphan pharmaceutical preparations. Copyright © 2017 John Wiley & Sons, Ltd.

[Accession to the PIC/S and pharmaceutical quality system in Japan].

PubMed

Katori, Noriko

2014-01-01

In March, 2012, Japan made the application for membership of the Pharmaceutical Inspection convention and Pharmaceutical Inspection Co-operation scheme (PIC/S) which is an international body of a GMP inspection. The globalization of pharmaceutical manufacturing and sales has been a driving force behind the decision to become a PIC/S member. For the application for membership, Japan's GMP inspectorate needs to fulfill PIC/S requirements, for example, the inspection organization has to have a quality system as a global standard. One of the other requirements is that the GMP inspectorate can access Official Medicines Control Laboratories (OMCL) having high analytical skills and also have a quality system based on ISO 17025. I would like to describe the process to make up a quality system in the National Institute of Health Sciences and also the circumstances around the PIC/S application in Japan.

Protein Aggregation and Its Impact on Product Quality

PubMed Central

Roberts, Christopher J.

2014-01-01

Protein pharmaceutical products are typically active as folded monomers that are composed of one or more protein chains, such as the heavy and light chains in monoclonal antibodies that are a mainstay of current drug pipelines. There are numerous possible aggregated states for a given protein, some of which are potentially useful, while most of which are considered deleterious from the perspective of pharmaceutical product quality and performance. This review provides an overview of how and why different aggregated states of proteins occur, how this potentially impacts product quality and performance, fundamental approaches to control aggregate formation, and the practical approaches that are currently used in the pharmaceutical industry. PMID:25173826

Effect of X-ray exposure on the pharmaceutical quality of drug tablets using X-ray inspection equipment.

PubMed

Uehara, Kazuaki; Tagami, Tatsuaki; Miyazaki, Itaru; Murata, Norikazu; Takahashi, Yoshifumi; Ohkubo, Hiroshi; Ozeki, Tetsuya

2015-06-01

X-ray inspection equipment is widely used to detect missing materials and defective goods in opaque containers. Its application has been expanded to the pharmaceutical industry to detect the presence of drug tablets in aluminum foil press-through packaging. However, the effect of X-rays on the pharmaceutical quality of drug tablets is not well known. In this study, the effect of X-rays on the pharmaceutical quality of drug tablets was investigated. Exposure of acetaminophen, loxoprofen and mefenamic acid tablets to X-ray doses of 0.34 mGy (thrice the dose by X-ray scanning) to 300 Gy (maximum dose from our X-ray equipment) was demonstrated, and the samples were evaluated by formulation tests. Exposure to X-rays did not affect the pharmaceutical quality of the drug content. The samples exposed to X-rays exhibited almost the same profile in formulation tests (dissolution test, disintegrating test and hardness test) as control samples (0 Gy). The combination of X-ray exposure with accelerated temperature and humidity tests (six months) also did not affect the pharmaceutical quality. The color change of light-sensitive drugs (nifedipine and furosemide tablets) after X-ray exposure was negligible (< 1.0). In contrast, tablet color was remarkably changed by light from a D65 lamp. The X-ray scanning and X-ray exposure under our experimental conditions did not affect the pharmaceutical quality of drug tablets.

Current Challenges and Potential Opportunities for the Pharmaceutical Sciences to Make Global Impact: An FIP Perspective.

PubMed

Tucker, Geoffrey; DeSilva, Binodh; Dressman, Jennifer; Ito, Michiho; Kumamoto, Takuya; Mager, Don; Mahler, Hanns-Christian; Maitland-van der Zee, Anke H; Pauletti, Giovanni M; Sasaki, Hitoshi; Shah, Vinod; Tang, Daniel; Ward, Michael

2016-09-01

The chairs of each of the 8 Special Interest Groups of the Board of Pharmaceutical Sciences of the International Pharmaceutical Federation have compiled opinions with regard to major challenges for the pharmaceutical sciences over the next 5-10 years. Areas covered are drug design and discovery, natural products, formulation design and pharmaceutical technology, pharmacokinetics/pharmacodynamics and systems pharmacology, translational and personalized medicine, biotechnology, analytical sciences and quality control, and regulatory science. Copyright © 2016. Published by Elsevier Inc.

Postproduction Handling and Administration of Protein Pharmaceuticals and Potential Instability Issues.

PubMed

Nejadnik, M Reza; Randolph, Theodore W; Volkin, David B; Schöneich, Christian; Carpenter, John F; Crommelin, Daan J A; Jiskoot, Wim

2018-04-14

The safety and efficacy of protein pharmaceuticals depend not only on biological activity but also on purity levels. Impurities may be process related because of limitations in manufacturing or product related because of protein degradation occurring throughout the life history of a product. Although the pharmaceutical biotechnology industry has made great progress in improving bulk and drug product manufacturing as well as company-controlled storage and transportation conditions to minimize the level of degradation, there is less control over the many factors that may subsequently affect product quality after the protein pharmaceuticals are released and shipped by the manufacturer. Routine handling or unintentional mishandling of therapeutic protein products may cause protein degradation that remains unnoticed but can potentially compromise the clinical safety and efficacy of the product. In this commentary, we address some potential risks associated with (mis)handling of protein pharmaceuticals after release by the manufacturer. We summarize the environmental stress factors that have been shown to cause protein degradation and that may be encountered during typical handling procedures of protein pharmaceuticals in a hospital setting or during self-administration by patients. Moreover, we provide recommendations for improvements in product handling to help ensure the quality of protein pharmaceuticals during use. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Drug innovation, price controls, and parallel trade.

PubMed

Matteucci, Giorgio; Reverberi, Pierfrancesco

2016-12-21

We study the long-run welfare effects of parallel trade (PT) in pharmaceuticals. We develop a two-country model of PT with endogenous quality, where the pharmaceutical firm negotiates the price of the drug with the government in the foreign country. We show that, even though the foreign government does not consider global R&D costs, (the threat of) PT improves the quality of the drug as long as the foreign consumers' valuation of quality is high enough. We find that the firm's short-run profit may be higher when PT is allowed. Nonetheless, this is neither necessary nor sufficient for improving drug quality in the long run. We also show that improving drug quality is a sufficient condition for PT to increase global welfare. Finally, we show that, when PT is allowed, drug quality may be higher with than without price controls.

Introduction to Quality Control in a Compounding Pharmacy.

PubMed

Allen, Loyd V

2016-01-01

A quality-based program is vital in every compounding pharmacy to ensure that each preparation is compounded properly and is stable for its expected duration of use. This article discusses quality control, quality assurance, continuous quality improvement, and also describes the components of an in-house (in-pharmacy) quality program, as well as the role of outside laboratories. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Continuous processing and the applications of online tools in pharmaceutical product manufacture: developments and examples.

PubMed

Ooi, Shing Ming; Sarkar, Srimanta; van Varenbergh, Griet; Schoeters, Kris; Heng, Paul Wan Sia

2013-04-01

Continuous processing and production in pharmaceutical manufacturing has received increased attention in recent years mainly due to the industries' pressing needs for more efficient, cost-effective processes and production, as well as regulatory facilitation. To achieve optimum product quality, the traditional trial-and-error method for the optimization of different process and formulation parameters is expensive and time consuming. Real-time evaluation and the control of product quality using an online process analyzer in continuous processing can provide high-quality production with very high-throughput at low unit cost. This review focuses on continuous processing and the application of different real-time monitoring tools used in the pharmaceutical industry for continuous processing from powder to tablets.

75 FR 22412 - Food and Drug Administration/Xavier University Global Outsourcing Conference

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-28

... relationships and supply chain control, as well as expectations from global regulators. Pharmaceutical companies...; Quality Agreement Development throughout the product and process lifecycle; Supply Chain Transparency and Pedigree; How to Audit the Supply Chain; Rx-360 and International Pharmaceutical Excipients Council...

The good laboratory practice and good clinical practice requirements for the production of radiopharmaceuticals in clinical research.

PubMed

De Vos, Filip J; De Decker, Mario; Dierckx, Rudi A

2005-07-01

Radiopharmaceuticals account for more than 95% of the group of sterile pharmaceutical products and should therefore be handled and produced with care. Since the introduction of the European directive, all pharmaceuticals used in clinical studies must be prepared under good manufacturing practice (GMP) conditions. This review aims to give an overview of the basic principles and guidelines for the preparation of radiopharmaceuticals. Special attention is given to the production area environment and personnel, the two basic requirements for GMP productions. Especially for the production area, two philosophies have to be combined: the cascade system of over-pressure for the production of pharmaceuticals and the under pressure system for the manufacturing of radioisotopes. Personnel should be selected based on education and regularly given special training for the handling of radioactive material. Compared to pharmaceuticals, radiopharmaceuticals have their own labels, taking into account their specific nature. Besides the standard quality control, other items for quality control of radiopharmaceuticals are also discussed in this article.

Nanocrystals: The preparation, precise control, and application toward the pharmaceutics and foods industry.

PubMed

Wu, Cao; Chen, Zhou; Hu, Ya; Rao, Zhiyuan; Wu, Wangping; Yang, Zhaogang

2018-05-15

Crystallization is a significant process employed to produce a wide variety of materials in pharmaceutical and food area. The control of crystal dimension, crystallinity, and shape is very important because they will affect the subsequent filtration, drying and grinding performance as well as the physical and chemical properties of the material. This review summarizes the special features of crystallization technology and the preparation methods of nanocrystals, and discusses analytical technology which is used to control crystal quality and performance. The crystallization technology applications in pharmaceutics and foods are also outlined. These illustrated examples further help us to gain a better understanding of the crystallization technology for pharmaceutics and foods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Chinese medicine industry 4.0：advancing digital pharmaceutical manufacture toward intelligent pharmaceutical manufacture].

PubMed

Cheng, Yi-Yu; Qu, Hai-Bin; Zhang, Bo-Li

2016-01-01

A perspective analysis on the technological innovation in pharmaceutical engineering of Chinese medicine unveils a vision on "Future Factory" of Chinese medicine industry in mind. The strategy as well as the technical roadmap of "Chinese medicine industry 4.0" is proposed, with the projection of related core technology system. It is clarified that the technical development path of Chinese medicine industry from digital manufacture to intelligent manufacture. On the basis of precisely defining technical terms such as process control, on-line detection and process quality monitoring for Chinese medicine manufacture, the technical concepts and characteristics of intelligent pharmaceutical manufacture as well as digital pharmaceutical manufacture are elaborated. Promoting wide applications of digital manufacturing technology of Chinese medicine is strongly recommended. Through completely informationized manufacturing processes and multi-discipline cluster innovation, intelligent manufacturing technology of Chinese medicine should be developed, which would provide a new driving force for Chinese medicine industry in technology upgrade, product quality enhancement and efficiency improvement. Copyright© by the Chinese Pharmaceutical Association.

Pharmaceuticals in Australia: priorities in a teaching hospital.

PubMed

Kearney, B J

1993-01-01

In spite of rigorous government programs for control of the pricing and dissemination of pharmaceutical products in Australia, the list of new drugs continues to grow and prices to increase. To regain control over drug usage at Royal Adelaide Hospital, the Hospital Drug Committee developed a rating method that judged drugs on the basis of their cost-benefit to patients. The ratio of a total quality score to a total cost score becomes the determinant of additions to the hospital formulary. The background for the Australian approach to pharmaceuticals and the new evaluation technique at the teaching hospital are described in this report.

Enhanced Quality Control in Pharmaceutical Applications by Combining Raman Spectroscopy and Machine Learning Techniques

NASA Astrophysics Data System (ADS)

Martinez, J. C.; Guzmán-Sepúlveda, J. R.; Bolañoz Evia, G. R.; Córdova, T.; Guzmán-Cabrera, R.

2018-06-01

In this work, we applied machine learning techniques to Raman spectra for the characterization and classification of manufactured pharmaceutical products. Our measurements were taken with commercial equipment, for accurate assessment of variations with respect to one calibrated control sample. Unlike the typical use of Raman spectroscopy in pharmaceutical applications, in our approach the principal components of the Raman spectrum are used concurrently as attributes in machine learning algorithms. This permits an efficient comparison and classification of the spectra measured from the samples under study. This also allows for accurate quality control as all relevant spectral components are considered simultaneously. We demonstrate our approach with respect to the specific case of acetaminophen, which is one of the most widely used analgesics in the market. In the experiments, commercial samples from thirteen different laboratories were analyzed and compared against a control sample. The raw data were analyzed based on an arithmetic difference between the nominal active substance and the measured values in each commercial sample. The principal component analysis was applied to the data for quantitative verification (i.e., without considering the actual concentration of the active substance) of the difference in the calibrated sample. Our results show that by following this approach adulterations in pharmaceutical compositions can be clearly identified and accurately quantified.

Colorimetry as Quality Control Tool for Individual Inkjet-Printed Pediatric Formulations.

PubMed

Wickström, Henrika; Nyman, Johan O; Indola, Mathias; Sundelin, Heidi; Kronberg, Leif; Preis, Maren; Rantanen, Jukka; Sandler, Niklas

2017-02-01

Printing technologies were recently introduced to the pharmaceutical field for manufacturing of drug delivery systems. Printing allows on demand manufacturing of flexible pharmaceutical doses in a personalized manner, which is critical for a successful and safe treatment of patient populations with specific needs, such as children and the elderly, and patients facing multimorbidity. Printing of pharmaceuticals as technique generates new demands on the quality control procedures. For example, rapid quality control is needed as the printing can be done on demand and at the point of care. This study evaluated the potential use of a handheld colorimetry device for quality control of printed doses of vitamin Bs on edible rice and sugar substrates. The structural features of the substrates with and without ink were also compared. A multicomponent ink formulation with vitamin B 1 , B 2 , B 3 , and B 6 was developed. Doses (4 cm 2 ) were prepared by applying 1-10 layers of yellow ink onto the white substrates using thermal inkjet technology. The colorimetric method was seen to be viable in detecting doses up to the 5th and 6th printed layers until color saturation of the yellow color parameter (b*) was observed on the substrates. Liquid chromatography mass spectrometry was used as a reference method for the colorimetry measurements plotted against the number of printed layers. It was concluded that colorimetry could be used as a quality control tool for detection of different doses. However, optimization of the color addition needs to be done to avoid color saturation within the planned dose interval.

International Conference on Harmonisation; guidance on Q10 Pharmaceutical Quality System; availability. Notice.

PubMed

2009-04-08

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q10 Pharmaceutical Quality System." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance describes a model for an effective quality management system for the pharmaceutical industry, referred to as the Pharmaceutical Quality System. The guidance is intended to provide a comprehensive approach to an effective pharmaceutical quality system that is based on International Organization for Standardization (ISO) concepts, includes applicable good manufacturing practice (GMP) regulations and complements ICH guidances on "Q8 Pharmaceutical Development" and "Q9 Quality Risk Management."

The reliability-quality relationship for quality systems and quality risk management.

PubMed

Claycamp, H Gregg; Rahaman, Faiad; Urban, Jason M

2012-01-01

Engineering reliability typically refers to the probability that a system, or any of its components, will perform a required function for a stated period of time and under specified operating conditions. As such, reliability is inextricably linked with time-dependent quality concepts, such as maintaining a state of control and predicting the chances of losses from failures for quality risk management. Two popular current good manufacturing practice (cGMP) and quality risk management tools, failure mode and effects analysis (FMEA) and root cause analysis (RCA) are examples of engineering reliability evaluations that link reliability with quality and risk. Current concepts in pharmaceutical quality and quality management systems call for more predictive systems for maintaining quality; yet, the current pharmaceutical manufacturing literature and guidelines are curiously silent on engineering quality. This commentary discusses the meaning of engineering reliability while linking the concept to quality systems and quality risk management. The essay also discusses the difference between engineering reliability and statistical (assay) reliability. The assurance of quality in a pharmaceutical product is no longer measured only "after the fact" of manufacturing. Rather, concepts of quality systems and quality risk management call for designing quality assurance into all stages of the pharmaceutical product life cycle. Interestingly, most assays for quality are essentially static and inform product quality over the life cycle only by being repeated over time. Engineering process reliability is the fundamental concept that is meant to anticipate quality failures over the life cycle of the product. Reliability is a well-developed theory and practice for other types of manufactured products and manufacturing processes. Thus, it is well known to be an appropriate index of manufactured product quality. This essay discusses the meaning of reliability and its linkages with quality systems and quality risk management.

Chromatographic multivariate quality control of pharmaceuticals giving strongly overlapped peaks based on the chromatogram profile.

PubMed

Escuder-Gilabert, L; Ruiz-Roch, D; Villanueva-Camañas, R M; Medina-Hernández, M J; Sagrado, S

2004-03-12

In the present paper, the simultaneous quantification of two analytes showing strongly overlapped chromatographic peaks (alpha = 1.02), under the assumption that both available equipment and training of the laboratory staff are basic, is studied. A pharmaceutical preparation (Mutabase) containing two drugs of similar physicochemical properties (amitriptyline and perphenazine) is selected as case of study. The assays are carried out under realistic working conditions (i.e. routine testing laboratories). Uncertainty considerations are introduced in the study. A partial least squares model is directly applied to the chromatographic data (with no previous signal transformation) to perform quality control of the pharmaceutical formulation. Under the adequate protocol, the relative error in prediction of analytes is within the tolerances found in the pharmacopeia (10%). For spiked samples simulating formulation mistakes, the errors found have the same magnitude and sign to those provoked.

21 CFR 211.22 - Responsibilities of quality control unit.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Responsibilities of quality control unit. 211.22 Section 211.22 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Organization and...

21 CFR 211.22 - Responsibilities of quality control unit.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Responsibilities of quality control unit. 211.22 Section 211.22 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Organization and...

21 CFR 211.22 - Responsibilities of quality control unit.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Responsibilities of quality control unit. 211.22 Section 211.22 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Organization and...

System-wide hybrid MPC-PID control of a continuous pharmaceutical tablet manufacturing process via direct compaction.

PubMed

Singh, Ravendra; Ierapetritou, Marianthi; Ramachandran, Rohit

2013-11-01

The next generation of QbD based pharmaceutical products will be manufactured through continuous processing. This will allow the integration of online/inline monitoring tools, coupled with an efficient advanced model-based feedback control systems, to achieve precise control of process variables, so that the predefined product quality can be achieved consistently. The direct compaction process considered in this study is highly interactive and involves time delays for a number of process variables due to sensor placements, process equipment dimensions, and the flow characteristics of the solid material. A simple feedback regulatory control system (e.g., PI(D)) by itself may not be sufficient to achieve the tight process control that is mandated by regulatory authorities. The process presented herein comprises of coupled dynamics involving slow and fast responses, indicating the requirement of a hybrid control scheme such as a combined MPC-PID control scheme. In this manuscript, an efficient system-wide hybrid control strategy for an integrated continuous pharmaceutical tablet manufacturing process via direct compaction has been designed. The designed control system is a hybrid scheme of MPC-PID control. An effective controller parameter tuning strategy involving an ITAE method coupled with an optimization strategy has been used for tuning of both MPC and PID parameters. The designed hybrid control system has been implemented in a first-principles model-based flowsheet that was simulated in gPROMS (Process System Enterprise). Results demonstrate enhanced performance of critical quality attributes (CQAs) under the hybrid control scheme compared to only PID or MPC control schemes, illustrating the potential of a hybrid control scheme in improving pharmaceutical manufacturing operations. Copyright © 2013 Elsevier B.V. All rights reserved.

Chemometrics-based process analytical technology (PAT) tools: applications and adaptation in pharmaceutical and biopharmaceutical industries.

PubMed

Challa, Shruthi; Potumarthi, Ravichandra

2013-01-01

Process analytical technology (PAT) is used to monitor and control critical process parameters in raw materials and in-process products to maintain the critical quality attributes and build quality into the product. Process analytical technology can be successfully implemented in pharmaceutical and biopharmaceutical industries not only to impart quality into the products but also to prevent out-of-specifications and improve the productivity. PAT implementation eliminates the drawbacks of traditional methods which involves excessive sampling and facilitates rapid testing through direct sampling without any destruction of sample. However, to successfully adapt PAT tools into pharmaceutical and biopharmaceutical environment, thorough understanding of the process is needed along with mathematical and statistical tools to analyze large multidimensional spectral data generated by PAT tools. Chemometrics is a chemical discipline which incorporates both statistical and mathematical methods to obtain and analyze relevant information from PAT spectral tools. Applications of commonly used PAT tools in combination with appropriate chemometric method along with their advantages and working principle are discussed. Finally, systematic application of PAT tools in biopharmaceutical environment to control critical process parameters for achieving product quality is diagrammatically represented.

International experience in controlling pharmaceutical expenditure: influencing patients and providers and regulating industry – a systematic review

PubMed Central

Lee, Iyn-Hyang; Hewitt, Catherine; Maynard, Alan

2015-01-01

Objective To review international policies to control expenditure on pharmaceuticals by influencing the behaviour of patients and providers and regulating the pharmaceutical industry. Method Systematic review of experimental and quasi-experimental studies. Published studies were identified with an electronic search strategy using MEDLINE and EMBASE from 1980 to May 2012. Studies were eligible if they assessed the effect of policies aimed at influencing the behaviour of patients and providers, and regulating the pharmaceutical industry. Outcome measures included pharmaceutical expenditure, prices or utilization; other resource use relating to pharmaceuticals; and health outcomes and patients’ or providers’ behaviour relating to pharmaceutical use. Quality assessment criteria for each study design were developed based on the standard criteria recommended by the Cochrane Effective Practice and Organisation of Care (EPOC) group. The review includes studies based on randomized controlled trials and rigorous quasi-experimental designs (interrupted time-series and controlled before-and-after studies). Studies were excluded if they were conducted within a single hospital or practice; related to pharmaceutical care services or disease management; had less than 6 months of follow-up period (or less than 12 months overall for interrupted time series); if data in controlled before-and-after studies were not collected contemporaneously or if no rationale was stated for the choice of control group; or if relevant and interpretable data were not presented. Results A total of 255 studies met the inclusion criteria for this review. The majority of the studies relating to patients evaluated cost sharing interventions such as user charges (52 studies). User charges do reduce utilization of pharmaceuticals, and reduce public expenditure by shifting costs to patients. But they reduce the use of essential as well as non-essential drugs, and without adequate exemptions they affect vulnerable groups disproportionately. The majority of studies relating to doctors evaluated the effects of educational approaches (78 studies), reimbursement restrictions (48 studies) and incentive systems (22 studies). Evidence on these policies is of mixed quality. It appears possible to influence prescribing modestly, through various means, but it is essential that messages to prescribers are based on good evidence of effectiveness and cost-effectiveness. Twenty-nine studies related to industry regulation, and they were of mixed quality. Evidence from studies of reference pricing suggests that this may result in cost savings. These are, however, achieved not by companies reducing or restraining prices, or by reductions in the overall volume of prescriptions, but by some shifts in use and shifting costs to patients, with consequent adverse effects on the equity of access to medicines. Other price and profit controls remain almost completely lacking in evaluative evidence. Conclusions It may be that the undesirable consequences of policies influencing patients, particularly user charges, can outweigh the benefits. To influence demand for pharmaceuticals, it is more appropriate to influence prescribing doctors and although interventions to improve prescribing practice have been developed, they often achieve relatively modest benefits and sometimes at high cost. Good evaluative evidence related to industry regulation is scarce despite its policy importance. PMID:25092883

International experience in controlling pharmaceutical expenditure: influencing patients and providers and regulating industry - a systematic review.

PubMed

Lee, Iyn-Hyang; Bloor, Karen; Hewitt, Catherine; Maynard, Alan

2015-01-01

To review international policies to control expenditure on pharmaceuticals by influencing the behaviour of patients and providers and regulating the pharmaceutical industry. Systematic review of experimental and quasi-experimental studies. Published studies were identified with an electronic search strategy using MEDLINE and EMBASE from 1980 to May 2012. Studies were eligible if they assessed the effect of policies aimed at influencing the behaviour of patients and providers, and regulating the pharmaceutical industry. Outcome measures included pharmaceutical expenditure, prices or utilization; other resource use relating to pharmaceuticals; and health outcomes and patients' or providers' behaviour relating to pharmaceutical use. Quality assessment criteria for each study design were developed based on the standard criteria recommended by the Cochrane Effective Practice and Organisation of Care (EPOC) group. The review includes studies based on randomized controlled trials and rigorous quasi-experimental designs (interrupted time-series and controlled before-and-after studies). Studies were excluded if they were conducted within a single hospital or practice; related to pharmaceutical care services or disease management; had less than 6 months of follow-up period (or less than 12 months overall for interrupted time series); if data in controlled before-and-after studies were not collected contemporaneously or if no rationale was stated for the choice of control group; or if relevant and interpretable data were not presented. A total of 255 studies met the inclusion criteria for this review. The majority of the studies relating to patients evaluated cost sharing interventions such as user charges (52 studies). User charges do reduce utilization of pharmaceuticals, and reduce public expenditure by shifting costs to patients. But they reduce the use of essential as well as non-essential drugs, and without adequate exemptions they affect vulnerable groups disproportionately. The majority of studies relating to doctors evaluated the effects of educational approaches (78 studies), reimbursement restrictions (48 studies) and incentive systems (22 studies). Evidence on these policies is of mixed quality. It appears possible to influence prescribing modestly, through various means, but it is essential that messages to prescribers are based on good evidence of effectiveness and cost-effectiveness. Twenty-nine studies related to industry regulation, and they were of mixed quality. Evidence from studies of reference pricing suggests that this may result in cost savings. These are, however, achieved not by companies reducing or restraining prices, or by reductions in the overall volume of prescriptions, but by some shifts in use and shifting costs to patients, with consequent adverse effects on the equity of access to medicines. Other price and profit controls remain almost completely lacking in evaluative evidence. It may be that the undesirable consequences of policies influencing patients, particularly user charges, can outweigh the benefits. To influence demand for pharmaceuticals, it is more appropriate to influence prescribing doctors and although interventions to improve prescribing practice have been developed, they often achieve relatively modest benefits and sometimes at high cost. Good evaluative evidence related to industry regulation is scarce despite its policy importance. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

[Discussion on research thinking of traditional Chinese medicine standardization system based on whole process quality control].

PubMed

Dong, Ling; Sun, Yu; Pei, Wen-Xuan; Dai, Jun-Dong; Wang, Zi-Yu; Pan, Meng; Chen, Jiang-Peng; Wang, Yun

2017-12-01

The concept of "Quality by design" indicates that good design for the whole life cycle of pharmaceutical production enables the drug to meet the expected quality requirements. Aiming at the existing problems of the traditional Chinese medicine (TCM) industry, the TCM standardization system was put forward in this paper from the national strategic level, under the guidance by the idea of quality control in international manufacturing industry and with considerations of TCM industry's own characteristics and development status. The connotation of this strategy was to establish five interrelated systems: multi-indicators system based on tri-indicators system, quality standard and specification system of TCM herbal materials and decoction pieces, quality traceability system, data monitoring system based on whole-process quality control, and whole-process quality management system of TCM, and achieve the whole process systematic and scientific study in TCM industry through "top-level design-implement in steps-system integration" workflow. This article analyzed the correlation between the quality standards of all links, established standard operating procedures of each link and whole process, and constructed a high standard overall quality management system for TCM industry chains, in order to provide a demonstration for the establishment of TCM whole-process quality control system and provide systematic reference and basis for standardization strategy in TCM industry. Copyright© by the Chinese Pharmaceutical Association.

2015/2016 Quality Risk Management Benchmarking Survey.

PubMed

Waldron, Kelly; Ramnarine, Emma; Hartman, Jeffrey

2017-01-01

This paper investigates the concept of quality risk management (QRM) maturity as it applies to the pharmaceutical and biopharmaceutical industries, using the results and analysis from a QRM benchmarking survey conducted in 2015 and 2016. QRM maturity can be defined as the effectiveness and efficiency of a quality risk management program, moving beyond "check-the-box" compliance with guidelines such as ICH Q9 Quality Risk Management , to explore the value QRM brings to business and quality operations. While significant progress has been made towards full adoption of QRM principles and practices across industry, the full benefits of QRM have not yet been fully realized. The results of the QRM Benchmarking Survey indicate that the pharmaceutical and biopharmaceutical industries are approximately halfway along the journey towards full QRM maturity. LAY ABSTRACT: The management of risks associated with medicinal product quality and patient safety are an important focus for the pharmaceutical and biopharmaceutical industries. These risks are identified, analyzed, and controlled through a defined process called quality risk management (QRM), which seeks to protect the patient from potential quality-related risks. This paper summarizes the outcomes of a comprehensive survey of industry practitioners performed in 2015 and 2016 that aimed to benchmark the level of maturity with regard to the application of QRM. The survey results and subsequent analysis revealed that the pharmaceutical and biopharmaceutical industries have made significant progress in the management of quality risks over the last ten years, and they are roughly halfway towards reaching full maturity of QRM. © PDA, Inc. 2017.

An in-depth analysis of pharmaceutical regulation in the Republic of Moldova

PubMed Central

2014-01-01

Objective Regulation of the pharmaceutical system is a crucial, yet often neglected, component in ensuring access to safe and effective medicines. The aim of this study was to provide an in-depth analysis of the existing pharmaceutical regulation, including recent changes, in the Republic of Moldova. Methods Data from field work conducted by the World Health Organization (WHO) together with a review of policy documents and quantitative secondary data analysis was used to achieve this aim. Results This analysis identified several ways in which pharmaceutical regulation affects availability of quality medicines in the Republic of Moldova. These include lack of full implementation bioequivalence requirements for generics registration, incomplete implementation of good manufacturing practices and no implementation of good distribution practices, use of quality control instead of quality assurance as a method to ensure quality of medicines, frequent change of power within the Medicines and Medical Devices Agency (MMDA) leading to lack of long-term strategy and plans, conflict of interest between the different functions of the MMDA, the lack of sufficient funding for the MMDA to conduct its activities and to invest in continuous training of its staff (particularly inspectors) and very weak post-marketing control. Notably, several improvements have been recently introduced, including a roadmap for change for the MMDA, the introduction of good manufacturing practices and the drafting of a quality manual for the Agency. Conclusion Based on these findings the authors propose a set of priority actions to address existing gaps and draw lessons learned from other countries. PMID:25848544

Influence of manufacturing practices on quality of pharmaceutical products manufactured in Kenya.

PubMed

Orwa, J A; Keter, L K; Ouko, S P A; Kibwage, I O; Rukunga, G M

2004-06-01

To establish the quality of pharmaceutical products manufactured by the respective industries in Kenya and determine the effect of manufacturing practices on the quality of these products. Cross-sectional study. Industries examined are in Nairobi, Kenya. Laboratory analysis was carried out using available facilities at Kenya Medical Research Institute and University of Nairobi, Faculty of Pharmacy. Structured Questionnaires were administered to examine how the code of good manufacturing practices has been used in the production of each pharmaceutical product by respective companies. Questionnaires designed to evaluate the distribution and carry out limited post-market surveillance study were administered to community pharmacy outlets. Drugs were sampled and analyzed for their quality according to the respective monographs. The questionnaires administered to the industry included the source of raw materials, quarantine procedure before and after manufacture, manufacturing procedure, quality audit, quality assurance procedure, equipment, and staff. That administered to the pharmacy outlet included availability, affordability and acceptability of locally manufactured pharmaceutical products. Quality analysis of products involved the establishment of the chemical content, dissolution profile, friability, uniformity of weight and identity. For antibiotic suspensions the stability after reconstitution was also determined. There were 15 respondents and two non-respondents from the industry and six out of nine respondents from the pharmacy outlets. The ratio of qualified staff to product range produced seemed to influence product quality. Industries producing several products with only limited number of pharmaceutical staff had more products failing to comply with pharmacopoeia specifications compared to those producing only few products. Nevertheless, all companies are well equipped with quality control equipment, in accordance with type of product manufactured. Private pharmacies stocked few of the locally manufactured products. The reason, they said, was due to low doctor and/or patient acceptance. Compliance with quality specifications as set out in respective monographs was overall 76%. Although the local pharmaceutical industries have adopted good manufacturing practices leading to many good quality products currently in commerce, these manufacturing practices are not comprehensive and measures need to be taken to continue improving them.

Features of Pharmaceutical Compounding in the Republic of Tajikistan.

PubMed

Alfred-Ugbenbo, D S; Valiev, A H; Zdoryk, O A; Georgiyants, V A

2017-01-01

Despite the deep assortment of finished pharmaceutical products and the reduction in the number of compounding and hospital pharmacies in the Republic of Tajikistan, the need for extemporal medicinal products is still preserved and remains relevant. This article discusses the practice of compounding in the Republic of Tajikistan. History, laws, limits, regulatory institutions, protocols for compounding pharmacy set up, challenges, equipment, extemporaneous formulations, quality control, and storage within regulatory framework are discussed. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Generic Pharmaceutical Association (GPhA) - 2015 CMC Workshop (June 9-10, 2015 - Bethesda, Maryland, USA).

PubMed

Komlos, D

2015-07-01

Nearly 400 professionals attended the 2-day Generic Pharmaceutical Association (GPhA) workshop dedicated to fostering discussions on the FDA's chemistry, manufacturing and controls (CMC) expectations for abbreviated new drug applications (ANDAs), enhanced regulatory filing requirements, and other topics, as CMC takes root in the Office of Pharmaceutical Quality (OPQ). Following the keynote address by Janet Woodcock, Director of the FDA's Center for Drug Evaluation and Research (CDER) and Acting Director of OPQ, and an update from the Office of Generic Drugs (OGD) by Ted Sherwood, Acting Director of the OGD's Office of Regulatory Operations, plenary sessions took place covering OPQ updates, management plans, Generic Drug User Fee Amendments of 2012 (GDUFA) backlog, year 1 and 2 cohorts, drug substance, defining starting materials, quality related refuse-to-receive standards, risk and team-based integrated quality assessment, deficiencies and information requests - CMC submissions, emerging technologies, compliance and inspection, lifecycle management of drug products, quality metrics, pharmaceutically relevant dissolution specifications, and communication and project management. This report will provide a summary of conference highlights. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

Legislative, educational, policy and other interventions targeting physicians' interaction with pharmaceutical companies: a systematic review.

PubMed

Alkhaled, Lina; Kahale, Lara; Nass, Hala; Brax, Hneine; Fadlallah, Racha; Badr, Kamal; Akl, Elie A

2014-07-01

Pharmaceutical company representatives likely influence the prescribing habits and professional behaviour of physicians. The objective of this study was to systematically review the effects of interventions targeting practising physicians' interactions with pharmaceutical companies. We included observational studies, non-randomised controlled trials (non-RCTs) and RCTs evaluating legislative, educational, policy or other interventions targeting the interactions between physicians and pharmaceutical companies. The search strategy included an electronic search of MEDLINE and EMBASE. Two reviewers performed duplicate and independent study selection, data abstraction and assessment of risk of bias. We assessed the risk of bias in each included study. We summarised the findings narratively because the nature of the data did not allow a meta-analysis to be conducted. We assessed the quality of evidence by outcome using the GRADE methodology. Of 11 189 identified citations, one RCT and three observational studies met the eligibility criteria. All four studies specifically targeted one type of interaction with pharmaceutical companies, that is, interactions with drug representatives. The RCT provided moderate quality evidence of no effect of a 'collaborative approach' between the pharmaceutical industry and a health authority. The three observational studies provided low quality evidence suggesting a positive effect of policies aiming to reduce interaction between physicians and pharmaceutical companies (by restricting free samples, promotional material, and meetings with pharmaceutical company representatives) on prescription behaviour. We identified too few studies to allow strong conclusions. Available evidence suggests a potential impact of policies aiming to reduce interaction between physicians and drug representatives on physicians' prescription behaviour. We found no evidence concerning interventions affecting other types of interaction with pharmaceutical companies. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Impact of pharmaceutical care on knowledge, quality of life and satisfaction of postmenopausal women with osteoporosis.

PubMed

Lai, Pauline Siew Mei; Chua, Siew Siang; Chan, Siew Pheng

2013-08-01

This study describes the analysis of secondary outcomes from a previously published randomised controlled trial, which assessed the effects of pharmaceutical care on medication adherence, persistence and bone turnover markers. The main focus of this manuscript is the effect of the provision of pharmaceutical care on these secondary outcomes, and details on the design of the intervention provided, the osteoporosis care plan and materials used to deliver the intervention. To evaluate the effects of pharmaceutical care on knowledge, quality of life (QOL) and satisfaction of postmenopausal osteoporotic women prescribed bisphosphonates, and their associating factors. Randomised controlled trial, performed at an osteoporosis clinic of a tertiary hospital in Malaysia. Postmenopausal women diagnosed with osteoporosis (T-score ≤-2.5/lowtrauma fracture), just been prescribed weekly alendronate/risedronate were randomly allocated to receive intervention or standard care (controls). Intervention participants received a medication review, education on osteoporosis, risk factors, lifestyle modifications, goals of therapy, side effects and the importance of medication adherence at months 0, 3, 6 and 12. Knowledge, QOL and satisfaction. A total of 198 postmenopausal osteoporotic women were recruited: intervention = 100 and control = 98. Intervention participants reported significantly higher knowledge scores at months 3 (72.50 vs. 62.50 %), 6 (75.00 vs. 65.00 %) and 12 (78.75 vs. 68.75 %) compared to control participants. QOL scores were also lower (which indicates better QOL) at months 3 (29.33 vs. 38.41), 6 (27.50 vs. 36.56) and 12 (27.53 vs. 37.56) compared to control participants. Similarly, satisfaction score was higher in intervention participants (93.67 vs. 84.83 %). More educated women, with back pain, who were provided pharmaceutical care had better knowledge levels. Similarly, older, more educated women, with previous falls and back pain tend to have poorer QOL, whilst women who exercised more frequently and were provided pharmaceutical care had better QOL. Satisfaction also increased as QOL increases and when provided pharmaceutical care. The provision of pharmaceutical care improved knowledge, QOL and satisfaction in Malaysian postmenopausal osteoporotic women, showing that pharmacists have the potential to improve patients' overall bone health. Policymakers should consider placing a clinical pharmacist in the osteoporosis clinic to provide counselling to improve these outcomes.

76 FR 57746 - Conference on the International Conference on Harmonisation Q10 Pharmaceutical Quality System: A...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

... ``Pharmaceutical Quality System (ICH Q10) Conference: A Practical Approach to Effective Life- Cycle Implementation... Pharmaceutical Quality System across the product life cycle according to the ICH Q10 model. These companies are...] Conference on the International Conference on Harmonisation Q10 Pharmaceutical Quality System: A Practical...

Control Systems Engineering in Continuous Pharmaceutical Manufacturing May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Myerson, Allan S; Krumme, Markus; Nasr, Moheb; Thomas, Hayden; Braatz, Richard D

2015-03-01

This white paper provides a perspective of the challenges, research needs, and future directions for control systems engineering in continuous pharmaceutical processing. The main motivation for writing this paper is to facilitate the development and deployment of control systems technologies so as to ensure quality of the drug product. Although the main focus is on small-molecule pharmaceutical products, most of the same statements apply to biological drug products. An introduction to continuous manufacturing and control systems is followed by a discussion of the current status and technical needs in process monitoring and control, systems integration, and risk analysis. Some key points are that: (1) the desired objective in continuous manufacturing should be the satisfaction of all critical quality attributes (CQAs), not for all variables to operate at steady-state values; (2) the design of start-up and shutdown procedures can significantly affect the economic operation of a continuous manufacturing process; (3) the traceability of material as it moves through the manufacturing facility is an important consideration that can at least in part be addressed using residence time distributions; and (4) the control systems technologies must assure quality in the presence of disturbances, dynamics, uncertainties, nonlinearities, and constraints. Direct measurement, first-principles and empirical model-based predictions, and design space approaches are described for ensuring that CQA specifications are met. Ways are discussed for universities, regulatory bodies, and industry to facilitate working around or through barriers to the development of control systems engineering technologies for continuous drug manufacturing. Industry and regulatory bodies should work with federal agencies to create federal funding mechanisms to attract faculty to this area. Universities should hire faculty interested in developing first-principles models and control systems technologies for drug manufacturing that are easily transportable to industry. Industry can facilitate the move to continuous manufacturing by working with universities on the conception of new continuous pharmaceutical manufacturing process unit operations that have the potential to make major improvements in product quality, controllability, or reduced capital and/or operating costs. Regulatory bodies should ensure that: (1) regulations and regulatory practices promote, and do not derail, the development and implementation of continuous manufacturing and control systems engineering approaches; (2) the individuals who approve specific regulatory filings are sufficiently trained to make good decisions regarding control systems approaches; (3) provide regulatory clarity and eliminate/reduce regulatory risks; (4) financially support the development of high-quality training materials for use of undergraduate students, graduate students, industrial employees, and regulatory staff; (5) enhance the training of their own technical staff by financially supporting joint research projects with universities in the development of continuous pharmaceutical manufacturing processes and the associated control systems engineering theory, numerical algorithms, and software; and (6) strongly encourage the federal agencies that support research to fund these research areas. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Control systems engineering in continuous pharmaceutical manufacturing. May 20-21, 2014 Continuous Manufacturing Symposium.

PubMed

Myerson, Allan S; Krumme, Markus; Nasr, Moheb; Thomas, Hayden; Braatz, Richard D

2015-03-01

This white paper provides a perspective of the challenges, research needs, and future directions for control systems engineering in continuous pharmaceutical processing. The main motivation for writing this paper is to facilitate the development and deployment of control systems technologies so as to ensure quality of the drug product. Although the main focus is on small-molecule pharmaceutical products, most of the same statements apply to biological drug products. An introduction to continuous manufacturing and control systems is followed by a discussion of the current status and technical needs in process monitoring and control, systems integration, and risk analysis. Some key points are that: (1) the desired objective in continuous manufacturing should be the satisfaction of all critical quality attributes (CQAs), not for all variables to operate at steady-state values; (2) the design of start-up and shutdown procedures can significantly affect the economic operation of a continuous manufacturing process; (3) the traceability of material as it moves through the manufacturing facility is an important consideration that can at least in part be addressed using residence time distributions; and (4) the control systems technologies must assure quality in the presence of disturbances, dynamics, uncertainties, nonlinearities, and constraints. Direct measurement, first-principles and empirical model-based predictions, and design space approaches are described for ensuring that CQA specifications are met. Ways are discussed for universities, regulatory bodies, and industry to facilitate working around or through barriers to the development of control systems engineering technologies for continuous drug manufacturing. Industry and regulatory bodies should work with federal agencies to create federal funding mechanisms to attract faculty to this area. Universities should hire faculty interested in developing first-principles models and control systems technologies for drug manufacturing that are easily transportable to industry. Industry can facilitate the move to continuous manufacturing by working with universities on the conception of new continuous pharmaceutical manufacturing process unit operations that have the potential to make major improvements in product quality, controllability, or reduced capital and/or operating costs. Regulatory bodies should ensure that: (1) regulations and regulatory practices promote, and do not derail, the development and implementation of continuous manufacturing and control systems engineering approaches; (2) the individuals who approve specific regulatory filings are sufficiently trained to make good decisions regarding control systems approaches; (3) provide regulatory clarity and eliminate/reduce regulatory risks; (4) financially support the development of high-quality training materials for use of undergraduate students, graduate students, industrial employees, and regulatory staff; (5) enhance the training of their own technical staff by financially supporting joint research projects with universities in the development of continuous pharmaceutical manufacturing processes and the associated control systems engineering theory, numerical algorithms, and software; and (6) strongly encourage the federal agencies that support research to fund these research areas. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

A tutorial for developing a topical cream formulation based on the Quality by Design approach.

PubMed

Simões, Ana; Veiga, Francisco; Vitorino, Carla; Figueiras, Ana

2018-06-20

The pharmaceutical industry has entered in a new era, as there is a growing interest in increasing the quality standards of dosage forms, through the implementation of more structured development and manufacturing approaches. For many decades, the manufacturing of drug products was controlled by a regulatory framework to guarantee the quality of the final product through a fixed process and exhaustive testing. Limitations related to the Quality by Test (QbT) system have been widely acknowledged. The emergence of Quality by Design (QbD) as a systematic and risk-based approach introduced a new quality concept based on a good understanding of how raw materials and process parameters influence the final quality profile. Although the QbD system has been recognized as a revolutionary approach to product development and manufacturing, its full implementation in the pharmaceutical field is still limited. This is particularly evident in the case of semisolid complex formulation development. The present review aims at establishing a practical QbD framework to describe all stages comprised in the pharmaceutical development of a conventional cream in a comprehensible manner. Copyright © 2018. Published by Elsevier Inc.

Near infrared spectroscopy based monitoring of extraction processes of raw material with the help of dynamic predictive modeling

NASA Astrophysics Data System (ADS)

Wang, Haixia; Suo, Tongchuan; Wu, Xiaolin; Zhang, Yue; Wang, Chunhua; Yu, Heshui; Li, Zheng

2018-03-01

The control of batch-to-batch quality variations remains a challenging task for pharmaceutical industries, e.g., traditional Chinese medicine (TCM) manufacturing. One difficult problem is to produce pharmaceutical products with consistent quality from raw material of large quality variations. In this paper, an integrated methodology combining the near infrared spectroscopy (NIRS) and dynamic predictive modeling is developed for the monitoring and control of the batch extraction process of licorice. With the spectra data in hand, the initial state of the process is firstly estimated with a state-space model to construct a process monitoring strategy for the early detection of variations induced by the initial process inputs such as raw materials. Secondly, the quality property of the end product is predicted at the mid-course during the extraction process with a partial least squares (PLS) model. The batch-end-time (BET) is then adjusted accordingly to minimize the quality variations. In conclusion, our study shows that with the help of the dynamic predictive modeling, NIRS can offer the past and future information of the process, which enables more accurate monitoring and control of process performance and product quality.

Multivariate analysis in the pharmaceutical industry: enabling process understanding and improvement in the PAT and QbD era.

PubMed

Ferreira, Ana P; Tobyn, Mike

2015-01-01

In the pharmaceutical industry, chemometrics is rapidly establishing itself as a tool that can be used at every step of product development and beyond: from early development to commercialization. This set of multivariate analysis methods allows the extraction of information contained in large, complex data sets thus contributing to increase product and process understanding which is at the core of the Food and Drug Administration's Process Analytical Tools (PAT) Guidance for Industry and the International Conference on Harmonisation's Pharmaceutical Development guideline (Q8). This review is aimed at providing pharmaceutical industry professionals an introduction to multivariate analysis and how it is being adopted and implemented by companies in the transition from "quality-by-testing" to "quality-by-design". It starts with an introduction to multivariate analysis and the two methods most commonly used: principal component analysis and partial least squares regression, their advantages, common pitfalls and requirements for their effective use. That is followed with an overview of the diverse areas of application of multivariate analysis in the pharmaceutical industry: from the development of real-time analytical methods to definition of the design space and control strategy, from formulation optimization during development to the application of quality-by-design principles to improve manufacture of existing commercial products.

Cost benefit of investment on quality in pharmaceutical manufacturing: WHO GMP pre- and post-certification of a Nigerian pharmaceutical manufacturer.

PubMed

Anyakora, Chimezie; Ekwunife, Obinna; Alozie, Faith; Esuga, Mopa; Ukwuru, Jonathan; Onya, Steve; Nwokike, Jude

2017-09-18

Pharmaceutical companies in Africa need to invest in both facilities and quality management systems to achieve good manufacturing practice (GMP) compliance. Compliance to international GMP standards is important to the attainment of World Health Organization (WHO) prequalification. However, most of the local pharmaceutical manufacturing companies may be deterred from investing in quality because of many reasons, ranging from financial constraints to technical capacity. This paper primarily evaluates benefits against the cost of investing in GMP, using a Nigerian pharmaceutical company, Chi Pharmaceuticals Limited, as a case study. This paper also discusses how to drive more local manufacturers to invest in quality to attain GMP compliance; and proffers practical recommendations for local manufacturers who would want to invest in quality to meet ethical and regulatory obligations. The cost benefit of improving the quality of Chi Pharmaceuticals Limited's facilities and system to attain WHO GMP certification for the production of zinc sulfate 20-mg dispersible tablets was calculated by dividing the annual benefits derived from quality improvement interventions by the annual costs of implementing quality improvement interventions, referred to as a benefit-cost ratio (BCR). Cost benefit of obtaining WHO GMP certification for the production of zinc sulfate 20-mg dispersible tablets was 5.3 (95% confidence interval of 5.0-5.5). Investment in quality improvement intervention is cost-beneficial for local manufacturing companies. Governments and regulators in African countries should support pharmaceutical companies striving to invest in quality. Collaboration of local manufacturing companies with global companies will further improve quality. Local pharmaceutical companies should be encouraged to key into development opportunities available for pharmaceutical companies in Africa.

21 CFR 211.160 - General requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... drafted by the appropriate organizational unit and reviewed and approved by the quality control unit. The...: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Laboratory Controls § 211.160... procedures, or other laboratory control mechanisms required by this subpart, including any change in such...

A practical discussion of risk management for manufacturing of pharmaceutical products.

PubMed

Mollah, A Hamid; Baseman, Harold S; Long, Mike; Rathore, Anurag S

2014-01-01

Quality risk management (QRM) is now a regulatory expectation, and it makes good business sense. The goal of the risk assessment is to increase process understanding and deliver safe and effective product to the patients. Risk analysis and management is an acceptable and effective way to minimize patient risk and determine the appropriate level of controls in manufacturing. While understanding the elements of QRM is important, knowing how to apply them in the manufacturing environment is essential for effective process performance and control. This article will preview application of QRM in pharmaceutical and biopharmaceutical manufacturing to illustrate how QRM can help the reader achieve that objective. There are several areas of risk that a drug company may encounter in pharmaceutical manufacturing, specifically addressing oral solid and liquid formulations. QRM tools can be used effectively to identify the risks and develop strategy to minimize or control them. Risks are associated throughout the biopharmaceutical manufacturing process-from raw material supply through manufacturing and filling operations to final distribution via a controlled cold chain process. Assessing relevant attributes and risks for biotechnology-derived products is more complicated and challenging for complex pharmaceuticals. This paper discusses key risk factors in biopharmaceutical manufacturing. Successful development and commercialization of pharmaceutical products is all about managing risks. If a company was to take zero risk, most likely the path to commercialization would not be commercially viable. On the other hand, if the risk taken was too much, the product is likely to have a suboptimal safety and efficacy profile and thus is unlikely to be a successful product. This article addresses the topic of quality risk management with the key objective of minimizing patient risk while creating an optimal process and product. Various tools are presented to aid implementation of these concepts. © PDA, Inc. 2014.

Impact of pharmaceutical care on the quality of life of patients with Chagas disease and heart failure: randomized clinical trial

PubMed Central

2012-01-01

Background Pharmaceutical care is the direct interaction between pharmacist and patient, in order to improve therapeutic compliance, promote adequate pharmacotherapeutic follow-up, and improve quality of life. Pharmaceutical care may be effective in reducing complications and in improving the quality of life of patients with chronic diseases, like Chagas heart disease, while bringing a positive impact on health system costs. The morbidity and mortality indexes for patients with Chagas heart disease are high, especially if this heart disease is complicated by heart failure. In this setting, we hypothesize that pharmaceutical care might be an important tool for the clinical management of these patients by improving their quality of life, as a better compliance to their treatment and the avoidance and prompt correction of drug-related problems will minimize their symptoms, improve their functional class, and decrease the number of hospital admissions. Therefore, the aim of this trial is to evaluate the contribution of pharmaceutical care to clinical treatment of patients with Chagas heart disease complicated by heart failure. Methods/design A prospective, single-center randomized clinical trial will be conducted in patients with Chagas heart disease complicated by heart failure. A total of 88 patients will be randomly assigned into two parallel groups: an intervention group will receive standard care and pharmaceutical care, and a control group will receive only standard care. Both groups will be subjected to a follow-up period of 12 months. The primary outcome of this trial is the evaluation of quality of life, measured by the 36-item short-form and the Minnesota Living with Heart Failure Questionnaire. Secondary outcomes include drug-related problems, exercise tolerance as measured by the standard six-minute-walk test, and compliance. Discussion Patients with Chagas heart disease complicated by heart failure under pharmaceutical care are expected to improve their quality of life, present with a lower incidence of drug-related problems, improve their functional capacity, and improve in their compliance to treatment. Trial registration ClinicalTrials.gov Identifier: NCT01566617 PMID:23270509

Impact of pharmaceutical care on the quality of life of patients with Chagas disease and heart failure: randomized clinical trial.

PubMed

Sperandio da Silva, Gilberto M; Chambela, Mayara C; Sousa, Andrea S; Sangenis, Luiz Henrique C; Xavier, Sergio S; Costa, Andréa R; Brasil, Pedro Emmanuel A A; Hasslocher-Moreno, Alejandro M; Saraiva, Roberto M

2012-12-27

Pharmaceutical care is the direct interaction between pharmacist and patient, in order to improve therapeutic compliance, promote adequate pharmacotherapeutic follow-up, and improve quality of life. Pharmaceutical care may be effective in reducing complications and in improving the quality of life of patients with chronic diseases, like Chagas heart disease, while bringing a positive impact on health system costs. The morbidity and mortality indexes for patients with Chagas heart disease are high, especially if this heart disease is complicated by heart failure. In this setting, we hypothesize that pharmaceutical care might be an important tool for the clinical management of these patients by improving their quality of life, as a better compliance to their treatment and the avoidance and prompt correction of drug-related problems will minimize their symptoms, improve their functional class, and decrease the number of hospital admissions. Therefore, the aim of this trial is to evaluate the contribution of pharmaceutical care to clinical treatment of patients with Chagas heart disease complicated by heart failure. A prospective, single-center randomized clinical trial will be conducted in patients with Chagas heart disease complicated by heart failure. A total of 88 patients will be randomly assigned into two parallel groups: an intervention group will receive standard care and pharmaceutical care, and a control group will receive only standard care. Both groups will be subjected to a follow-up period of 12 months. The primary outcome of this trial is the evaluation of quality of life, measured by the 36-item short-form and the Minnesota Living with Heart Failure Questionnaire. Secondary outcomes include drug-related problems, exercise tolerance as measured by the standard six-minute-walk test, and compliance. Patients with Chagas heart disease complicated by heart failure under pharmaceutical care are expected to improve their quality of life, present with a lower incidence of drug-related problems, improve their functional capacity, and improve in their compliance to treatment. ClinicalTrials.gov Identifier: NCT01566617.

Concentrations of selected pharmaceuticals and antibiotics in south-central Pennsylvania waters, March through September 2006

USGS Publications Warehouse

Loper, Connie A.; Crawford, J. Kent; Otto, Kim L.; Manning, Rhonda L.; Meyer, Michael T.; Furlong, Edward T.

2007-01-01

This report presents environmental and quality-control data from analyses of 15 pharmaceutical and 31 antibiotic compounds in water samples from streams and wells in south-central Pennsylvania. The analyses are part of a study by the U.S. Geological Survey (USGS) in cooperation with the Pennsylvania Department of Environmental Protection (PADEP) to define concentrations of selected emerging contaminants in streams and well water in Pennsylvania. Sampling was conducted at 11 stream sites and at 6 wells in 9 counties of south-central Pennsylvania. Five of the streams received municipal wastewater and 6 of the streams received runoff from agricultural areas dominated by animal-feeding operations. For all 11 streams, samples were collected at locations upstream and downstream of the municipal effluents or animal-feeding operations. All six wells were in agricultural settings. A total of 120 environmental samples and 21 quality-control samples were analyzed for the study. Samples were collected at each site in March/April, May, July, and September 2006 to obtain information on changes in concentration that could be related to seasonal use of compounds.For streams, 13 pharmaceuticals and 11 antibiotics were detected at least 1 time. Detections included analytical results that were estimated or above the minimum reporting limits. Seventy-eight percent of all detections were analyzed in samples collected downstream from municipal-wastewater effluents. For streams receiving wastewater effluents, the pharmaceuticals caffeine and para-xanthine (a degradation product of caffeine) had the greatest concentrations, 4.75 μg/L (micrograms per liter) and 0.853 μg/L, respectively. Other pharmaceuticals and their respective maximum concentrations were carbamazepine (0.516 μg/L) and ibuprofen (0.277 μg/L). For streams receiving wastewater effluents, the antibiotic azithromycin had the greatest concentration (1.65 μg/L), followed by sulfamethoxazole (1.34 μg/L), ofloxacin (0.329 μg/L), and trimethoprim (0.256 μg/L).For streams receiving runoff from animal-feeding operations, the only pharmaceuticals detected were acetaminophen, caffeine, cotinine, diphenhydramine, and carbamazepine. The maximum concentration for pharmaceuticals was 0.053 μg/L. Three streams receiving runoff from animal-feeding operations had detections of one or more antibiotic compound--oxytetracycline, sulfadimethoxine, sulfamethoxazole, and tylosin. The maximum concentration for antibiotics was 0.157 μg/L. The average number of compounds (pharmaceuticals and antibiotics) detected in sites downstream from animal-feeding operations was three. The average number of compounds detected downstream from municipal-wastewater effluents was 13.For wells used to supply livestock, four compounds were detected--two pharmaceuticals (cotinine and diphenhydramine) and two antibiotics (tylosin and sulfamethoxazole). There were five detections in all the well samples. The maximum concentration detected in well water was for cotinine, estimated to be 0.024 μg/L.Seasonal occurrence of pharmaceutical and antibiotic compounds in stream water varied by compound and site type. At four stream sites, the same compounds were detected in all four seasonal samples. At other sites, pharmaceutical or antibiotic compounds were detected only one time in seasonal samples. Winter samples collected in streams receiving municipalwastewater effluent had the greatest number of compounds detected (21). Research analytical methods were used to determine concentrations for pharmaceuticals and antibiotics. To assist in evaluating the quality of the analyses, detailed information is presented on laboratory methodology and results from qualitycontrol samples. Quality-control data include results for nine blanks, nine duplicate environmental sample pairs, and three laboratory-spiked environmental samples as well as the recoveries of compounds in laboratory surrogates and laboratory reagent spikes.

A new roadmap for biopharmaceutical drug product development: Integrating development, validation, and quality by design.

PubMed

Martin-Moe, Sheryl; Lim, Fredric J; Wong, Rita L; Sreedhara, Alavattam; Sundaram, Jagannathan; Sane, Samir U

2011-08-01

Quality by design (QbD) is a science- and risk-based approach to drug product development. Although pharmaceutical companies have historically used many of the same principles during development, this knowledge was not always formally captured or proactively submitted to regulators. In recent years, the US Food and Drug Administration has also recognized the need for more controls in the drug manufacturing processes, especially for biological therapeutics, and it has recently launched an initiative for Pharmaceutical Quality for the 21st Century to modernize pharmaceutical manufacturing and improve product quality. In the biopharmaceutical world, the QbD efforts have been mainly focused on active pharmaceutical ingredient processes with little emphasis on drug product development. We present a systematic approach to biopharmaceutical drug product development using a monoclonal antibody as an example. The approach presented herein leverages scientific understanding of products and processes, risk assessments, and rational experimental design to deliver processes that are consistent with QbD philosophy without excessive incremental effort. Data generated using these approaches will not only strengthen data packages to support specifications and manufacturing ranges but hopefully simplify implementation of postapproval changes. We anticipate that this approach will positively impact cost for companies, regulatory agencies, and patients, alike. Copyright © 2011 Wiley-Liss, Inc.

Ethical pharmaceutical promotion and communications worldwide: codes and regulations

PubMed Central

2014-01-01

The international pharmaceutical industry has made significant efforts towards ensuring compliant and ethical communication and interaction with physicians and patients. This article presents the current status of the worldwide governance of communication practices by pharmaceutical companies, concentrating on prescription-only medicines. It analyzes legislative, regulatory, and code-based compliance control mechanisms and highlights significant developments, including the 2006 and 2012 revisions of the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Code of Practice. Developments in international controls, largely built upon long-established rules relating to the quality of advertising material, have contributed to clarifying the scope of acceptable company interactions with healthcare professionals. This article aims to provide policy makers, particularly in developing countries, with an overview of the evolution of mechanisms governing the communication practices, such as the distribution of promotional or scientific material and interactions with healthcare stakeholders, relating to prescription-only medicines. PMID:24679064

Ethical pharmaceutical promotion and communications worldwide: codes and regulations.

PubMed

Francer, Jeffrey; Izquierdo, Jose Zamarriego; Music, Tamara; Narsai, Kirti; Nikidis, Chrisoula; Simmonds, Heather; Woods, Paul

2014-03-29

The international pharmaceutical industry has made significant efforts towards ensuring compliant and ethical communication and interaction with physicians and patients. This article presents the current status of the worldwide governance of communication practices by pharmaceutical companies, concentrating on prescription-only medicines. It analyzes legislative, regulatory, and code-based compliance control mechanisms and highlights significant developments, including the 2006 and 2012 revisions of the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA) Code of Practice.Developments in international controls, largely built upon long-established rules relating to the quality of advertising material, have contributed to clarifying the scope of acceptable company interactions with healthcare professionals. This article aims to provide policy makers, particularly in developing countries, with an overview of the evolution of mechanisms governing the communication practices, such as the distribution of promotional or scientific material and interactions with healthcare stakeholders, relating to prescription-only medicines.

[Analysis and countermeasure for quality risk in process of traditional Chinese medicine preparations].

PubMed

Yang, Ming; Yang, Yuan-Zhen; Wang, Ya-Qi; Wu, Zhen-Feng; Wang, Xue-Cheng; Luo, Jing

2017-03-01

Product quality relies on not only testing methods,but also the design and development, production control and product manufacturing all aspects of logistics management. Quality comes from the process control level.Therefore, it is very important to accurately identify the factors that may induce quality risk in the production process and quality control measures correspondingly.This article systematically analyzes the source of the quality risk of all aspects of the production process in traditional Chinese medicine preparation. Discussing ways and methods of quality risk identification of traditional Chinese medicine preparation and providing references for perfecting the whole process quality management of traditional Chinese medicine preparation. Copyright© by the Chinese Pharmaceutical Association.

Disintegration Test of Health Food Products Containing Ginkgo Biloba L. or Vitex Agnus-Castus L. in the Japanese Market.

PubMed

Sato-Masumoto, Naoko; Masada, Sayaka; Takahashi, Satoshi; Terasaki, Sachiko; Yokota, Yoichi; Hakamatsuka, Takashi; Goda, Yukihiro

2015-04-23

For many years now, a number of Western herbs have been widely used in health food products in Japan and as pharmaceuticals in Europe. There are few or no mandated criteria concerning the quality of these herbal health food products, thus clarification is warranted. Here, we performed disintegration tests of 26 pharmaceutical and health food products containing the Western herbs ginkgo leaf and chaste tree fruit, in accord with the Japanese Pharmacopoeia. All eight pharmaceutical herbal products found in the European market completely disintegrated within the defined test time, and 11 of the 18 tested herbal products distributed as health foods in Japan disintegrated. Among the incompatible products identified in the Pharmacopoeia test, some products remained intact after incubation in water for 60 min. To ensure the efficacy of Western herbal products sold as health food in Japan, quality control, including disintegration, is therefore recommended, even though these products are not regulated under the Pharmaceutical Affairs Law.

Disintegration Test of Health Food Products Containing Ginkgo Biloba L. or Vitex Agnus-Castus L. in the Japanese Market

PubMed Central

Sato-Masumoto, Naoko; Masada, Sayaka; Takahashi, Satoshi; Terasaki, Sachiko; Yokota, Yoichi; Hakamatsuka, Takashi; Goda, Yukihiro

2015-01-01

For many years now, a number of Western herbs have been widely used in health food products in Japan and as pharmaceuticals in Europe. There are few or no mandated criteria concerning the quality of these herbal health food products, thus clarification is warranted. Here, we performed disintegration tests of 26 pharmaceutical and health food products containing the Western herbs ginkgo leaf and chaste tree fruit, in accord with the Japanese Pharmacopoeia. All eight pharmaceutical herbal products found in the European market completely disintegrated within the defined test time, and 11 of the 18 tested herbal products distributed as health foods in Japan disintegrated. Among the incompatible products identified in the Pharmacopoeia test, some products remained intact after incubation in water for 60 min. To ensure the efficacy of Western herbal products sold as health food in Japan, quality control, including disintegration, is therefore recommended, even though these products are not regulated under the Pharmaceutical Affairs Law. PMID:28930200

Developing a tool for the preparation of GMP audit of pharmaceutical contract manufacturer.

PubMed

Linna, Anu; Korhonen, Mirka; Mannermaa, Jukka-Pekka; Airaksinen, Marja; Juppo, Anne Mari

2008-06-01

Outsourcing is rapidly growing in the pharmaceutical industry. When the manufacturing activities are outsourced, control of the product's quality has to be maintained. One way to confirm contract manufacturer's GMP (Good Manufacturing Practice) compliance is auditing. Audits can be supported for instance by using GMP questionnaires. The objective of this study was to develop a tool for the audit preparation of pharmaceutical contract manufacturers and to validate its contents by using Delphi method. At this phase of the study the tool was developed for non-sterile finished product contract manufacturers. A modified Delphi method was used with expert panel consisting of 14 experts from pharmaceutical industry, authorities and university. The content validity of the developed tool was assessed by a Delphi questionnaire round. The response rate in Delphi questionnaire round was 86%. The tool consisted of 103 quality items, from which 90 (87%) achieved the pre-defined agreement rate level (75%). Thirteen quality items which did not achieve the pre-defined agreement rate were excluded from the tool. The expert panel suggested only minor changes to the tool. The results show that the content validity of the developed audit preparation tool was good.

[Issues regarding the legal regulation of drugs in Argentina].

PubMed

Bignone, Inés M

2006-01-01

This work describes the main functions and attributions of the National Administration of Medicines, Food and Medical Technology (Administración Nacional de Medicamentos, Alimentos y Tecnología Médica, ANMAT) of Argentina in the control and supervision of pharmaceutical products. The four properties that a medicine must full-fill (efficacy, safety, quality and accessibility) are described, and the role of ANMAT with regard to each one is specified. Criteria employed in the classification of pharmaceutical products marketed in Argentina with the regulatory agency permission are specified, and a reference to pharmaceutical products not registered before the Agency is also included.

A case study: application of statistical process control tool for determining process capability and sigma level.

PubMed

Chopra, Vikram; Bairagi, Mukesh; Trivedi, P; Nagar, Mona

2012-01-01

Statistical process control is the application of statistical methods to the measurement and analysis of variation process. Various regulatory authorities such as Validation Guidance for Industry (2011), International Conference on Harmonisation ICH Q10 (2009), the Health Canada guidelines (2009), Health Science Authority, Singapore: Guidance for Product Quality Review (2008), and International Organization for Standardization ISO-9000:2005 provide regulatory support for the application of statistical process control for better process control and understanding. In this study risk assessments, normal probability distributions, control charts, and capability charts are employed for selection of critical quality attributes, determination of normal probability distribution, statistical stability, and capability of production processes, respectively. The objective of this study is to determine tablet production process quality in the form of sigma process capability. By interpreting data and graph trends, forecasting of critical quality attributes, sigma process capability, and stability of process were studied. The overall study contributes to an assessment of process at the sigma level with respect to out-of-specification attributes produced. Finally, the study will point to an area where the application of quality improvement and quality risk assessment principles for achievement of six sigma-capable processes is possible. Statistical process control is the most advantageous tool for determination of the quality of any production process. This tool is new for the pharmaceutical tablet production process. In the case of pharmaceutical tablet production processes, the quality control parameters act as quality assessment parameters. Application of risk assessment provides selection of critical quality attributes among quality control parameters. Sequential application of normality distributions, control charts, and capability analyses provides a valid statistical process control study on process. Interpretation of such a study provides information about stability, process variability, changing of trends, and quantification of process ability against defective production. Comparative evaluation of critical quality attributes by Pareto charts provides the least capable and most variable process that is liable for improvement. Statistical process control thus proves to be an important tool for six sigma-capable process development and continuous quality improvement.

75 FR 59973 - Approval and Promulgation of Air Quality Implementation Plans; Maryland; Control of Volatile...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-29

...; Cleaning of high precision optics; Stripping; Janitorial cleaning; cleaning of resin, coating, ink, and... laboratories; Cleaning operations in medical device or pharmaceutical manufacturing; and Cleaning operations related to performance or quality assurance testing of coatings, inks, or adhesives. COMAR 26.11.19.09-1...

Raman spectroscopy as a process analytical technology for pharmaceutical manufacturing and bioprocessing.

PubMed

Esmonde-White, Karen A; Cuellar, Maryann; Uerpmann, Carsten; Lenain, Bruno; Lewis, Ian R

2017-01-01

Adoption of Quality by Design (QbD) principles, regulatory support of QbD, process analytical technology (PAT), and continuous manufacturing are major factors effecting new approaches to pharmaceutical manufacturing and bioprocessing. In this review, we highlight new technology developments, data analysis models, and applications of Raman spectroscopy, which have expanded the scope of Raman spectroscopy as a process analytical technology. Emerging technologies such as transmission and enhanced reflection Raman, and new approaches to using available technologies, expand the scope of Raman spectroscopy in pharmaceutical manufacturing, and now Raman spectroscopy is successfully integrated into real-time release testing, continuous manufacturing, and statistical process control. Since the last major review of Raman as a pharmaceutical PAT in 2010, many new Raman applications in bioprocessing have emerged. Exciting reports of in situ Raman spectroscopy in bioprocesses complement a growing scientific field of biological and biomedical Raman spectroscopy. Raman spectroscopy has made a positive impact as a process analytical and control tool for pharmaceutical manufacturing and bioprocessing, with demonstrated scientific and financial benefits throughout a product's lifecycle.

Regulatory Perspectives on Continuous Pharmaceutical Manufacturing: Moving From Theory to Practice: September 26-27, 2016, International Symposium on the Continuous Manufacturing of Pharmaceuticals.

PubMed

Nasr, Moheb M; Krumme, Markus; Matsuda, Yoshihiro; Trout, Bernhardt L; Badman, Clive; Mascia, Salvatore; Cooney, Charles L; Jensen, Keith D; Florence, Alastair; Johnston, Craig; Konstantinov, Konstantin; Lee, Sau L

2017-11-01

Continuous manufacturing plays a key role in enabling the modernization of pharmaceutical manufacturing. The fate of this emerging technology will rely, in large part, on the regulatory implementation of this novel technology. This paper, which is based on the 2nd International Symposium on the Continuous Manufacturing of Pharmaceuticals, describes not only the advances that have taken place since the first International Symposium on Continuous Manufacturing of Pharmaceuticals in 2014, but the regulatory landscape that exists today. Key regulatory concepts including quality risk management, batch definition, control strategy, process monitoring and control, real-time release testing, data processing and management, and process validation/verification are outlined. Support from regulatory agencies, particularly in the form of the harmonization of regulatory expectations, will be crucial to the successful implementation of continuous manufacturing. Collaborative efforts, among academia, industry, and regulatory agencies, are the optimal solution for ensuring a solid future for this promising manufacturing technology. Copyright © 2017 American Pharmacists Association®. All rights reserved.

WHO Expert Committee on Specifications for Pharmaceutical Preparations.

PubMed

2012-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use: Development of monographs for The International Pharmacopoeia; WHO good manufacturing practices: water for pharmaceutical use; Pharmaceutical development of multisource (generic) pharmaceutical products--points to consider; Guidelines on submission of documentation for a multisource (generic) finished pharmaceutical product for the WHO Prequalification of Medicines Programme: quality part; Development of paediatric medicines: points to consider in formulation; Recommendations for quality requirements for artemisinin as a starting material in the production of antimalarial active pharmaceutical ingredients.

Introduction to the application of QbD principles for the development of monoclonal antibodies.

PubMed

Finkler, Christof; Krummen, Lynne

2016-09-01

Quality by Design (QbD) is a global regulatory initiative with the goal of enhancing pharmaceutical development through the proactive design of pharmaceutical manufacturing process and controls to consistently deliver the intended performance of the product. The principles of pharmaceutical development relevant to QbD are described in the ICH guidance documents (ICHQ8-11). An integrated set of risk assessments and their related elements developed at Roche/Genentech were designed to provide an overview of product and process knowledge for the production of a recombinant monoclonal antibody. This chapter introduces a publication series on the application of Quality by Design for biopharmaceuticals, with a focus on the development of recombinant monoclonal antibodies. The development of and overview on the QbD concept applied by Roche and Genentech is described and essential QbD elements are presented. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Connecting pills and people: an ethnography of the pharmaceutical nexus in Odisha, India.

PubMed

Seeberg, Jens

2012-06-01

This article explores the impact of intensive competition within the pharmaceutical industry and among private providers on health care in an Indian city. In-depth interviewing and clinical observation were used over a period of 18 months. Private practitioners and chemists who provided regular services to inhabitants of a poor neighborhood in central Bhubaneswar were included. Fierce competition in private health in Odisha, India, reduced quality of care for the poor. The pharmaceutical industry exploited weak links in the health system to push drugs aggressively, including through illegal channels. The private health market is organized in small "network molecules" that maximize profit at the cost of health. The large private share of health care in India and stiff competition are detrimental for primary care in urban India. Free government services are urgently needed and a planned health insurance scheme should be linked to quality control measures.

Application of attenuated total reflectance Fourier transform infrared spectroscopy for determination of cefixime in oral pharmaceutical formulations.

PubMed

Kandhro, Aftab A; Laghari, Abdul Hafeez; Mahesar, Sarfaraz A; Saleem, Rubina; Nelofar, Aisha; Khan, Salman Tariq; Sherazi, S T H

2013-11-01

A quick and reliable analytical method for the quantitative assessment of cefixime in orally administered pharmaceutical formulations is developed by using diamond cell attenuated total reflectance (ATR) Fourier transform infrared (FT-IR) spectroscopy as an easy procedure for quality control laboratories. The standards for calibration were prepared in aqueous medium ranging from 350 to 6000mg/kg. The calibration model was developed based on partial least square (PLS) using finger print region of FT-IR spectrum in the range from 1485 to 887cm(-1). Excellent coefficient of determination (R(2)) was achieved as high as 0.99976 with root mean square error of 44.8 for calibration. The application of diamond cell (smart accessory) ATR FT-IR proves a reliable determination of cefixime in pharmaceutical formulations to assess the quality of the final product. Copyright © 2013 Elsevier B.V. All rights reserved.

Towards quality by design in pharmaceutical manufacturing: modelling and control of air jet mills

NASA Astrophysics Data System (ADS)

Bhonsale, Satyajeet; Telen, Dries; Stokbroekx, Bard; Van Impe, Jan

2017-06-01

Milling is an important step in pharmaceutical manufacturing as it not only determines the final formulation of the drug product, but also influences the bioavailability and dissolution rate of the active pharmaceutical ingredient (API). In this respect, the air jet mill (AJM) is most commonly used in the pharmaceutical industry as it is a non-contaminating and non-degrading self-classifying process capable of delivering narrow particle size distributions (PSD). Keeping the principles of Quality by Design in mind, the Critical Process Parameters (CPPs) of the AJM have been identified to be the pressures at the grinding nozzles, and the feed rate which affect the PSD, surface charge and the morphology of the product (i.e. the Critical Material Attributes (CMAs)). For the purpose of this research, the PSD is considered to be the only relevant CMA. A population balance based model is proposed to simulate the dynamics milling operation by utilizing the concept of breakage functions. This model agrees qualitatively with experimental observations of the air jet mill unit present at Janssen Pharmaceutica but further steps for model validation need to be carried out.

Transformation in the pharmaceutical industry: transformation-induced quality risks--a survey.

PubMed

Shafiei, Nader; Ford, James L; Morecroft, Charles W; Lisboa, Paulo J; Taylor, Mark J; Mouzughi, Yusra

2013-01-01

This paper is the fourth in a series that explores ongoing transformation in the pharmaceutical industry and its impact on pharmaceutical quality from the perspective of risk identification. The aim of this paper is to validate proposed quality risks through elicitation of expert opinion and define the resultant quality risk model. Expert opinion was obtained using a questionnaire-based survey with participants with recognized expertise in pharmaceutical regulation, product lifecycle, or technology. The results of the survey validate the theoretical and operational evidence in support of the four main pharmaceutical transformation triggers previously identified. The quality risk model resulting from the survey indicated a firm relationship between the pharmaceutical quality risks and regulatory compliance outcomes during the marketing approval and post-marketing phases of the product lifecycle and a weaker relationship during the pre-market evaluation phase. In this paper through conduct of an expert opinion survey the proposed quality risks carried forward from an earlier part of the research are validated and resultant quality risk model is defined. The survey results validate the theoretical and operational evidence previously identified. The quality risk model indicates that transformation-related risks have a larger regulatory compliance impact during product approval, manufacturing, distribution, and commercial use than during the development phase.

Pharmaceutical Price Controls and Minimum Efficacy Regulation: Evidence from the United States and Italy

PubMed Central

Atella, Vincenzo; Bhattacharya, Jay; Carbonari, Lorenzo

2012-01-01

Objective This article examines the relationship between drug price and drug quality and how it varies across two of the most common regulatory regimes in the pharmaceutical market: minimum efficacy standards (MES) and a mix of MES and price control mechanisms (MES + PC). Data Sources Our primary data source is the Tufts-New England Medical Center-Cost Effectiveness Analysis Registry which have been merged with price data taken from MEPS (for the United States) and AIFA (for Italy). Study Design Through a simple model of adverse selection we model the interaction between firms, heterogeneous buyers, and the regulator. Principal Findings The theoretical analysis provides two results. First, an MES regime provides greater incentives to produce high-quality drugs. Second, an MES + PC mix reduces the difference in price between the highest and lowest quality drugs on the market. Conclusion The empirical analysis based on United States and Italian data corroborates these results. PMID:22091623

Occurrence of pharmaceuticals in a water supply system and related human health risk assessment.

PubMed

de Jesus Gaffney, Vanessa; Almeida, Cristina M M; Rodrigues, Alexandre; Ferreira, Elisabete; Benoliel, Maria João; Cardoso, Vitor Vale

2015-04-01

A monitoring study of 31 pharmaceuticals along Lisbon's drinking water supply system was implemented, which comprised the analysis of 250 samples including raw water (surface water and groundwater), and drinking water. Of the 31 pharmaceutical compounds, only sixteen were quantified in the analyzed samples, with levels ranging from 0.005 to 46 ng/L in raw water samples and 0.09-46 ng/L in drinking water samples. The human health risk assessment performed showed that appreciable risks to the consumer's health arising from exposure to trace levels of pharmaceuticals in drinking water are extremely unlikely, as RQs values were all below 0.001. Also, pharmaceuticals were selected as indicators to be used as a tool to control the quality of raw water and the treatment efficiency in the drinking water treatment plants. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pharmacy specialists' attitudes toward pharmaceutical service quality at community pharmacies.

PubMed

Urbonas, Gvidas; Jakušovaitė, Irayda; Savickas, Arūnas

2010-01-01

The main objective of this study was to analyze pharmacy specialists' attitudes toward the quality of pharmaceutical services at Lithuanian community pharmacies. Between April and June 2009, a total of 471 Lithuanian community pharmacy specialists completed a questionnaire designed to evaluate their attitudes toward the quality of pharmaceutical services at community pharmacies. The main dimensions of pharmaceutical service quality were extracted by principal component analysis. Two main dimensions of pharmaceutical service quality were extracted: pharmacotherapeutic aspects (provision of information about drug therapy, possible side effects, health promotion, the amount of time spent with a patient, and the ascertainment that a patient understood the provided information) and socioeconomic aspects (considering patient's needs and financial capabilities, making a patient confident with the services provided). Pharmacy specialists evaluated the quality of both dimensions positively, but the quality of the first dimension was rated significantly worse than that of the second dimension. The attitudes of pharmacy specialists working at independent pharmacies were more positive toward pharmacotherapeutic aspects as compared to the specialists working at chain or state pharmacies. Pharmacotherapeutic aspects were rated better by pharmacy specialists, aged ≥ 55 years, than those younger than 45 years. Moreover, the attitudes of 45-54-year-old pharmacy specialists toward the socioeconomic aspects were more positive as compared with those of 35-44-year olds. Pharmacists rated the socioeconomic aspects of pharmaceutical service quality worse as compared with pharmacy technicians. The attitudes of pharmacy specialists working at pharmacies with 6-9 specialists were more negative toward pharmacotherapeutic aspects than those of the pharmacies with 1-2 specialists. Pharmacy specialists working at pharmacies with ≥ 10 specialists reported lower scores of socioeconomic aspects as compared to those working at pharmacies with fewer specialists. Men evaluated both pharmacotherapeutic and socioeconomic aspects worse than women. The evaluation of pharmaceutical service quality did not differ by pharmacy location. Two dimensions of pharmaceutical service quality were determined. According to Lithuanian pharmacy specialists, the quality of pharmacotherapeutic aspects at community pharmacies was worse than that of socioeconomic aspects. The evaluation of the quality of pharmaceutical service significantly differed according to the specialists' sex, age, qualification, and type and size of pharmacies.

Recent trends in laboratory automation in the pharmaceutical industry.

PubMed

Rutherford, M L; Stinger, T

2001-05-01

The impact of robotics and automation on the pharmaceutical industry over the last two decades has been significant. In the last ten years, the emphasis of laboratory automation has shifted from the support of manufactured products and quality control of laboratory applications, to research and development. This shift has been the direct result of an increased emphasis on the identification, development and eventual marketing of innovative new products. In this article, we will briefly identify and discuss some of the current trends in laboratory automation in the pharmaceutical industry as they apply to research and development, including screening, sample management, combinatorial chemistry, ADME/Tox and pharmacokinetics.

Economic evaluation of a pharmaceutical care program for elderly diabetic and hypertensive patients in primary health care: a 36-month randomized controlled clinical trial.

PubMed

Obreli-Neto, Paulo Roque; Marusic, Srecko; Guidoni, Camilo Molino; Baldoni, André de Oliveira; Renovato, Rogério Dias; Pilger, Diogo; Cuman, Roberto Kenji Nakamura; Pereira, Leonardo Régis Leira

2015-01-01

Most diabetic and hypertensive patients, principally the elderly, do not achieve adequate disease control and consume 5%-15% of annual health care budgets. Previous studies verified that pharmaceutical care is useful for achieving adequate disease control in diabetes and hypertension. To evaluate the economic cost and the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) of pharmaceutical care in the management of diabetes and hypertension in elderly patients in a primary public health care system in a developing country. A 36-month randomized controlled clinical trial was performed with 200 patients who were divided into a control group (n = 100) and an intervention group (n = 100). The control group received the usual care offered by the Primary Health Care Unit (medical and nurse consultations). The intervention group received the usual care plus a pharmaceutical care intervention. The intervention and control groups were compared with regard to the direct costs of health services (i.e., general practitioner, specialist, nurse, and pharmacist appointments; emergency room visits; and drug therapy costs) and the ICER per QALY. These evaluations used the health system perspective. No statistically significant difference was found between the intervention and control groups in total direct health care costs ($281.97 ± $49.73 per patient vs. $212.28 ± $43.49 per patient, respectively; P = 0.089); pharmaceutical care added incremental costs of $69.60 (± $7.90) per patient. The ICER per QALY was $53.50 (95% CI = $51.60-$54.00; monetary amounts are given in U.S. dollars). Every clinical parameter evaluated improved for the pharmaceutical care group, whereas these clinical parameters remained unchanged in the usual care group. The difference in differences (DID) tests indicated that for each clinical parameter, the patients in the intervention group improved more from pre to post than the control group (P < 0.001). While pharmaceutical care did not significantly increase total direct health care costs, significantly improved health outcomes were seen. The mean ICER per QALY gained suggests a favorable cost-effectiveness.

Strategy for design NIR calibration sets based on process spectrum and model space: An innovative approach for process analytical technology.

PubMed

Cárdenas, V; Cordobés, M; Blanco, M; Alcalà, M

2015-10-10

The pharmaceutical industry is under stringent regulations on quality control of their products because is critical for both, productive process and consumer safety. According to the framework of "process analytical technology" (PAT), a complete understanding of the process and a stepwise monitoring of manufacturing are required. Near infrared spectroscopy (NIRS) combined with chemometrics have lately performed efficient, useful and robust for pharmaceutical analysis. One crucial step in developing effective NIRS-based methodologies is selecting an appropriate calibration set to construct models affording accurate predictions. In this work, we developed calibration models for a pharmaceutical formulation during its three manufacturing stages: blending, compaction and coating. A novel methodology is proposed for selecting the calibration set -"process spectrum"-, into which physical changes in the samples at each stage are algebraically incorporated. Also, we established a "model space" defined by Hotelling's T(2) and Q-residuals statistics for outlier identification - inside/outside the defined space - in order to select objectively the factors to be used in calibration set construction. The results obtained confirm the efficacy of the proposed methodology for stepwise pharmaceutical quality control, and the relevance of the study as a guideline for the implementation of this easy and fast methodology in the pharma industry. Copyright © 2015 Elsevier B.V. All rights reserved.

[Construction of NIRS-based total quality control system for compound Ejiao oral liquid and relative thinking].

PubMed

Zhang, Yan; Zhang, Lu; Tian, Shou-Sheng; Zhou, Xiang-Shan; Li, Wen-Long; Qu, Hai-Bin

2016-10-01

In this paper, near infrared spectroscopy (NIRS)-based total quality control system of compound Ejiao oral liquid is introduced briefly, including the quality control of raw traditional Chinese medicine (TCM) materials, monitoring and control of the extract and the alkaline precipitation technics, and also the inspection of finished products in both open bottle and non-opening modes. By analyzing and summing up the significance and difficulties, several important problems in the practical applications of NIRS technology are proposed, which will provide references for the similar studies of other TCM products. Copyright© by the Chinese Pharmaceutical Association.

Suspensions as a Valuable Alternative to Extemporaneously Compounded Capsules.

PubMed

Dijkers, Eli; Nanhekhan, Valerie; Thorissen, Astrid; Polonini, Hudson

2017-01-01

The objective of this study was to determine the variation in content of 74 different active pharmaceutical ingredients (APIs) and compare it with what is known in the literature for the content uniformity of extemporaneous prepared capsules. Active pharmaceutical ingredients quantification was performed by high-performance liquid chromatography, via a stability-indicating method. Samples for all active pharmaceutical ingredients were taken throughout a 90-day period and the content was determined. In total, 5,190 different samples were analyzed for 74 different active pharmaceutical ingredients at room (15°C to 25°C) or controlled refrigerated temperature (2°C to 8°C). Each of these datasets was analyzed according to the United States Pharmacopeia Content Uniformity monograph, corrected for the sample number. The mean acceptance values were well within specifications. In addition, all suspensions complied with the criteria defined by the British Pharmacopoeia monograph for Content Uniformity of Liquid Dispersions for both room and controlled refrigerated temperature. In previous studies, it was found that a routine weight variation check is often not sufficient for quality assurance of extemporaneous prepared capsules. Compounded oral liquids show little variation in content for 74 different active pharmaceutical ingredients; therefore, compounded oral liquids are a suitable alternative when compounding individualized medications for patients. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

78 FR 65667 - Agency Information Collection Activities; Submission for Office of Management and Budget Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... Request; Guidance for Industry on Chemistry, Manufacturing, and Controls Postapproval Manufacturing... chemistry, manufacturing, and controls (CMC) postapproval manufacturing changes that FDA has determined will... Pharmaceutical Product Quality Initiative and its risk-based approach to CMC review, FDA has evaluated the types...

Validation Study of Rapid Assays of Bioburden, Endotoxins and Other Contamination.

PubMed

Shintani, Hideharu

2016-01-01

Microbial testing performed in support of pharmaceutical and biopharmaceutical production falls into three main categories: detection (qualitative), enumeration (quantitative), and characterization/identification. Traditional microbiological methods are listed in the compendia and discussed by using the conventional growth-based techniques, which are labor intensive and time consuming. In general, such tests require several days of incubation for microbial contamination (bioburden) to be detected, and therefore management seldom is able to take proactive corrective measures. In addition, microbial growth is limited by the growth medium used and incubation conditions, thus impacting testing sensitivity, accuracy, and reproducibility. 　For more than 20 years various technology platforms for rapid microbiological methods (RMM) have been developed, and many have been readily adopted by the food industry and clinical microbiology laboratories. Their use would certainly offer drug companies faster test turnaround times to accommodate the aggressive deadlines for manufacturing processes and product release. Some rapid methods also offer the possibility for real-time microbial analyses, enabling management to respond to microbial contamination events in a more timely fashion, and can provide cost savings and higher efficiencies in quality control testing laboratories. Despite the many proven business and quality benefits and the fact that the FDA's initiative to promote the use of process analytical technology (PAT) includes rapid microbial methods, pharmaceutical and biopharmaceutical industries have been somewhat slow to embrace alternative microbial methodologies for several reasons. The major reason is that the bioburden counts detected by the incubation method and rapid assay are greatly divergent. 　The use of rapid methods is a dynamic field in applied microbiology and one that has gained increased attention nationally and internationally over time. This topic has been extensively addressed at conferences and in published documents around the world. More recently, the use of alternative methods for control of the microbiological quality of pharmaceutical products and materials used in pharmaceutical production has been addressed by the compendia in an attempt to facilitate implementation of these technologies by pharmaceutical companies. The author presents some of the rapid method technologies under evaluation or in use by pharmaceutical microbiologists and the current status of the implementation of alternative microbial methods.

Analytical quality by design: a tool for regulatory flexibility and robust analytics.

PubMed

Peraman, Ramalingam; Bhadraya, Kalva; Padmanabha Reddy, Yiragamreddy

2015-01-01

Very recently, Food and Drug Administration (FDA) has approved a few new drug applications (NDA) with regulatory flexibility for quality by design (QbD) based analytical approach. The concept of QbD applied to analytical method development is known now as AQbD (analytical quality by design). It allows the analytical method for movement within method operable design region (MODR). Unlike current methods, analytical method developed using analytical quality by design (AQbD) approach reduces the number of out-of-trend (OOT) results and out-of-specification (OOS) results due to the robustness of the method within the region. It is a current trend among pharmaceutical industry to implement analytical quality by design (AQbD) in method development process as a part of risk management, pharmaceutical development, and pharmaceutical quality system (ICH Q10). Owing to the lack explanatory reviews, this paper has been communicated to discuss different views of analytical scientists about implementation of AQbD in pharmaceutical quality system and also to correlate with product quality by design and pharmaceutical analytical technology (PAT).

Analytical Quality by Design: A Tool for Regulatory Flexibility and Robust Analytics

PubMed Central

Bhadraya, Kalva; Padmanabha Reddy, Yiragamreddy

2015-01-01

Very recently, Food and Drug Administration (FDA) has approved a few new drug applications (NDA) with regulatory flexibility for quality by design (QbD) based analytical approach. The concept of QbD applied to analytical method development is known now as AQbD (analytical quality by design). It allows the analytical method for movement within method operable design region (MODR). Unlike current methods, analytical method developed using analytical quality by design (AQbD) approach reduces the number of out-of-trend (OOT) results and out-of-specification (OOS) results due to the robustness of the method within the region. It is a current trend among pharmaceutical industry to implement analytical quality by design (AQbD) in method development process as a part of risk management, pharmaceutical development, and pharmaceutical quality system (ICH Q10). Owing to the lack explanatory reviews, this paper has been communicated to discuss different views of analytical scientists about implementation of AQbD in pharmaceutical quality system and also to correlate with product quality by design and pharmaceutical analytical technology (PAT). PMID:25722723

Effectiveness of the Dader Method for pharmaceutical care in patients with bipolar I disorder: EMDADER-TAB: study protocol for a randomized controlled trial

PubMed Central

2014-01-01

Background Bipolar I disorder (BD-I) is a chronic mental illness characterized by the presence of one or more manic episodes, or both depressive and manic episodes, usually separated by asymptomatic intervals. Pharmacists can contribute to the management of BD-I, mainly with the use of effective and safe drugs, and improve the patient’s life quality through pharmaceutical care. Some studies have shown the effect of pharmaceutical care in the achievement of therapeutic goals in different illnesses; however, to our knowledge, there is a lack of randomized controlled trials designed to assess the effect of pharmacist intervention in patients with BD. The aim of this study is to assess the effectiveness of the Dader Method for pharmaceutical care in patients with BD-I. Methods/design Randomized, controlled, prospective, single-center clinical trial with duration of 12 months will be performed to compare the effect of Dader Method of pharmaceutical care with the usual care process of patients in a psychiatric clinic. Patients diagnosed with BD-I aged between 18 and 65 years who have been discharged or referred from outpatients service of the San Juan de Dios Clinic (Antioquia, Colombia) will be included. Patients will be randomized into the intervention group who will receive pharmaceutical care provided by pharmacists working in collaboration with psychiatrists, or into the control group who will receive usual care and verbal-written counseling regarding BD. Study outcomes will be assessed at baseline and at 3, 6, 9, and 12 months after randomization. The primary outcome will be to measure the number of hospitalizations, emergency service consultations, and unscheduled outpatient visits. Effectiveness, safety, adherence, and quality of life will be assessed as secondary outcomes. Statistical analyses will be performed using two-tailed McNemar tests, Pearson chi-square tests, and Student’s t-tests; a P value <0.05 will be considered as statistically significant. Discussion As far as we know, this is the first randomized controlled trial to assess the effect of the Dader Method for pharmaceutical care in patients with BD-I and it could generate valuable information and recommendations about the role of pharmacists in the improvement of therapeutic goals, solution of drug-related problems, and adherence. Trial registration Registration number NCT01750255 on August 6, 2012. First patient randomized on 24 November 2011. PMID:24885673

Databases as policy instruments. About extending networks as evidence-based policy.

PubMed

de Bont, Antoinette; Stoevelaar, Herman; Bal, Roland

2007-12-07

This article seeks to identify the role of databases in health policy. Access to information and communication technologies has changed traditional relationships between the state and professionals, creating new systems of surveillance and control. As a result, databases may have a profound effect on controlling clinical practice. We conducted three case studies to reconstruct the development and use of databases as policy instruments. Each database was intended to be employed to control the use of one particular pharmaceutical in the Netherlands (growth hormone, antiretroviral drugs for HIV and Taxol, respectively). We studied the archives of the Dutch Health Insurance Board, conducted in-depth interviews with key informants and organized two focus groups, all focused on the use of databases both in policy circles and in clinical practice. Our results demonstrate that policy makers hardly used the databases, neither for cost control nor for quality assurance. Further analysis revealed that these databases facilitated self-regulation and quality assurance by (national) bodies of professionals, resulting in restrictive prescription behavior amongst physicians. The databases fulfill control functions that were formerly located within the policy realm. The databases facilitate collaboration between policy makers and physicians, since they enable quality assurance by professionals. Delegating regulatory authority downwards into a network of physicians who control the use of pharmaceuticals seems to be a good alternative for centralized control on the basis of monitoring data.

Investigation of pharmaceuticals in processed animal by-products by liquid chromatography coupled to high-resolution mass spectrometry.

PubMed

Nácher-Mestre, Jaime; Ibáñez, María; Serrano, Roque; Boix, Clara; Bijlsma, Lubertus; Lunestad, Bjørn Tore; Hannisdal, Rita; Alm, Martin; Hernández, Félix; Berntssen, Marc H G

2016-07-01

There is an on-going trend for developing more sustainable salmon feed in which traditionally applied marine feed ingredients are replaced with alternatives. Processed animal products (PAPs) have been re-authorized as novel high quality protein ingredients in 2013. These PAPs may harbor undesirable substances such as pharmaceuticals and metabolites which are not previously associated with salmon farming, but might cause a potential risk for feed and food safety. To control these contaminants, an analytical strategy based on a generic extraction followed by ultra-high performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-HRMS) using quadrupole time-of-flight mass analyzer (QTOF MS) was applied for wide scope screening. Quality control samples, consisting of PAP commodities spiked at 0.02, 0.1 and 0.2 mg/kg with 150 analytes, were injected in every sample batch to verify the overall method performance. The methodology was applied to 19 commercially available PAP samples from six different types of matrices from the EU animal rendering industry. This strategy allows assessing possible emergent risk exposition of the salmon farming industry to 1005 undesirables, including pharmaceuticals, several dyes and relevant metabolites. Copyright © 2016 Elsevier Ltd. All rights reserved.

Paper analytical devices for fast field screening of beta lactam antibiotics and antituberculosis pharmaceuticals.

PubMed

Weaver, Abigail A; Reiser, Hannah; Barstis, Toni; Benvenuti, Michael; Ghosh, Debarati; Hunckler, Michael; Joy, Brittney; Koenig, Leah; Raddell, Kellie; Lieberman, Marya

2013-07-02

Reports of low-quality pharmaceuticals have been on the rise in the past decade, with the greatest prevalence of substandard medicines in developing countries, where lapses in manufacturing quality control or breaches in the supply chain allow substandard medicines to reach the marketplace. Here, we describe inexpensive test cards for fast field screening of pharmaceutical dosage forms containing beta lactam antibiotics or combinations of the four first-line antituberculosis (TB) drugs. The devices detect the active pharmaceutical ingredients (APIs) ampicillin, amoxicillin, rifampicin, isoniazid, ethambutol, and pyrazinamide and also screen for substitute pharmaceuticals, such as acetaminophen and chloroquine that may be found in counterfeit pharmaceuticals. The tests can detect binders and fillers such as chalk, talc, and starch not revealed by traditional chromatographic methods. These paper devices contain 12 lanes, separated by hydrophobic barriers, with different reagents deposited in the lanes. The user rubs some of the solid pharmaceutical across the lanes and dips the edge of the paper into water. As water climbs up the lanes by capillary action, it triggers a library of different chemical tests and a timer to indicate when the tests are completed. The reactions in each lane generate colors to form a "color bar code" which can be analyzed visually by comparison with standard outcomes. Although quantification of the APIs is poor compared with conventional analytical methods, the sensitivity and selectivity for the analytes is high enough to pick out suspicious formulations containing no API or a substitute API as well as formulations containing APIs that have been "cut" with inactive ingredients.

Paper analytical devices for fast field screening of beta lactam antibiotics and anti-tuberculosis pharmaceuticals

PubMed Central

Weaver, Abigail A.; Reiser, Hannah; Barstis, Toni; Benvenuti, Michael; Ghosh, Debarati; Hunckler, Michael; Joy, Brittney; Koenig, Leah; Raddell, Kellie; Lieberman, Marya

2013-01-01

Reports of low quality pharmaceuticals have been on the rise in the last decade with the greatest prevalence of substandard medicines in developing countries, where lapses in manufacturing quality control or breaches in the supply chain allow substandard medicines to reach the marketplace. Here, we describe inexpensive test cards for fast field screening of pharmaceutical dosage forms containing beta lactam antibiotics or combinations of the four first-line antituberculosis (TB) drugs. The devices detect the active pharmaceutical ingredients (APIs) ampicillin, amoxicillin, rifampicin, isoniazid, ethambutol, and pyrazinamide, and also screen for substitute pharmaceuticals such as acetaminophen and chloroquine that may be found in counterfeit pharmaceuticals. The tests can detect binders and fillers like chalk, talc, and starch not revealed by traditional chromatographic methods. These paper devices contain twelve lanes, separated by hydrophobic barriers, with different reagents deposited in the lanes. The user rubs some of the solid pharmaceutical across the lanes and dips the edge of the paper into water. As water climbs up the lanes by capillary action, it triggers a library of different chemical tests and a timer to indicate when the tests are completed. The reactions in each lane generate colors to form a “color bar code” which can be analyzed visually by comparison to standard outcomes. While quantification of the APIs is poor compared to conventional analytical methods, the sensitivity and selectivity for the analytes is high enough to pick out suspicious formulations containing no API or a substitute API, as well as formulations containing APIs that have been “cut” with inactive ingredients. PMID:23725012

Donated chemical probes for open science

PubMed Central

Ackloo, Suzanne; Arrowsmith, Cheryl H; Bauser, Marcus; Baryza, Jeremy L; Blagg, Julian; Böttcher, Jark; Bountra, Chas; Brown, Peter J; Bunnage, Mark E; Carter, Adrian J; Damerell, David; Dötsch, Volker; Drewry, David H; Edwards, Aled M; Edwards, James; Elkins, Jon M; Fischer, Christian; Frye, Stephen V; Gollner, Andreas; Grimshaw, Charles E; IJzerman, Adriaan; Hanke, Thomas; Hartung, Ingo V; Hitchcock, Steve; Howe, Trevor; Hughes, Terry V; Laufer, Stefan; Li, Volkhart MJ; Liras, Spiros; Marsden, Brian D; Matsui, Hisanori; Mathias, John; O'Hagan, Ronan C; Owen, Dafydd R; Pande, Vineet; Rauh, Daniel; Rosenberg, Saul H; Roth, Bryan L; Schneider, Natalie S; Scholten, Cora; Singh Saikatendu, Kumar; Simeonov, Anton; Takizawa, Masayuki; Tse, Chris; Thompson, Paul R; Treiber, Daniel K; Viana, Amélia YI; Wells, Carrow I; Willson, Timothy M; Zuercher, William J; Knapp, Stefan

2018-01-01

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of innovative high-quality probes, including all probe-associated data, control compounds and recommendations on use (https://openscienceprobes.sgc-frankfurt.de/). Here we describe the chemical tools and target-related knowledge that have been made available, and encourage others to join the project. PMID:29676732

Industry's View on Using Quality Control, Biorelevant, and Clinically Relevant Dissolution Tests for Pharmaceutical Development, Registration, and Commercialization.

PubMed

Grady, Haiyan; Elder, David; Webster, Gregory K; Mao, Yun; Lin, Yiqing; Flanagan, Talia; Mann, James; Blanchard, Andy; Cohen, Michael J; Lin, Judy; Kesisoglou, Filippos; Hermans, Andre; Abend, Andreas; Zhang, Limin; Curran, David

2018-01-01

This article intends to summarize the current views of the IQ Consortium Dissolution Working Group, which comprises various industry companies, on the roles of dissolution testing throughout pharmaceutical product development, registration, commercialization, and beyond. Over the past 3 decades, dissolution testing has evolved from a routine and straightforward test as a component of end-product release into a comprehensive set of tools that the developer can deploy at various stages of the product life cycle. The definitions of commonly used dissolution approaches, how they relate to one another and how they may be applied in modern drug development, and life cycle management is described in this article. Specifically, this article discusses the purpose, advantages, and limitations of quality control, biorelevant, and clinically relevant dissolution methods. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

[Importance of Post-Marketing Studies in Gathering of Clinical Evidences for Proper Usage of Anti-Cancer Drugs, and the StudyRequirements for Their Credibility].

PubMed

Inagaki, Osamu

2016-04-01

Pharmaceutical companies recognize the importance of post-marketing studies because they are crucial in the generation of clinical evidences for the usage of new medicines. To generate clinical evidences, quality of post-marketing studies should be well controlled from view point of "ethical conduction" and "reliability of results". In addition, control of conflict of interest (COI) between researchers and industries is also indispensable and is requested for the transparency of the studies. Japan Pharmaceutical Manufacturers Association(JPMA)stresses its commitment to the progressof transparency in post-marketing studies.

Quality Assurance and Quality Control, Part 2.

PubMed

Akers, Michael J

2015-01-01

The tragedy surrounding the New England Compounding Center and contaminated steroid syringe preparations clearly points out what can happen if quality-assurance and quality-control procedures are not strictly practiced in the compounding of sterile preparations. This article is part 2 of a two-part article on requirements to comply with United States Pharmacopeia general chapters <797> and <1163> with respect to quality assurance of compounded sterile preparations. Part 1 covered documentation requirements, inspection procedures, compounding accuracy checks, and part of a discussion on bacterial endotoxin testing. Part 2 covers sterility testing, the completion from part 1 on bacterial endotoxin testing, a brief dicussion of United States Pharmacopeia <1163>, and advances in pharmaceutical quality systems.

Quality in the pharmaceutical industry - A literature review.

PubMed

Haleem, Reham M; Salem, Maissa Y; Fatahallah, Faten A; Abdelfattah, Laila E

2015-10-01

The aim of this study is to:a.Highlight the most important guidelines and practices of quality in the pharmaceutical industry.b.Organize such guidelines and practices to create a guide to pave the way for other researchers who would like to dig deeper into these guidelines and practices. A review was conducted of 102 publications; 56 publications were concerned with the pharmaceutical quality directly while 46 publications were concerned with the general quality practices. The content of those sources was analyzed and the following themes were identified:a.Research theme 1: Guidelines of the pharmaceutical quality.b.Research theme 2: General practices recently applied in the pharmaceutical industry. The following guidelines were identified and reviewed: WHO guidelines, FDA guidelines, EU guidelines and ICH guidelines in the research theme I. In research theme II; the following topics were identified and reviewed: quality risk management, quality by design, corrective actions and preventive actions, process capability analysis, Six Sigma, process analytical technology, lean manufacturing, total quality management, ISO series and HACCP. Upon reviewing the previously highlighted guidelines and the practices that are widely applied in the pharmaceutical industry, it was noticed that there is an abundant number of papers and articles that explain the general guidelines and practices but the literature lack those describing application; case studies of the pharmaceutical factories applying those guidelines and significance of those guidelines and practices. It is recommended that the literature would invest more in the area of application and significance of guidelines and practices. New case studies should be done to prove the feasibility of such practices.

WHO Expert Committee on Specifications for Pharmaceutical Preparations.

PubMed

2014-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use, in addition to 20 monographs and general texts for inclusion in The International Pharmacopoeia and 11 new International Chemical Reference Substances. The International Pharmacopoeia--updating mechanism for the section on radiopharmaceuticals; WHO good manufacturing practices for pharmaceutical products: main principles; Model quality assurance system for procurement agencies; Assessment tool based on the model quality assurance system for procurement agencies: aide-memoire for inspection; Guidelines on submission of documentation for prequalification of finished pharmaceutical products approved by stringent regulatory authorities; and Guidelines on submission of documentation for a multisource (generic) finished pharmaceutical product: quality part.

Innovations in coating technology.

PubMed

Behzadi, Sharareh S; Toegel, Stefan; Viernstein, Helmut

2008-01-01

Despite representing one of the oldest pharmaceutical techniques, coating of dosage forms is still frequently used in pharmaceutical manufacturing. The aims of coating range from simply masking the taste or odour of drugs to the sophisticated controlling of site and rate of drug release. The high expectations for different coating technologies have required great efforts regarding the development of reproducible and controllable production processes. Basically, improvements in coating methods have focused on particle movement, spraying systems, and air and energy transport. Thereby, homogeneous distribution of coating material and increased drying efficiency should be accomplished in order to achieve high end product quality. Moreover, given the claim of the FDA to design the end product quality already during the manufacturing process (Quality by Design), the development of analytical methods for the analysis, management and control of coating processes has attracted special attention during recent years. The present review focuses on recent patents claiming improvements in pharmaceutical coating technology and intends to first familiarize the reader with the available procedures and to subsequently explain the application of different analytical tools. Aiming to structure this comprehensive field, coating technologies are primarily divided into pan and fluidized bed coating methods. Regarding pan coating procedures, pans rotating around inclined, horizontal and vertical axes are reviewed separately. On the other hand, fluidized bed technologies are subdivided into those involving fluidized and spouted beds. Then, continuous processing techniques and improvements in spraying systems are discussed in dedicated chapters. Finally, currently used analytical methods for the understanding and management of coating processes are reviewed in detail in the last section of the review.

Information from pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing: a systematic review.

PubMed

Spurling, Geoffrey K; Mansfield, Peter R; Montgomery, Brett D; Lexchin, Joel; Doust, Jenny; Othman, Noordin; Vitry, Agnes I

2010-10-19

Pharmaceutical companies spent $57.5 billion on pharmaceutical promotion in the United States in 2004. The industry claims that promotion provides scientific and educational information to physicians. While some evidence indicates that promotion may adversely influence prescribing, physicians hold a wide range of views about pharmaceutical promotion. The objective of this review is to examine the relationship between exposure to information from pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing. We searched for studies of physicians with prescribing rights who were exposed to information from pharmaceutical companies (promotional or otherwise). Exposures included pharmaceutical sales representative visits, journal advertisements, attendance at pharmaceutical sponsored meetings, mailed information, prescribing software, and participation in sponsored clinical trials. The outcomes measured were quality, quantity, and cost of physicians' prescribing. We searched Medline (1966 to February 2008), International Pharmaceutical Abstracts (1970 to February 2008), Embase (1997 to February 2008), Current Contents (2001 to 2008), and Central (The Cochrane Library Issue 3, 2007) using the search terms developed with an expert librarian. Additionally, we reviewed reference lists and contacted experts and pharmaceutical companies for information. Randomized and observational studies evaluating information from pharmaceutical companies and measures of physicians' prescribing were independently appraised for methodological quality by two authors. Studies were excluded where insufficient study information precluded appraisal. The full text of 255 articles was retrieved from electronic databases (7,185 studies) and other sources (138 studies). Articles were then excluded because they did not fulfil inclusion criteria (179) or quality appraisal criteria (18), leaving 58 included studies with 87 distinct analyses. Data were extracted independently by two authors and a narrative synthesis performed following the MOOSE guidelines. Of the set of studies examining prescribing quality outcomes, five found associations between exposure to pharmaceutical company information and lower quality prescribing, four did not detect an association, and one found associations with lower and higher quality prescribing. 38 included studies found associations between exposure and higher frequency of prescribing and 13 did not detect an association. Five included studies found evidence for association with higher costs, four found no association, and one found an association with lower costs. The narrative synthesis finding of variable results was supported by a meta-analysis of studies of prescribing frequency that found significant heterogeneity. The observational nature of most included studies is the main limitation of this review. With rare exceptions, studies of exposure to information provided directly by pharmaceutical companies have found associations with higher prescribing frequency, higher costs, or lower prescribing quality or have not found significant associations. We did not find evidence of net improvements in prescribing, but the available literature does not exclude the possibility that prescribing may sometimes be improved. Still, we recommend that practitioners follow the precautionary principle and thus avoid exposure to information from pharmaceutical companies. Please see later in the article for the Editors' Summary.

Information from Pharmaceutical Companies and the Quality, Quantity, and Cost of Physicians' Prescribing: A Systematic Review

PubMed Central

Spurling, Geoffrey K.; Mansfield, Peter R.; Montgomery, Brett D.; Lexchin, Joel; Doust, Jenny; Othman, Noordin; Vitry, Agnes I.

2010-01-01

Background Pharmaceutical companies spent $57.5 billion on pharmaceutical promotion in the United States in 2004. The industry claims that promotion provides scientific and educational information to physicians. While some evidence indicates that promotion may adversely influence prescribing, physicians hold a wide range of views about pharmaceutical promotion. The objective of this review is to examine the relationship between exposure to information from pharmaceutical companies and the quality, quantity, and cost of physicians' prescribing. Methods and Findings We searched for studies of physicians with prescribing rights who were exposed to information from pharmaceutical companies (promotional or otherwise). Exposures included pharmaceutical sales representative visits, journal advertisements, attendance at pharmaceutical sponsored meetings, mailed information, prescribing software, and participation in sponsored clinical trials. The outcomes measured were quality, quantity, and cost of physicians' prescribing. We searched Medline (1966 to February 2008), International Pharmaceutical Abstracts (1970 to February 2008), Embase (1997 to February 2008), Current Contents (2001 to 2008), and Central (The Cochrane Library Issue 3, 2007) using the search terms developed with an expert librarian. Additionally, we reviewed reference lists and contacted experts and pharmaceutical companies for information. Randomized and observational studies evaluating information from pharmaceutical companies and measures of physicians' prescribing were independently appraised for methodological quality by two authors. Studies were excluded where insufficient study information precluded appraisal. The full text of 255 articles was retrieved from electronic databases (7,185 studies) and other sources (138 studies). Articles were then excluded because they did not fulfil inclusion criteria (179) or quality appraisal criteria (18), leaving 58 included studies with 87 distinct analyses. Data were extracted independently by two authors and a narrative synthesis performed following the MOOSE guidelines. Of the set of studies examining prescribing quality outcomes, five found associations between exposure to pharmaceutical company information and lower quality prescribing, four did not detect an association, and one found associations with lower and higher quality prescribing. 38 included studies found associations between exposure and higher frequency of prescribing and 13 did not detect an association. Five included studies found evidence for association with higher costs, four found no association, and one found an association with lower costs. The narrative synthesis finding of variable results was supported by a meta-analysis of studies of prescribing frequency that found significant heterogeneity. The observational nature of most included studies is the main limitation of this review. Conclusions With rare exceptions, studies of exposure to information provided directly by pharmaceutical companies have found associations with higher prescribing frequency, higher costs, or lower prescribing quality or have not found significant associations. We did not find evidence of net improvements in prescribing, but the available literature does not exclude the possibility that prescribing may sometimes be improved. Still, we recommend that practitioners follow the precautionary principle and thus avoid exposure to information from pharmaceutical companies. Please see later in the article for the Editors' Summary PMID:20976098

Emerging technology: A key enabler for modernizing pharmaceutical manufacturing and advancing product quality.

PubMed

O'Connor, Thomas F; Yu, Lawrence X; Lee, Sau L

2016-07-25

Issues in product quality have produced recalls and caused drug shortages in United States (U.S.) in the past few years. These quality issues were often due to outdated manufacturing technologies and equipment as well as lack of an effective quality management system. To ensure consistent supply of safe, effective and high-quality drug products available to the patients, the U.S. Food and Drug Administration (FDA) supports modernizing pharmaceutical manufacturing for improvements in product quality. Specifically, five new initiatives are proposed here to achieve this goal. They include: (i) advancing regulatory science for pharmaceutical manufacturing; (ii) establishing a public-private institute for pharmaceutical manufacturing innovation; (iii) creating incentives for investment in the technological upgrade of manufacturing processes and facilities; (iv) leveraging external expertise for regulatory quality assessment of emerging technologies; and (v) promoting the international harmonization of approaches for expediting the global adoption of emerging technologies. Published by Elsevier B.V.

Terahertz pulsed imaging as an advanced characterisation tool for film coatings--a review.

PubMed

Haaser, Miriam; Gordon, Keith C; Strachan, Clare J; Rades, Thomas

2013-12-05

Solid dosage forms are the pharmaceutical drug delivery systems of choice for oral drug delivery. These solid dosage forms are often coated to modify the physico-chemical properties of the active pharmaceutical ingredients (APIs), in particular to alter release kinetics. Since the product performance of coated dosage forms is a function of their critical coating attributes, including coating thickness, uniformity, and density, more advanced quality control techniques than weight gain are required. A recently introduced non-destructive method to quantitatively characterise coating quality is terahertz pulsed imaging (TPI). The ability of terahertz radiation to penetrate many pharmaceutical materials enables structural features of coated solid dosage forms to be probed at depth, which is not readily achievable with other established imaging techniques, e.g. near-infrared (NIR) and Raman spectroscopy. In this review TPI is introduced and various applications of the technique in pharmaceutical coating analysis are discussed. These include evaluation of coating thickness, uniformity, surface morphology, density, defects and buried structures as well as correlation between TPI measurements and drug release performance, coating process monitoring and scale up. Furthermore, challenges and limitations of the technique are discussed. Copyright © 2013 Elsevier B.V. All rights reserved.

Drug policy in China. Transformations, current status and future prospects.

PubMed

Liu, X; Li, S

1997-07-01

The pharmaceutical sector in China developed rapidly with the implementation of the market-oriented economic reforms, which began at the end of the 1970s. From 1980 to 1988 the production of drugs quadrupled, subsequently increasing at an annual rate of 20%, and consumption of drugs correspondingly increased. The increase in drug production was largely a result of the increase in the number of pharmaceutical companies, particularly the number of private joint ventures, of which there were none in 1980 and 1900 in 1994, accounting for 37% of the total number of pharmaceutical companies. With the transformation of the Chinese pharmaceutical market, some new problems have appeared. The low efficiency of pharmaceutical companies, poor-quality drugs, unfair competition and misuse of drugs have been of great concern to the Chinese government. Some countermeasures have been taken, but the problems remain. Increases in the age of the Chinese population, increases in income and changes in disease patterns, together with membership of the World Trade Organization will promote the development of the pharmaceutical market. However, health-insurance reform, an essential drug list, the separation of drugs from services, and controls on the increases in hospital revenue will reduce the demand for drugs. Pharmaceutical companies in China face both opportunities and challenges. The trend in development of the pharmaceutical market depends on the outcome of the interaction between the factors that increase, and those that decrease, the demand for drugs. While the general trend is towards an increase in the demand for drugs and the expansion of the pharmaceutical market, downward fluctuation is inevitable if effective health reforms of cost control are introduced nationwide.

[Pharmaceutical research progress of rhynchophylla based on chemical stability].

PubMed

Hao, Bo; Yang, Xiu-Juan; Feng, Yi; Hong, Yan-Long

2014-12-01

Rhynchophylla is a Chinese herb commonly used in clinical practice. It's also the primary herb of some famous Chinese herbal compound such as Tianma Gouteng decoction, and Lingyang Gouteng decoction. According the record from many previous materia medica literatures, rhynchophylla should be added later during decoction. Pharmaceutical research showed that rhynchophylla alkaloids were not stable. Which has resulted in many problems in the research and its application. For example, there was not a quantitative determination method in "Chinese Pharmacopoeia" of past and present versions, which seriously impacted its quality control and product application. Firstly, records from previous materia medica literatures and "Chinese Pharmacopoeia" were systematically sorted based on the chemical stability of rhynchophylla. Secondly, pharmaceutical research including chemical compositions and their stability, pharmacological effects, extraction process and quality analysis, was reviewed after reference of literatures published at home and abroad in recent decades. Positive reference and evidence for further research and development of rhynchophylla will be provided in the article.

Quality By Design: Concept To Applications.

PubMed

Swain, Suryakanta; Padhy, Rabinarayan; Jena, Bikash Ranjan; Babu, Sitty Manohar

2018-03-08

Quality by Design is associated to the modern, systematic, scientific and novel approach which is concerned with pre-distinct objectives that not only focus on product, process understanding but also leads to process control. It predominantly signifies the design and product improvement and the manufacturing process in order to fulfill the predefined manufactured goods or final products quality characteristics. It is quite essential to identify desire and required product performance report such as Target Product Profile, typical Quality Target Product Profile (QTPP) and Critical Quality attributes (CQA). This review highlighted about the concepts of QbD design space, for critical material attributes (CMAs) as well as the critical process parameters that can totally affect the CQAs within which the process shall be unaffected and consistently manufacture the required product. Risk assessment tools and design of experiments are its prime components. This paper outlines the basic knowledge of QbD, the key elements; steps as well as various tools for QbD implementation in pharmaceutics field are presented briefly. In addition to this, quite a lot of applications of QbD in numerous pharmaceutical related unit operations are discussed and summarized. This article provides a complete data as well as the road map for universal implementation and application of QbD for pharmaceutical products. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

A Review on Advanced Treatment of Pharmaceutical Wastewater

NASA Astrophysics Data System (ADS)

Guo, Y.; Qi, P. S.; Liu, Y. Z.

2017-05-01

The composition of pharmaceutical wastewater is complex, which is high concentration of organic matter, microbial toxicity, high salt, and difficult to biodegrade. After secondary treatment, there are still trace amounts of suspended solids and dissolved organic matter. To improve the quality of pharmaceutical wastewater effluent, advanced treatment is essential. In this paper, the classification of the pharmaceutical technology was introduced, and the characteristics of pharmaceutical wastewater effluent quality were summarized. The methods of advanced treatment of pharmaceutical wastewater were reviewed afterwards, which included coagulation and sedimentation, flotation, activated carbon adsorption, membrane separation, advanced oxidation processes, membrane separation and biological treatment. Meanwhile, the characteristics of each process were described.

Quality in the pharmaceutical industry – A literature review

PubMed Central

Haleem, Reham M.; Salem, Maissa Y.; Fatahallah, Faten A.; Abdelfattah, Laila E.

2013-01-01

Objectives The aim of this study is to:a.Highlight the most important guidelines and practices of quality in the pharmaceutical industry.b.Organize such guidelines and practices to create a guide to pave the way for other researchers who would like to dig deeper into these guidelines and practices. Design A review was conducted of 102 publications; 56 publications were concerned with the pharmaceutical quality directly while 46 publications were concerned with the general quality practices. The content of those sources was analyzed and the following themes were identified:a.Research theme 1: Guidelines of the pharmaceutical quality.b.Research theme 2: General practices recently applied in the pharmaceutical industry. Main outcome measures The following guidelines were identified and reviewed: WHO guidelines, FDA guidelines, EU guidelines and ICH guidelines in the research theme I. In research theme II; the following topics were identified and reviewed: quality risk management, quality by design, corrective actions and preventive actions, process capability analysis, Six Sigma, process analytical technology, lean manufacturing, total quality management, ISO series and HACCP. Results Upon reviewing the previously highlighted guidelines and the practices that are widely applied in the pharmaceutical industry, it was noticed that there is an abundant number of papers and articles that explain the general guidelines and practices but the literature lack those describing application; case studies of the pharmaceutical factories applying those guidelines and significance of those guidelines and practices. Conclusions It is recommended that the literature would invest more in the area of application and significance of guidelines and practices. New case studies should be done to prove the feasibility of such practices. PMID:26594110

THz spectroscopy: An emerging technology for pharmaceutical development and pharmaceutical Process Analytical Technology (PAT) applications

NASA Astrophysics Data System (ADS)

Wu, Huiquan; Khan, Mansoor

2012-08-01

As an emerging technology, THz spectroscopy has gained increasing attention in the pharmaceutical area during the last decade. This attention is due to the fact that (1) it provides a promising alternative approach for in-depth understanding of both intermolecular interaction among pharmaceutical molecules and pharmaceutical product quality attributes; (2) it provides a promising alternative approach for enhanced process understanding of certain pharmaceutical manufacturing processes; and (3) the FDA pharmaceutical quality initiatives, most noticeably, the Process Analytical Technology (PAT) initiative. In this work, the current status and progress made so far on using THz spectroscopy for pharmaceutical development and pharmaceutical PAT applications are reviewed. In the spirit of demonstrating the utility of first principles modeling approach for addressing model validation challenge and reducing unnecessary model validation "burden" for facilitating THz pharmaceutical PAT applications, two scientific case studies based on published THz spectroscopy measurement results are created and discussed. Furthermore, other technical challenges and opportunities associated with adapting THz spectroscopy as a pharmaceutical PAT tool are highlighted.

Laser-induced breakdown spectroscopy-based investigation and classification of pharmaceutical tablets using multivariate chemometric analysis

PubMed Central

Myakalwar, Ashwin Kumar; Sreedhar, S.; Barman, Ishan; Dingari, Narahara Chari; Rao, S. Venugopal; Kiran, P. Prem; Tewari, Surya P.; Kumar, G. Manoj

2012-01-01

We report the effectiveness of laser-induced breakdown spectroscopy (LIBS) in probing the content of pharmaceutical tablets and also investigate its feasibility for routine classification. This method is particularly beneficial in applications where its exquisite chemical specificity and suitability for remote and on site characterization significantly improves the speed and accuracy of quality control and assurance process. Our experiments reveal that in addition to the presence of carbon, hydrogen, nitrogen and oxygen, which can be primarily attributed to the active pharmaceutical ingredients, specific inorganic atoms were also present in all the tablets. Initial attempts at classification by a ratiometric approach using oxygen to nitrogen compositional values yielded an optimal value (at 746.83 nm) with the least relative standard deviation but nevertheless failed to provide an acceptable classification. To overcome this bottleneck in the detection process, two chemometric algorithms, i.e. principal component analysis (PCA) and soft independent modeling of class analogy (SIMCA), were implemented to exploit the multivariate nature of the LIBS data demonstrating that LIBS has the potential to differentiate and discriminate among pharmaceutical tablets. We report excellent prospective classification accuracy using supervised classification via the SIMCA algorithm, demonstrating its potential for future applications in process analytical technology, especially for fast on-line process control monitoring applications in the pharmaceutical industry. PMID:22099648

Analysis of pharmaceutical preparations containing antihistamine drugs by micellar liquid chromatography.

PubMed

Martínez-Algaba, C; Bermúdez-Saldaña, J M; Villanueva-Camañas, R M; Sagrado, S; Medina-Hernández, M J

2006-02-13

Rapid chromatographic procedures for analytical quality control of pharmaceutical preparations containing antihistamine drugs, alone or together with other kind of compounds are proposed. The method uses C18 stationary phases and micellar mobile phases of cetyltrimethylammonium bromide (CTAB) with either 1-propanol or 1-butanol as organic modifier. The proposed procedures allow the determination of the antihistamines: brompheniramine, chlorcyclizine, chlorpheniramine, diphenhydramine, doxylamine, flunarizine, hydroxyzine, promethazine, terfenadine, tripelennamine and triprolidine, in addition to caffeine, dextromethorphan, guaifenesin, paracetamol and pyridoxine in different pharmaceutical presentations (tablets, capsules, suppositories, syrups and ointments). The methods require minimum handling sample and are rapid (between 3 and 12 min at 1 mLmin(-1) flow rate) and reproducible (R.S.D. values<5%). Limits of detection are lower than 1 microgmL(-1) and the recoveries of the analytes in the pharmaceutical preparations are in the range 100+/-10%.

Process analytical technology in the pharmaceutical industry: a toolkit for continuous improvement.

PubMed

Scott, Bradley; Wilcock, Anne

2006-01-01

Process analytical technology (PAT) refers to a series of tools used to ensure that quality is built into products while at the same time improving the understanding of processes, increasing efficiency, and decreasing costs. It has not been widely adopted by the pharmaceutical industry. As the setting for this paper, the current pharmaceutical manufacturing paradigm and PAT guidance to date are discussed prior to the review of PAT principles and tools, benefits, and challenges. The PAT toolkit contains process analyzers, multivariate analysis tools, process control tools, and continuous improvement/knowledge management/information technology systems. The integration and implementation of these tools is complex, and has resulted in uncertainty with respect to both regulation and validation. The paucity of staff knowledgeable in this area may complicate adoption. Studies to quantitate the benefits resulting from the adoption of PAT within the pharmaceutical industry would be a valuable addition to the qualitative studies that are currently available.

Application of the near-infrared spectroscopy in the pharmaceutical technology.

PubMed

Jamrógiewicz, Marzena

2012-07-01

Near-infrared (NIR) spectroscopy is currently the fastest-growing and the most versatile analytical method not only in the pharmaceutical sciences but also in the industry. This review focuses on recent NIR applications in the pharmaceutical technology. This article covers monitoring, by NIR, of many manufacturing processes, such as granulation, mixing or drying, in order to determine the end-point of these processes. In this paper, apart from basic theoretical information concerning the NIR spectra, there are included determinations of the quality and quantity of pharmaceutical compounds. Some examples of measurements and control of physicochemical parameters of the final medicinal products, such as hardness, porosity, thickness size, compression strength, disintegration time and potential counterfeit are included. Biotechnology and plant drug analysis using NIR is also described. Moreover, some disadvantages of this method are stressed and future perspectives are anticipated. Copyright © 2012 Elsevier B.V. All rights reserved.

Microwave-assisted digestion using nitric acid for heavy metals and sulfated ash testing in active pharmaceutical ingredients.

PubMed

Pluhácek, T; Hanzal, J; Hendrych, J; Milde, D

2016-04-01

The monitoring of inorganic impurities in active pharmaceutical ingredients plays a crucial role in the quality control of the pharmaceutical production. The heavy metals and residue on ignition/sulfated ash methods employing microwave-assisted digestion with concentrated nitric acid have been demonstrated as alternatives to inappropriate compendial methods recommended in United States Pharmacopoeia (USP) and European Pharmacopoeia (Ph. Eur.). The recoveries using the heavy metals method ranged between 89% and 122% for nearly all USP and Ph. Eur. restricted elements as well as the recoveries of sodium sulfate spikes were around 100% in all tested matrices. The proposed microwave-assisted digestion method allowed simultaneous decomposition of 15 different active pharmaceutical ingredients with sample weigh up to 1 g. The heavy metals and sulfated ash procedures were successfully applied to the determination of heavy metals and residue on ignition/sulfated ash content in mycophenolate mofetil, nicergoline and silymarin.

Relational Capital Quality and Client Loyalty: Firm-Level Evidence from Pharmaceuticals, Pakistan

ERIC Educational Resources Information Center

Mubarik, Shujaat; Chandran, V. G. R.; Devadason, Evelyn S.

2016-01-01

Purpose: This study aims to examine the influence of relational capital quality on client loyalty, comprising both behavioral and attitudinal, in the pharmaceutical industry of Pakistan. Design/methodology/approach: The partial least squares technique is used to test the relationship using a sample of 111 pharmaceutical firms. We applied a…

The Belgian commitment to pharmaceutical quality: a model policy to improve quality assurance of medicines available through humanitarian and development programs.

PubMed

Ravinetto, Raffaella; Roosen, Tim; Dujardin, Catherine

2018-01-01

Today, a combination of globalization of pharmaceutical production, lack of regulatory harmonization, and weakness of Medicines Regulatory Authorities, creates the "perfect conditions" for poor-quality medicine to circulate in the global market and to penetrate the less-regulated countries. Medicines regulation is the responsibility of the national regulatory authorities in the recipient country, but in the poorer countries, in practice, the responsibility of supply of quality-assured medicines is often taken by Non-Governmental Organizations and other implementers. But with some notable exceptions, many donors lack a pharmaceutical procurement policy with adequate quality requirements; and many implementers lack the skills and expertise needed to orient themselves in the complex web of global pharmaceutical supply. Thus, patients served by humanitarian or development programs may remain exposed to the risk of poor-quality medicines. When public money is used to purchase medicines for medical programs to be carried out overseas, adequate policies should be in place to assure that the same quality requirements are set that would be required for medicines marketed in the "donor" country. We will describe here a policy recently adopted in Belgium, i.e. the "Commitment to Quality Assurance for Pharmaceutical Products", signed in October 2017 by the Vice Prime Minister and Minister for Development Cooperation and 19 Belgian implementing agencies. By signing the new policy, the counterparts committed to ensure quality of medicines in the programs funded by Belgium's Official Development Assistance, and to build quality-assurance capacity in the recipient countries. Implementers are requested to integrate in their financing applications a section for pharmaceutical quality assurance, with a justified budget. They are also invited to consider how costs could be rationalized and mutualized by aligning the strengths of the various implementers. This model policy has the potential to be considered for adoption by other donors, to help to reduce the current multiple standards in pharmaceutical quality, and to contribute to protect vulnerable communities from the plague of poor-quality medicines. The online version of this article (10.1186/s40545-018-0136-z) contains an additional file, which is available to authorized users.

Advancing pharmaceutical quality: An overview of science and research in the U.S. FDA's Office of Pharmaceutical Quality.

PubMed

Fisher, Adam C; Lee, Sau L; Harris, Daniel P; Buhse, Lucinda; Kozlowski, Steven; Yu, Lawrence; Kopcha, Michael; Woodcock, Janet

2016-12-30

Failures surrounding pharmaceutical quality, particularly with respect to product manufacturing issues and facility remediation, account for the majority of drug shortages and product recalls in the United States. Major scientific advancements pressure established regulatory paradigms, especially in the areas of biosimilars, precision medicine, combination products, emerging manufacturing technologies, and the use of real-world data. Pharmaceutical manufacturing is increasingly globalized, prompting the need for more efficient surveillance systems for monitoring product quality. Furthermore, increasing scrutiny and accelerated approval pathways provide a driving force to be even more efficient with limited regulatory resources. To address these regulatory challenges, the Office of Pharmaceutical Quality (OPQ) in the Center for Drug Evaluation and Research (CDER) at the U.S. Food and Drug Administration (FDA) harbors a rigorous science and research program in core areas that support drug quality review, inspection, surveillance, standards, and policy development. Science and research is the foundation of risk-based quality assessment of new drugs, generic drugs, over-the-counter drugs, and biotechnology products including biosimilars. This is an overview of the science and research activities in OPQ that support the mission of ensuring that safe, effective, and high-quality drugs are available to the American public. Published by Elsevier B.V.

[Pharmaceutical logistic in turnover of pharmaceutical products of Azerbaijan].

PubMed

Dzhalilova, K I

2009-11-01

Development of pharmaceutical logistic system model promotes optimal strategy for pharmaceutical functioning. The goal of such systems is organization of pharmaceutical product's turnover in required quantity and assortment, at preset time and place, at a highest possible degree of consumption readiness with minimal expenses and qualitative service. Organization of the optimal turnover chain in the region is offered to start from approximate classification of medicaments by logistic characteristics. Supplier selection was performed by evaluation of timeliness of delivery, quality of delivered products (according to the minimum acceptable level of quality) and time-keeping of time spending for orders delivery.

[The "pharmaceutical chain", important asset of health safety in France. Synthesis of the session].

PubMed

Santini, C

2008-01-01

The National Academy of Pharmacy underlines the importance of health safety guarantees, provided by the "pharmaceutical chain" that bring the medicine until his user (from manufacturers to dispensing pharmacists), chain of which the security of each link is controlled and guaranteed by pharmacists. The first of the safety rules lies in the very fast availability of the medicine for the patients, in every respect of the national territory, due to an efficient system of pharmaceutical distribution and to a tightened network of pharmaceutical dispensaries (that constitutes a network of expertises especially to the service of patients and public health). All along the chain, also exists a same concern to guarantee and to preserve the pharmaceutical quality of the medicines. An essential element of the health safety is the right usage of the medicine, to which contribute: information associated with the marketing of the medicine, the very important role of the dispensing pharmacist as such sanitary adviser and therapeutic education teacher, the intervention of the hospital dispensary in clinical pharmacy, the "Pharmaceutical File" under setting up, pharmacovigilance, traceability of medicines ... Pharmacists, responsible at the level of the different steps of the chain, get appropriate skills, carry out themselves their duties and are responsible in front of the National Board of Pharmacists, and their common professional knowledge reinforces the cohesion and the robustness of the chain. Facing the serious issue of counterfeiting of medicines, the pharmaceutical chain constitutes an important line of defence against the entry of counterfeited drugs into commercial channels. The academy of Pharmacy warns against all evolution that would consist to break, even partially, of the mandatory and continuous pharmaceutical control.

Pharmaceutical care for elderly patients shared between community pharmacists and general practitioners: a randomised evaluation. RESPECT (Randomised Evaluation of Shared Prescribing for Elderly people in the Community over Time) [ISRCTN16932128

PubMed Central

Wong, I; Campion, P; Coulton, S; Cross, B; Edmondson, H; Farrin, A; Hill, G; Hilton, A; Philips, Z; Richmond, S; Russell, I

2004-01-01

Background This trial aims to investigate the effectiveness and cost implications of 'pharmaceutical care' provided by community pharmacists to elderly patients in the community. As the UK government has proposed that by 2004 pharmaceutical care services should extend nationwide, this provides an opportunity to evaluate the effect of pharmaceutical care for the elderly. Design The trial design is a randomised multiple interrupted time series. We aim to recruit 700 patients from about 20 general practices, each associated with about three community pharmacies, from each of the five Primary Care Trusts in North and East Yorkshire. We shall randomise the five resulting groups of practices, pharmacies and patients to begin pharmaceutical care in five successive phases. All five will act as controls until they receive the intervention in a random sequence. Until they receive training community pharmacists will provide their usual dispensing services and so act as controls. The community pharmacists and general practitioners will receive training in pharmaceutical care for the elderly. Once trained, community pharmacists will meet recruited patients, either in their pharmacies (in a consultation room or dispensary to preserve confidentiality) or at home. They will identify drug-related issues/problems, and design a pharmaceutical care plan in conjunction with both the GP and the patient. They will implement, monitor, and update this plan monthly. The primary outcome measure is the 'Medication Appropriateness Index'. Secondary measures include adverse events, quality of life, and patient knowledge and compliance. We shall also investigate the cost of pharmaceutical care to the NHS, to patients and to society as a whole. PMID:15182379

In-line quality control of moving objects by means of spectral-domain OCT

NASA Astrophysics Data System (ADS)

Markl, Daniel; Hannesschläger, Günther; Buchsbaum, Andreas; Sacher, Stephan; Khinast, Johannes G.; Leitner, Michael

2014-08-01

In-line quality control of intermediate and final products is essential in various industries. This may imply determining the thickness of a foil or evaluating the homogeneity of coating applied to a pharmaceutical tablet. Such a qualitative and quantitative monitoring in a depth-resolved manner can be accomplished using optical coherence tomography (OCT). In-line quality control based on OCT requires additional consideration of motion effects for the system design as well as for data interpretation. This study focuses on transverse motion effects that can arise in spectral-domain (SD-) OCT systems. The impact of a transverse movement is analyzed for a constant relative speed difference up to 0.7 m/s between sample and sensor head. In particular, transverse motion is affecting OCT system properties such as the beam displacement (distance between adjacent A-scans) and transverse resolution. These properties were evaluated theoretically and experimentally for OCT images of a resolution target and pharmaceutical film-coated tablets. Both theoretical and experimental analyses highlight the shift of the transverse resolution limiting factor from the optics to the beam displacement above a relative speed difference between sensor head and sample of 0.42 m/s (for the presented SD-OCT setup). Speeds above 0.4 m/s are often demanded when monitoring industrial processes, such as a coating process when producing film-coated tablets. This emphasizes the importance of a fast data acquisition when using OCT as in-line quality control tool.

[Physical fingerprint for quality control of traditional Chinese medicine extract powders].

PubMed

Zhang, Yi; Xu, Bing; Sun, Fei; Wang, Xin; Zhang, Na; Shi, Xin-Yuan; Qiao, Yan-Jiang

2016-06-01

The physical properties of both raw materials and excipients are closely correlated with the quality of traditional Chinese medicine preparations in oral solid dosage forms. In this paper, based on the concept of the chemical fingerprint for quality control of traditional Chinese medicine products, the method of physical fingerprint for quality evaluation of traditional Chinese medicine extract powders was proposed. This novel physical fingerprint was built by the radar map, and consisted of five primary indexes (i.e. stackablity, homogeneity, flowability, compressibility and stability) and 12 secondary indexes (i.e. bulk density, tap density, particle size<50 μm percentage, relative homogeneity index, hausner ratio, angle of repose, powder flow time, inter-particle porosity, Carr index, cohesion index, loss on drying, hygroscopicity). Panax notoginseng saponins (PNS) extract was taken for an example. This paper introduced the application of physical fingerprint in the evaluation of source-to-source and batch-to-batch quality consistence of PNS extract powders. Moreover, the physical fingerprint of PNS was built by calculating the index of parameters, the index of parametric profile and the index of good compressibility, in order to successfully predict the compressibility of the PNS extract powder and relevant formulations containing PNS extract powder and conventional pharmaceutical excipients. The results demonstrated that the proposed method could not only provide new insights into the development and process control of traditional Chinese medicine solid dosage forms. Copyright© by the Chinese Pharmaceutical Association.

Transforming nanomedicine manufacturing toward Quality by Design and microfluidics.

PubMed

Colombo, Stefano; Beck-Broichsitter, Moritz; Bøtker, Johan Peter; Malmsten, Martin; Rantanen, Jukka; Bohr, Adam

2018-04-05

Nanopharmaceuticals aim at translating the unique features of nano-scale materials into therapeutic products and consequently their development relies critically on the progression in manufacturing technology to allow scalable processes complying with process economy and quality assurance. The relatively high failure rate in translational nanopharmaceutical research and development, with respect to new products on the market, is at least partly due to immature bottom-up manufacturing development and resulting sub-optimal control of quality attributes in nanopharmaceuticals. Recently, quality-oriented manufacturing of pharmaceuticals has undergone an unprecedented change toward process and product development interaction. In this context, Quality by Design (QbD) aims to integrate product and process development resulting in an increased number of product applications to regulatory agencies and stronger proprietary defense strategies of process-based products. Although QbD can be applied to essentially any production approach, microfluidic production offers particular opportunities for QbD-based manufacturing of nanopharmaceuticals. Microfluidics provides unique design flexibility, process control and parameter predictability, and also offers ample opportunities for modular production setups, allowing process feedback for continuously operating production and process control. The present review aims at outlining emerging opportunities in the synergistic implementation of QbD strategies and microfluidic production in contemporary development and manufacturing of nanopharmaceuticals. In doing so, aspects of design and development, but also technology management, are reviewed, as is the strategic role of these tools for aligning nanopharmaceutical innovation, development, and advanced industrialization in the broader pharmaceutical field. Copyright © 2018 Elsevier B.V. All rights reserved.

Quality of Pharmaceutical Advertisements in Medical Journals: A Systematic Review

PubMed Central

Othman, Noordin; Vitry, Agnes; Roughead, Elizabeth E.

2009-01-01

Background Journal advertising is one of the main sources of medicines information to doctors. Despite the availability of regulations and controls of drug promotion worldwide, information on medicines provided in journal advertising has been criticized in several studies for being of poor quality. However, no attempt has been made to systematically summarise this body of research. We designed this systematic review to assess all studies that have examined the quality of pharmaceutical advertisements for prescription products in medical and pharmacy journals. Methods and Findings Studies were identified via searching electronic databases, web library, search engine and reviewing citations (1950 – February 2006). Only articles published in English and examined the quality of information included in pharmaceutical advertisements for prescription products in medical or pharmacy journals were included. For each eligible article, a researcher independently extracted the data on the study methodology and outcomes. The data were then reviewed by a second researcher. Any disagreements were resolved by consensus. The data were analysed descriptively. The final analysis included 24 articles. The studies reviewed advertisements from 26 countries. The number of journals surveyed in each study ranged from four to 24 journals. Several outcome measures were examined including references and claims provided in advertisements, availability of product information, adherence to codes or guidelines and presentation of risk results. The majority of studies employed a convenience-sampling method. Brand name, generic name and indications were usually provided. Journal articles were commonly cited to support pharmaceutical claims. Less than 67% of the claims were supported by a systematic review, a meta-analysis or a randomised control trial. Studies that assessed misleading claims had at least one advertisement with a misleading claim. Two studies found that less than 28% of claims were unambiguous clinical claims. Most advertisements with quantitative information provided risk results as relative risk reduction. Studies were conducted in 26 countries only and then the generalizability of the results is limited. Conclusions Evidence from this review indicates that low quality of journal advertising is a global issue. As information provided in journal advertising has the potential to change doctors' prescribing behaviour, ongoing efforts to increase education about drug promotion are crucial. The results from our review suggest the need for a global pro-active and effective regulatory system to ensure that information provided in medical journal advertising is supporting the quality use of medicines. PMID:19623259

Gamma sterilization of pharmaceuticals--a review of the irradiation of excipients, active pharmaceutical ingredients, and final drug product formulations.

PubMed

Hasanain, Fatima; Guenther, Katharina; Mullett, Wayne M; Craven, Emily

2014-01-01

Sterilization by gamma irradiation has shown a strong applicability for a wide range of pharmaceutical products. Due to the requirement for terminal sterilization where possible in the pharmaceutical industry, gamma sterilization has proven itself to be an effective method as indicated by its acceptance in the European Pharmacopeia and the United States Pharmacopeia ( ). Some of the advantages of gamma over competitive procedures include high penetration power, isothermal character (small temperature rise), and no residues. It also provides a better assurance of product sterility than aseptic processing, as well as lower validation demands. Gamma irradiation is capable of killing microorganisms by breaking their chemical bonds, producing free radicals that attack the nucleic acid of the microorganism. Sterility by gamma irradiation is achieved mainly by the alteration of nucleic acid and preventing the cellular division. This review focuses on the extensive application of gamma sterilization to a wide range of pharmaceutical components including active pharmaceutical ingredients, excipients, final drug products, and combination drug-medical devices. A summary of the published literature for each class of pharmaceutical compound or product is presented. The irradiation conditions and various quality control characterization methodologies that were used to determine final product quality are included, in addition to a summary of the investigational outcomes. Based on this extensive literature review and in combination with regulatory guidelines and other published best practices, a decision tree for implementation of gamma irradiation for pharmaceutical products is established. This flow chart further facilitates the implementation of gamma irradiation in the pharmaceutical development process. The summary therefore provides a useful reference to the application and versatility of gamma irradiation for pharmaceutical sterilization. Many pharmaceutical products require sterilization to ensure their safe and effective use. Sterility is therefore a critical quality attribute and is essential for direct injection products. Due to the requirement for terminal sterilization, where possible in the pharmaceutical industry sterilization by gamma irradiation has been commonly used as an effective method to sterilize pharmaceutical products as indicated by its acceptance in the European Pharmacopeia. Gamma sterilization is a very attractive terminal sterilization method in view of its ability to attain 10(-6) probability of microbial survival without excessive heating of the product or exposure to toxic chemicals. However, radiation compatibility of a product is one of the first aspects to evaluate when considering gamma sterilization. Gamma radiation consists of high-energy photons that result in the generation of free radicals and the subsequent ionization of chemical bonds, leading to cleavage of DNA in microorganisms and their subsequent inactivation. This can result in a loss of active pharmaceutical ingredient potency, the creation of radiolysis by-products, a reduction of the molecular weight of polymer excipients, and influence drug release from the final product. There are several strategies for mitigating degradation effects, including optimization of the irradiation dose and conditions. This review will serve to highlight the extensive application of gamma sterilization to a broad spectrum of pharmaceutical components including active pharmaceutical ingredients, excipients, final drug products, and combination drug-medical devices.

A critical assessment of the photodegradation of pharmaceuticals in aquatic environments: defining our current understanding and identifying knowledge gaps.

PubMed

Challis, Jonathan K; Hanson, Mark L; Friesen, Ken J; Wong, Charles S

2014-04-01

This work presents a critical assessment of the state and quality of knowledge around the aquatic photochemistry of human- and veterinary-use pharmaceuticals from laboratory experiments and field observations. A standardized scoring rubric was used to assess relevant studies within four categories: experimental design, laboratory-based direct and indirect photolysis, and field/solar photolysis. Specific metrics for each category are defined to evaluate various aspects of experimental design (e.g., higher scores are given for more appropriate characterization of light source wavelength distribution). This weight of evidence-style approach allowed for identification of knowledge strengths and gaps covering three areas: first, the general extent of photochemical data for specific pharmaceuticals and classes; second, the overall quality of existing data (i.e., strong versus weak); and finally, trends in the photochemistry research around these specific compounds, e.g. the observation of specific and consistent oversights in experimental design. In general, those drugs that were most studied also had relatively good quality data. The four pharmaceuticals studied experimentally at least ten times in the literature had average total scores (lab and field combined) of ≥29, considered decent quality; carbamazepine (13 studies; average score of 31), diclofenac (12 studies; average score of 31), sulfamethoxazole (11 studies; average score of 34), and propranolol (11 studies; average score of 29). Major oversights and errors in data reporting and/or experimental design included: lack of measurement and reporting of incident light source intensity, lack of appropriate controls, use of organic co-solvents in irradiation solutions, and failure to consider solution pH. Consequently, a number of these experimental parameters were likely a cause of inconsistent measurements of direct photolysis rate constants and quantum yields, two photochemical properties that were highly variable in the literature. Overall, the assessment rubric provides an objective and scientifically-defensible set of metrics for assessing the quality of a study. A major recommendation is the development of a method guideline, based on this rubric, for conducting and reporting on photochemical studies that would produce consistent and reliable data for quantitative comparison across studies. Furthermore, an emphasis should be placed on conducting more dual-fate studies involving controlled photolysis experiments in natural sunlight, and whole system fate studies in either natural or artificial systems. This would provide accurate data describing the actual contribution of photolysis to the overall fate of pharmaceuticals in the environment.

The drug regulatory and review process in Guyana.

PubMed

Woo-Ming, R B

1993-01-01

After the old "Sale of Food and Drugs" Ordinance, Cap. 144 was repealed, the new Food and Drugs Act was enacted in 1971. This new Act has considerable flexibility and gives the Minister extensive authority to make Regulations (for carrying out the purposes and provisions of the Act). The Act controls the manufacture, importation, sale, advertising, labeling, packaging, and distribution of drug samples, and the testing of drugs. The Act also controls raw materials and finished products of drugs at the point of entry into the country, with a single agency coordinating both the inspection and analytical services. Developing countries could ensure the procurement of safe, good quality, and effective drugs and devices with the enactment of a similar Food and Drugs Act only. Rapid assessment of Drug Safety, Quality and Efficacy is done through Guyana's participation in the WHO Certification Scheme on the Quality of Pharmaceutical Products moving in International Commerce. This certification scheme is highly commendable especially to third-world countries. The Food and Drug Regulations (1977) have several unique features for drug, cosmetic and device control and they allow for a system of centralized control with limited staff to enforce the legislation. In summary, enforcement of legislative control of imported pharmaceuticals and product evaluation can be considered strong points in the drug regulatory and review process in Guyana. A cautious attitude is observed so as to ensure efficacy, safety, and quality of drugs entering the market. This Drug Regulatory and Review Process is recommended for implementation by third-world countries with outdated drug legislation.(ABSTRACT TRUNCATED AT 250 WORDS)

Advanced Taste Sensors Based on Artificial Lipids with Global Selectivity to Basic Taste Qualities and High Correlation to Sensory Scores

PubMed Central

Kobayashi, Yoshikazu; Habara, Masaaki; Ikezazki, Hidekazu; Chen, Ronggang; Naito, Yoshinobu; Toko, Kiyoshi

2010-01-01

Effective R&D and strict quality control of a broad range of foods, beverages, and pharmaceutical products require objective taste evaluation. Advanced taste sensors using artificial-lipid membranes have been developed based on concepts of global selectivity and high correlation with human sensory score. These sensors respond similarly to similar basic tastes, which they quantify with high correlations to sensory score. Using these unique properties, these sensors can quantify the basic tastes of saltiness, sourness, bitterness, umami, astringency and richness without multivariate analysis or artificial neural networks. This review describes all aspects of these taste sensors based on artificial lipid, ranging from the response principle and optimal design methods to applications in the food, beverage, and pharmaceutical markets. PMID:22319306

GMP in blood collection and processing.

PubMed

Wagstaff, W

1998-01-01

The principles of Good Manufacturing Practice have, in the main, been universally developed for the guidance of the pharmaceutical industry rather than for transfusion services. However, these rules and guides are increasingly being adapted for use in blood centres, in the production of labile blood components and of plasma for fractionation. The guide for pharmaceutical industries produced by the commission of the European Communities is used as a model here, the nine basic requirements being those applicable to Quality Management, personnel, premises and equipment, document, production, Quality Control, contract manufacture and analysis, complaints and product recall, and self-inspection. Though having more direct application to the production laboratory preparing blood components, the majority of these requirements and principles are also directly applicable to all of the activities involved in blood collection.

Model-Based PAT for Quality Management in Pharmaceuticals Freeze-Drying: State of the Art

PubMed Central

Fissore, Davide

2017-01-01

Model-based process analytical technologies can be used for the in-line control and optimization of a pharmaceuticals freeze-drying process, as well as for the off-line design of the process, i.e., the identification of the optimal operating conditions. This paper aims at presenting the state of the art in this field, focusing, particularly, on three groups of systems, namely, those based on the temperature measurement (i.e., the soft sensor), on the chamber pressure measurement (i.e., the systems based on the test of pressure rise and of pressure decrease), and on the sublimation flux estimate (i.e., the tunable diode laser absorption spectroscopy and the valveless monitoring system). The application of these systems for in-line process optimization (e.g., using a model predictive control algorithm) and to get a true quality by design (e.g., through the off-line calculation of the design space of the process) is presented and discussed. PMID:28224123

Regulatory considerations of pharmaceutical solid polymorphism in Abbreviated New Drug Applications (ANDAs).

PubMed

Raw, Andre S; Furness, M Scott; Gill, Devinder S; Adams, Richard C; Holcombe, Frank O; Yu, Lawrence X

2004-02-23

A sponsor of an Abbreviated New Drug Application (ANDA) must have information to show that the proposed generic product and the innovator product are both pharmaceutically equivalent and bioequivalent, and therefore, therapeutically equivalent. Many pharmaceutical solids exist in several crystalline forms and thus exhibit polymorphism. Polymorphism may result in differences in the physico-chemical properties of the active ingredient and variations in these properties may render a generic drug product to be bioinequivalent to the innovator brand. For this reason, in ANDAs, careful attention is paid to the effect of polymorphism in the context of generic drug product equivalency. This review discusses the impact of polymorphism on drug product manufacturability, quality, and performance. Conclusions from this analysis demonstrate that pharmaceutical solid polymorphism has no relevance to the determination of drug substance "sameness" in ANDAs. Three decision trees for solid oral dosage forms or liquid suspensions are provided for evaluating when and how polymorphs of drug substances should be monitored and controlled in ANDA submissions. Case studies from ANDAs are provided which demonstrate the irrelevance of polymorphism to the determination of drug substance "sameness". These case studies also illustrate the conceptual framework from these decision trees and illustrate how their general principles are sufficient to assure both the quality and the therapeutic equivalence of marketed generic drug products.

Evaluation of physicochemical properties as supporting information on quality control of raw materials and veterinary pharmaceutical formulations.

PubMed

Anacleto, Sara da Silva; Borges, Marcella Matos Cordeiro; de Oliveira, Hanna Leijoto; Vicente, Andressa Reis; de Figueiredo, Eduardo Costa; de Oliveira, Marcone Augusto Leal; Borges, Bárbara Juliana Pinheiro; de Oliveira, Marcelo Antonio; Borges, Warley de Souza; Borges, Keyller Bastos

2018-06-01

This study aimed to show that the physicochemical proprieties obtained by Fourier transform infrared spectroscopy (FTIR), thermogravimetry (TG), and scanning electronic microscopy (SEM) can be useful tools for evaluating the quality of active pharmaceutical ingredients (APIs) and pharmaceutical products. In addition, a simple, sensitive, and efficient method employing HPLC-DAD was developed for simultaneous determination of lidocaine (LID), ciprofloxacin (CFX) and enrofloxacin (EFX) in raw materials and in veterinary pharmaceutical formulations. Compounds were separated using a Gemini C 18 (250 mm × 4.6 mm, 5 µm) Phenomenex ® column, at a temperature of 25 °C, with a mobile phase containing 10 mM of phosphoric acid (pH 3.29): acetonitrile (85.7:14.3, v/v) and a flow rate of 1.5 mL/min. Physicochemical characterization by TG, FTIR, and SEM of raw materials of LID, CFX, and EFX provided information useful for the evaluation, differentiation, and qualification of raw materials. Finally, the HPLC method was proved to be useful for evaluation of raw material and finished products, besides satisfying the need for an analytical method that allows simultaneous determination of EFX, CFX, and LID, which can also be extended to other matrices and applications.

Semi-quantitative prediction of a multiple API solid dosage form with a combination of vibrational spectroscopy methods.

PubMed

Hertrampf, A; Sousa, R M; Menezes, J C; Herdling, T

2016-05-30

Quality control (QC) in the pharmaceutical industry is a key activity in ensuring medicines have the required quality, safety and efficacy for their intended use. QC departments at pharmaceutical companies are responsible for all release testing of final products but also all incoming raw materials. Near-infrared spectroscopy (NIRS) and Raman spectroscopy are important techniques for fast and accurate identification and qualification of pharmaceutical samples. Tablets containing two different active pharmaceutical ingredients (API) [bisoprolol, hydrochlorothiazide] in different commercially available dosages were analysed using Raman- and NIR Spectroscopy. The goal was to define multivariate models based on each vibrational spectroscopy to discriminate between different dosages (identity) and predict their dosage (semi-quantitative). Furthermore the combination of spectroscopic techniques was investigated. Therefore, two different multiblock techniques based on PLS have been applied: multiblock PLS (MB-PLS) and sequential-orthogonalised PLS (SO-PLS). NIRS showed better results compared to Raman spectroscopy for both identification and quantitation. The multiblock techniques investigated showed that each spectroscopy contains information not present or captured with the other spectroscopic technique, thus demonstrating that there is a potential benefit in their combined use for both identification and quantitation purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

Automated pharmaceutical tablet coating layer evaluation of optical coherence tomography images

NASA Astrophysics Data System (ADS)

Markl, Daniel; Hannesschläger, Günther; Sacher, Stephan; Leitner, Michael; Khinast, Johannes G.; Buchsbaum, Andreas

2015-03-01

Film coating of pharmaceutical tablets is often applied to influence the drug release behaviour. The coating characteristics such as thickness and uniformity are critical quality parameters, which need to be precisely controlled. Optical coherence tomography (OCT) shows not only high potential for off-line quality control of film-coated tablets but also for in-line monitoring of coating processes. However, an in-line quality control tool must be able to determine coating thickness measurements automatically and in real-time. This study proposes an automatic thickness evaluation algorithm for bi-convex tables, which provides about 1000 thickness measurements within 1 s. Beside the segmentation of the coating layer, optical distortions due to refraction of the beam by the air/coating interface are corrected. Moreover, during in-line monitoring the tablets might be in oblique orientation, which needs to be considered in the algorithm design. Experiments were conducted where the tablet was rotated to specified angles. Manual and automatic thickness measurements were compared for varying coating thicknesses, angles of rotations, and beam displacements (i.e. lateral displacement between successive depth scans). The automatic thickness determination algorithm provides highly accurate results up to an angle of rotation of 30°. The computation time was reduced to 0.53 s for 700 thickness measurements by introducing feasibility constraints in the algorithm.

WHO expert committee on specifications for pharmaceutical preparations. Fortieth report.

PubMed

2006-01-01

This report presents the recommendations of an international group of experts convened by the World Health Organization to consider matters concerning the quality assurance of pharmaceuticals and specifications for drug substances and dosage forms. The report is complemented by a number of annexes. These include: a list of available International Chemical Reference Substances and International Infrared Spectra; supplementary guidelines on good manufacturing practices for heating, ventilation and air-conditioning systems for non-sterile pharmaceutical dosage forms; updated supplementary guidelines on good manufacturing practices for the manufacture of herbal medicines; supplementary guidelines on good manufacturing practices for validation; good distribution practices for pharmaceutical products; a model quality assurance system for procurement agencies (recommendations for quality assurance systems focusing on prequalification of products and manufacturers, purchasing, storage and distribution of pharmaceutical products); multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability; a proposal to waive in vivo bioequivalence requirements for WHO Model List of Essential Medicines immediate-release, solid oral dosage forms; and additional guidance for organizations performing in vivo bioequivalence studies.

[Quality improvement potential in the pharmaceutical industry].

PubMed

Nusser, Michael

2007-01-01

The performance of the German pharmaceutical industry, future challenges and obstacles to quality improvement are assessed from a systems-of-innovation perspective, using appropriate innovation indicators. The current close-to-market performance indicators paint an unfavourable picture. Early R&D indicators (e.g., publications, patents), however, reveal a positive trend. A lot of obstacles to quality improvements are identified with respect to knowledge base, knowledge/technology transfer, industrial R&D processes, capital markets, market attractiveness and both regulatory and political framework conditions. On this basis, recommendations will finally be derived to improve quality in the pharmaceutical industry.

Characteristics of good quality pharmaceutical services common to community pharmacies and dispensing general practices.

PubMed

Grey, Elisabeth; Harris, Michael; Rodham, Karen; Weiss, Marjorie C

2016-10-01

In the United Kingdom, pharmaceutical services can be delivered by both community pharmacies (CPs) and dispensing doctor practices (DPs). Both must adhere to minimum standards set out in NHS regulations; however, no common framework exists to guide quality improvement. Previous phases of this research had developed a set of characteristics indicative of good pharmaceutical service provision. To ask key stakeholders to confirm, and rank the importance of, a set of characteristics of good pharmaceutical service provision. A two-round Delphi-type survey was conducted in south-west England and was sent to participants representing three stakeholder groups: DPs, CPs and patients/lay members. Participants were asked to confirm, and rank, the importance of these characteristics as representing good quality pharmaceutical services. Thirty people were sent the first round survey; 22 participants completed both rounds. Median ratings for the 23 characteristics showed that all were seen to represent important aspects of pharmaceutical service provision. Participants' comments highlighted potential problems with the practicality of the characteristics. Characteristics relating to patient safety were deemed to be the most important and those relating to public health the least important. A set of 23 characteristics for providing good pharmaceutical services in CPs and DPs was developed and attained approval from a sample of stakeholders. With further testing and wider discussion, it is hoped that the characteristics will form the basis of a quality improvement tool for CPs and DPs. © 2016 Royal Pharmaceutical Society.

Pharmaceutical quality of "party pills" raises additional safety concerns in the use of illicit recreational drugs.

PubMed

Young, Simon A; Thrimawithana, Thilini R; Antia, Ushtana; Fredatovich, John D; Na, Yonky; Neale, Peter T; Roberts, Amy F; Zhou, Huanyi; Russell, Bruce

2013-06-14

To determine the content and release kinetics of 1-benzylpiperazine (BZP) and 1-(3-trifluoromethyl-phenyl)piperazine (TFMPP) from "party pill" formulations. From these data, the possible impact of pharmaceutical quality upon the safety of such illicit formulations may be inferred. The amount of BZP and TFMPP in party pill formulations was determined using a validated HPLC method. The in-vitro release kinetics of selected party pill brands were determined using a USP dissolution apparatus (75 rpm, 37.5 degrees Celsius). The release data were then fitted to a first order release model using PLOT software and the time taken to achieve 90% release reported. Many of the tested party pill brands contained amounts of BZP and TFMPP that varied considerably from that stated on the packaging; including considerable TFMPP content in some brands not labelled to contain this drug. Dissolution studies revealed that there was considerable variability in the release kinetics between brands; in one case 90% release required >30 minutes. Lack of quality control in party pill manufacture may have led to the toxic effects reported by users unaware of the true content and release of drug from pills. More stringent regulation in the manufacture and quality control of "new generation party pills" is essential to the harm reduction campaign.

The importance of quality control in validating concentrations ...

EPA Pesticide Factsheets

A national-scale survey of 247 contaminants of emerging concern (CECs), including organic and inorganic chemical compounds, and microbial contaminants, was conducted in source and treated drinking water samples from 25 treatment plants across the United States. Multiple methods were used to determine these CECs, including six analytical methods to measure 174 pharmaceuticals, personal care products, and pesticides. A three-component quality assurance/quality control (QA/QC) program was designed for the subset of 174 CECs which allowed us to assess and compare performances of the methods used. The three components included: 1) a common field QA/QC protocol and sample design, 2) individual investigator-developed method-specific QA/QC protocols, and 3) a suite of 46 method comparison analytes that were determined in two or more analytical methods. Overall method performance for the 174 organic chemical CECs was assessed by comparing spiked recoveries in reagent, source, and treated water over a two-year period. In addition to the 247 CECs reported in the larger drinking water study, another 48 pharmaceutical compounds measured did not consistently meet predetermined quality standards. Methodologies that did not seem suitable for these analytes are overviewed. The need to exclude analytes based on method performance demonstrates the importance of additional QA/QC protocols. This paper compares the method performance of six analytical methods used to measure 174 emer

Tracing origins of complex pharmaceutical preparations using surface desorption atmospheric pressure chemical ionization mass spectrometry.

PubMed

Zhang, Xinglei; Jia, Bin; Huang, Keke; Hu, Bin; Chen, Rong; Chen, Huanwen

2010-10-01

A novel strategy to trace the origins of commercial pharmaceutical products has been developed based on the direct chemical profiling of the pharmaceutical products by surface desorption atmospheric pressure chemical ionization mass spectrometry (DAPCI-MS). Besides the unambiguous identification of active drug components, various compounds present in the matrixes are simultaneously detected without sample pretreatment, providing valuable information for drug quality control and origin differentiation. Four sources of commercial amoxicillin products made by different manufacturers have been successfully differentiated. This strategy has been extended to secerning six sources of Liuwei Dihuang Teapills, which are herbal medicine preparations with extremely complex matrixes. The photolysis status of chemical drug products and the inferior natural herd medicine products prepared with different processes (e.g., extra heating) were also screened using the method reported here. The limit of detection achieved in the MS/MS experiments was estimated to be 1 ng/g for amoxicillin inside the capsule product. Our experimental data demonstrate that DAPCI-MS is a useful tool for rapid pharmaceutical analysis, showing promising perspectives for tracking the entire pharmaceutical supply chain to prevent counterfeit intrusions.

[Development ideas of fine pharmaceutical materials of traditional Chinese medicine preparations based on active cluster theory].

PubMed

Ke, Zhong-Cheng; Hou, Xue-Feng; Jia, Xiao-Bin

2016-07-01

The pharmaceutical materials are divided into coarse and fine types in the development of traditional Chinese medicine preparations. Fine materials with clear composition, stable content and high quality control conform to the international development trend of traditional Chinese medicine preparations. In this paper, the status of fine materials was analyzed, and the development ideas were tentatively put forward. On the one hand, the study on simple methods and efficient equipment shall be strengthened for the simultaneous separation of multiple components of traditional Chinese medicine; on the other hand, the knowledge for traditional Chinese medicine shall be broadened to further develop the scientific compatibility of monomers under the guidance of the theory of traditional Chinese medicine. Copyright© by the Chinese Pharmaceutical Association.

Validation of a method to monitor the occurrence of 20 relevant pharmaceuticals and personal care products in 167 bottled waters.

PubMed

Lardy-Fontan, Sophie; Le Diouron, Véronique; Drouin, Catherine; Lalere, Béatrice; Vaslin-Reimann, Sophie; Dauchy, Xavier; Rosin, Christophe

2017-06-01

Research on emerging substances in drinking water presents major interest and the possibility of trace contamination has seen increasing concern from the scientific community and the public authorities. More particularly, residues of pharmaceuticals and personal care products (PPCPs) in bottled water are a very important issue due to societal concerns and potential media impact. In this context, it has become necessary to carry out reliable monitoring. This requires measurements of high quality with demonstration of accuracy and well-defined uncertainty. In this study, 20 pharmaceutical compounds were targeted for the first time in 167 bottled waters from France and other European countries. An isotope dilution-solid phase extraction-liquid chromatography mass spectrometry method, together with stringent quality control and quality assurance protocols, was developed and validated according to French mandatory standards. Recoveries between 87% and 112% were obtained with coefficient of variation below 20%. Operational limits of quantification (LOQ) were comprised between 5 and 30ngL -1 . Expanded uncertainties (k=2) ranged between 16% and 43% and were below 35% for half of the compounds. The survey showed only four positive quantifications, thereby highlighting the rarity of contamination. Copyright © 2017 Elsevier B.V. All rights reserved.

Real-time assessment of critical quality attributes of a continuous granulation process.

PubMed

Fonteyne, Margot; Vercruysse, Jurgen; Díaz, Damián Córdoba; Gildemyn, Delphine; Vervaet, Chris; Remon, Jean Paul; De Beer, Thomas

2013-02-01

There exists the intention to shift pharmaceutical manufacturing of solid dosage forms from traditional batch production towards continuous production. The currently applied conventional quality control systems, based on sampling and time-consuming off-line analyses in analytical laboratories, would annul the advantages of continuous processing. It is clear that real-time quality assessment and control is indispensable for continuous production. This manuscript evaluates strengths and weaknesses of several complementary Process Analytical Technology (PAT) tools implemented in a continuous wet granulation process, which is part of a fully continuous from powder-to-tablet production line. The use of Raman and NIR-spectroscopy and a particle size distribution analyzer is evaluated for the real-time monitoring of critical parameters during the continuous wet agglomeration of an anhydrous theophylline- lactose blend. The solid state characteristics and particle size of the granules were analyzed in real-time and the critical process parameters influencing these granule characteristics were identified. The temperature of the granulator barrel, the amount of granulation liquid added and, to a lesser extent, the powder feed rate were the parameters influencing the solid state of the active pharmaceutical ingredient (API). A higher barrel temperature and a higher powder feed rate, resulted in larger granules.

The pharmaceutical vial capping process: Container closure systems, capping equipment, regulatory framework, and seal quality tests.

PubMed

Mathaes, Roman; Mahler, Hanns-Christian; Buettiker, Jean-Pierre; Roehl, Holger; Lam, Philippe; Brown, Helen; Luemkemann, Joerg; Adler, Michael; Huwyler, Joerg; Streubel, Alexander; Mohl, Silke

2016-02-01

Parenteral drug products are protected by appropriate primary packaging to protect against environmental factors, including potential microbial contamination during shelf life duration. The most commonly used CCS configuration for parenteral drug products is the glass vial, sealed with a rubber stopper and an aluminum crimp cap. In combination with an adequately designed and controlled aseptic fill/finish processes, a well-designed and characterized capping process is indispensable to ensure product quality and integrity and to minimize rejections during the manufacturing process. In this review, the health authority requirements and expectations related to container closure system quality and container closure integrity are summarized. The pharmaceutical vial, the rubber stopper, and the crimp cap are described. Different capping techniques are critically compared: The most common capping equipment with a rotating capping plate produces the lowest amount of particle. The strength and challenges of methods to control the capping process are discussed. The residual seal force method can characterize the capping process independent of the used capping equipment or CCS. We analyze the root causes of several cosmetic defects associated with the vial capping process. Copyright © 2015 Elsevier B.V. All rights reserved.

Process Analytical Technology (PAT): batch-to-batch reproducibility of fermentation processes by robust process operational design and control.

PubMed

Gnoth, S; Jenzsch, M; Simutis, R; Lübbert, A

2007-10-31

The Process Analytical Technology (PAT) initiative of the FDA is a reaction on the increasing discrepancy between current possibilities in process supervision and control of pharmaceutical production processes and its current application in industrial manufacturing processes. With rigid approval practices based on standard operational procedures, adaptations of production reactors towards the state of the art were more or less inhibited for long years. Now PAT paves the way for continuous process and product improvements through improved process supervision based on knowledge-based data analysis, "Quality-by-Design"-concepts, and, finally, through feedback control. Examples of up-to-date implementations of this concept are presented. They are taken from one key group of processes in recombinant pharmaceutical protein manufacturing, the cultivations of genetically modified Escherichia coli bacteria.

Quality Control Analysis of Student-Generated Pharmaceutical Capsules

ERIC Educational Resources Information Center

Bucholtz, Ehren C.; French, Lisa M.; Lavoie, Jaie P.; Gaebelein, Claude J.

2010-01-01

Pharmacists, although not practicing chemists, often use skills and knowledge obtained in chemistry courses that are essential for success in their profession. This is especially apparent when preparing prescriptions for drugs that do not have a commercially available dosage form. Some well-publicized events indicate the potency of these drugs is…

Mapping of quantitative trait loci for butter content and hardness in cocoa beans (Theobroma cacao L.)

USDA-ARS?s Scientific Manuscript database

Cocoa butter is an important raw material for the chocolate, pharmaceutical, and cosmetic industries. The butter content and quality in cocoa beans are genetically controlled characteristics, and affect its commercial values and industrial applicability. In the present work, an F2 population derived...

Pharmaceutical quality assurance of local private distributors: a secondary analysis in 13 low-income and middle-income countries.

PubMed

Van Assche, Kerlijn; Nebot Giralt, Ariadna; Caudron, Jean Michel; Schiavetti, Benedetta; Pouget, Corinne; Tsoumanis, Achilleas; Meessen, Bruno; Ravinetto, Raffaella

2018-01-01

The rapid globalisation of the pharmaceutical production and distribution has not been supported by harmonisation of regulatory systems worldwide. Thus, the supply systems in low-income and middle-income countries (LMICs) remain exposed to the risk of poor-quality medicines. To contribute to estimating this risk in the private sector in LMICs, we assessed the quality assurance system of a convenient sample of local private pharmaceutical distributors. This descriptive study uses secondary data derived from the audits conducted by the QUAMED group at 60 local private pharmaceutical distributors in 13 LMICs. We assessed the distributors' compliance with good distribution practices (GDP), general quality requirements (GQR) and cold chain management (CCM), based on an evaluation tool inspired by the WHO guidelines 'Model Quality Assurance System (MQAS) for procurement agencies'. Descriptive statistics describe the compliance for the whole sample, for distributors in sub-Saharan Africa (SSA) versus those in non-SSA, and for those in low-income countries (LICs) versus middle-income countries (MICs). Local private pharmaceutical distributors in our sample were non-compliant, very low-compliant or low-compliant for GQR (70%), GDP (60%) and CCM (41%). Only 7/60 showed good to full compliance for at least two criteria. Observed compliance varies by geographical region and by income group: maximum values are higher in non-SSA versus SSA and in MICs versus LICs, while minimum values are the same across different groups. The poor compliance with WHO quality standards observed in our sample indicates a concrete risk that patients in LMICs are exposed to poor-quality or degraded medicines. Significant investments are needed to strengthen the regulatory supervision, including on private pharmaceutical distributors. An adapted standardised evaluation tool inspired by the WHO MQAS would be helpful for self-evaluation, audit and inspection purposes.

Developing a quality by design approach to model tablet dissolution testing: an industrial case study.

PubMed

Yekpe, Ketsia; Abatzoglou, Nicolas; Bataille, Bernard; Gosselin, Ryan; Sharkawi, Tahmer; Simard, Jean-Sébastien; Cournoyer, Antoine

2018-07-01

This study applied the concept of Quality by Design (QbD) to tablet dissolution. Its goal was to propose a quality control strategy to model dissolution testing of solid oral dose products according to International Conference on Harmonization guidelines. The methodology involved the following three steps: (1) a risk analysis to identify the material- and process-related parameters impacting the critical quality attributes of dissolution testing, (2) an experimental design to evaluate the influence of design factors (attributes and parameters selected by risk analysis) on dissolution testing, and (3) an investigation of the relationship between design factors and dissolution profiles. Results show that (a) in the case studied, the two parameters impacting dissolution kinetics are active pharmaceutical ingredient particle size distributions and tablet hardness and (b) these two parameters could be monitored with PAT tools to predict dissolution profiles. Moreover, based on the results obtained, modeling dissolution is possible. The practicality and effectiveness of the QbD approach were demonstrated through this industrial case study. Implementing such an approach systematically in industrial pharmaceutical production would reduce the need for tablet dissolution testing.

[Quality of medicines in least developed countries].

PubMed

Videau, J Y

2006-12-01

Due to worsening economic conditions and poor enforcement of existing pharmaceutical and customs regulations, third world countries are faced with a growing threat from counterfeit and substandard medicines. With the expansion of illicit markets in urban areas, the sales of medicines of uncertain quality and origin are increasing. Most victims of this illicit trade are among the world's poorest populations that cannot afford to buy quality drugs through private-sector distribution channels. National pharmaceutical programs promoting universal access to essential generic medicines at reasonable cost are the key to curbing this problem. A system based on strict, rational pharmaceutical purchasing and distribution policies with quality assurance at every level of the supply chain is needed to guarantee that patients receive safe effective high quality healthcare products.

Development of Taiwan's strategies for regulating nanotechnology-based pharmaceuticals harmonized with international considerations.

PubMed

Guo, Jiun-Wen; Lee, Yu-Hsuan; Huang, Hsiau-Wen; Tzou, Mei-Chyun; Wang, Ying-Jan; Tsai, Jui-Chen

2014-01-01

Nanotechnology offers potential in pharmaceuticals and biomedical developments for improving drug delivery systems, medical imaging, diagnosis, cancer therapy, and regenerative medicine. Although there is no international regulation or legislation specifically for nanomedicine, it is agreed worldwide that considerably more attention should be paid to the quality, safety, and efficacy of nanotechnology-based drugs. The US Food and Drug Administration and the European Medicines Agency have provided several draft regulatory guidance and reflection papers to assist the development of nanomedicines. To cope with the impact of nanotechnology and to foster its pharmaceutical applications and development in Taiwan, this article reviews the trends of regulating nanotechnology-based pharmaceuticals in the international community and proposes strategies for Taiwan's regulation harmonized with international considerations. The draft regulatory measures include a chemistry, manufacturing, and controls (CMC) review checklist and guidance for CMC review of liposomal products. These have been submitted for discussion among an expert committee, with membership comprised of multidisciplinary academia, research institutions, the pharmaceutical industry, and regulators, and are currently approaching final consensus. Once a consensus is reached, these mechanisms will be recommended to the Taiwan Food and Drug Administration for jurisdiction and may be initiated as the starting point for regulating nanotechnology-based pharmaceuticals in Taiwan.

Development of Taiwan’s strategies for regulating nanotechnology-based pharmaceuticals harmonized with international considerations

PubMed Central

Guo, Jiun-Wen; Lee, Yu-Hsuan; Huang, Hsiau-Wen; Tzou, Mei-Chyun; Wang, Ying-Jan; Tsai, Jui-Chen

2014-01-01

Nanotechnology offers potential in pharmaceuticals and biomedical developments for improving drug delivery systems, medical imaging, diagnosis, cancer therapy, and regenerative medicine. Although there is no international regulation or legislation specifically for nanomedicine, it is agreed worldwide that considerably more attention should be paid to the quality, safety, and efficacy of nanotechnology-based drugs. The US Food and Drug Administration and the European Medicines Agency have provided several draft regulatory guidance and reflection papers to assist the development of nanomedicines. To cope with the impact of nanotechnology and to foster its pharmaceutical applications and development in Taiwan, this article reviews the trends of regulating nanotechnology-based pharmaceuticals in the international community and proposes strategies for Taiwan’s regulation harmonized with international considerations. The draft regulatory measures include a chemistry, manufacturing, and controls (CMC) review checklist and guidance for CMC review of liposomal products. These have been submitted for discussion among an expert committee, with membership comprised of multidisciplinary academia, research institutions, the pharmaceutical industry, and regulators, and are currently approaching final consensus. Once a consensus is reached, these mechanisms will be recommended to the Taiwan Food and Drug Administration for jurisdiction and may be initiated as the starting point for regulating nanotechnology-based pharmaceuticals in Taiwan. PMID:25342901

Could the Pharmaceutical Industry Benefit from Full-Scale Adoption of Radio-Frequency Identification (RFID) Technology with New Regulations?

PubMed

Coustasse, Alberto; Kimble, Craig A; Stanton, Robert B; Naylor, Mariah

2016-01-01

Healthcare regulators are directing attention to the pharmaceutical supply chain with the passage of the Drug Quality and Security Act (DQSA) and the Drug Supply Chain Security Act (DSCSA). Adoption of Radio-Frequency Identification (RFID) technology has the ability to improve compliance, reduce costs, and improve safety in the supply chain but its implementation has been limited; primarily because of hardware and tag costs. The purpose of this research study was to analyze the benefits to the pharmaceutical industry and healthcare system of the adoption of RFID technology as a result of newly implemented supply chain regulations. The methodology was a review following the steps of a systematic review with a total of 96 sources used. With the DSCSA, pharmaceutical companies must track and trace prescription drugs across the supply chain, and RFID can resolve many track-and-trace issues with manufacturer control of data. The practical implication of this study is that pharmaceutical companies must continue to have the potential to increase revenues, decrease associated costs, and increase compliance with new FDA regulations with RFID. Still, challenges related to regulatory statute wording, implementation of two-dimensional barcode technology, and the variety of interfaces within the pharmaceutical supply chain have delayed adoption and its full implementation.

Could the Pharmaceutical Industry Benefit from Full-Scale Adoption of Radio-Frequency Identification (RFID) Technology with New Regulations?

PubMed Central

Coustasse, Alberto; Kimble, Craig A.; Stanton, Robert B.; Naylor, Mariah

2016-01-01

Healthcare regulators are directing attention to the pharmaceutical supply chain with the passage of the Drug Quality and Security Act (DQSA) and the Drug Supply Chain Security Act (DSCSA). Adoption of Radio-Frequency Identification (RFID) technology has the ability to improve compliance, reduce costs, and improve safety in the supply chain but its implementation has been limited; primarily because of hardware and tag costs. The purpose of this research study was to analyze the benefits to the pharmaceutical industry and healthcare system of the adoption of RFID technology as a result of newly implemented supply chain regulations. The methodology was a review following the steps of a systematic review with a total of 96 sources used. With the DSCSA, pharmaceutical companies must track and trace prescription drugs across the supply chain, and RFID can resolve many track-and-trace issues with manufacturer control of data. The practical implication of this study is that pharmaceutical companies must continue to have the potential to increase revenues, decrease associated costs, and increase compliance with new FDA regulations with RFID. Still, challenges related to regulatory statute wording, implementation of two-dimensional barcode technology, and the variety of interfaces within the pharmaceutical supply chain have delayed adoption and its full implementation. PMID:27843419

Methodological Quality of Meta-Analyses: Matched-Pairs Comparison over Time and between Industry-Sponsored and Academic-Sponsored Reports

ERIC Educational Resources Information Center

Lane, Peter W.; Higgins, Julian P. T.; Anagnostelis, Betsy; Anzures-Cabrera, Judith; Baker, Nigel F.; Cappelleri, Joseph C.; Haughie, Scott; Hollis, Sally; Lewis, Steff C.; Moneuse, Patrick; Whitehead, Anne

2013-01-01

Context: Meta-analyses are regularly used to inform healthcare decisions. Concerns have been expressed about the quality of meta-analyses and, in particular, about those supported by the pharmaceutical industry. Objective: The objective of this study is to compare the quality of pharmaceutical-industry-supported meta-analyses with academic…

Characterization of the evolution of the pharmaceutical regulatory environment.

PubMed

Shafiei, Nader; Ford, James L; Morecroft, Charles W; Lisboa, Paulo J; Taylor, Mark J

2013-01-01

This paper is part of a research study that is intended to identify pharmaceutical quality risks induced by the ongoing transformation in the industry. This study establishes the current regulatory context by characterizing the development of the pharmaceutical regulatory environment. The regulatory environment is one of the most important external factors that affects a company's organization, processes, and technological strategy. This is especially the case with the pharmaceutical industry, where its products affect the quality of life of the consumers. The quantitative analysis of regulatory events since 1813 and review of the associated literature resulted in identification of six factors influencing the regulatory environment, namely public health protection, public health promotion, crisis management, harmonization, innovation, and modernization. From 1813 to the 1970s the focus of regulators was centered on crisis management and public health protection-a basic mission that has remained consistent over the years. Since the 1980s a gradual move in the regulatory environment towards a greater focus on public health promotion, international harmonization, innovation, and agency modernization may be seen. The pharmaceutical industry is currently going through changes that affect the way it performs its research, manufacturing, and regulatory activities. The impact of these changes on the approaches to quality risk management requires more understanding. The authors are engaged in research to identify elements of the changes that influence pharmaceutical quality. As quality requirements are an integral part of the pharmaceutical regulations, a comprehensive understanding of these regulations is seen as the first step. The results of this study show that (i) public health protection, public health promotion, crisis management, harmonization, innovation, and modernization are factors that affect regulations in the pharmaceutical industry; (ii) the regulators' main mission of public health protection has remained a constant feature over the years; and (iii) since the 1970s other factors such as public health promotion, international harmonization, innovation, and agency modernization are playing more important role in regulatory agency thinking and actions.

78 FR 22269 - International Conference on Harmonisation; Draft Guidance on M7 Assessment and Control of DNA...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-15

...The Food and Drug Administration (FDA) is announcing the availability of a draft guidance entitled ``M7 Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to Limit Potential Carcinogenic Risk.'' The draft guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The draft guidance emphasizes considerations of both safety and quality risk management in establishing levels of mutagenic impurities that are expected to pose negligible carcinogenic risk. It outlines recommendations for assessment and control of mutagenic impurities that reside or are reasonably expected to reside in a final drug substance or product, taking into consideration the intended conditions of human use. The draft guidance is intended to provide guidance for new drug substances and new drug products during their clinical development and subsequent applications for marketing.

Near-infrared spectroscopy monitoring and control of the fluidized bed granulation and coating processes-A review.

PubMed

Liu, Ronghua; Li, Lian; Yin, Wenping; Xu, Dongbo; Zang, Hengchang

2017-09-15

The fluidized bed granulation and pellets coating technologies are widely used in pharmaceutical industry, because the particles made in a fluidized bed have good flowability, compressibility, and the coating thickness of pellets are homogeneous. With the popularization of process analytical technology (PAT), real-time analysis for critical quality attributes (CQA) was getting more attention. Near-infrared (NIR) spectroscopy, as a PAT tool, could realize the real-time monitoring and control during the granulating and coating processes, which could optimize the manufacturing processes. This article reviewed the application of NIR spectroscopy in CQA (moisture content, particle size and tablet/pellet thickness) monitoring during fluidized bed granulation and coating processes. Through this review, we would like to provide references for realizing automated control and intelligent production in fluidized bed granulation and pellets coating of pharmaceutical industry. Copyright © 2017 Elsevier B.V. All rights reserved.

A need for the standardization of the pharmaceutical sector in Libya

PubMed Central

Mustafa, Asma Abubakr; Kowalski, Stefan Robert

2010-01-01

Medicines are health technologies that can translate into tangible benefits for numerous acute as well as chronic health conditions. A nation's pharmaceutical sector needs to be appropriately structured and managed in order to ensure a safe, effective and quality supply of medicines to society. The process of medicines management involves the sequential management of five critical activity areas; namely; registration, selection, procurement, distribution and use. Formalized and standardized management of all five critical activity areas positively influences the availability, quality and affordability of medicines and ultimately increases the reliability and quality of the national healthcare system. Aim The aim of this review is to examine the current structure and operation of medicines management (i.e. the pharmaceutical sector) in Libya. Conclusion In the Libyan healthcare system all five critical activity areas are compromised. Restructuring of the pharmaceutical sector in Libya is required in order to provide and sustain sound pharmaceutical services for Libyan society and improve the national public health outcomes. PMID:21483563

A cross-sectional investigation of acceptance of health information technology: A nationwide survey of community pharmacists in Turkey.

PubMed

Sezgin, Emre; Özkan-Yıldırım, Sevgi

Health information technologies have become vital to health care services. In that regard, successful use of information technologies in pharmaceutical services is important to manage, control and maintain pharmaceutical transactions, which increase the quality of health care delivery. This study aimed to identify influencing factors on pharmacists' acceptance of pharmaceutical service systems. A cross-sectional study was conducted employing a research model based on technology acceptance theories. A parsimonious model was developed, and a self-reported questionnaire was distributed online. Community pharmacists participated voluntarily via the website of Turkish Pharmacists' Association. The data was analyzed employing Structural Equation Modeling. From 77 out of 81 cities of Turkey, 2169 community pharmacists participated to the survey with 43% response rate. Perceived usefulness, perceived ease of use, system factors and perceived behavioral control explained 47% of total variance in pharmacists' intention to use the pharmaceutical technology. The findings of the research provided insight about relations of influencing factors and practical implications regarding perceived behaviors and system use. Future researchers would benefit from the study design and findings. The study is also valuable for being the first nationwide study conducted on pharmacists about user attitudes toward a technology. Copyright © 2015 Elsevier Inc. All rights reserved.

Curbing the costly trend: exploring the need for a progressive approach to the management of specialty pharmaceuticals under the medical benefit.

PubMed

Jacobs, Michael S; Johnson, Kjel A

2012-07-01

Specialty injectables and protein-based biologic therapies represent the fastest growing segment of the drug trend for many plan sponsors. Coupled with the decline in spending on traditional pharmaceuticals and so-called blockbuster drugs coming off patent, the upward trend of specialty drug spending continues at an unprecedented rate, precipitating a shift in the focus of payers who manage prescription drugs. To characterize the current and future specialty drug spending and describe contemporary trends among payers for managing cost and quality in this segment, as well as to elucidate the shortcomings of the current efforts and to explore a comprehensive approach for addressing the cost and quality concerns directly associated with specialty injectables and protein-based biologics through interrelated management interventions. Although a notable decrease in spending on traditional pharmaceuticals was realized in 2010, disproportionate increases in specialty drug utilization and cost per unit fueled the continuing growth of the injectable and biologic markets. Each course of these therapies can cost in the tens of thousands of dollars, and this upward trend of specialty spending represents an escalation of an already significant spending for payers, employers, and members. Beyond the high cost and growing utilization of specialty pharmaceuticals, current management efforts have been met with variable degrees of success and have often proved challenging and, in some cases, even counterproductive. Common interventions used by payers nationwide for addressing specialty drug spending trend include specialty drug formularies, provider reimbursement strategies, distribution channel management, benefit design modifications, utilization management, and operational and administrative improvements such as postclaim edits. Although often overlooked, appropriate implementation of these tactics, and the extent to which they are integrated with overall drug benefit management, are key to the success of the pharmaceutical management program. Conventional specialty pharmaceutical management initiatives offer promise in various areas, but incentives for the best protocols may be misaligned when they are applied individually. Conversely, a comprehensive approach that integrates effective components of the specialty pharmaceutical management interventions can improve the quality of care and control costs associated with these agents, with significant specialty drug management expertise and access to benchmarking data serving as the foundation for appropriate decision-making.

The importance of quality control in validating concentrations of contaminants of emerging concern in source and treated drinking water samples.

PubMed

Batt, Angela L; Furlong, Edward T; Mash, Heath E; Glassmeyer, Susan T; Kolpin, Dana W

2017-02-01

A national-scale survey of 247 contaminants of emerging concern (CECs), including organic and inorganic chemical compounds, and microbial contaminants, was conducted in source and treated drinking water samples from 25 treatment plants across the United States. Multiple methods were used to determine these CECs, including six analytical methods to measure 174 pharmaceuticals, personal care products, and pesticides. A three-component quality assurance/quality control (QA/QC) program was designed for the subset of 174 CECs which allowed us to assess and compare performances of the methods used. The three components included: 1) a common field QA/QC protocol and sample design, 2) individual investigator-developed method-specific QA/QC protocols, and 3) a suite of 46 method comparison analytes that were determined in two or more analytical methods. Overall method performance for the 174 organic chemical CECs was assessed by comparing spiked recoveries in reagent, source, and treated water over a two-year period. In addition to the 247 CECs reported in the larger drinking water study, another 48 pharmaceutical compounds measured did not consistently meet predetermined quality standards. Methodologies that did not seem suitable for these analytes are overviewed. The need to exclude analytes based on method performance demonstrates the importance of additional QA/QC protocols. Published by Elsevier B.V.

Advanced qualification of pharmaceutical excipient suppliers by multiple analytics and multivariate analysis combined.

PubMed

Hertrampf, A; Müller, H; Menezes, J C; Herdling, T

2015-11-10

Pharmaceutical excipients have different functions within a drug formulation, consequently they can influence the manufacturability and/or performance of medicinal products. Therefore, critical to quality attributes should be kept constant. Sometimes it may be necessary to qualify a second supplier, but its product will not be completely equal to the first supplier product. To minimize risks of not detecting small non-similarities between suppliers and to detect lot-to-lot variability for each supplier, multivariate data analysis (MVA) can be used as a more powerful alternative to classical quality control that uses one-parameter-at-a-time monitoring. Such approach is capable of supporting the requirements of a new guideline by the European Parliament and Council (2015/C-95/02) demanding appropriate quality control strategies for excipients based on their criticality and supplier risks in ensuring quality, safety and function. This study compares calcium hydrogen phosphate from two suppliers. It can be assumed that both suppliers use different manufacturing processes. Therefore, possible chemical and physical differences were investigated by using Raman spectroscopy, laser diffraction and X-ray powder diffraction. Afterwards MVA was used to extract relevant information from each analytical technique. Both CaHPO4 could be discriminated by their supplier. The gained knowledge allowed to specify an enhanced strategy for second supplier qualification. Copyright © 2015 Elsevier B.V. All rights reserved.

Donated chemical probes for open science.

PubMed

Müller, Susanne; Ackloo, Suzanne; Arrowsmith, Cheryl H; Bauser, Marcus; Baryza, Jeremy L; Blagg, Julian; Böttcher, Jark; Bountra, Chas; Brown, Peter J; Bunnage, Mark E; Carter, Adrian J; Damerell, David; Dötsch, Volker; Drewry, David H; Edwards, Aled M; Edwards, James; Elkins, Jon M; Fischer, Christian; Frye, Stephen V; Gollner, Andreas; Grimshaw, Charles E; IJzerman, Adriaan; Hanke, Thomas; Hartung, Ingo V; Hitchcock, Steve; Howe, Trevor; Hughes, Terry V; Laufer, Stefan; Li, Volkhart Mj; Liras, Spiros; Marsden, Brian D; Matsui, Hisanori; Mathias, John; O'Hagan, Ronan C; Owen, Dafydd R; Pande, Vineet; Rauh, Daniel; Rosenberg, Saul H; Roth, Bryan L; Schneider, Natalie S; Scholten, Cora; Singh Saikatendu, Kumar; Simeonov, Anton; Takizawa, Masayuki; Tse, Chris; Thompson, Paul R; Treiber, Daniel K; Viana, Amélia Yi; Wells, Carrow I; Willson, Timothy M; Zuercher, William J; Knapp, Stefan; Mueller-Fahrnow, Anke

2018-04-20

Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of innovative high-quality probes, including all probe-associated data, control compounds and recommendations on use (https://openscienceprobes.sgc-frankfurt.de/). Here we describe the chemical tools and target-related knowledge that have been made available, and encourage others to join the project. © 2018, Müller et al.

[Hospital pharmacist has a rule for best practice use and French hospital activity tariffs. Example of a pharmaceutical quality control for drugs reimbursed in addition of DRGs].

PubMed

Hedoux, S; Dode, X; Pivot, C; Couray-Targe, S; Aulagner, G

2012-07-01

The best practice contract has given a new objective to the hospital pharmacists for the reimbursement in addition to Diagnosis Related Groups' (DRGs) tariffs. We built our pharmaceutical quality control for the administration traceability follow-up regarding the DRGs and the cost of care, for two reasons: the nominal drugs dispensation in link with the prescription made by pharmacist and the important expenditure of these drugs. Our organization depends on the development level of the informatized drugs circuit and minimizes the risk of financial shortfalls or wrong benefits, possible causes of economic penalties for our hospital. On the basis of this follow-up, we highlighted our activity and identified problems of management and drugs circuit organization. The quality of the administration traceability impacts directly on the quality of the medical records and the reimbursements of the expensive drugs. A better knowledge of prescription software is also required for a better quality and security of the medical data used in the medical informatic systems. The drugs management and the personal treatment in and between the care units need to be improved too. We have to continue and improve our organization with the future financial model for ATU drugs and the FIDES project. The health personnel awareness and the development of best informatic tools are also required. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation.

PubMed

Patil, Hemlata; Tiwari, Roshan V; Repka, Michael A

2016-02-01

Hot-melt extrusion (HME) is a promising technology for the production of new chemical entities in the developmental pipeline and for improving products already on the market. In drug discovery and development, industry estimates that more than 50% of active pharmaceutical ingredients currently used belong to the biopharmaceutical classification system II (BCS class II), which are characterized as poorly water-soluble compounds and result in formulations with low bioavailability. Therefore, there is a critical need for the pharmaceutical industry to develop formulations that will enhance the solubility and ultimately the bioavailability of these compounds. HME technology also offers an opportunity to earn intellectual property, which is evident from an increasing number of patents and publications that have included it as a novel pharmaceutical formulation technology over the past decades. This review had a threefold objective. First, it sought to provide an overview of HME principles and present detailed engineered extrusion equipment designs. Second, it included a number of published reports on the application of HME techniques that covered the fields of solid dispersions, microencapsulation, taste masking, targeted drug delivery systems, sustained release, films, nanotechnology, floating drug delivery systems, implants, and continuous manufacturing using the wet granulation process. Lastly, this review discussed the importance of using the quality by design approach in drug development, evaluated the process analytical technology used in pharmaceutical HME monitoring and control, discussed techniques used in HME, and emphasized the potential for monitoring and controlling hot-melt technology.

Methodologic quality and relevance of references in pharmaceutical advertisements in a Canadian medical journal.

PubMed

Lexchin, J; Holbrook, A

1994-07-01

To evaluate the methodologic quality and relevance of references in pharmaceutical advertisements in the Canadian Medical Association Journal (CMAJ). Analytic study. All 114 references cited in the first 22 distinct pharmaceutical advertisements in volume 146 of CMAJ. Mean methodologic quality score (modified from the 6-point scale used to assess articles in the American College of Physicians' Journal Club) and mean relevance score (based on a new 5-point scale) for all references in each advertisement. Twenty of the 22 companies responded, sending 78 (90%) of the 87 references requested. The mean methodologic quality score was 58% (95% confidence limits [CL] 51% and 65%) and the mean relevance score 76% (95% CL 72% and 80%). The two mean scores were statistically lower than the acceptable score of 80% (p < 0.05), and the methodologic quality score was outside the preset clinically significant difference of 15%. The poor rating for methodologic quality was primarily because of the citation of references to low-quality review articles and "other" sources (i.e., other than reports of clinical trials). Half of the advertisements had a methodologic quality score of less than 65%, but only five had a relevance score of less than 65%. Although the relevance of most of the references was within minimal acceptable limits, the methodologic quality was often unacceptable. Because advertisements are an important part of pharmaceutical marketing and education, we suggest that companies develop written standards for their advertisements and monitor their advertisements for adherence to these standards. We also suggest that the Pharmaceutical Advertising Advisory Board develop more stringent guidelines for advertising and that it enforce these guidelines in a consistent, rigorous fashion.

Methodologic quality and relevance of references in pharmaceutical advertisements in a Canadian medical journal.

PubMed Central

Lexchin, J; Holbrook, A

1994-01-01

OBJECTIVE: To evaluate the methodologic quality and relevance of references in pharmaceutical advertisements in the Canadian Medical Association Journal (CMAJ). DESIGN: Analytic study. DATA SOURCE: All 114 references cited in the first 22 distinct pharmaceutical advertisements in volume 146 of CMAJ. MAIN OUTCOME MEASURES: Mean methodologic quality score (modified from the 6-point scale used to assess articles in the American College of Physicians' Journal Club) and mean relevance score (based on a new 5-point scale) for all references in each advertisement. MAIN RESULTS: Twenty of the 22 companies responded, sending 78 (90%) of the 87 references requested. The mean methodologic quality score was 58% (95% confidence limits [CL] 51% and 65%) and the mean relevance score 76% (95% CL 72% and 80%). The two mean scores were statistically lower than the acceptable score of 80% (p < 0.05), and the methodologic quality score was outside the preset clinically significant difference of 15%. The poor rating for methodologic quality was primarily because of the citation of references to low-quality review articles and "other" sources (i.e., other than reports of clinical trials). Half of the advertisements had a methodologic quality score of less than 65%, but only five had a relevance score of less than 65%. CONCLUSIONS: Although the relevance of most of the references was within minimal acceptable limits, the methodologic quality was often unacceptable. Because advertisements are an important part of pharmaceutical marketing and education, we suggest that companies develop written standards for their advertisements and monitor their advertisements for adherence to these standards. We also suggest that the Pharmaceutical Advertising Advisory Board develop more stringent guidelines for advertising and that it enforce these guidelines in a consistent, rigorous fashion. PMID:8004560

[Application of quality by design in granulation process for ginkgo leaf tablet (Ⅱ)： identification of critical quality attributes].

PubMed

Xu, Bing; Cui, Xiang-Long; Yang, Chan; Wang, Xin; Shi, Xin-Yuan; Qiao, Yan-Jiang

2017-03-01

Quality by design (QbD) highlights the concept of "begin with the end", which means to thoroughly understand the target product quality first, and then guide pharmaceutical process development and quality control throughout the whole manufacturing process. In this paper, the Ginkgo biloba granules intermediates were taken as the research object, and the requirements of the tensile strength of tablets were treated as the goals to establish the methods for identification of granules' critical quality attributes (CQAs) and establishment of CQAs' limits. Firstly, the orthogonal partial least square (OPLS) model was adopted to build the relationship between the micromeritic properties of 29 batches of granules and the tensile strength of ginkgo leaf tablets, and thereby the potential critical quality attributes (pCQAs) were screened by variable importance in the projection (VIP) indexes. Then, a series of OPLS models were rebuilt by reducing pCQAs variables one by one in view of the rule of VIP values from low to high in sequence. The model performance results demonstrated that calibration and predictive performance of the model had no decreasing trend after variables reduction. In consideration of the results from variables selection as well as the collinearity test and testability of the pCQAs, the median particle size (D₅₀) and the bulk density (Da) were identified as critical quality attributes (CQAs). The design space of CQAs was developed based on a multiple linear regression model established between the CQAs (D₅₀ and Da) and the tensile strength. The control constraints of the CQAs were determined as 170 μm< D₅₀<500 μm and 0.30 g•cm⁻³

Are All Clinical Studies Sponsored by Industry Not Valid?

PubMed Central

Heinemann, Lutz

2008-01-01

Industry-sponsored studies have such a bad reputation that some journals require an additional statistical analysis by an independent statistician. This commentary discusses some of the reasons why academic people tend to believe that “academic” science is better than industry-driven science. Most likely, when it comes to publications, the risk of fraud exists in both worlds as the pressure to publish “significant” data is prevalent in both worlds. In contrast to the academic world, the level of control by regulatory bodies for industry-sponsored studies is much higher. Therefore, the quality of industry-driven studies is high, at least when it comes to the quality of data. One of the main reasons why academic people are so skeptical about the pharmaceutical industry is a lack of knowledge about the work done in industry. It is as demanding and scientific as in other industries. In turn, many physicians working in the pharmaceutical industry have low self-esteem. Also, the pharmaceutical industry should improve its self-presentation adequately to get rid of its bad image. There is a clear need for more communication between both worlds in order to better understand the mutual difficulties and needs. PMID:19885307

Cross-Linked Hydrogel for Pharmaceutical Applications: A Review

PubMed Central

2017-01-01

Hydrogels are promising biomaterials because of their important qualities such as biocompatibility, biodegradability, hydrophilicity and non-toxicity. These qualities make hydrogels suitable for application in medical and pharmaceutical field. Recently, a tremendous growth of hydrogel application is seen, especially as gel and patch form, in transdermal drug delivery. This review mainly focuses on the types of hydrogels based on cross-linking and; secondly to describe the possible synthesis methods to design hydrogels for different pharmaceutical applications. The synthesis and chemistry of these hydrogels are discussed using specific pharmaceutical examples. The structure and water content in a typical hydrogel have also been discussed. PMID:29399542

Impact of Practice-Based Instruction on Graduate Programs in the Pharmaceutical Sciences.

ERIC Educational Resources Information Center

Zografi, George

1979-01-01

Graduate education in the pharmaceutical sciences is examined. It is suggested that greater flexibility and quality of masters and PhD programs in pharmacy could increase enrollment levels in the graduate pharmaceutical studies. (SF)

Intelligent MONitoring System for antiviral pharmacotherapy in patients with chronic hepatitis C (SiMON-VC).

PubMed

Margusino-Framiñán, Luis; Cid-Silva, Purificación; Mena-de-Cea, Álvaro; Sanclaudio-Luhía, Ana Isabel; Castro-Castro, José Antonio; Vázquez-González, Guillermo; Martín-Herranz, Isabel

2017-01-01

Two out of six strategic axes of pharmaceutical care in our hospital are quality and safety of care, and the incorporation of information technologies. Based on this, an information system was developed in the outpatient setting for pharmaceutical care of patients with chronic hepatitis C, SiMON-VC, which would improve the quality and safety of their pharmacotherapy. The objective of this paper is to describe requirements, structure and features of Si- MON-VC. Requirements demanded were that the information system would enter automatically all critical data from electronic clinical records at each of the visits to the Outpatient Pharmacy Unit, allowing the generation of events and alerts, documenting the pharmaceutical care provided, and allowing the use of data for research purposes. In order to meet these requirements, 5 sections were structured for each patient in SiMON-VC: Main Record, Events, Notes, Monitoring Graphs and Tables, and Follow-up. Each section presents a number of tabs with those coded data needed to monitor patients in the outpatient unit. The system automatically generates alerts for assisted prescription validation, efficacy and safety of using antivirals for the treatment of this disease. It features a completely versatile Indicator Control Panel, where temporary monitoring standards and alerts can be set. It allows the generation of reports, and their export to the electronic clinical record. It also allows data to be exported to the usual operating systems, through Big Data and Business Intelligence. Summing up, we can state that SiMON-VC improves the quality of pharmaceutical care provided in the outpatient pharmacy unit to patients with chronic hepatitis C, increasing the safety of antiviral therapy. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Global pharmaceutical regulation: the challenge of integration for developing states.

PubMed

Pezzola, Anthony; Sweet, Cassandra M

2016-12-20

This paper has set out to map the state of pharmaceutical regulation in the developing world through the construction of cross-national indices drawing from World Health Organization data. The last two decades have been characterized by deep changes for the pharmaceutical sector, including the complete transformation of intellectual property systems at the behest of the World Trade Organization and the consolidation of global active ingredient suppliers in China and India. Although the rules for ownership of medicine have been set and globally implemented, we know surprisingly little about how the standards for market entrance and regulation of pharmaceutical products have changed at the national level. How standardized are national pharmaceutical market systems? Do we find homogeneity or variation across the developing world? Are their patterns for understanding why some countries have moved closer to one global norm for pharmaceutical regulation and others have developed hybrid models for oversight of this sector? Access to medicine is a core tool in public health. This paper gauges the levels of standards in public and private generics markets for developing countries building on national-level pharmaceutical market surveys for 78 countries to offer three indicators of market oversight: State Regulatory Infrastructure, Monitoring the Private Market and Public Quality Control. Identifying the different variables that affect a state's institutional capacity and current standard level offers new insights to the state of pharmaceuticals in the developing world. It is notable that there are very few (none at the time of this paper) studies that map out the new global terrain for pharmaceutical regulation in the post-TRIPS context. This paper uses item response theory to develop original indicators of pharmaceutical regulation. We find remarkable resistance to the implementation of global pharmaceutical norms for quality standards in developing states and in regulatory infrastructure. Human capacity across many developing countries remains limited. Most notably, variation among states is stark. Countries that have been leaders in establishing global norms do not appear to have influenced their neighbors in establishing regional patterns. Finally, in contrast to traditional theories of international norms diffusion, global standard-setters such as the United States or European Union appear to have surprisingly little influence on standard setting across our survey. Our research has implications for the framing of technical support on public health initiatives aimed at strengthening local public institutions in medicine and offers a new methodological approach for analyzing drug regulation systems in developing countries.

Analysis of different beta-lactams antibiotics in pharmaceutical preparations using micellar electrokinetic capillary chromatography.

PubMed

Pérez, M I Bailón; Rodríguez, L Cuadros; Cruces-Blanco, C

2007-01-17

The potential of micellar electrokinetic capillary chromatography (MEKC) for analyzing nine beta-lactams antibiotics (cloxacillin, dicloxacillin, oxacillin, penicillin G, penicillin V, ampicillin, nafcillin, piperacillin, amoxicillin) in different pharmaceutical preparations, have been demonstrated. An experimental design strategy has been applied to optimize the main variables: pH and buffer concentration, concentration of the micellar medium, separation voltage and capillary temperature. Borate buffer (26mM) at pH 8.5 containing 100mM sodium dodecyl sulphate (SDS) was used as the background electrolyte. The method was validated. Linearity, limit of detection and quantitation and precision were established for each compound. The analysis of some of the beta-lactams in Orbenin capsules, Britapen tables and in Veterin-Micipen injectable, all used in human and veterinary medicine, have demonstrated the applicability of these technique for quality control in the pharmaceutical industry.

77 FR 16264 - Manufacturer of Controlled Substances, Notice of Registration; Johnson Matthey Pharmaceutical...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

..., Notice of Registration; Johnson Matthey Pharmaceutical Materials Inc. By Notice dated November 18, 2011... Pharmaceutical Materials Inc., Pharmaceutical Service, 25 Patton Road, Devens, Massachusetts 01434, made... Matthey Pharmaceutical Materials Inc. to manufacture the listed basic classes of controlled substances is...

Quality indicators for pharmaceutical care: a comprehensive set with national scores for Dutch community pharmacies.

PubMed

Teichert, Martina; Schoenmakers, Tim; Kylstra, Nico; Mosk, Berend; Bouvy, Marcel L; van de Vaart, Frans; De Smet, Peter A G M; Wensing, Michel

2016-08-01

Background The quality of pharmaceutical care in community pharmacies in the Netherlands has been assessed annually since 2008. The initial set has been further developed with pharmacists and patient organizations, the healthcare inspectorate, the government and health insurance companies. The set over 2012 was the first set of quality indicators for community pharmacies which was validated and supported by all major stakeholders. The aims of this study were to describe the validated set of quality indicators for community pharmacies and to report their scores over 2012. In subanalyses the score development over 5 years was described for those indicators, that have been surveyed before and remained unchanged. Methods Community pharmacists in the Netherlands were invited in 2013 to provide information for the set of 2012. Quality indicators were mapped by categories relevant for pharmaceutical care and defined for structures, processes and dispensing outcomes. Scores for categorically-measured quality indicators were presented as the percentage of pharmacies reporting the presence of a quality aspect. For numerical quality indicators, the mean of all reported scores was expressed. In subanalyses for those indicators that had been questioned previously, scores were collected from earlier measurements for pharmacies providing their scores in 2012. Multilevel analysis was used to assess the consistency of scores within one pharmacy over time by the intra-class correlation coefficient (ICC). Results For the set in 2012, 1739 Dutch community pharmacies (88 % of the total) provided information for 66 quality indicators in 10 categories. Indicator scores on the presence of quality structures showed relatively high quality levels. Scores for processes and dispensing outcomes were lower. Subanalyses showed that overall indicators scores improved within pharmacies, but this development differed between pharmacies. Conclusions A set of validated quality indicators provided insight into the quality of pharmaceutical care in the Netherlands. The quality of pharmaceutical care improved over time. As of 2012 quality structures were present in at least 80 % of the community pharmacies. Variation in scores on care processes and outcomes between individual pharmacies and over time can initiate future research to better understand and facilitate quality improvement in community pharmacies.

Association between hospital size and quality improvement for pharmaceutical services.

PubMed

Nau, David P; Garber, Mathew C; Lipowski, Earlene E; Stevenson, James G

2004-01-15

The relationship between hospital size and quality improvement (QI) for pharmaceutical services was studied. A questionnaire on QI was sent to hospital pharmacy directors in Michigan and Florida in 2002. The questionnaire included items on QI lead-team composition, QI tools, QI training, and QI culture. Usable responses were received from 162 (57%) of 282 pharmacy directors. Pharmacy QI lead teams were present in 57% of institutions, with larger teams in large hospitals (> or = 300 patients). Only two QI tools were used by a majority of hospitals: root-cause analysis (62%) and flow charts (66%). Small hospitals (< 50 patients) were less likely than medium-sized hospitals (50-299 patients) and large hospitals to use several QI tools, including control charts, cause-and-effect diagrams, root-cause analysis, flow charts, and histograms. Large hospitals were more likely than small and medium-sized hospitals to use root-cause analysis and control charts. There was no relationship between hospital size and the frequency with which physician or patient satisfaction with pharmaceutical services was measured. There were no differences in QI training or QI culture across hospital size categories. A survey suggested that a majority of hospital pharmacies in Michigan and Florida have begun to adopt QI techniques but that most are not using rigorous QI tools. Pharmacies in large hospitals had more QI lead-team members and were more likely to use certain QI tools, but there was no relationship between hospital size and satisfaction measurements, QI training, or QI culture.

Pharmaceutical quality assurance of local private distributors: a secondary analysis in 13 low-income and middle-income countries

PubMed Central

Caudron, Jean Michel; Schiavetti, Benedetta; Pouget, Corinne; Tsoumanis, Achilleas; Meessen, Bruno; Ravinetto, Raffaella

2018-01-01

Introduction The rapid globalisation of the pharmaceutical production and distribution has not been supported by harmonisation of regulatory systems worldwide. Thus, the supply systems in low-income and middle-income countries (LMICs) remain exposed to the risk of poor-quality medicines. To contribute to estimating this risk in the private sector in LMICs, we assessed the quality assurance system of a convenient sample of local private pharmaceutical distributors. Methods This descriptive study uses secondary data derived from the audits conducted by the QUAMED group at 60 local private pharmaceutical distributors in 13 LMICs. We assessed the distributors’ compliance with good distribution practices (GDP), general quality requirements (GQR) and cold chain management (CCM), based on an evaluation tool inspired by the WHO guidelines ’Model Quality Assurance System (MQAS) for procurement agencies'. Descriptive statistics describe the compliance for the whole sample, for distributors in sub-Saharan Africa (SSA) versus those in non-SSA, and for those in low-income countries (LICs) versus middle-income countries (MICs). Results Local private pharmaceutical distributors in our sample were non-compliant, very low-compliant or low-compliant for GQR (70%), GDP (60%) and CCM (41%). Only 7/60 showed good to full compliance for at least two criteria. Observed compliance varies by geographical region and by income group: maximum values are higher in non-SSA versus SSA and in MICs versus LICs, while minimum values are the same across different groups. Conclusion The poor compliance with WHO quality standards observed in our sample indicates a concrete risk that patients in LMICs are exposed to poor-quality or degraded medicines. Significant investments are needed to strengthen the regulatory supervision, including on private pharmaceutical distributors. An adapted standardised evaluation tool inspired by the WHO MQAS would be helpful for self-evaluation, audit and inspection purposes. PMID:29915671

[Development of whole process quality control and management system of traditional Chinese medicine decoction pieces based on traditional Chinese medicine quality tree].

PubMed

Yu, Wen-Kang; Dong, Ling; Pei, Wen-Xuan; Sun, Zhi-Rong; Dai, Jun-Dong; Wang, Yun

2017-12-01

The whole process quality control and management of traditional Chinese medicine (TCM) decoction pieces is a system engineering, involving the base environment, seeds and seedlings, harvesting, processing and other multiple steps, so the accurate identification of factors in TCM production process that may induce the quality risk, as well as reasonable quality control measures are very important. At present, the concept of quality risk is mainly concentrated in the aspects of management and regulations, etc. There is no comprehensive analysis on possible risks in the quality control process of TCM decoction pieces, or analysis summary of effective quality control schemes. A whole process quality control and management system for TCM decoction pieces based on TCM quality tree was proposed in this study. This system effectively combined the process analysis method of TCM quality tree with the quality risk management, and can help managers to make real-time decisions while realizing the whole process quality control of TCM. By providing personalized web interface, this system can realize user-oriented information feedback, and was convenient for users to predict, evaluate and control the quality of TCM. In the application process, the whole process quality control and management system of the TCM decoction pieces can identify the related quality factors such as base environment, cultivation and pieces processing, extend and modify the existing scientific workflow according to their own production conditions, and provide different enterprises with their own quality systems, to achieve the personalized service. As a new quality management model, this paper can provide reference for improving the quality of Chinese medicine production and quality standardization. Copyright© by the Chinese Pharmaceutical Association.

Quality of Artemisinin-based Combination Therapy for malaria found in Ghanaian markets and public health implications of their use.

PubMed

Tivura, Mathilda; Asante, Isaac; van Wyk, Albert; Gyaase, Stephaney; Malik, Naiela; Mahama, Emmanuel; Hostetler, Dana M; Fernandez, Facundo M; Asante, Kwaku Poku; Kaur, Harparkash; Owusu-Agyei, Seth

2016-10-28

Ghana changed their antimalarial drug policy from monotherapies to Artemisinin-based Combination Therapies in 2004 in order to provide more efficacious medicines for treatment of malaria. The policy change can be eroded if poor quality Artemisinin-based Combination Therapies are allowed to remain on the Ghanaian market unchecked by regulatory bodies and law enforcement agencies. The presence and prevalence of substandard and counterfeit Artemisinin-based Combination Therapies need to be determined on open markets in Ghana; a review of the current policy; identifying any gaps and making recommendations on actions to be taken in addressing gaps identified are essential as the data provided and recommendations made will help in ensuring effective control of malaria in Ghana. A field survey of antimalarial drugs was conducted in the central part of Ghana. The amount of active pharmaceutical ingredient in each Artemisinin-based Combination Therapy sample identified in the survey was measured using high performance liquid chromatographic analyses. Active pharmaceutical ingredient within the range of 85-115 % was considered as standard and active pharmaceutical ingredient results out of the range were considered as substandard. All samples were screened to confirm stated active pharmaceutical ingredient presence using mass spectrometry. A total of 256 Artemisinin-based Combination Therapies were purchased from known medicine outlets, including market stalls, hospitals/clinics, pharmacies, drug stores. Artemether lumefantrine (52.5 %) and artesunate amodiaquine (43.2 %) were the predominant Artemisinin-based Combination Therapies purchased. Of the 256 Artemisinin-based Combination Therapies purchased, 254 were tested, excluding two samples of Artesunate-SP. About 35 % of Artemisinin-based Combination Therapies were found to be substandard. Nine percent of Artemisinin-based Combination Therapies purchased were past their expiry date; no counterfeit (falsified) medicine samples were detected by either high performance liquid chromatographic or mass spectrometry. A high proportion of Artemisinin-based Combination Therapies sold in central Ghana were found to be substandard. Manufacturing of medicines that do not adhere to good manufacturing practices may have contributed to the poor quality of the Artemisinin-based Combination Therapies procured. A strict law enforcement and quality monitoring systems is recommended to ensure effective malaria case management as part of malaria control.

WHO Expert Committee on Specifications for Pharmaceutical Preparations.

PubMed

2009-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new standards and guidelines were adopted and recommended for use: the current list of available International Chemical Reference Substances and International Infrared Reference Spectra; guidelines on stability testing of active pharmaceutical ingredients and finished pharmaceutical products; procedure for prequalification of pharmaceutical products; and the procedure for assessing the acceptability, in principle, of active pharmaceutical ingredients for use in pharmaceutical products.

A new method for long-term storage of titred microbial standard solutions suitable for microbiologic quality control activities of pharmaceutical companies.

PubMed

Chiellini, Carolina; Mocali, Stefano; Fani, Renato; Ferro, Iolanda; Bruschi, Serenella; Pinzani, Alessandro

2016-08-01

Commercially available lyophilized microbial standards are expensive and subject to reduction in cell viability due to freeze-drying stress. Here we introduce an inexpensive and straightforward method for in-house microbial standard preparation and cryoconservation that preserves constant cell titre and cell viability over 14 months.

Sharp Absorption Peaks in THz Spectra Valuable for Crystal Quality Evaluation of Middle Molecular Weight Pharmaceuticals

NASA Astrophysics Data System (ADS)

Sasaki, Tetsuo; Sakamoto, Tomoaki; Otsuka, Makoto

2018-05-01

Middle molecular weight (MMW) pharmaceuticals (MW 400 4000) are attracting attention for their possible use in new medications. Sharp absorption peaks were observed in MMW pharmaceuticals at low temperatures by measuring with a high-resolution terahertz (THz) spectrometer. As examples, high-resolution THz spectra for amoxicillin trihydrate, atorvastatin calcium trihydrate, probucol, and α,β,γ,δ-tetrakis(1-methylpyridinium-4-yl)porphyrin p-toluenesulfonate (TMPyP) were obtained at 10 K. Typically observed as peaks with full width at half-height (FWHM) values as low as 5.639 GHz at 0.96492 THz in amoxicillin trihydrate and 8.857 GHz at 1.07974 THz for probucol, many sharp peaks of MMW pharmaceuticals could be observed. Such narrow absorption peaks enable evaluation of the crystal quality of MMW pharmaceuticals and afford sensitive detection of impurities.

Dissolution testing of orally disintegrating tablets.

PubMed

Kraemer, Johannes; Gajendran, Jayachandar; Guillot, Alexis; Schichtel, Julian; Tuereli, Akif

2012-07-01

For industrially manufactured pharmaceutical dosage forms, product quality tests and performance tests are required to ascertain the quality of the final product. Current compendial requirements specify a disintegration and/or a dissolution test to check the quality of oral solid dosage forms. These requirements led to a number of compendial monographs for individual products and, at times, the results obtained may not be reflective of the dosage form performance. Although a general product performance test is desirable for orally disintegrating tablets (ODTs), the complexity of the release controlling mechanisms and short time-frame of release make such tests difficult to establish. For conventional oral solid dosage forms (COSDFs), disintegration is often considered to be the prerequisite for subsequent dissolution. Hence, disintegration testing is usually insufficient to judge product performance of COSDFs. Given the very fast disintegration of ODTs, the relationship between disintegration and dissolution is worthy of closer scrutiny. This article reviews the current status of dissolution testing of ODTs to establish the product quality standards. Based on experimental results, it appears that it may be feasible to rely on the dissolution test without a need for disintegration studies for selected ODTs on the market. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Changing tides: Adaptive monitoring, assessment, and management of pharmaceutical hazards in the environment through time.

PubMed

Gaw, Sally; Brooks, Bryan W

2016-04-01

Pharmaceuticals are ubiquitous contaminants in aquatic ecosystems. Adaptive monitoring, assessment, and management programs will be required to reduce the environmental hazards of pharmaceuticals of concern. Potentially underappreciated factors that drive the environmental dose of pharmaceuticals include regulatory approvals, marketing campaigns, pharmaceutical subsidies and reimbursement schemes, and societal acceptance. Sales data for 5 common antidepressants (duloxetine [Cymbalta], escitalopram [Lexapro], venlafaxine [Effexor], bupropion [Wellbutrin], and sertraline [Zoloft]) in the United States from 2004 to 2008 were modeled to explore how environmental hazards in aquatic ecosystems changed after patents were obtained or expired. Therapeutic hazard ratios for Effexor and Lexapro did not exceed 1; however, the therapeutic hazard ratio for Zoloft declined whereas the therapeutic hazard ratio for Cymbalta increased as a function of patent protection and sale patterns. These changes in therapeutic hazard ratios highlight the importance of considering current and future drivers of pharmaceutical use when prioritizing pharmaceuticals for water quality monitoring programs. When urban systems receiving discharges of environmental contaminants are examined, water quality efforts should identify, prioritize, and select target analytes presently in commerce for effluent monitoring and surveillance. © 2015 SETAC.

Pharmaceutical pricing and reimbursement in China: When the whole is less than the sum of its parts.

PubMed

Hu, Jia; Mossialos, Elias

2016-05-01

In recent years, there has been rapid growth in pharmaceutical spending in China. In addition, the country faces many challenges with regards to the quality, pricing and affordability of drugs. Pricing and reimbursement are important aspects of pharmaceutical policy that must be prioritised in order to address the many challenges. This review draws on multiple sources of information. A review of the academic and grey literature along with official government statistics were combined with information from seminars held by China's State Council Development Research Center to provide an overview of pharmaceutical pricing and reimbursement in China. Pricing and reimbursement policy were analysed through a framework that incorporates supply-side policies, proxy-demand policies and demand-side policies. China's current pharmaceutical policies interact in such a way to create dysfunction in the form of high prices, low drug quality, irrational prescribing and problems with access. Finally, the country's fragmented regulatory environment hampers pharmaceutical policy reform. The pricing and reimbursement policy landscape can be improved through higher drug quality standards, greater market concentration, an increase in government subsidies, quality-oriented tendering, wider implementation of the zero mark-up policy, through linking reimbursement with rational prescribing, and the promotion of health technology assessment and comparative effectiveness research. Addressing broader issues of regulatory fragmentation, the lack of transparency and corruption will help ensure that policies are created in a coherent, evidence-based fashion. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Transformation in the pharmaceutical industry--a systematic review of the literature.

PubMed

Shafiei, Nader; Ford, James L; Morecroft, Charles W; Lisboa, Paulo J; Taylor, Mark J; Mouzughi, Yusra

2013-01-01

The evolutionary development of pharmaceutical transformation was studied through systematic review of the literature. Fourteen triggers were identified that will affect the pharmaceutical business, regulatory science, and enabling technologies in future years. The relative importance ranking of the transformation triggers was computed based on their prevalence within the articles studied. The four main triggers with the strongest literature evidence were Fully Integrated Pharma Network, Personalized Medicine, Translational Research, and Pervasive Computing. The theoretical quality risks for each of the four main transformation triggers are examined, and the remaining ten triggers are described. The pharmaceutical industry is currently going through changes that affect the way it performs its research, manufacturing, and regulatory activities (this is termed pharmaceutical transformation). The impact of these changes on the approaches to quality risk management requires more understanding. In this paper, a comprehensive review of the academic, regulatory, and industry literature were used to identify 14 triggers that influence pharmaceutical transformation. The four main triggers, namely Fully Integrated Pharma Network, Personalized Medicine, Translational Research, and Pervasive Computing, were selected as the most important based on the strength of the evidence found during the literature review activity described in this paper. Theoretical quality risks for each of the four main transformation triggers are examined, and the remaining ten triggers are described.

Public perceptions of non-pharmaceutical interventions for reducing transmission of respiratory infection: systematic review and synthesis of qualitative studies

PubMed Central

2014-01-01

Background Non-pharmaceutical public health interventions may provide simple, low-cost, effective ways of minimising the transmission and impact of acute respiratory infections in pandemic and non-pandemic contexts. Understanding what influences the uptake of non-pharmaceutical interventions such as hand and respiratory hygiene, mask wearing and social distancing could help to inform the development of effective public health advice messages. The aim of this synthesis was to explore public perceptions of non-pharmaceutical interventions that aim to reduce the transmission of acute respiratory infections. Methods Five online databases (MEDLINE, PsycINFO, CINAHL, EMBASE and Web of Science) were systematically searched. Reference lists of articles were also examined. We selected papers that used a qualitative research design to explore perceptions and beliefs about non-pharmaceutical interventions to reduce transmission of acute respiratory infections. We excluded papers that only explored how health professionals or children viewed non-pharmaceutical respiratory infection control. Three authors performed data extraction and assessment of study quality. Thematic analysis and components of meta-ethnography were adopted to synthesise findings. Results Seventeen articles from 16 studies in 9 countries were identified and reviewed. Seven key themes were identified: perceived benefits of non-pharmaceutical interventions, perceived disadvantages of non-pharmaceutical interventions, personal and cultural beliefs about infection transmission, diagnostic uncertainty in emerging respiratory infections, perceived vulnerability to infection, anxiety about emerging respiratory infections and communications about emerging respiratory infections. The synthesis showed that some aspects of non-pharmaceutical respiratory infection control (particularly hand and respiratory hygiene) were viewed as familiar and socially responsible actions to take. There was ambivalence about adopting isolation and personal distancing behaviours in some contexts due to their perceived adverse impact and potential to attract social stigma. Common perceived barriers included beliefs about infection transmission, personal vulnerability to respiratory infection and concerns about self-diagnosis in emerging respiratory infections. Conclusions People actively evaluate non-pharmaceutical interventions in terms of their perceived necessity, efficacy, acceptability, and feasibility. To enhance uptake, it will be necessary to address key barriers, such as beliefs about infection transmission, rejection of personal risk of infection and concern about the potential costs and stigma associated with some interventions. PMID:24920395

The legal framework governing the quality of (traditional) herbal medicinal products in the European Union.

PubMed

Kroes, Burt H

2014-12-02

In the European Union a complex regulatory framework is in place for the regulation of (traditional) herbal medicinal products. It is based on the principle that a marketing authorisation granted by the competent authorities is required for placing medicinal products on the market. The requirements and procedures for acquiring such a marketing authorisation are laid down in regulations, directives and scientific guidelines. This paper gives an overview of the quality requirements for (traditional) herbal medicinal products that are contained in European pharmaceutical legislation. Pharmaceutical quality of medicinal product is the basis for ensuring safe and effective medicines. The basic principles governing the assurance of the quality of medicinal products in the European Union are primarily defined in the amended Directive 2001/83/EC and Directive 2003/63/EC. Quality requirements of herbal medicinal products are also laid down in scientific guidelines. Scientific guidelines provide a basis for practical harmonisation of how the competent authorities of EU Member States interpret and apply the detailed requirements for the demonstration of quality laid down in regulations and directives. Detailed quality requirements for herbal medicinal products on the European market are contained in European Union (EU) pharmaceutical legislation. They include a system of manufacturing authorisations which ensures that all herbal medicinal products on the European market are manufactured/imported only by authorised manufacturers, whose activities are regularly inspected by the competent authorities. Additionally, as starting materials only active substances are allowed which have been manufactured in accordance with the GMP for starting materials as adopted by the Community. The European regulatory framework encompasses specific requirements for herbal medicinal products. These requirements are independent from the legal status. Thus, the same quality standards equally apply to herbal products based on clinical evidence and traditional herbal medicinal products. The basic principle is that the quality of herbal medicinal products is intrinsically associated with the quality standard of the herbal substances and/or herbal preparations. Furthermore, the herbal substance or herbal preparation in its entirety is regarded as the active substance. Consequently, a mere determination of the content of marker(s) or constituents with known therapeutic activity is not sufficient for the quality control of herbal medicinal products. Specific quality requirements include thorough product characterisation, adherence to the Good Agricultural and Collection Practices, good manufacturing practices and validated manufacturing process, e.g., raw material testing, in-process testing, fingerprint characterisation etc. Quality control of herbal medicinal products is primarily intended to define the quality of the herbal substance/preparation and herbal medicinal product rather than to establish full characterisation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Clinical safety data management in company non-sponsored trials].

PubMed

Saito, Akiko; Sakai, Junko; Kurihara, Masaaki; Kami, Masahiro; Kanda, Yoshinobu; Mori, Shin-ichiro; Takaue, Yoichi; Ohashi, Yasuo

2003-09-01

There is currently no harmonized way in Japan to manage safety data which are obtained during clinical trials supported by Government funds. There are two types of clinical trials, 'sponsored trials(sponsored by industrial companies)' and 'non-sponsored trials(funded by the Government, etc.)'. The Japanese Ministry of Health and Welfare has issued many of pharmaceutical laws(GCP, GPMSP etc.) for the regulation of sponsored trials, while none has ever established for non-sponsored trials, thus leaving the most important quality control/assurance unregulated. In this manuscript we discuss that the simple application of pharmaceutical laws to government-sponsored trials can not be a proper answer because of the different nature of the two types of trials.

LIFT Tenant Is Off and Running

NASA Technical Reports Server (NTRS)

Steele, Gynelle C.

2001-01-01

Lewis Incubator for Technology (LIFT) tenant, Analiza Inc., graduated from the incubator July 2000. Analiza develops technology and products for the early diagnosis of diseases, quality control of bio-pharmaceutical therapeutics, and other applications involving protein analyses. Technology links with NASA from existing and planned work are in areas of microfluidics and laser light scattering. Since their entry in LIFT in May, 1997, Analiza has: Received a $750,000 grant from the National Institutes of Health. Collaborated with a Nobel Prize winner on drug design. Collaborated with Bristol-Myers Squibb on the characterization of biological therapeutics. Added a Ph.D. senior scientist and several technicians. Received significant interest from major pharmaceutical companies about collaborating and acquiring Analiza technology.

Total quality through computer integrated manufacturing in the pharmaceutical industry.

PubMed

Ufret, C M

1995-01-01

The role of Computer Integrated Manufacturing (CIM) in the pursue of total quality in pharmaceutical manufacturing is assessed. CIM key objectives, design criteria, and performance measurements, in addition to its scope and implementation in a hierarchical structure, are explored in detail. Key elements for the success of each phase in a CIM project and a brief status of current CIM implementations in the pharmaceutical industry are presented. The role of World Class Manufacturing performance standards and other key issues to achieve full CIM benefits are also addressed.

Pharmaceutical compounds in shallow groundwater in non-agricultural areas of Minnesota: study design, methods, and data, 2013

USGS Publications Warehouse

Elliott, Sarah M.; Erickson, Melinda L.

2014-01-01

The U.S. Geological Survey, in cooperation with the Minnesota Pollution Control Agency, completed a study on the occurrence of pharmaceutical compounds and other contaminants of emerging concern in shallow groundwater in non-agricultural areas of Minnesota during 2013. This report describes the study design and methods for the study on the occurrence of pharmaceuticals and other contaminants of emerging concern, and presents the data collected on pharmaceutical compounds. Samples were analyzed by the U.S. Geological Survey National Water Quality Laboratory for 110 pharmaceutical compounds using research method 9017. Samples from 21 of 45 wells had detectable concentrations of at least one of the 110 compounds analyzed. One sample contained detectable concentrations of nine compounds, which was the most detected in a single sample. Fewer than five compounds were detected in most samples. Among all samples, 27 of the 110 compounds were detected in groundwater from at least one well. Desmethyldiltiazem and nicotine were the most frequently detected compounds, each detected in 5 of 46 environmental samples (one well was sampled twice so a total of 46 environmental samples were collected from 45 wells). Caffeine had the highest detectable concentration of all the compounds at 2,060 nanograms per liter.

Analysis of molecular interactions in solid dosage forms; challenge to molecular pharmaceutics.

PubMed

Yamamoto, Keiji; Limwikrant, Waree; Moribe, Kunikazu

2011-01-01

The molecular states of active pharmaceutical ingredients (APIs) in pharmaceutical dosage forms strongly affect the properties and quality of a drug. Various important fundamental physicochemical studies were reviewed from the standpoint of molecular pharmaceutics. Mechanochemical effects were evaluated in mixtures of APIs and pharmaceutical additives. Amorphization, complex formation and nanoparticle formation are observed after grinding process depending on the combination of APIs and pharmaceutical additives. Sealed-heating method and mesoporous materials have been used to investigate drug molecular interactions in dosage forms. Molecular states have been investigated using powder X-ray diffraction, thermal analysis, IR, solid state fluorometry, and NMR. © 2011 Pharmaceutical Society of Japan

78 FR 19017 - Manufacturer of Controlled Substances; Notice of Application; Johnson Matthey Pharmaceutical...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Johnson Matthey Pharmaceutical Materials, Inc. Pursuant to Sec. 1301.33(a), Title... Matthey Pharmaceutical Materials, Inc., Pharmaceutical Service, 25 Patton Road, Devens, Massachusetts...

Effectiveness of pharmaceutical care at discharge in the emergency department: study protocol of a randomized controlled trial.

PubMed

Kuhmmer, Regina; Lima, Karine Margarites; Ribeiro, Rodrigo Antonini; Hammes, Luciano Serpa; Bastos, Gisele Alsina Nader; Cotta de Souza, Maria Claudia Schardosim; Polanczyk, Carisi Anne; Soares Rollin, Guilherme Alcides Flores; Caon, Suhelen; Guterres, Cátia Moreira; Araújo Leite, Leni Everson; Delabary, Tássia Scholante; Falavigna, Maicon

2015-02-25

Patient education on pharmacological therapy may increase medication adherence and decrease hospitalizations. Our aim is to evaluate the effectiveness of pharmaceutical care at emergency department discharge in patients with hypertension and/or diabetes. This is a randomized controlled trial. Participants will be recruited from a public emergency department at Restinga district in Porto Alegre, southern Brazil. A total of 380 patients will be randomly assigned into 2 groups at the moment of emergency department discharge after receiving medical orientations: an intervention group, consisting of a structured individual counseling session by a pharmacist in addition to written orientations, or a control group, consisting only of written information about the disease. Outcomes will be assessed in an ambulatory visit 2 months after the randomization. The primary outcome is the proportion of patients with high medication adherence assessed using the Morisky-Green Test and the Brief Medication Questionnaire. The secondary outcomes are reduction of blood pressure, glycated hemoglobin, fasting plasma glucose, quality of life and number of visits to the emergency department. Pharmaceutical care interventions have shown to be feasible and effective in increasing medication adherence in both hospital outpatient and community pharmacy settings. However, there have been no previous assessments of the effectiveness of pharmacy care interventions initiated in patients discharged from emergency departments. Our hypothesis is that pharmaceutical counseling is also effective in this population. ClinicalTrials.gov registration number: NCT01978925 (11 November 2013) and Brazilian Registry of Clinical Trials U1111-1149-8922 (5 November 2013).

75 FR 67623 - Approval and Promulgation of Air Quality Implementation Plans; Illinois; Volatile Organic...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-03

... amendments to its pharmaceutical manufacturing rules for approval into its SIP. These amendments consist of a... of this action? EPA is approving revisions to Illinois' pharmaceutical manufacturing rule for three... plan. * * * * * (c) * * * (186) On July 17, 2009, Illinois submitted amendments to its pharmaceutical...

Jordanian pharmaceutical companies: are their marketing efforts paying off?

PubMed

Al-Shaikh, Mustafa S; Torres, Ivonne M; Zuniga, Miguel A; Ghunaim, Ayman

2011-04-01

The pharmaceuticals industry is one of the main industries in Jordan. Jordanian pharmaceuticals rank third in the export industry of this country. This study aims to examine the strengths that Jordanian pharmaceutical companies have, which, in turn, form their competitiveness base. In addition, this study aims to identify their weaknesses and the effects of marketing their products in the local market. What is the relationship between Jordanian pharmaceutical product quality, price and value, and the competitiveness of pharmaceutical companies in the local market? Our study aims to answer this and other questions. Our results and practical implications are discussed.

Production of GMP-grade radioactive holmium loaded poly(L-lactic acid) microspheres for clinical application.

PubMed

Zielhuis, S W; Nijsen, J F W; de Roos, R; Krijger, G C; van Rijk, P P; Hennink, W E; van het Schip, A D

2006-03-27

Radioactive holmium-166 loaded poly(L-lactic acid) microspheres are promising systems for the treatment of liver malignancies. The microspheres are loaded with holmium acetylacetonate (HoAcAc) and prepared by a solvent evaporation method. After preparation, the microspheres (Ho-PLLA-MS) are activated by neutron irradiation in a nuclear reactor. In this paper, the aspects of the production of a (relatively) large-scale GMP batch (4 g, suitable for treatment of 5-10 patients) of Ho-PLLA-MS are described. The critical steps of the Ho-PLLA-MS production process (sieving procedure, temperature control during evaporation and raw materials) were considered and the pharmaceutical quality of the microspheres was evaluated. The pharmaceutical characteristics (residual solvents, possible bacterial contaminations and endotoxins) of the produced Ho-PLLA-MS batches were in compliance with the requirements of the European Pharmacopoeia. Moreover, neutron irradiated Ho-PLLA-MS retained their morphological integrity and the holmium remained stably associated with the microspheres; it was observed that after 270h (10 times the half-life of Ho-166) only 0.3+/-0.1% of the loading was released from the microspheres in an aqueous solution. In conclusion, Ho-PLLA-MS which are produced as described in this paper, can be clinically applied, with respect to their pharmaceutical quality.

A drop penetration method to measure powder blend wettability.

PubMed

Wang, Yifan; Liu, Zhanjie; Muzzio, Fernando; Drazer, German; Callegari, Gerardo

2018-03-01

Water wettability of pharmaceutical blends affects important quality attributes of final products. We investigate the wetting properties of a pharmaceutical blend lubricated with Magnesium Stearate (MgSt) as a function of the mechanical shear strain applied to the blend. We measure the penetration dynamics of sessile drops deposited on slightly compressed powder beds. We consider a blend composed of 9% Acetaminophen 90% Lactose and 1% MgSt by weight. Comparing the penetration time of water and a reference liquid Polydimethylsiloxane (silicon oil) we obtain an effective cosine of the contact angle with water, based on a recently developed drop penetration method. We repeat the experiments for blends exposed to increasing levels of shear strain and demonstrate a significant decrease in water wettability (decrease in the cosine of the contact angle). The results are consistent with the development of a hydrophobic film coating the powder particles as a result of the increased shear strain. Finally, we show that, as expected dissolution times increase with the level of shear strain. Therefore, the proposed drop penetration method could be used to directly assess the state of lubrication of a pharmaceutical blend and act as a quality control on powder blend attributes before the blend is tableted. Copyright © 2017 Elsevier B.V. All rights reserved.

The evolution and challenges for the international harmonization of the regulation of pharmaceutical excipients in Taiwan.

PubMed

Chang, Lin-Chau; Kang, Jaw-Jou; Gau, Churn-Shiouh

2015-12-01

Excipients, once considered an inert component, have been shown to greatly influence the characteristics of the drug product, such as quality and safety. Functionality-related characteristics of excipients could affect the performance of the drug product. Moreover, the impact of globalization has complicated the issue and made the supervision of supply chain highly important. Taiwan, a member of the Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme, makes efforts to harmonize with international regulations and to strengthen the protection of patients through regulatory controls. In order to improve the harmonization and the transparency of regulatory requirements, the aim of the present study was to investigate the regulatory framework and considerations of stringent regulatory authorities and to propose the draft regulatory requirements to the Taiwan Food and Drug Administration for jurisdiction. The proposal which was extensively discussed in the expert committee includes the regulatory considerations to ensure the safety and quality of the excipients and may serve as a platform to facilitate the communication with industries about the current thinking on related issues. Moreover, through the review of the recent guidelines published by the stringent regulatory authorities, the trend of the regulatory considerations was revealed and discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

Approach to method development and validation in capillary electrophoresis for enantiomeric purity testing of active basic pharmaceutical ingredients.

PubMed

Sokoliess, Torsten; Köller, Gerhard

2005-06-01

A chiral capillary electrophoresis system allowing the determination of the enantiomeric purity of an investigational new drug was developed using a generic method development approach for basic analytes. The method was optimized in terms of type and concentration of both cyclodextrin (CD) and electrolyte, buffer pH, temperature, voltage, and rinsing procedure. Optimal chiral separation of the analyte was obtained using an electrolyte with 2.5% carboxymethyl-beta-CD in 25 mM NaH2PO4 (pH 4.0). Interchanging the inlet and outlet vials after each run improved the method's precision. To assure the method's suitability for the control of enantiomeric impurities in pharmaceutical quality control, its specificity, linearity, precision, accuracy, and robustness were validated according to the requirements of the International Conference on Harmonization. The usefulness of our generic method development approach for the validation of robustness was demonstrated.

Development of NIRS method for quality control of drug combination artesunate–azithromycin for the treatment of severe malaria

PubMed Central

Boyer, Chantal; Gaudin, Karen; Kauss, Tina; Gaubert, Alexandra; Boudis, Abdelhakim; Verschelden, Justine; Franc, Mickaël; Roussille, Julie; Boucher, Jacques; Olliaro, Piero; White, Nicholas J.; Millet, Pascal; Dubost, Jean-Pierre

2012-01-01

Near infrared spectroscopy (NIRS) methods were developed for the determination of analytical content of an antimalarial-antibiotic (artesunate and azithromycin) co-formulation in hard gelatin capsule (HGC). The NIRS consists of pre-processing treatment of spectra (raw spectra and first-derivation of two spectral zones), a unique principal component analysis model to ensure the specificity and then two partial least-squares regression models for the determination content of each active pharmaceutical ingredient. The NIRS methods were developed and validated with no reference method, since the manufacturing process of HGC is basically mixed excipients with active pharmaceutical ingredients. The accuracy profiles showed β-expectation tolerance limits within the acceptance limits (±5%). The analytical control approach performed by reversed phase (HPLC) required two different methods involving two different preparation and chromatographic methods. NIRS offers advantages in terms of lower costs of equipment and procedures, time saving, environmentally friendly. PMID:22579599

American export control, technology spillover and innovation of Chinese pharmaceutical Industry.

PubMed

Hui, Jiang

2017-05-01

This paper was aimed to analyze whether the U.S. strict export control to China affects the technological innovation of Chinese pharmaceutical industry. This paper selected the data of technological innovation and the expenditure of high and new technology adoption in China's pharmaceutical industry from 1995 to 2014, created panel regression model to study the impact of export controls on technology spillovers and the impact of technology spillovers on innovation capacity. The results show that US export control has a significant impact on technology spillovers, but foreign technology spillovers have no significant impact on the innovation of Chinese pharmaceutical industry. Although the US export control prevented foreign technology spillovers to China, but indirectly stimulated the domestic technology spillovers to pharmaceutical manufacturing industry in China. Statistical analysis show that the correlation coefficient between innovation capacity and expenditure for high technology adoption is not significant, but the expenditure of purchasing domestic technical is essential to pharmaceutical innovation. This study shows that US export control indirectly, not directly, affected the technological innovation of China's pharmaceutical industry, affected the allocation of innovative resources, but failed to prevent the technological progress and competitiveness improvement of Chinese pharmaceutical industry.

Soft regulations in pharmaceutical policy making: an overview of current approaches and their consequences.

PubMed

Wettermark, Björn; Godman, Brian; Jacobsson, Bengt; Haaijer-Ruskamp, Flora M

2009-01-01

It is a challenge to improve public health within limited resources. Pharmaceutical policy making is a greater challenge due to conflicting interests between key stakeholder groups. This paper reviews current and future strategies to help improve the quality and efficiency of care, with special emphasis on demand-side controls for pharmaceutical prescribing. A large number of different educational, organizational, financial and regulatory strategies have been applied in pharmaceutical policy making. However, the effectiveness of most strategies has not been thoroughly evaluated and there is evidence that the behaviour of healthcare professionals is difficult to influence with traditional methods. During the last decades, new modes of governing and new governing constellations have also appeared in healthcare. However, relationships between those who regulate and those regulated are often unclear. New approaches have recently been introduced, including extensive dissemination strategies for guidelines and extensive quality assessment programmes where physicians' performances are measured against agreed standards or against each other. The main components of these 'soft regulations' are standardization, monitoring and agenda setting. However, the impact of these new modes on health provision and overall costs is often unknown, and the increased focus on monitoring may result in a higher conformity and uniformity that may not always benefit all key stakeholders. Alongside this, a substantial growth of auditing associations controlling a diminishing minority of people actually performing the tasks may be costly and counter-productive. As a result, new effective strategies are urgently needed to help maintain comprehensive healthcare without prohibitively raising taxes or insurance premiums. This is especially important where countries are faced with extreme financial problems. Healthcare researchers may benefit from researching other areas of society. However, any potential strategies initiated must be adequately researched, debated and evaluated to enhance implementation. We hope this opinion paper is the first step in the process to develop and implement new demand-side initiatives building on existing 'soft regulations'.

Pharmaceutical Regulatory Framework in Ethiopia: A Critical Evaluation of Its Legal Basis and Implementation.

PubMed

Suleman, Sultan; Woliyi, Abdulkadir; Woldemichael, Kifle; Tushune, Kora; Duchateau, Luc; Degroote, Agnes; Vancauwenberghe, Roy; Bracke, Nathalie; De Spiegeleer, Bart

2016-05-01

Effective and enforceable national regulations describing the manufacture and (re)packaging, export and import, distribution and storage, supply and sale, information and pharmaco-vigilance of medicines are required to consistently ensure optimal patient benefit. Expansion of pharmaceutical industries in many countries with advancement in transport technologies facilitated not only trade of genuine pharmaceutical products but also the circulation of poor quality medicines across the globe. In Ethiopia, even though "The Pharmacists and Druggists Proclamation No 43/1942" was used to regulate both the professions and the facilities where they were practiced, comprehensive regulation of the pharmaceutical market was introduced in 1964 by a regulation called "Pharmacy Regulation No. 288/ 1964". This legislation formed the legal basis for official establishment of drug regulation in the history of Ethiopia, enabling the regulation of the practice of pharmacists, druggists and pharmacy technicians; manufacturing, distribution, and sale of medicines. In June 1999, a new regulation called the "Drug Administration and Control Proclamation No. 176/1999" repealed most parts of the regulation 288/1964. The law established an independent Drug Administration and Control Authority (DACA) with further mandate of setting standards of competence for licensing institutions/facilities. DACA was re-structured as Food, Medicine and Health Care Administration and Control Authority (EFMHACA) of Ethiopia by the "Proclamation No. 661/2009" in 2010 bearing additional responsibilities like regulation of food, health care personnel and settings. The mere existence of this legal framework does not guarantee complete absence of illegal, substandard and falsified products as well as illegal establishments in the pharmaceutical chain. Therefore, the objective of the research is to assess the pharmaceutical regulatory system in Ethiopia and to reveal possible reasons for deficiencies in the pharmaceutical chain. An archival review, an in-depth interview of key informants and an institutions-based cross-sectional survey study were conducted during March to April 2013. The comprehensiveness of the pharmaceutical law to protect public health relative to three selected African countries (South Africa, Tanzania and Uganda) and European Union, and implementation was assessed. The study revealed that Ethiopia does have a written national drug policy upon which the Medicines Regulatory Proclamation 661/2009 is based. According to this proclamation, the Ethiopian The Food, Medicines and Healthcare Administration and Control Authority is mandated to execute the regulatory activities as per the council of ministers regulation 189/2010. The legal framework for pharmaceutical regulation of Ethiopia was founded to fulfill all the medicines regulatory functions potentially enabling to combat illegal, substandard and falsified medicines and illegal establishments. Moreover, all the key informants witnessed that the government is commited and proclamation 661/2009 is comprehensive, but they stressed the compelling need of regulatory tools for effective implementation. From the institution-based cross-sectional study, it was revealed that there exist illegal sources formedicine in the pharmaceutical market. The main reasons for their existence were regulatory factors including weak regulatory enforcement (64.5%), lack of informal market control (60.8%), weak port control (50.0%), and poor cooperation between executive bodies (39.6%); and resource constraint (27.8%), which is an institutional factor. From legislative point of view, the medicines regulatory framework in Ethiopia fulfils all regulatory functions required for effective medicines regulation. However, the existence of the legislation by its own is not a guarantee to prevent the existence of unauthorized/illegal medicine sources since this requires effective implementation of the legislation, which is in fact affected by the governments political commitment, resource and intergovernmental cooperation.

A risk-based auditing process for pharmaceutical manufacturers.

PubMed

Vargo, Susan; Dana, Bob; Rangavajhula, Vijaya; Rönninger, Stephan

2014-01-01

The purpose of this article is to share ideas on developing a risk-based model for the scheduling of audits (both internal and external). Audits are a key element of a manufacturer's quality system and provide an independent means of evaluating the manufacturer's or the supplier/vendor's compliance status. Suggestions for risk-based scheduling approaches are discussed in the article. Pharmaceutical manufacturers are required to establish and implement a quality system. The quality system is an organizational structure defining responsibilities, procedures, processes, and resources that the manufacturer has established to ensure quality throughout the manufacturing process. Audits are a component of the manufacturer's quality system and provide a systematic and an independent means of evaluating the manufacturer's overall quality system and compliance status. Audits are performed at defined intervals for a specified duration. The intention of the audit process is to focus on key areas within the quality system and may not cover all relevant areas during each audit. In this article, the authors provide suggestions for risk-based scheduling approaches to aid pharmaceutical manufacturers in identifying the key focus areas for an audit.

The method of quality marker research and quality evaluation of traditional Chinese medicine based on drug properties and effect characteristics.

PubMed

Zhang, Tiejun; Bai, Gang; Han, Yanqi; Xu, Jun; Gong, Suxiao; Li, Yazhuo; Zhang, Hongbing; Liu, Changxiao

2018-05-15

Quality of traditional Chinese medicine (TCM) plays a critical role in industry of TCM. Rapid development of TCM pharmaceutical areas is, however, greatly limited, since there are many issues not been resolved, concerning the quality study of TCM. Core concept of TCM quality as well as the characteristics of TCM was discussed, in order to guide the quality research and evaluation of TCM, further improve the level of TCM quality control. In this review, on the basis of systematic analysis of fundamental property and features of TCM in clinical application, the approaches and methods of quality marker (Q-marker) study were proposed through combination of transitivity and traceability of essentials of quality, correlation between chemical ingredients and drug property/efficacy, as well as analysis of endemicity of ingredients sharing similar pharmacophylogenetic and biosynthetic approaches. The approaches and methods of Q-marker study were proposed and the novel integrated pattern for quality assessment and control of TCM was established. The core concept of Q-marker has helped to break through the bottleneck of the current fragmented quality research of TCM and improved the scientificity, integrity and systematicness of quality control. Copyright © 2018 Elsevier GmbH. All rights reserved.

[Quality assurance in interventional cardiology].

PubMed

Gülker, H

2009-10-01

Quality assurance in clinical studies aiming at approval of pharmaceutical products is submitted to strict rules, controls and auditing regulations. Comparative instruments to ensure quality in diagnostic and therapeutic procedures are not available in interventional cardiology, likewise in other fields of cardiovascular medicine. Quality assurance simply consists of "quality registers" with basic data not externally controlled. Based on the experiences of clinical studies and their long history of standardization it is assumed that these data may be severely flawed thus being inappropriate to set standards for diagnostic and therapeutic strategies. The precondition for quality assurance are quality data. In invasive coronary angiography and intervention medical indications, the decision making process interventional versus surgical revascularization, technical performance and after - care are essential aspects affecting quality of diagnostics and therapy. Quality data are externally controlled data. To collect quality data an appropriate infrastructure is a necessary precondition which is not existent. For an appropriate infrastructure investments have to be done both to build up as well as to sustain the necessary preconditions. As long as there are no infrastructure and no investments there will be no "quality data". There exist simply registers of data which are not proved to be a basis for significant assurance and enhancement in quality in interventional coronary cardiology. Georg Thieme Verlag KG Stuttgart, New York.

Validated spectroscopic methods for determination of anti-histaminic drug azelastine in pure form: Analytical application for quality control of its pharmaceutical preparations.

PubMed

El-Masry, Amal A; Hammouda, Mohammed E A; El-Wasseef, Dalia R; El-Ashry, Saadia M

2018-02-15

Two simple, sensitive, rapid, validated and cost effective spectroscopic methods were established for quantification of antihistaminic drug azelastine (AZL) in bulk powder as well as in pharmaceutical dosage forms. In the first method (A) the absorbance difference between acidic and basic solutions was measured at 228nm, whereas in the second investigated method (B) the binary complex formed between AZL and Eosin Y in acetate buffer solution (pH3) was measured at 550nm. Different criteria that have critical influence on the intensity of absorption were deeply studied and optimized so as to achieve the highest absorption. The proposed methods obeyed Beer ' s low in the concentration range of (2.0-20.0μg·mL -1 ) and (0.5-15.0μg·mL -1 ) with % recovery±S.D. of (99.84±0.87), (100.02±0.78) for methods (A) and (B), respectively. Furthermore, the proposed methods were easily applied for quality control of pharmaceutical preparations without any conflict with its co-formulated additives, and the analytical results were compatible with those obtained by the comparison one with no significant difference as insured by student's t-test and the variance ratio F-test. Validation of the proposed methods was performed according the ICH guidelines in terms of linearity, limit of quantification, limit of detection, accuracy, precision and specificity, where the analytical results were persuasive. Copyright © 2017 Elsevier B.V. All rights reserved.

Drop-on-Demand System for Manufacturing of Melt-based Solid Oral Dosage: Effect of Critical Process Parameters on Product Quality.

PubMed

Içten, Elçin; Giridhar, Arun; Nagy, Zoltan K; Reklaitis, Gintaras V

2016-04-01

The features of a drop-on-demand-based system developed for the manufacture of melt-based pharmaceuticals have been previously reported. In this paper, a supervisory control system, which is designed to ensure reproducible production of high quality of melt-based solid oral dosages, is presented. This control system enables the production of individual dosage forms with the desired critical quality attributes: amount of active ingredient and drug morphology by monitoring and controlling critical process parameters, such as drop size and product and process temperatures. The effects of these process parameters on the final product quality are investigated, and the properties of the produced dosage forms characterized using various techniques, such as Raman spectroscopy, optical microscopy, and dissolution testing. A crystallization temperature control strategy, including controlled temperature cycles, is presented to tailor the crystallization behavior of drug deposits and to achieve consistent drug morphology. This control strategy can be used to achieve the desired bioavailability of the drug by mitigating variations in the dissolution profiles. The supervisor control strategy enables the application of the drop-on-demand system to the production of individualized dosage required for personalized drug regimens.

Quality of pharmaceutical advertising and gender bias in medical journals (1998-2008): a review of the scientific literature.

PubMed

Cambronero Saiz, Belén; Ruiz Cantero, María Teresa; Papí Gálvez, Natalia

2012-01-01

To review the scientific literature on pharmaceutical advertising aimed at health professionals in order to determine whether gender bias has decreased and the quality of information in pharmaceutical advertising has improved over time. We performed a content analysis of original articles dealing with medical drug promotion (1998-2008), according to quality criteria such as (a) the number, validity and accessibility of bibliographic references provided in pharmaceutical advertising and (b) the extent to which gender representations were consistent with the prevalence of the diseases. Databases: PUBMED, Medline, Scopus, Sociological Abstract, Eric and LILACS. We reviewed 31 articles that analyzed advertising in medical journals from 1975-2005 and were published between 1998 and 2008. We found that the number of references used to support pharmaceutical advertising claims increased from 1975 but that 50% of these references were not valid. There was a tendency to depict men in paid productive roles, while women appeared inside the home or in non-occupational social contexts. Advertisements for psychotropic and cardiovascular drugs overrepresented women and men respectively. The use of bibliographic references increased between 1998 and 2008. However, representation of traditional male-female roles was similar in 1975 and 2005. Pharmaceutical advertisements may contribute to reinforcing the perception that certain diseases are associated with the most frequently portrayed sex. Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.

Medicines information provided by pharmaceutical representatives: a comparative study in Australia and Malaysia

PubMed Central

2010-01-01

Background Pharmaceutical representatives provide medicines information on their promoted products to doctors. However, studies have shown that the quality of this information is often low. No study has assessed the medicines information provided by pharmaceutical representatives to doctors in Malaysia and no recent evidence in Australia is present. We aimed to compare the provision of medicines information by pharmaceutical representatives to doctors in Australia and Malaysia. Methods Following a pharmaceutical representative's visit, general practitioners in Australia and Malaysia who had agreed to participate, were asked to fill out a questionnaire on the main product and claims discussed during the encounter. The questionnaire focused on provision of product information including indications, adverse effects, precautions, contraindications and the provision of information on the Pharmaceutical Benefit Scheme (PBS) listings and restrictions (in Australia only). Descriptive statistics were produced. Chi-square analysis and clustered linear regression were used to assess differences in Australia and Malaysia. Results Significantly more approved product information sheets were provided in Malaysia (78%) than in Australia (53%) (P < 0.001). In both countries, general practitioners reported that indications (Australia, 90%, Malaysia, 93%) and dosages (Australia, 76%, Malaysia, 82%) were frequently provided by pharmaceutical representatives. Contraindications, precautions, drug interactions and adverse effects were often omitted in the presentations (range 25% - 41%). General practitioners in Australia and Malaysia indicated that in more than 90% of presentations, pharmaceutical representatives partly or fully answered their questions on contraindications, precautions, drug interactions and adverse effects. More general practitioners in Malaysia (85%) than in Australia (60%) reported that pharmaceutical representatives should have mentioned contraindications, precautions for use, drug interaction or adverse effects spontaneously (P < 0.001). In 48% of the Australian presentations, general practitioners reported the pharmaceutical representatives failed to mention information on PBS listings to general practitioners. Conclusions Information on indications and dosages were usually provided by pharmaceutical representatives in Australia and Malaysia. However, risk and harmful effects of medicines were often missing in their presentations. Effective control of medicines information provided by pharmaceutical representatives is needed. PMID:21118551

Quality of pharmaceutical care at the pharmacy counter: patients' experiences versus video observation.

PubMed

Koster, Ellen S; Blom, Lyda; Overbeeke, Marloes R; Philbert, Daphne; Vervloet, Marcia; Koopman, Laura; van Dijk, Liset

2016-01-01

Consumer Quality Index questionnaires are used to assess quality of care from patients' experiences. To provide insight into the agreement about quality of pharmaceutical care, measured both by a patient questionnaire and video observations. Pharmaceutical encounters in four pharmacies were video-recorded. Patients completed a questionnaire based upon the Consumer Quality Index Pharmaceutical Care after the encounter containing questions about patients' experiences regarding information provision, medication counseling, and pharmacy staff's communication style. An observation protocol was used to code the recorded encounters. Agreement between video observation and patients' experiences was calculated. In total, 109 encounters were included for analysis. For the domains "medication counseling" and "communication style", agreement between patients' experiences and observations was very high (>90%). Less agreement (45%) was found for "information provision", which was rated more positive by patients compared to the observations, especially for the topic, encouragement of patients' questioning behavior. A questionnaire is useful to assess the quality of medication counseling and pharmacy staff's communication style, but might be less suitable to evaluate information provision and pharmacy staff's encouragement of patients' questioning behavior. Although patients may believe that they have received all necessary information to use their new medicine, some information on specific instructions was not addressed during the encounter. When using questionnaires to get insight into information provision, observations of encounters are very informative to validate the patient questionnaires and make necessary adjustments.

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Forty-ninth report.

PubMed

2015-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use. Revised procedure for the development of monographs and other texts for The International Pharmacopoeia; Revised updating mechanism for the section on radiopharmaceuticals in The International Pharmacopoeia; Revision of the supplementary guidelines on good manufacturing practices: validation, Appendix 7: non-sterile process validation; General guidance for inspectors on hold-time studies; 16 technical supplements to Model guidance for the storage and transport of time- and temperature-sensitive pharmaceutical products; Recommendations for quality requirements when plant-derived artemisinin is used as a starting material in the production of antimalarial active pharmaceutical ingredients; Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability: revision; Guidance on the selection of comparator pharmaceutical products for equivalence assessment of interchangeable multisource (generic) products: revision; and Good review practices: guidelines for national and regional regulatory authorities.

WHO expert committee on specifications for pharmaceutical preparations.

PubMed

2013-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use: Release procedure for International Chemical Reference Substances; WHO guidelines on quality risk management; WHO guidelines on variations to a prequalified product; and the Collaborative procedure between the World Health Organization Prequalification of Medicines Programme and national medicines regulatory authorities in the assessment and accelerated national registration of WHO-prequalified pharmaceutical products.

[Basic considerations during outsourcing of clinical data management services].

PubMed

Shen, Tong; Liu, Yan

2015-11-01

With worldwide improvements in the regulations of international and domestic clinical trial conductions, the quality of clinical trials and trial data management are receiving a great deal of attention. To ensure the quality of clinical trials, maintain business flexibilities and effectively utilize internal and external resources, the outsourcing model is used in the management of clinical data in operation of pharmaceutical companies. The essential criteria of a successful outsourcing mode in clinical trial are selection of qualified contract research organizations (CRO); establishment of appropriate outsourcing model, and generation of effective quality control systems to ensure the authenticity, integrity and accuracy of the clinical trial data.

Advance in quality assessment of Chinese materia medica using microscopic and morphological methods.

PubMed

Miao, Xiao-Su; Cui, Qing-Yu; Wang, Zhao-Yi; Liu, Xiao-Na; Zhao, An-Bang; Qiao, Yan-Jiang; Wu, Zhi-Sheng

2017-09-01

Quality evaluation plays a vital role in ensuring safety and effectiveness of Chinese materia medica (CMM). Microscopic and morphological technologies can be used to distinguish CMM's characteristics, such as shape, size, texture, section, and smell, for authenticity and quality control of CMM. The microscopic and morphological applications of novel micro-technology, colorimeter, and texture analyzer for CMM identification are summarized and the future prospect is discussed in this paper. Various styles and complex sources of CMM are systemically reviewed, including cormophyte medicinal materials, fruit and seeds, pollen grain, and spore materials. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Antibiotic mixture effects on growth of the leaf-shredding stream detritivore Gammarus fossarum.

PubMed

Bundschuh, Mirco; Hahn, Torsten; Gessner, Mark O; Schulz, Ralf

2017-05-01

Pharmaceuticals contribute greatly to human and animal health. Given their specific biological targets, pharmaceuticals pose a significant environmental risk by affecting organisms and ecosystem processes, including leaf-litter decomposition. Although litter decomposition is a central process in forest streams, the consequences of exposure to pharmaceuticals remain poorly known. The present study assessed the impact of antibiotics as an important class of pharmaceuticals on the growth of the leaf-shredding amphipod Gammarus fossarum over 24 days. Exposure scenarios involved an antibiotic mixture (i.e. sulfamethoxazole, trimethoprim, erythromycin-H 2 O, roxithromycin, clarithromycin) at 0, 2 and 200 µg/L to assess impacts resulting from exposure to both water and food. The antibiotics had no effect on either leaf-associated fungal biomass or bacterial abundance. However, modification of leaf quality (e.g. through shifts in leaf-associated microbial communities) may have triggered faster growth of gammarids (assessed in terms of body mass gain) at the low antibiotic concentration relative to the control. At 200 µg/L, however, gammarid growth was not stimulated. This outcome might be due to a modified ability of the gut microflora to assimilate nutrients and carbon. Furthermore, the observed lack of increases in the diameter of the gammarids' peduncles, despite an increase in gammarid mass, suggests antibiotic-induced effects in the moulting cycle. Although the processes responsible for the observed effects have not yet been identified, these results suggest a potential role of food-quality, gammarid gut microflora and alteration in the moulting cycle in mediating impacts of antibiotics on these detritivores and the leaf decomposition process in streams.

[The significance of quality of life from a socio-legal perspective].

PubMed

Axer, Peter

2014-01-01

Only rarely is the term quality of life explicitly mentioned in the Social Security Code (Sozialgesetzbuch, SGB). In the statutory health insurance law (Book V of the Social Security Code, SGB V), the term is explicitly regulated within the context of the entitlement to pharmaceuticals. While there are pharmaceuticals that have the priority to increase the quality of life but are excluded from the provision of healthcare (Section 34 (1) Sentence 7 SGB V), the improvement of the quality of life has to be taken into account for the cost-benefit assessment (Section 35b SGB V) as well as for the early pharmaceutical benefit assessment (Section 35a SGB V) and for the formation of reference price groups (Section 35 SGB V) for and in the case of an entitlement to benefits in the event of illness. Copyright © 2014. Published by Elsevier GmbH.

78 FR 19016 - Importer of Controlled Substances; Notice of Registration; Mylan Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... Registration; Mylan Pharmaceuticals, Inc. By Notice dated November 27, 2012, and published in the Federal Register on December 5, 2012, 77 FR 72409, Mylan Pharmaceuticals, Inc., 781 Chestnut Ridge Road, Morgantown... that the registration of Mylan Pharmaceuticals, Inc. to import the basic classes of controlled...

78 FR 39340 - Manufacturer of Controlled Substances; Notice of Registration; Patheon Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-01

...; Notice of Registration; Patheon Pharmaceuticals, Inc. By Notice dated March 20, 2013, and published in... Patheon Pharmaceuticals, Inc., to manufacture the listed basic class of controlled substance is consistent with the public interest at this time. DEA has investigated Patheon Pharmaceuticals, Inc., to ensure...

PHARMACEUTICAL QUALITY OF GENERIC ATORVASTATIN PRODUCTS COMPARED WITH THE INNOVATOR PRODUCT: A NEED FOR REVISING PRICING POLICY IN PALESTINE.

PubMed

Shawahna, Ramzi; Hroub, Abdel Kareem; Abed, Eliama; Jibali, Sondos; Al-Saghir, Ruba; Zaid, Abdel Naser

2016-01-01

Atorvastatin reduces morbidity and mortality due to cardiovascular events. This study was conducted to assess the prices and pharmaceutical quality of innovator atorvastatin 20 mg with its locally available generics in Palestine and to assess the suitability of their interchangeability. The prices of innovator and generic atorvastatin 20 mg were determined and compared. Innovator atorvastatin and four generic products were tested for their pharmaceutical quality. Tablets were tested for their drug contents, weight uniformity, hardness, disintegration and dissolution. Three out of four generics were less expensive than the innovator. Pharmaceutical quality assessments were satisfactory and within limits for all atorvastatin tested products. The average weight ranged from 206.6 ± 8.40 to 330 ± 3.92 mg and the %RSDs were within the permitted limits as per USP. Tablet hardness ranged from 102 ± 1.41 to 197.4 ± 6.88 kg and drug contents ranged from 92.2% to 105.3%. All products disintegrated within permitted time limits and showed very rapid dissolution. Products released more than 85% of their drug contents in less than 15 min. Our results showed that all tested innovator and generic atorvastatin products were of good pharmaceutical quality. Despite the lack of in vivo evaluation, our results indicate that these products are equivalent in vitro. Considering the in vitro release characteristics, these products might be used interchangeably. However, regulatory authorities permit the use of in vitro data in establishing similarity between immediate release oral dosage forms containing biopharmaceutical classification system class I and III drugs only.

Clinical trial allocation in multinational pharmaceutical companies - a qualitative study on influential factors.

PubMed

Dombernowsky, Tilde; Haedersdal, Merete; Lassen, Ulrik; Thomsen, Simon F

2017-06-01

Clinical trial allocation in multinational pharmaceutical companies includes country selection and site selection. With emphasis on site selection, the overall aim of this study was to examine which factors pharmaceutical companies value most when allocating clinical trials. The specific aims were (1) to identify key decision makers during country and site selection, respectively, (2) to evaluate by which parameters subsidiaries are primarily assessed by headquarters with regard to conducting clinical trials, and (3) to evaluate which site-related qualities companies value most when selecting trial sites. Eleven semistructured interviews were conducted among employees engaged in trial allocation at 11 pharmaceutical companies. The interviews were analyzed by deductive content analysis, which included coding of data to a categorization matrix containing categories of site-related qualities. The results suggest that headquarters and regional departments are key decision makers during country selection, whereas subsidiaries decide on site selection. Study participants argued that headquarters primarily value timely patient recruitment and quality of data when assessing subsidiaries. The site-related qualities most commonly emphasized during interviews were study population availability, timely patient recruitment, resources at the site, and site personnel's interest and commitment. Costs of running the trials were described as less important. Site personnel experience in conducting trials was described as valuable but not imperative. In conclusion, multinational pharmaceutical companies consider recruitment-related factors as crucial when allocating clinical trials. Quality of data and site personnel's interest and commitment are also essential, whereas costs seem less important. While valued, site personnel experience in conducting clinical trials is not imperative.

Current Pharmaceutical Treatments and Alternative Therapies of Parkinson's Disease

PubMed Central

Dong, Jie; Cui, Yanhua; Li, Song; Le, Weidong

2016-01-01

Over the decades, pharmaceutical treatments, particularly dopaminergic (DAergic) drugs have been considered as the main therapy against motor symptoms of Parkinson's disease (PD). It is proposed that DAergic drugs in combination with other medications, such as monoamine oxidase type B inhibitors, catechol-O-methyl transferase inhibitors, anticholinergics and other newly developed non-DAergic drugs can make a better control of motor symptoms or alleviate levodopa-induced motor complications. Moreover, non-motor symptoms of PD, such as cognitive, neuropsychiatric, sleep, autonomic and sensory disturbances caused by intrinsic PD pathology or drug-induced side effects, are gaining increasing attention and urgently need to be taken care of due to their impact on quality of life. Currently, neuroprotective therapies have been investigated extensively in pre-clinical studies, and some of them have been subjected to clinical trials. Furthermore, non-pharmaceutical treatments, including deep brain stimulation (DBS), gene therapy, cell replacement therapy and some complementary managements, such as Tai chi, Yoga, traditional herbs and molecular targeted therapies have also been considered as effective alternative therapies to classical pharmaceutics. This review will provide us updated information regarding the current drugs and non-drugs therapies for PD. PMID:26585523

Development and validation of an MEKC method for determination of nitrogen-containing drugs in pharmaceutical preparations.

PubMed

Buiarelli, Francesca; Coccioli, Franco; Jasionowska, Renata; Terracciano, Alessandro

2008-09-01

A fast and accurate micellar electrokinetic capillary chromatography method was developed for quality control of pharmaceutical preparations containing cold remedies as acetaminophen, salicylamide, caffeine, phenylephrine, pseudoephedrine, norephedrine and chlorpheniramine. The method optimization was realized on a Beckman P/ACE System MDQ instrument. The baseline separation of seven analytes was performed in an uncoated fused silica capillary internal diameter (ID)=50 microm using tris-borate (20 mM, pH=8.5) containing sodium dodecyl sulphate 30 mM BGE. On line-UV detection at 214 nm was performed and the applied voltage was 10 kV. The operating temperature was 25 degrees C. After experimental conditions optimization, the proposed method was validated. The evaluated parameters were: precision of migration time and of corrected peak area ratio, linearity range, limit of detection, limit of quantification, accuracy (recovery), ruggedness and applicability. The method was then successfully applied for the analysis of three pharmaceutical preparations containing some of the analytes listed before.

Simultaneous spectrophotometric determination of indacaterol and glycopyrronium in a newly approved pharmaceutical formulation using different signal processing techniques of ratio spectra

NASA Astrophysics Data System (ADS)

Abdel Ghany, Maha F.; Hussein, Lobna A.; Magdy, Nancy; Yamani, Hend Z.

2016-03-01

Three spectrophotometric methods have been developed and validated for determination of indacaterol (IND) and glycopyrronium (GLY) in their binary mixtures and novel pharmaceutical dosage form. The proposed methods are considered to be the first methods to determine the investigated drugs simultaneously. The developed methods are based on different signal processing techniques of ratio spectra namely; Numerical Differentiation (ND), Savitsky-Golay (SG) and Fourier Transform (FT). The developed methods showed linearity over concentration range 1-30 and 10-35 (μg/mL) for IND and GLY, respectively. The accuracy calculated as percentage recoveries were in the range of 99.00%-100.49% with low value of RSD% (< 1.5%) demonstrating an excellent accuracy of the proposed methods. The developed methods were proved to be specific, sensitive and precise for quality control of the investigated drugs in their pharmaceutical dosage form without the need for any separation process.

The effect of water on the solid state characteristics of pharmaceutical excipients: Molecular mechanisms, measurement techniques, and quality aspects of final dosage form

PubMed Central

Szakonyi, Gergely; Zelkó, Romána

2012-01-01

In this paper we give an overview about the interaction of water molecules with pharmaceutical excipients. Most of these excipients are amorphous or partially amorphous polymers and their characteristics are very sensitive to the water content. In the course of the manufacturing processes water sorption is possible, therefore in some cases it is important to strictly control the residual moisture content of a dosage form. There are several mechanisms of water sorption, like water is able to bind to polar groups of hygroscopic excipients and could also exist in the capillary system of amorphous excipients. Several techniques are available to characterise the states of water inside the materials and the effects of residual water on polymers. For this purpose water sorption measurements, differential scanning calorimetry and the Fourier-transform infrared spectroscopy are reviewed. The importance of water content and storage conditions of pharmaceuticals on the properties of the final dosage forms are also demonstrated with practical examples. PMID:23071956

Comparative evaluation of two asthma care quality measures among Medicaid beneficiaries.

PubMed

Samnaliev, Mihail; Baxter, Jeffrey D; Clark, Robin E

2009-05-01

The relative performance of asthma care quality measures has not been evaluated in Medicaid populations. Using complete claims and pharmaceutical data for 19,076 patients with persistent asthma (based on Health Effectiveness and Data Information Set criteria) in five Medicaid populations, we compared the following two measures of asthma care quality: filling prescriptions for controller asthma medications within 1 year and the ratio of controller medication to the total number of asthma medication prescriptions filled within 1 year. We calculated whether meeting each quality measure was associated with decreased odds of emergency department (ED) treatment episodes. We then compared the odds ratios, receiver operating characteristic (ROC) curves, and deviances between models, using each measure to predict ED utilization in Medicaid populations. Although meeting each measure was associated with lower odds of ED utilization, this decrease was larger if the controller asthma medication measure was met rather than the ratio measure. Additionally, models using the controller medication measure had greater areas under the ROC curve and smaller deviances than models using the ratio measure. Both administrative measures of asthma care quality were associated with lower odds of ED utilization. The controller medication measure of asthma care quality may be better than the ratio measure in relation to emergency asthma care utilization by Medicaid beneficiaries.

Drug packaging in 2014: authorities should direct more efforts towards medication safety.

PubMed

2015-05-01

In 2014, Prescrire examined the packaging quality of about 250 drugs. A few advances stand out, mainly involving recent drugs, but on the whole, the situation is worrisome in terms of medication safety. Although pharmaceutical companies and drug regulatory agencies seem to be taking more account of the risk of accidental poisoning in children, the level of protection remains low overall in the absence of stringent measures on the part of the authorities. New drugs too often have poor-quality or even dangerous packaging at the time of their market introduction. And the packaging quality of older drugs is disturbing. Pharmaceutical companies no longer invest in the packaging of these products, and agencies often fail to take advantage of the opportunities provided by their reassessment to improve the situation. The inappropriate labelling of certain injectable drugs remains a source of medication errors, sometimes resulting in very serious consequences. In 2014, signs of progress in the packaging of several drugs show that its role in medication safety is better appreciated. But the persistence of dangers in the pharmaceuticals market, created by "unfinished", overly complex or poor-quality packaging, raises the question of the responsibility of pharmaceutical companies and agencies for past and present accidents.

Normal and reverse flow injection–spectrophotometric determination of thiamine hydrochloride in pharmaceutical preparations using diazotized metoclopramide

PubMed Central

Al Abachi, Mouayed Q.; Hadi, Hind

2012-01-01

Simple and sensitive normal and reverse flow injection methods for spectrophotometric determination of thiamine hydrochloride (THC) at the microgram level were proposed and optimized. Both methods are based on the reaction between THC and diazotized metoclopramide in alkaline medium. Beer’s law was obeyed over the range of 10–300 and 2–90 μg/mL, the limits of detection were 2.118 and 0.839 μg/mL and the sampling rates were 80 and 95 injections per hour for normal and reverse flow injection methods respectively. The application of both methods to commercially available pharmaceuticals produced acceptable results. The flow system is suitable for application in quality control processes. PMID:29403765

Determination of lead in Smilax myosotiflora herbal preparations obtained in Malaysia.

PubMed

Ang, H H; Lee, K L; Kiyoshi, M

2004-08-01

The DCA (Drug Control Authority), Malaysia implemented the phase 3 registration of traditional medicines on 1 January 1992 with special emphasis on the quality, efficacy and safety (including the presence of heavy metals) in all pharmaceutical dosage forms of traditional medicinal preparations. As such, a total of 100 traditional medicinal preparations, containing Smilax myosotiflora, in various pharmaceutical dosage forms, which were bought in the Malaysian market, were analysed for lead content using atomic absorption spectrophotometry. Results showed that 15% of the products analysed possessed 10.23-23.05 ppm of lead, and therefore, do not comply with the quality requirement for traditional medicines in Malaysia. The quality requirement for traditional medicines in Malaysia is that they should not exceed 10 ppm of lead. Out of these 15 products, five products exhibited 10.23-23.05 ppm of lead, in fact they have already been registered with the DCA Malaysia. However, the rest of the products, which possessed 12.24-20.72 ppm of lead, have still not been registered with the DCA Malaysia. Although this study successfully showed that only 85% of the products complied with the quality requirement for traditional medicines in Malaysia pertaining to lead, they cannot, however, be assumed to be safe from lead contamination because of batch-to-batch inconsistency.

77 FR 34072 - Importer of Controlled Substances; Notice of Registration; Meda Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-08

... Registration; Meda Pharmaceuticals, Inc. By Notice dated April 2, 2012, and published in the Federal Register on April 12, 2012, 77 FR 21998, Meda Pharmaceuticals, Inc., 705 Eldorado Street, Decatur, Illinois... that the registration of Meda Pharmaceuticals Inc. to import the basic class of controlled substance is...

78 FR 12104 - Manufacturer of Controlled Substances; Notice of Registration; INB Hauser Pharmaceutical Services...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-21

...; Notice of Registration; INB Hauser Pharmaceutical Services, Inc. By Notice dated November 1, 2012, and published in the Federal Register on November 9, 2012, 77 FR 67398, InB Hauser Pharmaceutical Services, Inc... Hauser Pharmaceutical Services, Inc., to manufacture the listed basic class of controlled substance is...

Gap Analysis for Chinese Drug Control Institutes to Achieve the Standards of World Health Organization Medicine Prequalification.

PubMed

Mao, Xin; Yang, Yue

2017-02-01

The study aims to explore the challenges and the gaps faced by Chinese Drug Control Institutes in achieving the standards of World Health Organization (WHO) Medicine Prequalification. The study was undertaken with 6 Provincial Drug Control Institutes in China from November 2012 to November 2013. The study assessed key elements required to comply with WHO Good Practices for Pharmaceutical Quality Control Laboratories (GPPQCL). For GPPQCL, the study found gaps in quality management system, control of documentation, data-processing equipment, premises and equipment, contracts, reagents (water), reference substances and reference materials, calibration, verification of performance and qualification of equipment, instruments and other devices, analytical worksheet, evaluation of test results, personnel, and validation of analytical procedures. The study indicates that gaps are attributed to differences between the standards of Chinese Accreditation Standards and WHO-GPPQCL. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Surface-Water to Groundwater Transport of Pharmaceuticals in a Wastewater-Impacted Stream in the U.S.

NASA Astrophysics Data System (ADS)

Bradley, P. M.; Barber, L. B.; Duris, J. W.; Foreman, W. T.; Furlong, E. T.; Hubbard, L. E.; Hutchinson, K. J.; Keefe, S. H.; Kolpin, D. W.

2014-12-01

Wastewater pharmaceutical contamination of shallow groundwater is a substantial concern in effluent-dominated streams, due to aqueous mobility and designed bioactivity of pharmaceuticals and due to effluent-driven hydraulic gradients. Improved understanding of the environmental fate and transport of wastewater-derived pharmaceuticals is essential for effective protection of vital aquatic ecosystem services, environmental health, and drinking-water supplies. Substantial longitudinal (downstream) transport of pharmaceutical contaminants has been documented in effluent-impacted streams. The comparative lack of information on vertical and lateral transport (infiltration) of wastewater contaminants from surface-water to hyporheic and shallow groundwater compartments is a critical scientific data gap, given the potential for contamination of groundwater supplies in effluent-impacted systems. Growing dependencies on bank filtration and artificial recharge applications for release of wastewater to the environment and for pretreatment of poor-quality surface-water for drinking water emphasize the critical need to better understand the exchange of wastewater contaminants, like pharmaceuticals, between surface-water and groundwater compartments. The potential transport of effluent-derived pharmaceutical contaminants from surface-water to hyporheic-water and shallow groundwater compartments was examined in a wastewater-treatment-facility (WWTF) impacted stream in Ankeny, Iowa under effluent-dominated (71-99% of downstream flow) conditions. Strong hydraulic gradients and hydrologic connectivity were evident between surface-water and shallow-groundwater compartments in the vicinity of the WWTF outfall. Carbamazepine, sulfamethoxazole, and immunologically-related compounds were detected in groundwater 10-20 meters from the stream bank. Direct aqueous-injection HPLC-MS/MS revealed high percentage detections of pharmaceuticals (110 total analytes) in surface-water and groundwater samples. The results demonstrate the importance of effluent discharge as a driver of local hydrologic conditions in an effluent-impacted stream and thus as a fundamental control on surface-water to groundwater transport of effluent-derived pharmaceutical contaminants.

A Process Analytical Technology (PAT) approach to control a new API manufacturing process: development, validation and implementation.

PubMed

Schaefer, Cédric; Clicq, David; Lecomte, Clémence; Merschaert, Alain; Norrant, Edith; Fotiadu, Frédéric

2014-03-01

Pharmaceutical companies are progressively adopting and introducing Process Analytical Technology (PAT) and Quality-by-Design (QbD) concepts promoted by the regulatory agencies, aiming the building of the quality directly into the product by combining thorough scientific understanding and quality risk management. An analytical method based on near infrared (NIR) spectroscopy was developed as a PAT tool to control on-line an API (active pharmaceutical ingredient) manufacturing crystallization step during which the API and residual solvent contents need to be precisely determined to reach the predefined seeding point. An original methodology based on the QbD principles was designed to conduct the development and validation of the NIR method and to ensure that it is fitted for its intended use. On this basis, Partial least squares (PLS) models were developed and optimized using chemometrics methods. The method was fully validated according to the ICH Q2(R1) guideline and using the accuracy profile approach. The dosing ranges were evaluated to 9.0-12.0% w/w for the API and 0.18-1.50% w/w for the residual methanol. As by nature the variability of the sampling method and the reference method are included in the variability obtained for the NIR method during the validation phase, a real-time process monitoring exercise was performed to prove its fit for purpose. The implementation of this in-process control (IPC) method on the industrial plant from the launch of the new API synthesis process will enable automatic control of the final crystallization step in order to ensure a predefined quality level of the API. In addition, several valuable benefits are expected including reduction of the process time, suppression of a rather difficult sampling and tedious off-line analyses. © 2013 Published by Elsevier B.V.

Survey to Identify Substandard and Falsified Tablets in Several Asian Countries with Pharmacopeial Quality Control Tests and Principal Component Analysis of Handheld Raman Spectroscopy.

PubMed

Kakio, Tomoko; Nagase, Hitomi; Takaoka, Takashi; Yoshida, Naoko; Hirakawa, Junichi; Macha, Susan; Hiroshima, Takashi; Ikeda, Yukihiro; Tsuboi, Hirohito; Kimura, Kazuko

2018-06-01

The World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer. Some samples showed delayed dissolution and failed to meet the pharmacopeial specification, whereas others failed the assay test. These products appeared to be substandard. Principal component analysis showed that all Raman spectra could be explained in terms of two components: the amount of the active pharmaceutical ingredient and the kinds of excipients. Principal component analysis score plot indicated one substandard, and the falsified tablets have similar principal components in Raman spectra, in contrast to authentic products. The locations of samples within the PCA score plot varied according to the source country, suggesting that manufacturers in different countries use different excipients. Our results indicate that the handheld Raman device will be useful for detection of SFs in the field. Principal component analysis of that Raman data clarify the difference in chemical properties between good quality products and SFs that circulate in the Asian market.

Identification of a Multicomponent Traditional Herbal Medicine by HPLC-MS and Electron and Light Microscopy.

PubMed

Liu, Ju-Han; Cheng, Yung-Yi; Hsieh, Chen-Hsi; Tsai, Tung-Hu

2017-12-15

Commercial pharmaceutical herbal products have enabled people to take traditional Chinese medicine (TCM) in a convenient and accessible form. However, the quantity and quality should be additionally inspected. To address the issue, a combination of chemical and physical inspection methods were developed to evaluate the amount of an herbal formula, Xiang-Sha-Liu-Jun-Zi-Tang (XSLJZT), in clinical TCM practice. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) method with electrospray ionization was developed to measure the herbal biomarkers of guanosine, atractylenolide III, glycyrrhizic acid, dehydrocostus lactone, hesperidin, and oleanolic acid from XSLJZT. Scanning electron microscopy (SEM) photographs and light microscopy photographs with Congo red and iodine-KI staining were used to identify the cellulose fibers and starch content. Furthermore, solubility analysis, swelling power test, and crude fiber analysis were contributed to measure the starch additive in pharmaceutical products. The results demonstrated large variations in the chemical components of different pharmaceutical brands. The SEM photographs revealed that the starch was oval, smooth, and granular, and that the raw herbal powder appears stripy, stretched, and filiform. The stained light microscopy photographs of all of the pharmaceutical products showed added starch and raw herbal powder as extenders. The developed chemical and physical methods provide a standard operating procedure for the quantity control of the herbal pharmaceutical products of XSLJZT.

Determination of mercury by cold vapor atomic absorption spectrophotometer in Tongkat Ali preparations obtained in Malaysia.

PubMed

Ang, Hooi-Hoon; Lee, Ee-Lin; Cheang, Hui-Seong

2004-01-01

The DCA (Drug Control Authority), Malaysia, has implemented the phase 3 registration of traditional medicines on 1 January 1992, with special emphasis on the quality, efficacy, and safety (including the presence of heavy metals) in all pharmaceutical dosage forms of traditional medicine preparations. As such, a total of 100 products in various pharmaceutical dosage forms of a herbal preparation, containing Tongkat Ali, were analyzed for mercury content using cold vapor atomic absorption spectrophotometer. Results showed that 36% of the above products possessed 0.52 to 5.30 ppm of mercury and, therefore, do not comply with the quality requirement for traditional medicines in Malaysia. Out of these 36 products, 5 products that possessed 1.05 to 4.41 ppm of mercury were in fact have already registered with the DCA, Malaysia. However, the rest of the products that contain 0.52 to 5.30 ppm of mercury still have not registered with the DCA, Malaysia. Although this study showed that only 64% of the products complied with the quality requirement for traditional medicines in Malaysia pertaining to mercury, they cannot be assumed safe from mercury contamination because of batch-to-batch inconsistency.

[Preliminary studies on critical control point of traceability system in wolfberry].

PubMed

Liu, Sai; Xu, Chang-Qing; Li, Jian-Ling; Lin, Chen; Xu, Rong; Qiao, Hai-Li; Guo, Kun; Chen, Jun

2016-07-01

As a traditional Chinese medicine, wolfberry (Lycium barbarum) has a long cultivation history and a good industrial development foundation. With the development of wolfberry production, the expansion of cultivation area and the increased attention of governments and consumers on food safety, the quality and safety requirement of wolfberry is higher demanded. The quality tracing and traceability system of production entire processes is the important technology tools to protect the wolfberry safety, and to maintain sustained and healthy development of the wolfberry industry. Thus, this article analyzed the wolfberry quality management from the actual situation, the safety hazard sources were discussed according to the HACCP (hazard analysis and critical control point) and GAP (good agricultural practice for Chinese crude drugs), and to provide a reference for the traceability system of wolfberry. Copyright© by the Chinese Pharmaceutical Association.

Dispensing doctor practices and community pharmacies: exploring the quality of pharmaceutical services.

PubMed

Weiss, Marjorie C; Grey, Elisabeth; Harris, Michael; Rodham, Karen

2016-01-01

This research sought (a) to investigate the similarities and differences in how pharmaceutical services are provided by community pharmacies (CPs) and dispensing doctor practices (DPs) and (b) to identify the issues relevant to determining the quality of pharmaceutical services in these settings. UK pharmaceutical services, including dispensing prescriptions and public health advice, can be provided from both (CP) and, in rural areas, (DP). While there is much similarity between CPs and DPs in the types of services provided, there is also the potential for variation in service quality across settings. A postal questionnaire of DPs and CPs in South West England was conducted to provide a descriptive overview of pharmaceutical services across the settings. A subsection of questionnaire respondent sites were selected to take part in case studies, which involved documentary analyses, observation and staff interviews. Survey response was 39% for CPs (52/134) and 48% (31/64) for DPs. There were three CP and four DP case study sites, with 17 staff interviews. More pharmacies than practices were open at the weekend and they had more staff trained above NVQ level 2. Both doctors and pharmacists saw themselves as medicines experts, as being accessible and having good relationships with patients. Workplace practices and organisational ethos varied both within and across settings, with good practice observed in both. Overall, CPs and DPs have much in common. Workplace culture and an evidence-based approach to checking prescriptions and error reporting need to be considered in future assessments of service quality.

Pharmaceutical patents and price controls.

PubMed

Vogel, Ronald J

2002-07-01

Since 1995, every member-country of the World Trade Organization (WTO) has agreed to honor a 20-year patent-life, from the date of a pharmaceutical company's application for the patent, in the country of application. Patent protection retards competitive imitation of an invented product. This kind of protection is particularly important for pharmaceuticals, because pharmaceuticals that are not derived from biotechnology can be imitated easily and inexpensively. The economic function of a patent is to allow a period of above-normal profits for a technically and commercially successful product; these profits stimulate further investment and invention. However, direct price controls, or permutations of direct price controls on pharmaceutical compounds, can fully or partially circumvent the economic intent of patent agreements. This paper formulates an economic model that takes into account demand and cost/supply dimensions of the output and pricing of a hypothetical pharmaceutical, extrapolating about the respective effects of direct price controls and lack of price controls, and describing permutations of direct price controls in different countries. The pharmaceutical industry depends on patents to fund the development and introduction of new products. A country can indirectly circumvent the economic logic of a patent by using price controls, but it cannot shift the economic costs of such a policy to another country that does not use price controls. Instead, less money is available for research and development (R&D). Pharmaceutical price controls allow some countries to avoid the constraints of patent agreements without breaking those agreements outright. This, in turn, reduces the amount of profit available for further R&D, which is a detriment to consumers worldwide.

Delivery of pharmaceutical services at ward level in a teaching hospital.

PubMed

Schellack, N; Martins, V; Botha, N; Meyer, J C

2009-03-01

Poor management of pharmaceuticals could lead to wastage of financial resources and poor services in the public sector. The main aim of the study was to investigate the quality of pharmaceutical services at ward level in a teaching hospital. The design of the study was descriptive. Three data collection instruments were designed and pilot-tested prior to the actual data collection. Two structured questionnaires were used to interview the sister-in-charge of each ward and the stock and drug controller at the pharmacy. A checklist for the management of pharmaceuticals was completed for each ward. Descriptive statistics were used to describe and summarise the data. Sisters-in-charge of 30 wards and the stock and drug controller at the pharmacy participated in the study. The relationship with the pharmacy was perceived to be average by 54% (n = 30) of the sisters-in-charge of the wards. Communication with the pharmacy was mainly by telephone and 57% of the sisters-in-charge mentioned that they experienced difficulties in conveying messages to the pharmacy. Ten of the wards received regular ward visits by a pharmacist. Expiry dates were checked by all wards but at different intervals. The majority of the wards (90%) used patient cards, which refer to prescription charts, for stock control and ordering from the pharmacy. Fridge temperatures were checked and charted on a daily basis by 30% of the wards. Written standard operating procedures (SOPs) were used by the pharmacy for issuing ward stock. Although 83% of the wards indicated that they used SOPs, evidence of written SOPs was not available. The results indicated that the management of pharmaceutical services at ward level could be improved. Implementation of appropriate communication systems will enhance cooperation between the pharmacy and the wards. A uniform ward stock control system, either by computer or stock cards, should be introduced. Regular ward visits by a pharmacist to oversee ward stock management are recommended. Standard operating procedures for use in the wards should be developed and implemented.

International Conference on Harmonisation; guidance on Q9 Quality Risk Management; availability. Notice.

PubMed

2006-06-02

The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q9 Quality Risk Management."' The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance provides principles and examples of tools for quality risk management that can be applied to all aspects of pharmaceutical quality throughout the lifecycle of drug substances, drug products, and biological and biotechnological products. The guidance is intended to enable regulators and industry to make more effective and consistent risk-based decisions.

Strategic funding priorities in the pharmaceutical sciences allied to Quality by Design (QbD) and Process Analytical Technology (PAT).

PubMed

Aksu, Buket; De Beer, Thomas; Folestad, Staffan; Ketolainen, Jarkko; Lindén, Hans; Lopes, Joao Almeida; de Matas, Marcel; Oostra, Wim; Rantanen, Jukka; Weimer, Marco

2012-09-29

Substantial changes in Pharmaceutical R&D strategy are required to address existing issues of low productivity, imminent patent expirations and pressures on pricing. Moves towards personalized healthcare and increasing diversity in the nature of portfolios including the rise of biopharmaceuticals however have the potential to provide considerable challenges to the establishment of cost effective and robust supply chains. To guarantee product quality and surety of supply for essential medicines it is necessary that manufacturing science keeps pace with advances in pharmaceutical R&D. In this position paper, the EUFEPS QbD and PAT Sciences network make recommendations that European industry, academia and health agencies focus attention on delivering step changes in science and technology in a number of key themes. These subject areas, all underpinned by the sciences allied to QbD and PAT, include product design and development for personalized healthcare, continuous-processing in pharmaceutical product manufacture, quantitative quality risk assessment for pharmaceutical development including life cycle management and the downstream processing of biopharmaceutical products. Plans are being established to gain commitment for inclusion of these themes into future funding priorities for the Innovative Medicines Initiative (IMI). Copyright © 2012 Elsevier B.V. All rights reserved.

Pharmaceutical laws and regulations in Iran: An overview

PubMed Central

Zaboli, Pardis; Hashemi-Meshkini, Amir; Varmaghani, Mehdi; Gholami, Hadi; Vazirian, Iman; Zekri, Hedieh-Sadat; Eslamitabar, Shahriar; Kebriaeezadeh, Abbas

2016-01-01

The pharmaceutical legal framework is a very important infrastructure in achieving predefined goals in pharmaceutical sector: Accessibility, quality, and rational use of medicine. This study aims to review the current pharmaceutical sector-related legal provisions in Iran where the Food and Drug Organization (FDO) is in charge of regulating all issues related to the pharmaceutical sector. The main laws and regulations enacted by parliament and cabinet and even internal regulations enacted by the Ministry of Health or Iran FDO are reviewed. Different laws and regulations are categorized according to the main goals of Iran national drug policy. PMID:27512704

Future European health care: cost containment, health care reform and scientific progress in drug research.

PubMed

Emilien, G

1997-01-01

The cost of the development of a new pharmaceutical product from its conception and synthesis through to the regulatory approval process has more than quadrupled in the last 20 years. Both clinical and total development times have increased substantially. To amortize the costs incurred, the pharmaceutical industry has taken an international dimension. The incentives for pharmaceutical firms to discover and develop new drugs depend on the length of the development and regulatory review process plus the potential market size. Recent regulatory, economic and political changes may have significant implications for the future of new drug developments in Europe. The European Union industrial policy felt that there is a need for convergence in the area of pricing. It is recommended that the policy should aim to contain growth in pharmaceutical expenses by means specific to reimbursement rather than direct price controls. By encouraging doctors to prescribe and customers to use generics, competition is enhanced to bring down drug prices. More emphasis is being laid by government in educating customers to cost-awareness and cost-benefit ratios with regard to pharmaceuticals. Concerning clinical trials, European harmonization has been achieved by significant developments: the rights and integrity of the trial subjects are protected; the credibility of the data is established; and the ethical, scientific and technical quality of the trials has improved. Future European health care forecasts a whole change in the pharmaceutical business. Important issues in cost and outcome measurement should be carefully planned and considered in drug development. Due to important mergers and acquisitions, the pharmaceutical sector will consist mainly of important multinational corporations. In this way, valuable new products may be brought to the market.

Acceptability and characteristics of 124 human bioequivalence studies with active substances classified according to the Biopharmaceutic Classification System

PubMed Central

Ramirez, Elena; Laosa, Olga; Guerra, Pedro; Duque, Blanca; Mosquera, Beatriz; Borobia, Alberto M; Lei, Suhua H; Carcas, Antonio J; Frias, Jesus

2010-01-01

AIM The aim of this study was to evaluate the acceptability of 124 bioequivalence (BE) studies with 80 active substances categorized according to the Biopharmaceutics Classification System (BCS) in order to establish if there were different probabilities of proving BE between the different BCS classes. METHODS We evaluated the differences between pharmaceutical products with active substances from different BCS classes in terms of acceptability, number of subjects in the study (n), the point estimates, and intra- and inter-subject coefficients of variation data from BE studies with generic products. RESULTS Out of 124 BE studies 89 (71.77%) were performed with pharmaceutical products containing active substances classified by the BCS. In all BCS classes there were non-bioequivalent pharmaceutical products: 4 out of 26 (15.38%) in class 1, 14 out of 28 (50%) in class 2, 3 out of 22 (13.63%) in class 3 and 1 out of 13 (7.69%) in class 4. When we removed those pharmaceutical products in which intra-subject variability was higher than predicted (2 in class 1 active substances, 9 in class 2 and 2 in class 3) there were still non-BE pharmaceutical products in classes 1, 2 and 3. CONCLUSIONS Comparisons between pharmaceutical products with active substances from the four BCS classes have not allowed us to define differential characteristics of each class in terms of n, inter and intra-subject variability for Cmax or AUC. Despite the usually employed test dissolution methodology proposed as quality control, pharmaceutical products with active substances from the four classes of BCS showed non-BE studies. PMID:21039763

Quality of pharmaceutical care at the pharmacy counter: patients’ experiences versus video observation

PubMed Central

Koster, Ellen S; Blom, Lyda; Overbeeke, Marloes R; Philbert, Daphne; Vervloet, Marcia; Koopman, Laura; van Dijk, Liset

2016-01-01

Introduction Consumer Quality Index questionnaires are used to assess quality of care from patients’ experiences. Objective To provide insight into the agreement about quality of pharmaceutical care, measured both by a patient questionnaire and video observations. Methods Pharmaceutical encounters in four pharmacies were video-recorded. Patients completed a questionnaire based upon the Consumer Quality Index Pharmaceutical Care after the encounter containing questions about patients’ experiences regarding information provision, medication counseling, and pharmacy staff’s communication style. An observation protocol was used to code the recorded encounters. Agreement between video observation and patients’ experiences was calculated. Results In total, 109 encounters were included for analysis. For the domains “medication counseling” and “communication style”, agreement between patients’ experiences and observations was very high (>90%). Less agreement (45%) was found for “information provision”, which was rated more positive by patients compared to the observations, especially for the topic, encouragement of patients’ questioning behavior. Conclusion A questionnaire is useful to assess the quality of medication counseling and pharmacy staff’s communication style, but might be less suitable to evaluate information provision and pharmacy staff’s encouragement of patients’ questioning behavior. Although patients may believe that they have received all necessary information to use their new medicine, some information on specific instructions was not addressed during the encounter. When using questionnaires to get insight into information provision, observations of encounters are very informative to validate the patient questionnaires and make necessary adjustments. PMID:27042025

A new definition of pharmaceutical quality: assembly of a risk simulation platform to investigate the impact of manufacturing/product variability on clinical performance.

PubMed

Short, Steven M; Cogdill, Robert P; D'Amico, Frank; Drennen, James K; Anderson, Carl A

2010-12-01

The absence of a unanimous, industry-specific definition of quality is, to a certain degree, impeding the progress of ongoing efforts to "modernize" the pharmaceutical industry. This work was predicated on requests by Dr. Woodcock (FDA) to re-define pharmaceutical quality in terms of risk by linking production characteristics to clinical attributes. A risk simulation platform that integrates population statistics, drug delivery system characteristics, dosing guidelines, patient compliance estimates, production metrics, and pharmacokinetic, pharmacodynamic, and in vitro-in vivo correlation models to investigate the impact of manufacturing variability on clinical performance of a model extended-release theophylline solid oral dosage system was developed. Manufacturing was characterized by inter- and intra-batch content uniformity and dissolution variability metrics, while clinical performance was described by a probabilistic pharmacodynamic model that expressed the probability of inefficacy and toxicity as a function of plasma concentrations. Least-squares regression revealed that both patient compliance variables, percent of doses taken and dosing time variability, significantly impacted efficacy and toxicity. Additionally, intra-batch content uniformity variability elicited a significant change in risk scores for the two adverse events and, therefore, was identified as a critical quality attribute. The proposed methodology demonstrates that pharmaceutical quality can be recast to explicitly reflect clinical performance. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association

[Impact of pharmaceutical interventions on antibiotic therapy of urinary tract infections in rehabilitation center].

PubMed

Rochefolle, A; Maison, O; Chazaud, C; Rioufol, C; Rode, G; Luaute, J; Jacquin-Courtois, S; Guinet-Lacoste, A; Carré, E

2017-06-01

The aim of this study was to assess the impact of medico-pharmaceutical partnership on the quality of antibiotic treatment in urinary tract infection (UTI) within rehabilitation center. All antibiotic prescriptions were validated by the pharmacist at the start of treatment and twice a week. All patients with symptomatic urinary tract infection between January 1, 2014 to December 31, 2015 were included in this study. Addition to awareness among specifiers to promoting the appropriate use of antibiotics, the pharmacist suggested pharmaceutical interventions (PI) in order to improve the quality of antibiotic treatments. At the same time, 3 quality indicators (QI) were followed: duration, dosage, antibiotic susceptibility. The compliance rates of this 3 QI allowed to assess the quality of the antibiotic treatment in urinary tract infection. The study population included 154 patients corresponding to 252 UTI. Sixty-eight PI were made by pharmacist about urinary tract infection treatment (overdosage or under-dosing, duration unknown, inadequate route of administration). These QI achieved 96.4% compliance with duration, 98.8% compliance with dosage and 99.2% with the antibiotic susceptibility. This study allowed showing the medico-pharmaceutical impact on the quality of antibiotic treatments in UTI. The awareness among specifiers with a daily validation of prescription by the pharmacist allowed to improve urinary tract infections care in rehabilitation center. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Adaptation of the quality by design concept in early pharmaceutical development of an intranasal nanosized formulation.

PubMed

Pallagi, Edina; Ambrus, Rita; Szabó-Révész, Piroska; Csóka, Ildikó

2015-08-01

Regulatory science based pharmaceutical development and product manufacturing is highly recommended by the authorities nowadays. The aim of this study was to adapt regulatory science even in the nano-pharmaceutical early development. Authors applied the quality by design (QbD) concept in the early development phase of nano-systems, where the illustration material was meloxicam. The meloxicam nanoparticles produced by co-grinding method for nasal administration were studied according to the QbD policy and the QbD based risk assessment (RA) was performed. The steps were implemented according to the relevant regulatory guidelines (quality target product profile (QTPP) determination, selection of critical quality attributes (CQAs) and critical process parameters (CPPs)) and a special software (Lean QbD Software(®)) was used for the RA, which represents a novelty in this field. The RA was able to predict and identify theoretically the factors (e.g. sample composition, production method parameters, etc.) which have the highest impact on the desired meloxicam-product quality. The results of the practical research justified the theoretical prediction. This method can improve pharmaceutical nano-developments by achieving shorter development time, lower cost, saving human resource efforts and more effective target-orientation. It makes possible focusing the resources on the selected parameters and area during the practical product development. Copyright © 2015 Elsevier B.V. All rights reserved.

Method Description, Quality Assurance, Environmental Data, and other Information for Analysis of Pharmaceuticals in Wastewater-Treatment-Plant Effluents, Streamwater, and Reservoirs, 2004-2009

USGS Publications Warehouse

Phillips, Patrick J.; Smith, Steven G.; Kolpin, Dana W.; Zaugg, Steven D.; Buxton, Herbert T.; Furlong, Edward T.

2010-01-01

Abstract Wastewater-treatment-plant (WWTP) effluents are a demonstrated source of pharmaceuticals to the environment. During 2004-09, a study was conducted to identify pharmaceutical compounds in effluents from WWTPs (including two that receive substantial discharges from pharmaceutical formulation facilities), streamwater, and reservoirs. The methods used to determine and quantify concentrations of seven pharmaceuticals are described. In addition, the report includes information on pharmaceuticals formulated or potentially formulated at the two pharmaceutical formulation facilities that provide substantial discharge to two of the WWTPs, and potential limitations to these data are discussed. The analytical methods used to provide data on the seven pharmaceuticals (including opioids, muscle relaxants, and other pharmaceuticals) in filtered water samples also are described. Data are provided on method performance, including spike data, method detection limit results, and an estimation of precision. Quality-assurance data for sample collection and handling are included. Quantitative data are presented for the seven pharmaceuticals in water samples collected at WWTP discharge points, from streams, and at reservoirs. Occurrence data also are provided for 19 pharmaceuticals that were qualitatively identified. Flow data at selected WWTP and streams are presented. Between 2004-09, 35-38 effluent samples were collected from each of three WWTPs in New York and analyzed for seven pharmaceuticals. Two WWTPs (NY2 and NY3) receive substantial inflows (greater than 20 percent of plant flow) from pharmaceutical formulation facilities (PFF) and one (NY1) receives no PFF flow. Samples of effluents from 23 WWTPs across the United States were analyzed once for these pharmaceuticals as part of a national survey. Maximum pharmaceutical effluent concentrations for the national survey and NY1 effluent samples were generally less than 1 ug/L. Four pharmaceuticals (methadone, oxycodone, butalbital and metaxalone) in samples of NY3 effluent had median concentrations ranging from 3.4 to greater than 400 ug/L. Maximum concentrations of oxycodone (1,700 ug/L) and metaxalone (3,800 ug/L) in samples from NY3 effluent exceeded 1,000 ug/L. Three pharmaceuticals (butalbital, carisoprodol, and oxycodone) in samples of NY2 effluent had median concentrations ranging from 2 to 11 ug/L. These findings suggest that current 2 manufacturing practices at these PFFs can result in pharmaceutical concentrations from 10 to 1,000 times higher than those typically found in WWTP effluents.

Methodological quality of economic evaluations of new pharmaceuticals in The Netherlands.

PubMed

Hoomans, Ties; Severens, Johan L; van der Roer, Nicole; Delwel, Gepke O

2012-03-01

In the Netherlands, decisions about the reimbursement of new pharmaceuticals are based on cost effectiveness, as well as therapeutic value and budget impact. Since 1 January 2005, drug manufacturers are formally required to substantiate the cost effectiveness of drugs that have therapeutic added value in comparison with existing ones through pharmacoeconomic evaluations. Dutch guidelines for pharmacoeconomic research provide methods guidance, ensuring consistency in both the evidence and the decision-making process about drug reimbursement. This study reviewed the methodological quality of all 21 formally required pharmacoeconomic evaluations of new pharmaceuticals between 1 January 2005 and 1 October 2008, and verified whether these evaluations complied with pharmacoeconomic guidelines. Data on the quality of the pharmacoeconomic evaluations were extracted from the pharmacoeconomic reports published by the Dutch Health Care Insurance Board (CVZ). The Board's newsletters provided information on the advice to, and reimbursement decisions made by, the Dutch Minister of Health. All data extraction was carried out by two independent reviewers, and descriptive analyses were conducted. The methodological quality was sound in only 8 of the 21 pharmacoeconomic evaluations. In most cases, the perspective of analysis, the comparator drugs, and the reporting of both total and incremental costs and effects were correct. However, drug indication, form (i.e. cost utility/cost effectiveness) and time horizon of the evaluations were frequently flawed. Moreover, the costs and effects of the pharmaceuticals were not always analysed correctly, and modelling studies were often non-transparent. Twelve drugs were reimbursed, and nine were not. The compliance with pharmacoeconomic guidelines in economic evaluations of new pharmaceuticals can be improved. This would improve the methodological quality of the pharmacoeconomic evaluations and ensure consistency in the evidence and the decision-making process for drug reimbursement in the Netherlands.

Improved quality monitoring of multi-center acupuncture clinical trials in China

PubMed Central

2009-01-01

Background In 2007, the Chinese Science Division of the State Administration of Traditional Chinese Medicine(TCM) convened a special conference to discuss quality control for TCM clinical research. Control and assurance standards were established to guarantee the quality of clinical research. This paper provides practical guidelines for implementing strict and reproducible quality control for acupuncture randomized controlled trials (RCTs). Methods A standard quality control program (QCP) was established to monitor the quality of acupuncture trials. Case report forms were designed; qualified investigators, study personnel and data management personnel were trained. Monitors, who were directly appointed by the project leader, completed the quality control programs. They guaranteed data accuracy and prevented or detected protocol violations. Clinical centers and clinicians were audited, the randomization system of the centers was inspected, and the treatment processes were audited as well. In addition, the case report forms were reviewed for completeness and internal consistency, the eligibility and validity of the patients in the study was verified, and data was monitored for compliance and accuracy. Results and discussion The monitors complete their reports and submit it to quality assurance and the sponsors. Recommendations and suggestions are made for improving performance. By holding regular meetings to discuss improvements in monitoring standards, the monitors can improve quality and efficiency. Conclusions Supplementing and improving the existed guidelines for quality monitoring will ensure that large multi-centre acupuncture clinical trials will be considered as valid and scientifically stringent as pharmaceutical clinical trials. It will also develop academic excellence and further promote the international recognition of acupuncture. PMID:20035630

Quality of claims and references found in Australian pharmacy journal advertisements.

PubMed

Mandoh, Mona; Curtain, Colin Michael

2017-10-01

To evaluate the quality of pharmaceutical advertisement claims and supporting references in Australian pharmacy journals that target community pharmacists. All full-page advertisements for a medicinal product, found in two Australian pharmacy journals from the year 2012 to 2015 were included. Advertisement claims and references were evaluated by claim type (unambiguous to immeasurable) and level of evidence (strong to irrelevant) in supporting references. Two hundred and ninety distinct advertisements and 598 claims were identified, with a median of 2 claims per advertisement. Twenty-seven percent of claims were unambiguous, 40% were vague, 16% were emotive/immeasurable and 17% were non-clinical or other marketing claims. Half of all claims were referenced. Although 68% of unambiguous claims were referenced, 63% of those were supported by studies that were funded directly or indirectly by pharmaceutical companies. Only 13% of claims were supported with strong or moderate independent evidence. Pharmaceutical advertisements continue to present vague and emotive claims with little independent supporting evidence. Pharmacists need to be aware of these limitations when providing patient care. Increased awareness of this issue among pharmaceutical companies, Australian pharmaceutical journal publishers, regulators and pharmacists will assist in promoting optimised healthcare outcomes for the Australian public. © 2016 Royal Pharmaceutical Society.

21 CFR 26.15 - Monitoring continued equivalence.

Code of Federal Regulations, 2010 CFR

2010-04-01

... MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM... COMMUNITY Specific Sector Provisions for Pharmaceutical Good Manufacturing Practices § 26.15 Monitoring... number of joint inspections; and the conduct of common training sessions. ...

21 CFR 26.15 - Monitoring continued equivalence.

Code of Federal Regulations, 2011 CFR

2011-04-01

... MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM... COMMUNITY Specific Sector Provisions for Pharmaceutical Good Manufacturing Practices § 26.15 Monitoring... number of joint inspections; and the conduct of common training sessions. ...

The application of quality risk management to the bacterial endotoxins test: use of hazard analysis and critical control points.

PubMed

Annalaura, Carducci; Giulia, Davini; Stefano, Ceccanti

2013-01-01

Risk analysis is widely used in the pharmaceutical industry to manage production processes, validation activities, training, and other activities. Several methods of risk analysis are available (for example, failure mode and effects analysis, fault tree analysis), and one or more should be chosen and adapted to the specific field where they will be applied. Among the methods available, hazard analysis and critical control points (HACCP) is a methodology that has been applied since the 1960s, and whose areas of application have expanded over time from food to the pharmaceutical industry. It can be easily and successfully applied to several processes because its main feature is the identification, assessment, and control of hazards. It can be also integrated with other tools, such as fishbone diagram and flowcharting. The aim of this article is to show how HACCP can be used to manage an analytical process, propose how to conduct the necessary steps, and provide data templates necessary to document and useful to follow current good manufacturing practices. In the quality control process, risk analysis is a useful tool for enhancing the uniformity of technical choices and their documented rationale. Accordingly, it allows for more effective and economical laboratory management, is capable of increasing the reliability of analytical results, and enables auditors and authorities to better understand choices that have been made. The aim of this article is to show how hazard analysis and critical control points can be used to manage bacterial endotoxins testing and other analytical processes in a formal, clear, and detailed manner.

Removal of pharmaceutical residue in municipal wastewater by DAF (dissolved air flotation)-MBR (membrane bioreactor) and ozone oxidation.

PubMed

Choi, Miyoung; Choi, Dong Whan; Lee, Jung Yeol; Kim, Young Suk; Kim, Bun Su; Lee, Byoung Ho

2012-01-01

Growing attention is given to pharmaceutical residue in the water environment. It is known that pharmaceuticals are able to survive from a series of wastewater treatment processes. Concerns regarding pharmaceutical residues are attributed to the fact that they are being detected in water and sediment environment ubiquitously. Pharmaceutical treatment using a series of wastewater treatment processes of the DAF (dissolved air flotation)-MBR (membrane bioreactor)-ozone oxidation was conducted in the study. DAF, without addition of coagulant, could remove COD(cr) (chemical oxygen demand by Cr) up to over 70%, BOD 73%, SS 83%, T-N 55%, NH₄(+) 23%, and T-P 65% in influent of municipal wastewater. Average removal rates of water quality parameters by the DAF-MBR system were very high, e.g. COD(cr) 95.88%, BOD₅ 99.66%, COD(mn) (chemical oxygen demand by Mn) 93.63%, T-N 69.75%, NH₄-N 98.46%, T-P 78.23%, and SS 99.51%, which satisfy effluent water quality standards. Despite the high removal rate of the wastewater treatment system, pharmaceuticals were eliminated to be about 50-99% by the MBR system, depending on specific pharmaceuticals. Ibuprofen was well removed by MBR system up to over 95%, while removal rate of bezafibrate ranged between 50 and 90%. With over 5 mg/l of ozone oxidation, most pharmaceuticals which survived the DAF-MBR process were removed completely or resulted in very low survival rate within the range of few micrograms per litre. However, some pharmaceuticals such as bezafibrate and naproxen tended to be resistant to ozone oxidation.

Randomised controlled trials cited in pharmaceutical advertisements targeting New Zealand health professionals: do they support the advertising claims and what is the risk of bias?

PubMed

Ma, Alison; Parkin, Lianne

2015-09-04

To determine whether pharmaceutical advertisement claims targeting health professionals were supported by the randomised controlled trials (RCTs) cited in the advertisements, and to assess the risk of bias in those trials. Pharmaceutical advertisements were obtained from New Zealand Doctor and Pharmacy Today for the period July 2013 to June 2014. All claims made regarding efficacy, safety, and indications were identified and RCTs cited to substantiate these claims were examined. A claim was defined as supported by an RCT if the conclusions drawn in the paper were consistent with the claim. The quality of the RCT was assessed separately, using the Cochrane Risk of Bias Assessment Tool. In 25 (19%) of the 133 instances in which an RCT was cited, the published paper did not support the promotional claim. Moreover, there were only 10 (8%) instances in which the claim was supported by an RCT with a low risk of bias. Of the 78 cited RCTs, only 14% had a low risk of bias, while 49% had an unclear risk and 37% had a high risk. A high proportion of advertisements failed to meet New Zealand regulatory requirements that claims "are valid and have been substantiated".

[Basic principles, planning and implementation of non-commercial clinical trials].

PubMed

Finger, R P; Coch, C; Coenen, M; Mengel, M; Hartmann, G; Holz, F G

2011-01-01

The proof of a drug's efficacy in randomized controlled trials is fundamental to therapeutic concepts determined by evidence-based medicine. Clinical trials according to the German Medicinal Products Act are performed by the pharmaceutical industry as company-sponsored trials (CST) driven by commercial interests or by non-commercial facilities as investigator-initiated trials (IIT), typically implemented by University Hospitals. In areas with no commercial interest, IITs are the driving force that generate scientific progress leading to treatment optimization. Therefore, non-commercial or investigator-initiated clinical trials are indispensable for improving medical care. To ensure the safety of trial participants and the quality of the data obtained, clinical trials are controlled by many legal regulations and internationally accepted quality standards. Therefore implementation of a clinical trial requires profound knowledge, qualified personnel, appropriate infrastructure, and substantial financial resources. In IITs unlike CSTs this has to be accomplished by the University without the assistance of the pharmaceutical industry. Since teaching of skills needed to perform clinical trials is still largely neglected in medical school and during residency this review addresses the (in clinical trials) inexperienced physician and outlines the characterization of a clinical trial, the range and division of responsibilities and the performance of clinical trials according to the German Medicinal Products Act.

Sri Lankan students campaign for rational medicine: the story of SIRHA.

PubMed

Ranwella, S

1993-01-01

Students Involved in Rational Health Activities (SIRHA) is a group of Sri Lankan medical students dedicated to increasing awareness of rational health care. SIRHA has hosted a seminar on rational therapeutics for medical students. Clinicians and academicians discussed case histories of inappropriate drug treatment at the seminar. A panel organized by the International Advertisers Association addressed the levels of control needed for medical drug advertising. Another seminar focused on how to facilitate the provision of low cost quality drugs based on rational prescriptions to all Sri Lankans. The Director-General of Health Services, the Chairman of the State Pharmaceuticals Corporation, and other government officials discussed drug registration, tenders, local manufacture of drugs, quality assurance, distribution, and pricing. At the annual meeting of the Sri Lankan Medical Association, SIRHA members prepared a leaflet comparing statements on promotional material of pharmaceutical companies with the text of internationally recognized standard works of reference. Company representatives were at the meeting. The Medical Lobby for Appropriate Marketing addressed one of the promotional materials in an August 1993 international letter. SIRHA members have also targeted irrational and misleading advertising of health-related products in the mass media. They have succeeded in bringing about the withdrawal of a misleading ad with unsubstantiated claims by a multinational company operating in Sri Lanka. SIRHA has submitted a complaint to the People's Tribunal on pharmaceutical pricing, unethical promotion, and the availability of an irrationally large number of me-too drugs in Sri Lanka. The Tribunal found the complaint justified and recommended the adoption of regulations proposed by SIRHA. SIRHA continues to monitor pharmaceutical advertising practices in Sri Lanka. It has established good relations with local and international groups.

Biomedical applications of a real-time terahertz color scanner

PubMed Central

Schirmer, Markus; Fujio, Makoto; Minami, Masaaki; Miura, Jiro; Araki, Tsutomu; Yasui, Takeshi

2010-01-01

A real-time THz color scanner has the potential to further expand the application scope of THz spectral imaging based on its rapid image acquisition rate. We demonstrated three possible applications of a THz color scanner in the biomedical field: imaging of pharmaceutical tablets, human teeth, and human hair. The first application showed the scanner’s potential in total inspection for rapid quality control of pharmaceutical tablets moving on a conveyor belt. The second application demonstrated that the scanner can be used to identify a potential indicator for crystallinity of dental tissue. In the third application, the scanner was successfully used to visualize the drying process of wet hairs. These demonstrations indicated the high potential of the THz color scanner for practical applications in the biomedical field. PMID:21258472

Managing laboratory automation in a changing pharmaceutical industry

PubMed Central

Rutherford, Michael L.

1995-01-01

The health care reform movement in the USA and increased requirements by regulatory agencies continue to have a major impact on the pharmaceutical industry and the laboratory. Laboratory management is expected to improve effciency by providing more analytical results at a lower cost, increasing customer service, reducing cycle time, while ensuring accurate results and more effective use of their staff. To achieve these expectations, many laboratories are using robotics and automated work stations. Establishing automated systems presents many challenges for laboratory management, including project and hardware selection, budget justification, implementation, validation, training, and support. To address these management challenges, the rationale for project selection and implementation, the obstacles encountered, project outcome, and learning points for several automated systems recently implemented in the Quality Control Laboratories at Eli Lilly are presented. PMID:18925014

[HERA-QUEST: HTA evaluation of generic pharmaceutical products to improve quality, economic efficiency, patient safety and transparency in drug product changes in hospitals].

PubMed

Gyalrong-Steur, Miriam; Kellermann, Anita; Bernard, Rudolf; Berndt, Georg; Bindemann, Meike; Nusser-Rothermundt, Elfriede; Amann, Steffen; Brakebusch, Myga; Brüggmann, Jörg; Tydecks, Eva; Müller, Markus; Dörje, Frank; Kochs, Eberhard; Riedel, Rainer

2017-04-01

In view of the rising cost pressure and an increasing number of drug shortages, switches between generic drug preparations have become a daily routine in hospitals. To ensure consistently high treatment quality and best possible patient safety, the equivalence of the new and the previous drug preparation must be ensured before any change in the purchase of pharmaceutical products takes place. So far, no easily usable, transparent and standardized instrument for this kind of comparison between generic drug products has been available. A group of pharmaceutical experts has developed the drug HTA (health technology assessment) model "HERA" (HTA Evaluation of geneRic phArmaceutical products) through a multi-step process. The instrument is designed to perform both a qualitative and economic comparison of equivalent drug preparations ("aut idem" substitution) before switching products. The economic evaluation does not only consider unit prices and consumption quantity, but also the processing costs associated with a product change process. The qualitative comparison is based on the evaluation of 34 quality criteria belonging to six evaluation fields (e.g., approval status, practical handling, packaging design). The objective evaluation of the quality criteria is complemented by an assessment of special features of the individual hospital for complex drug switches, including the feedback of the physicians utilizing the drug preparation. Thus potentially problematic switches of pharmaceutical products can be avoided at the best possible rate, contributing to the improvement of patient safety. The novel drug HTA model HERA is a tool used in clinical practice that can add to an increase in quality, therapeutic safety and transparency of drug use while simultaneously contributing to the economic optimization of drug procurement in hospitals. Combining these two is essential for hospitals facing the tension between rising cost pressure and at the same time increasing demands on quality and transparency, triggered by, amongst others, current legislation (Hospital Structures Act, anti-corruption legislation). Copyright © 2017. Published by Elsevier GmbH.

[Which one is more important, raw materials or productive technology?--a case study for quality consistency control of Gegen Qinlian decoction].

PubMed

Zhong, Wen; Chen, Sha; Zhang, Jun; Wang, Yu-Sheng; Liu, An

2016-03-01

To investigate the effect of Chinese medicine raw materials and production technology on quality consistency of Chinese patent medicines with Gegen Qinlian decoction as an example, and establish a suitable method for the quality consistency control of Chinese patent medicines. The results showed that the effect of production technology on the quality consistency was generally not more than 5%, while the effect of raw materials was even more than 30%, indicating that the effect of raw materials was much greater than that of the production technology. In this study, blend technology was used to improve the quality consistency of raw materials. As a result, the difference between the product produced by raw materials and reference groups was less than 5%, thus increasing the quality consistence of finished products. The results showed that under the current circumstances, the main factor affecting the quality consistency of Chinese patent medicines was raw materials, so we shall pay more attention to the quality of Chinese medicine's raw materials. Finally, a blend technology can improve the quality consistency of Chinese patent medicines. Copyright© by the Chinese Pharmaceutical Association.

Internet pharmaceutical sales: attributes, concerns, and future forecast.

PubMed

Bruckel, Katy; Capozzoli, Ernest A

2003-01-01

Internet pharmaceutical sales continue to skyrocket as healthcare providers and consumers are increasingly relying on the efficiencies and convenience that is available via such transactions. Managed care companies, increasing demands to reduce healthcare inefficiencies while maximizing the quality of patient care is a significant contributing factor to the expanding utilization and success of online pharmaceutical sales. However, with the expansion of Internet pharmaceutical sales, healthcare providers, pharmacy benefit management and insurance companies, and consumers realize new opportunities and risks. This paper will review the attributes and concerns associated with online pharmaceutical sales, discussing current and pending legislation intended to more effectively manage these parameters.

[Application of microscopic spectroscopy in quality control of Niuhuang Qingxin pills].

PubMed

Nie, Li-Xing; Zhang, Ye; Zhang, Nan-Ping; Hu, Xiao-Ru; Kang, Shuai; Hou, Jian-Zhong; Dai, Zhong; Ma, Shuang-Cheng

2016-10-01

Application of microscopic spectroscopy in quality control of Niuhuang Qingxin pills was discussed. First, microscopic characteristics specified by the statutory standard of Niuhuang Qingxin pills were summarized. Then new identification method was established for Dioscoreae Rhizoma, Saigae Tataricae Cornu, Cinnamomi Cortex and Saposhnikoviae Radix. Finally, microscopic spectroscopy was used for test of Dioscoreae Rhizoma's adulterant Dioscoreae Fordii Rhizoma.It was the first time for this technology being applied in adulteration test of Chinese patent medicine.The results showed that Saigae Tataricae Cornu was not detected in 2 batches of Niuhuang Qingxin pills from 1 manufacturer while Dioscoreae Fordii Rhizoma was detected in 3 batches of samples from 2 manufacturers. The proposed methods were accurate, simple, rapid, objective and economic, which offered a more comprehensive approach for quality control of Niuhuang Qingxin pills. It was indicated that conventional technology such as microscopic spectroscopy could play an important role in identification of traditional Chinese medicine whose index ingredient was deficient or tiny. Copyright© by the Chinese Pharmaceutical Association.

Quality control in the year 2000.

PubMed

Schade, B

1992-01-01

'Just-in-time' production is a prerequisite for a company to meet the challenges of competition. Manufacturing cycles have been so successfully optimized that release time now has become a significant factor. A vision for a major quality-control (QC) contribution to profitability in this decade seems to be the just-in-time release. Benefits will go beyond cost savings for lower inventory. The earlier detection of problems will reduce rejections and scrap. In addition, problem analysis and problem-solving will be easier. To achieve just-in-time release, advanced automated systems like robots will become the workhorses in QC for high volume pharmaceutical production. The requirements for these systems are extremely high in terms of quality, reliability and ruggedness. Crucial for the success might be advances in use of microelectronics for error checks, system recording, trouble shooting, etc. as well as creative new approaches (for example the use of redundant assay systems).

Quality control in the year 2000

PubMed Central

Schade, Bernd

1992-01-01

‘Just-in-time’ production is a prerequisite for a company to meet the challenges of competition. Manufacturing cycles have been so successfully optimized that release time now has become a significant factor. A vision for a major quality-control (QC) contribution to profitability in this decade seems to be the just-in-time release. Benefits will go beyond cost savings for lower inventory. The earlier detection of problems will reduce rejections and scrap. In addition, problem analysis and problem-solving will be easier. To achieve just-in-time release, advanced automated systems like robots will become the workhorses in QC for high volume pharmaceutical production. The requirements for these systems are extremely high in terms of quality, reliability and ruggedness. Crucial for the success might be advances in use of microelectronics for error checks, system recording, trouble shooting, etc. as well as creative new approaches (for example the use of redundant assay systems). PMID:18924930

A non-clinical randomised controlled trial to assess the impact of pharmaceutical care intervention on satisfaction level of newly diagnosed diabetes mellitus patients in a tertiary care teaching hospital in Nepal.

PubMed

Upadhyay, Dinesh Kumar; Mohamed Ibrahim, Mohamed Izham; Mishra, Pranaya; Alurkar, Vijay M

2015-02-12

Patient satisfaction is the ultimate goal of healthcare system which can be achieved from good patient-healthcare professional relationship and quality of healthcare services provided. Study was conducted to determine the baseline satisfaction level of newly diagnosed diabetics and to explore the impact of pharmaceutical care intervention on patients' satisfaction during their follow-ups in a tertiary care teaching hospital in Nepal. An interventional, pre-post non-clinical randomised controlled study was designed among randomly distributed 162 [control group (n = 54), test 1 group (n = 54) and test 2 group (n = 54)] newly diagnosed diabetes mellitus patients by consecutive sampling method for 18 months. Diabetes Patient Satisfaction Questionnaire was used to evaluate patient's satisfaction scores at baseline, three, six, nine and, twelve months' follow-ups. Test groups patients were provided pharmaceutical care whereas control group patients only received their usual care from physician/nurses. The responses were entered in SPSS version 16. Data distribution was not normal on Kolmogorov-Smirnov test. Non-parametric tests i.e. Friedman test, Mann-Whitney U test and Wilcoxon signed rank test were used to find the differences among the groups before and after the intervention (p ≤0.05). There were significant (p < 0.001) improvements in patients' satisfaction scores in the test groups on Friedman test. Mann-Whitney U test identified the significant differences in satisfaction scores between test 1 and test 2 groups, control and test 1 groups and, control and test 2 groups at 3-months (p = 0.008), (p < 0.001) and (p < 0.001), 6-months (p = 0.010), (p < 0.001) and (p < 0.001), 9-months (p < 0.001), (p < 0.001) and (p < 0.001) and, 12-months (p < 0.001), (p < 0.001) and (p < 0.001) follow-ups respectively. Pharmaceutical care intervention significantly improved the satisfaction level of diabetics in the test groups compare to the control group. Diabetic kit demonstration strengthened the satisfaction level among the test 2 group patients. Therefore, pharmacist can act as a counsellor through pharmaceutical care program and assist the patients in managing their disease. This will not only modify the patients' related outcomes and their level of satisfaction but also improve the healthcare system.

In-line monitoring of pellet coating thickness growth by means of visual imaging.

PubMed

Oman Kadunc, Nika; Sibanc, Rok; Dreu, Rok; Likar, Boštjan; Tomaževič, Dejan

2014-08-15

Coating thickness is the most important attribute of coated pharmaceutical pellets as it directly affects release profiles and stability of the drug. Quality control of the coating process of pharmaceutical pellets is thus of utmost importance for assuring the desired end product characteristics. A visual imaging technique is presented and examined as a process analytic technology (PAT) tool for noninvasive continuous in-line and real time monitoring of coating thickness of pharmaceutical pellets during the coating process. Images of pellets were acquired during the coating process through an observation window of a Wurster coating apparatus. Image analysis methods were developed for fast and accurate determination of pellets' coating thickness during a coating process. The accuracy of the results for pellet coating thickness growth obtained in real time was evaluated through comparison with an off-line reference method and a good agreement was found. Information about the inter-pellet coating uniformity was gained from further statistical analysis of the measured pellet size distributions. Accuracy and performance analysis of the proposed method showed that visual imaging is feasible as a PAT tool for in-line and real time monitoring of the coating process of pharmaceutical pellets. Copyright © 2014 Elsevier B.V. All rights reserved.

Development and validation of a capillary electrophoresis method for the determination of codeine, diphenhydramine, ephedrine and noscapine in pharmaceuticals.

PubMed

Gomez, María R; Sombra, Lorena; Olsina, Roberto A; Martínez, Luis D; Silva, María F

2005-01-01

The present work describes a simple, accurate and rapid method for the separation and simultaneous determination of codeine, diphenhydramine, ephedrine and noscapine present in cough-cold syrup formulations by capillary zone electrophoresis. Factors affecting the separation were the buffer pH and concentration, applied voltage, and presence of additives. Separations were carried out in less than 10 min with a 20 mM sodium tetraborate buffer, pH 8.50. The carrier electrolyte gave baseline separation with good resolution, great reproducibility and accuracy. Calibration plots were linear over at least three orders of magnitude of analyte concentrations, the lower limits of detection being within the range 0.42-1.33 microg ml(-1). Detection was performed by UV absorbance at wavelengths of 205 and 250 nm. Quantification of the components in actual syrup formulations was calculated against the responses of freshly prepared external standard solutions. The method was validated and met all analysis requirements of quality assurance and quality control. The procedure was fast and reliable and commercial pharmaceuticals could be analyzed without prior sample clean-up procedure.

Joint CDRH (Center for Devices and Radiological Health) and state quality-assurance surveys in nuclear medicine: Phase 2 - radiopharmaceuticals

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamilton, D.R.; Evans, C.D.

The report discusses survey results on aspects of the quality assurance of radio-pharmaceuticals from 180 nuclear-medicine facilities in the United States. Data were collected from facilities in 8 states. Demographic information about nuclear-medicine operations and quality-assurance programs was gathered by state radiation-control-program personnel. The data collected from the survey show an incomplete acceptance of quality-assurance practices for radiopharmaceuticals. Most of the facilities in the survey indicated that, because an inferior radiopharmaceutical was prepared so infrequently, they did not believe it was cost-effective to perform extensive quality-assurance testing. The Center for Devices and Radiological Health hopes that the information from themore » survey will stimulate nuclear-medicine professionals and their organizations to encourage appropriate testing of all radiopharmaceuticals.« less

Healthcare professionals' perceptions related to the provision of clinical pharmacy services in the public health sector of Mexico: a case study.

PubMed

Díaz de León-Castañeda, Christian; Gutiérrez-Godínez, Jéssica; Colado-Velázquez, Juventino Iii; Toledano-Jaimes, Cairo

2018-04-22

In Mexico, the Modelo Nacional de Farmacia Hospitalaria (MNFH, or National Hospital Pharmacy Model), published in 2009, mainly aims to promote the provision of clinical pharmacy services in private and public hospitals. However, there is little scientific documentation about the quality of these services. To explore healthcare professionals' perceptions related to the quality of clinical pharmacy services provision. A case-study based on a qualitative approach was performed at the pharmaceutical services unit at a public hospital located in Mexico City, which operates under the administrative control of the Ministry of Health. Donabedian's conceptual model was adapted to explore health care professionals' perceptions of the quality of clinical pharmacy services provision. Semi-structured interviews were carried out with pharmacists, physicians and nurses and then transcribed and analyzed via discourse analysis and codification techniques, using the software package Atlas. ti. Limitations in pharmaceutical human resources were identified as the main factor affecting coverage and quality in clinical pharmacy services provision. However, the development in pharmacy staff of technical competences and skills for clinical pharmacy service provision were recognized. Significant improvements in the rational use of medicines were associated with clinical pharmacy services provision. The perception analysis performed in this study suggested that it is necessary to increase pharmacy staff in order to improve interprofessional relationships and the quality of clinical pharmacy services provision. Copyright © 2018 Elsevier Inc. All rights reserved.

Managing the interface with marketing to improve delivery of pharmacovigilance within the pharmaceutical industry.

PubMed

Edwards, Brian

2004-01-01

The pharmaceutical industry is under pressure to improve the scientific quality of its decisions concerning the benefit and risks of its products while ensuring compliance with acceptable standards of marketing. All those in a pharmaceutical company who currently work within pharmacovigilance should be encouraged to lead from the front to examine ongoing marketing activities to see how they can be adapted more towards pharmacovigilance and risk management. The current irony is that the personnel who have the greatest influence on benefit-risk decisions of a product are not necessarily those who acknowledge that they are performing pharmacovigilance. Indeed, for all concerned, whether their orientation is scientific and commercial, effective communication with prescribers and consumers usually underpins product success. Also, a substantial 'marketing' budget is culturally acceptable for the pharmaceutical industry so it is logical to assume that resource for postmarketing activity is often made available. Given these realities, I suggest we should strive for an integrated marketing and risk-management plan based on the best available evidence and that being fully aware and in control of the safety issues for your products is the best way to commercialise them successfully. This approach can still be consistent with other corporate responsibilities such as trying to reduce the financial burden of product development. If this article stimulates further debate about how the pharmaceutical industry can more effectively organise resources and operations to support pharmacovigilance, risk management, and marketing, then it will have achieved its purpose.

Development and validation of an ICP-MS method for the determination of elemental impurities in TP-6076 active pharmaceutical ingredient (API) according to USP 〈232〉/〈233〉.

PubMed

Chahrour, Osama; Malone, John; Collins, Mark; Salmon, Vrushali; Greenan, Catherine; Bombardier, Amy; Ma, Zhongze; Dunwoody, Nick

2017-10-25

The new guidelines of the United States pharmacopeia (USP), European pharmacopeia (EP) and international conference on harmonization (ICH) regulating elemental impurities limits in pharmaceuticals signify the end of unspecific analysis of metals as outlined in USP 〈231〉. The new guidelines specify both daily doses and concentration/limits of elemental impurities in pharmaceutical final products, active pharmaceutical ingredients (API) and excipients. In chapter USP 〈233〉 method implementation, validation and quality control during the analytical process are described. We herein report the use of a stabilising matrix that overcomes low spike recovery problem encountered with Os and allows the determination of all USP required elemental impurities (As, Cd, Hg, Pb, V, Cr, Ni, Mo, Cu, Pt, Pd, Ru, Rh, Os and Ir) in a single analysis. The matrix was used in the validation of a method to determine elemental impurities in TP-6076 active pharmaceutical ingredient (API) by ICP-MS according to the procedures defined in USP〈233〉 and to GMP requirements. This validation will support the regulatory submission of TP-6076 which is a novel tetracycline analogue effective against the most urgent multidrug-resistant gram-negative bacteria. Evaluation of TP-6076 in IND-enabling toxicology studies has led to the initiation of a phase 1 clinical trial. Copyright © 2017 Elsevier B.V. All rights reserved.

Medicine and pharmacy--facts and myths about the development of an innovative pharmaceutical industry in Poland.

PubMed

Kubiak, Włodzimierz

2005-01-01

Innovation is fundamental to the pharmaceutical industry and a key to improvements in healthcare. Its effectiveness depends on huge, constant investments in research. This innovative industry directly affects the course of studies in healthcare and medicine. Its efforts translate directly into the length and quality of our lives. For several years now, the progress underway in pharmaceutical industry has produced measurable benefits. Doctors have new pharmaceuticals at their disposal, including many types of antibiotics and anti-viral drugs, vaccines and a wide range of drugs which save lives or make them more comfortable. In the near future, ever more efficient cures for neoplastic, rheumatic, neurological, psychic, metabolic, circulatory or respiratory diseases can be expected. Innovation is necessary. The human population is ageing, and the task of an innovative pharmaceutical industry is to keep it in a good condition. The use of innovative drugs can translate directly into lowering the costs of illness. A continuous reduction in spending on healthcare has been observed. The costs of inventing an innovative drug are enormous though (US dollar 800 million), and studies on a new drug last between 10 and 13 years. An essential element in recovering the incurred costs and ensuring funds needed for new research is protection by patent. Innovative pharmaceutical companies in Poland are committed to increasing the competitiveness and sustaining the development of not only the market, but also the entire pharmaceutical sector. It is a group of companies of crucial importance to the Polish healthcare system, as it influences improvement in the quality of medical services. Through their investments and spending on research and development, innovative companies accelerate economic growth. In Poland, the innovative pharmaceutical industry is represented by the Association of Pharmaceutical Companies Representatives in Poland (SPFFwP).

In-line and Real-time Monitoring of Resonant Acoustic Mixing by Near-infrared Spectroscopy Combined with Chemometric Technology for Process Analytical Technology Applications in Pharmaceutical Powder Blending Systems.

PubMed

Tanaka, Ryoma; Takahashi, Naoyuki; Nakamura, Yasuaki; Hattori, Yusuke; Ashizawa, Kazuhide; Otsuka, Makoto

2017-01-01

Resonant acoustic ® mixing (RAM) technology is a system that performs high-speed mixing by vibration through the control of acceleration and frequency. In recent years, real-time process monitoring and prediction has become of increasing interest, and process analytical technology (PAT) systems will be increasingly introduced into actual manufacturing processes. This study examined the application of PAT with the combination of RAM, near-infrared spectroscopy, and chemometric technology as a set of PAT tools for introduction into actual pharmaceutical powder blending processes. Content uniformity was based on a robust partial least squares regression (PLSR) model constructed to manage the RAM configuration parameters and the changing concentration of the components. As a result, real-time monitoring may be possible and could be successfully demonstrated for in-line real-time prediction of active pharmaceutical ingredients and other additives using chemometric technology. This system is expected to be applicable to the RAM method for the risk management of quality.

Direct Determination of ECD in ECD Kit: A Solid Sample Quantitation Method for Active Pharmaceutical Ingredient in Drug Product

PubMed Central

Chao, Ming-Yu; Liu, Kung-Tien; Hsia, Yi-Chih; Liao, Mei-Hsiu; Shen, Lie-Hang

2011-01-01

Technetium-99m ethyl cysteinate dimer (Tc-99m-ECD) is an essential imaging agent used in evaluating the regional cerebral blood flow in patients with cerebrovascular diseases. Determination of active pharmaceutical ingredient, that is, L-Cysteine, N, N′-1,2-ethanediylbis-, diethyl ester, dihydrochloride (ECD) in ECD Kit is a relevant requirement for the pharmaceutical quality control in processes of mass fabrication. We here presented a direct solid sample determination method of ECD in ECD Kit without sample dissolution to avoid the rapid degradation of ECD. An elemental analyzer equipped with a nondispersive infrared detector and a calibration curve of coal standard was used for the quantitation of sulfur in ECD Kit. No significant matrix effect was found. The peak area of coal standard against the amount of sulfur was linear over the range of 0.03–0.10 mg, with a correlation coefficient (r) of 0.9993. Method validation parameters were achieved to demonstrate the potential of this method. PMID:21687539

[The pharmaceutical industry and the sustainability of healthcare systems in developed countries and in Latin America].

PubMed

Iñesta, Antonio; Oteo, Luis Angel

2011-06-01

The global economic crisis and its impact on public finances in most developed countries are giving rise to cost-containment policies in healthcare systems. Prevailing legislation on medication requires the safety, quality, and efficacy of these products. A few countries include efficiency criteria, primarily for new medication that they wish to include in public financing. The appropriate use of generic and "biosimilar medication" is very important for maintaining the financial equilibrium of the Health Services. The problem in Latin America is that not all multisource products are bioequivalent and not all countries have the resources to conduct bioequivalence studies in vivo. The European Medicines Agency in 2005 adopted guidelines on "biosimilar medicines" and thirteen of them were subsequently approved for general release. Benchmarking of this model by other countries would be important. The influence of the pharmaceutical industry on political and administrative areas is enormous and control is necessary. The pharmaceutical companies claim that they act with corporate social responsibility, therefore, they must ensure this responsibility toward society.

Development and validation of simple spectrophotometric and chemometric methods for simultaneous determination of empagliflozin and metformin: Applied to recently approved pharmaceutical formulation

NASA Astrophysics Data System (ADS)

Ayoub, Bassam M.

2016-11-01

New univariate spectrophotometric method and multivariate chemometric approach were developed and compared for simultaneous determination of empagliflozin and metformin manipulating their zero order absorption spectra with application on their pharmaceutical preparation. Sample enrichment technique was used to increase concentration of empagliflozin after extraction from tablets to allow its simultaneous determination with metformin without prior separation. Validation parameters according to ICH guidelines were satisfactory over the concentration range of 2-12 μg mL- 1 for both drugs using simultaneous equation with LOD values equal to 0.20 μg mL- 1 and 0.19 μg mL- 1, LOQ values equal to 0.59 μg mL- 1 and 0.58 μg mL- 1 for empagliflozin and metformin, respectively. While the optimum results for the chemometric approach using partial least squares method (PLS-2) were obtained using concentration range of 2-10 μg mL- 1. The optimized validated methods are suitable for quality control laboratories enable fast and economic determination of the recently approved pharmaceutical combination Synjardy® tablets.

78 FR 46372 - Manufacturer of Controlled Substances; Notice of Application; Apertus Pharmaceuticals

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Apertus Pharmaceuticals Pursuant to Sec. 1301.33(a), Title 21 of the Code of Federal Regulations (CFR), this is notice that on June 14, 2013, Apertus Pharmaceuticals, 331 Consort...

77 FR 67676 - Manufacturer of Controlled Substances; Notice of Application; Cedarburg Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-13

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Cedarburg Pharmaceuticals, Inc. Pursuant to Sec. 1301.33(a), of Title 21 of the Code of Federal Regulations (CFR), this is notice that on September 21, 2012, Cedarburg Pharmaceuticals...

Self-care Improvement After a Pharmaceutical Intervention in Elderly Type 2 Diabetic Patients.

PubMed

Nascimentoa, Tania; Braz, Nídia; Gomes, Eurico; Fernandez-Arche, Angeles; De La Puerta, Rocio

2015-01-01

Diabetes mellitus involves long-term complications that affect diabetic patients' quality of life. The best way to prevent these complications is that patients achieve good metabolic control. In order to reach this goal, patients are requested to acquire daily behaviours (self-care). Such behaviours are sometimes hard to adhere, because they require changes in habits acquired over time. The aim of the present study is to evaluate the improvement on self-care after a pharmaceutical intervention on home regime patients. We performed a controlled experimental comparative study with a follow up of 6 months, on 87 patients, randomized in control group (n=43) and intervention group (n=44). We accessed sociodemographic and clinical data (glycaemic profile), as well as adherence to drug therapy and self-assessed care (before/after). In the intervention group, mean age was 74.2±5.4 years, and the median time of T2DM diagnosis was 14.7±8.5 years. At the end of study, the decrease in fasting blood glucose was higher in the intervention group patients than that observed in the control group (50.2mg/dL), with statistically significant difference (p<0.05), as well as the decrease verified in HbA1c. In self-care adherence, alterations in the levels of adherence of the general nutrition and physical exercise dimensions became evident, with an increase in the number of days of adherence. On medication adherence statistically significant alterations (p<0.05) were also recorded. We can conclude that an individualized pharmaceutical intervention can improve self-care behaviours, as well as medication adherence, contributing to better metabolic control.

Framework for industry engagement and quality principles for industry-provided medical education in Europe.

PubMed

Allen, Tamara; Donde, Nina; Hofstädter-Thalmann, Eva; Keijser, Sandra; Moy, Veronique; Murama, Jean-Jacques; Kellner, Thomas

2017-01-01

Lifelong learning through continuing professional development (CPD) and medical education is critical for healthcare professionals to stay abreast of knowledge and skills and provide an optimal standard of care to patients. In Europe, CPD and medical education are fragmented as there are numerous models, providers and national regulations and a lack of harmonisation of qualitative criteria. There is continued debate on the appropriate role of pharmaceutical companies in the context of medical education. Accrediting bodies such as European Accreditation Council for Continuing Medical Education do not permit active involvement of the pharmaceutical industry due to concerns around conflicts of interest and potential for bias. However, many examples of active collaboration between pharmaceutical companies and medical societies and scientific experts exist, demonstrating high integrity, clear roles and responsibilities, and fair and balanced content. Medical education experts from 16 pharmaceutical companies met to develop a set of quality principles similar to standards that have been established for clinical trials and in alignment with existing principles of accrediting bodies. This paper outlines their proposal for a framework to improve and harmonise medical education quality standards in Europe, and is also an invitation for all stakeholders to join a discussion on this integrative model.

Causes of drug shortages in the legal pharmaceutical framework.

PubMed

De Weerdt, Elfi; Simoens, Steven; Hombroeckx, Luc; Casteels, Minne; Huys, Isabelle

2015-03-01

Different causes of drug shortages can be linked to the pharmaceutical legal framework, such as: parallel trade, quality requirements, economic decisions to suspend or cease production, etc. However until now no in-depth study of the different regulations affecting drug shortages is available. The aim of this paper is to provide an analysis of relevant legal and regulatory measures in the European pharmaceutical framework which influence drug shortages. Different European and national legislations governing human medicinal products were analyzed (e.g. Directive 2001/83/EC and Directive 2011/62/EU), supplemented with literature studies. For patented drugs, external price referencing may encompass the largest impact on drug shortages. For generic medicines, internal or external reference pricing, tendering as well as price capping may affect drug shortages. Manufacturing/quality requirements also contribute to drug shortages, since non-compliance leads to recalls. The influence of parallel trade on drug shortages is still rather disputable. Price and quality regulations are both important causes of drug shortages or drug unavailability. It can be concluded that there is room for improvement in the pharmaceutical legal framework within the lines drawn by the EU to mitigate drug shortages. Copyright © 2015 Elsevier Inc. All rights reserved.

Diffractive optical element in materials testing

NASA Astrophysics Data System (ADS)

Silvennoinen, Raimo V. J.; Peiponen, Kai-Erik

1998-09-01

The object of this paper is to present a sensor based on diffractive optics that can be applied for the materials testing. The present sensor, which is based on the use of a computer-generated hologram (CGH) exploits the holographic imagery. The CGH-sensor was introduced for inspection of surface roughness and flatness of metal surfaces. The results drawn out by the present sensor are observed to be in accordance with the experimental data. Together with the double exposure holographic interferometry (DEHI) and digital electronic speckle pattern interferometry (DSPI) in elasticity inspection, the sensor was applied for the investigations of surface quality of opaque fragile materials, which are pharmaceutical compacts. The optical surface quality was observed to be related to the porosity of the pharmaceutical tablets. The CGH-sensor was also applied for investigations of optical quality of thin films as PLZT ceramics and coating of pharmaceutical compacts. The surfaces of PLZT samples showed fluctuations in optical curvature, and wedgeness for all the cases studied. For pharmaceutical compacts, the optical signals were observed to depend to a great extent on the optical constants of the coatings and the substrates, and in addition to the surface porosity under the coating.

Pharmaceutical innovation: impact on expenditure and outcomes and subsequent challenges for pharmaceutical policy, with a special reference to Greece.

PubMed

Karampli, E; Souliotis, K; Polyzos, N; Kyriopoulos, J; Chatzaki, E

2014-04-01

Over the recent decades, advances in healthcare technology have led to significant improvements in the quality of healthcare and in population health. At the same time, technological change in healthcare, rising national income and expansion of insurance coverage have been acknowledged as the main determinants of the historical growth in health spending in industrialized countries. The pharmaceutical sector is of particular interest as it constitutes a market characterized by rapid technological change and high expenditure growth rates. The purpose of this article is to provide an overview of research findings on the impact of pharmaceutical innovation on pharmaceutical expenditure growth, total health expenditure and population health outcomes and to bring forward the challenges that arise for pharmaceutical policy in Greece.

78 FR 64017 - Manufacturer of Controlled Substances; Notice of Application; Cedarburg Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-25

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Cedarburg Pharmaceuticals, Inc. Pursuant to Sec. 1301.33(a), of Title 21 of the Code of Federal Regulations (CFR), this is notice that on May 8, 2013, Cedarburg Pharmaceuticals, Inc...

78 FR 15975 - Manufacturer of Controlled Substances, Notice of Registration; Johnson Matthey, Inc...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-13

..., Notice of Registration; Johnson Matthey, Inc., Pharmaceuticals Materials By Notice dated November 1, 2012...., Pharmaceuticals Materials, 900 River Road, Conshohocken, Pennsylvania 19428, made application by renewal to the...., Pharmaceuticals Materials to manufacture the listed basic classes of controlled substances is consistent with the...

78 FR 19016 - Manufacturer of Controlled Substances; Notice of Application; Patheon Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-28

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Patheon Pharmaceuticals, Inc. Pursuant to Sec. 1301.33(a), Title 21 of the Code of Federal Regulations (CFR), this is notice that on February 22, 2013, Patheon Pharmaceuticals, Inc., 2110 E...

78 FR 17231 - Manufacturer of Controlled Substances; Notice of Application: Morton Grove Pharmaceuticals

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-20

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application: Morton Grove Pharmaceuticals Pursuant to Sec. 1301.33(a), Title 21 of the Code of Federal Regulations (CFR), this is notice that on December 14, 2012, Morton Grove Pharmaceuticals, 6451...

77 FR 60144 - Manufacturer of Controlled Substances; Notice of Application; Morton Grove Pharmaceuticals

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-02

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Morton Grove Pharmaceuticals Pursuant to 1301.33(a), Title 21 of the Code of Federal Regulations (CFR), this is notice that on July 12, 2012, Morton Grove Pharmaceuticals, 6451 Main...

77 FR 12620 - Importer of Controlled Substances, Notice of Application, Mylan Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-01

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer of Controlled Substances, Notice of Application, Mylan Pharmaceuticals, Inc. Pursuant to 21 U.S.C. 958(i), the Attorney General shall, prior to... on December 30, 2011, Mylan Pharmaceuticals, Inc., 781 Chestnut Ridge Road, Morgantown, West Virginia...

78 FR 69133 - Manufacturer of Controlled Substances; Notice of Application; Morton Grove Pharmaceuticals

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-18

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Morton Grove Pharmaceuticals Pursuant to Sec. 1301.33(a), Title 21 of the Code of Federal Regulations (CFR), this is notice that on October 7, 2013, Morton Grove Pharmaceuticals, 6451 Main...

77 FR 35058 - Manufacturer of Controlled Substances; Notice of Application; Apertus Pharmaceuticals, LLC

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-12

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Apertus Pharmaceuticals, LLC Pursuant to Sec. 1301.33(a), Title 21 of the Code of Federal Regulations (CFR), this is notice that on March 27, 2012, Apertus Pharmaceuticals, LLC, 331...

78 FR 12101 - Importer of Controlled Substances; Notice of Application; Meda Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-21

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer of Controlled Substances; Notice of Application; Meda Pharmaceuticals, Inc. Pursuant to Title 21 Code of Federal Regulations 1301.34 (a), this is notice that on December 4, 2012, Meda Pharmaceuticals, Inc., 705 Eldorado Street, Decatur, Illinois 62523...

78 FR 39336 - Importer of Controlled Substances; Notice of Application; Mylan Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-01

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer of Controlled Substances; Notice of Application; Mylan Pharmaceuticals, Inc. Pursuant to Title 21 Code of Federal Regulations 1301.34 (a), this is notice that on March 8, 2013, Mylan Pharmaceuticals, Inc., 3711 Collins Ferry Road, Morgantown, West...

78 FR 51210 - Manufacturer of Controlled Substances; Notice of Application; Halo Pharmaceutical, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-20

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Halo Pharmaceutical, Inc. Pursuant to Sec. 1301.33(a), Title 21 of the Code of Federal Regulations (CFR), this is notice that on July 8, 2013, Halo Pharmaceutical, Inc., 30 North...

77 FR 67398 - Manufacturer of Controlled Substances; Notice of Application; INB Hauser Pharmaceutical Services...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-09

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; INB Hauser Pharmaceutical Services, Inc. Pursuant to Sec. 1301.33(a), Title 21 of... Pharmaceutical Services, Inc., 6880 N. Broadway, Suite H, Denver, Colorado 80221, made application by letter to...

78 FR 12101 - Importer of Controlled Substances; Notice of Application; Caraco Pharmaceutical Laboratories, LTD.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-21

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Importer of Controlled Substances; Notice of Application; Caraco Pharmaceutical Laboratories, LTD. Pursuant to Title 21 Code of Federal Regulations 1301.34 (a), this is notice that on November 22, 2012, Caraco Pharmaceutical Laboratories, Ltd., 270 Prospect...

77 FR 47114 - Manufacturer of Controlled Substances; Notice of Application; Halo Pharmaceutical Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-07

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application; Halo Pharmaceutical Inc. Pursuant to Sec. 1301.33(a), Title 21 of the Code of Federal Regulations (CFR), this is notice that on July 6, 2012, Halo Pharmaceutical Inc., 30 North...

75 FR 15642 - Schedules of Controlled Substances: Exempted Prescription Product; River Edge Pharmaceutical...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-30

... 1117-AB28 Schedules of Controlled Substances: Exempted Prescription Product; River Edge Pharmaceutical... new applications for exemption. DEA has received one new application for exemption for River Edge... application for exemption pursuant to the provisions of 21 CFR 1308.32 for: River Edge Pharmaceutical's...

Integrated LC-MS/MS Analytical Systems and Physical Inspection for the Analysis of a Botanical Herbal Preparation.

PubMed

Lai, Kuan-Ming; Cheng, Yung-Yi; Tsai, Tung-Hu

2015-06-09

The herbal decoction process is generally inconvenient and unpleasant. To avoid using herbal medicine decoctions, various high-quality industrial and pharmaceutical herbal decoction products have been used in clinical applications for more than ten years in Taiwan. However, the consistency and standardization of the quality of these herbal medicines are goals that remain to be achieved. The aim of study was to develop a validated liquid chromatography-tandem electrospray ionization mass spectrometry (LC-MS/MS) method to determine the biomarkers astragaloside I, astragaloside IV, formononetin, cinnamic acid, paeoniflorin and gingerol in the herbal preparation known as Huangqi-Guizhi-Wuwu (HGW). To investigate the physical quality of HGW, methods such as scanning electron microscopy, light microscopy with Congo red and potassium iodine staining, solubility measurements, swelling power tests, and crude fiber analysis were used to identify additives in commercial pharmaceutical products. The optimal LC-MS/MS multiple reaction-monitoring system included a gradient program using 5 mM ammonium acetate buffer with 0.05% formic acid/methanol. The results demonstrate deviations in biomarker content across different brands. In addition to the herbal extract, starch and excipients in the pharmaceutical granule, and crushed crude herb powder was added to the pharmaceutical products to increase their herbal ingredient content. In conclusion, a rigorous examination should be performed to certify the quality of the herbal products.

[The Destruction of Pharmaceutical Products as an Element of the Efficiency of State Control (Supervision) Over the Circulation of Medicines].

PubMed

Bidarova, F N

2015-01-01

The modern system of state quality control over medicine makes it possible to reveal and withdraw drugs, that do not meet the requirements. However the problem of the turnover of substandard andfake drug and their destruction in the Russian Federation is still urgent. to evaluate the effectiveness of state quality control over medicine and the practice offake medicine destruction. data of the official websites of the Ministry of Health of the Russian Federation and the Republic of North Ossetia--Alania, Russian Sanitary Inspection, National Center of Quality control and Certification of Drugs were included in the investigation. Method of unrepeated samples was used in sociological investigations. 225 questionnaires have been worked out. The research was carried out in the North-Ossetian State Medical academy during the periodfrom 2013 to 2015 with the help of the National Center of Quality Control and Certification of Drugs. The shortcomings of the state quality control over the rules of fake drug destruction were studied. It was found out that the mechanism ofpermanent data collection monitoring of revealing, moving and destruction of substandard and fake drug destruction has not been determined. The ineffectiveness of controlling measures under the condition of critical legal base deficiency has been confirmed. The analysis of terminology characterizing the order of fake drug destruction was carried out. deficiencies related to the implementation of the state quality control over the fake drug destruction rules revealed during the course of investigations prove the necessity of adopting measures in creating new model of controlfunctions, increasing the results of activity.

Analysis of Sheng-Mai-San, a Ginseng-Containing Multiple Components Traditional Chinese Herbal Medicine Using Liquid Chromatography Tandem Mass Spectrometry and Physical Examination by Electron and Light Microscopies.

PubMed

Cheng, Yung-Yi; Tsai, Tung-Hu

2016-09-01

Sheng-Mai-San is a multi-component traditional Chinese herbal preparation. Due to the fact granulated additives, such as starch, carboxymethyl cellulose, lactose and raw herbal powder may alter the content of the bioactive markers in the herbal products, a developed ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was used to measure the herbal biomarkers of ginsenoside Rb₁, Rb₂, Rc, Rd, Re, Rg₁, Rh₁, compound K, ophiopogonin D and schizandrin from the Sheng-Mai-San herbal formulation. Besides, scanning electron microscopy (SEM) was used to observe the morphology of the herbal granular powders. Light microscopy with Congo red and iodine-KI reagent staining was used to identify the cellulose fiber and cornstarch added to pharmaceutical herbal products. The swelling power (SP), water solubility index (WSI), and crude fiber analysis were used to determine the contents of cellulose fiber and cornstarch in pharmaceutical herbal products. In this study, we developed a novel skill to assess the quantification of appended cornstarch in pharmaceutical herbal products using Aperio ImageScope software. Compared with the traditional cornstarch analysis, our analysis method is a rapid, simple and conversion process which could be applied to detect the percentage of added cornstarch in unknown powder products. The various range of the herbal content for the five pharmaceutical manufacturers varied by up to several hundreds-fold. The physical examination reveals that the morphology of the herbal pharmaceutical products is rough and irregular with sharp layers. This study provides a reference standard operating procedure guide for the quality control of the Chinese herbal pharmaceutical products of Sheng-Mai-San.

Why trash don't pass? pharmaceutical licensing and safety performance of drugs.

PubMed

Banerjee, Tannista; Nayak, Arnab

2017-01-01

This paper examines how asymmetric information in pharmaceutical licensing affects the safety standards of licensed drugs. Pharmaceutical companies often license potential drug molecules at different stages of drug development from other pharmaceutical or biotechnology companies and complete the remaining of research stages before submitting the new drug application(NDA) to the food and drug administration. The asymmetric information associated with the quality of licensed molecules might result in the molecules which are less likely to succeed to be licensed out, while those with greater potential of success being held internally for development. We identify the NDAs submitted between 1993 and 2004 where new molecular entities were acquired through licensing. Controlling for other drug area specific and applicant firm specific factors, we investigate whether drugs developed with licensed molecules face higher probability of safety based recall and ultimate withdrawal from the market than drugs developed internally. Results suggest the opposite of Akerlof's (Q J Econ 84:488-500, 1970) lemons problem. Licensed molecules rather have less probability of facing safety based recalls and ultimate withdrawal from the market comparing to internally developed drug molecules. This suggests that biotechnology and small pharmaceutical firms specializing in pharmaceutical research are more efficient in developing good potential molecules because of their concentrated research. Biotechnology firms license out good potential molecules because it increases their market value and reputation. In addition, results suggest that both the number of previous approved drugs in the disease area, and also the applicant firms' total number of previous approvals in all disease areas reduce the probability that an additional approved drug in the same drug area will potentially be harmful.

Quantitative Microbial Risk Assessment of Pharmaceutical Products.

PubMed

Eissa, Mostafa Essam

2017-01-01

Monitoring of microbiological quality in the pharmaceutical industry is an important criterion that is required to justify safe product release to the drug market. Good manufacturing practice and efficient control on bioburden level of product components are critical parameters that influence the microbiological cleanliness of medicinal products. However, because microbial dispersion through the samples follows Poisson distribution, the rate of detection of microbiologically defective samples lambda (λ) decreases when the number of defective units per batch decreases. When integrating a dose-response model of infection (P inf ) of a specific objectionable microbe with a contamination module, the overall probability of infection from a single batch of pharmaceutical product can be estimated. The combination of P inf with detectability chance of the test (P det ) will yield a value that could be used as a quantitative measure of the possibility of passing contaminated batch units of product with a certain load of a specific pathogen and infecting the final consumer without being detected in the firm. The simulation study can be used to assess the risk of contamination and infection from objectionable microorganisms for sterile and non-sterile products. LAY ABSTRACT: Microbial contamination of pharmaceutical products is a global problem that may lead to infection and possibly death. While reputable pharmaceutical companies strive to deliver microbiologically safe products, it would be helpful to apply an assessment system for the current risk associated with pharmaceutical batches delivered to the drug market. The current methodology may be helpful also in determining the degree of improvement or deterioration on the batch processing flow until reaching the final consumer. Moreover, the present system is flexible and can be applied to other industries such as food, cosmetics, or medical devices manufacturing and processing fields to assess the microbiological risk of the processed and manufactured batch. © PDA, Inc. 2017.

Advances and new directions in crystallization control.

PubMed

Nagy, Zoltan K; Braatz, Richard D

2012-01-01

The academic literature on and industrial practice of control of solution crystallization processes have seen major advances in the past 15 years that have been enabled by progress in in-situ real-time sensor technologies and driven primarily by needs in the pharmaceutical industry for improved and more consistent quality of drug crystals. These advances include the accurate measurement of solution concentrations and crystal characteristics as well as the first-principles modeling and robust model-based and model-free feedback control of crystal size and polymorphic identity. Research opportunities are described in model-free controller design, new crystallizer designs with enhanced control of crystal size distribution, strategies for the robust control of crystal shape, and interconnected crystallization systems for multicomponent crystallization.

Quality of 99mTcO4- from 99Mo Produced by 100Mo(n,2n)99Mo

NASA Astrophysics Data System (ADS)

Nagai, Yasuki; Nakahara, Yuto; Kawabata, Masako; Hatsukawa, Yuichi; Hashimoto, Kazuyuki; Saeki, Hideya; Motoishi, Shoji; Ohta, Akio; Shiina, Takayuki; Kawauchi, Yukimasa

2017-05-01

The pharmaceutical quality of 99mTc pertechnetate solution obtained from 99Mo, the 100Mo(n,2n) reaction product, was investigated for the first time with an emphasis on the nonradioactive Mo content and endotoxin concentration. They were less than the tolerance dose given in international guidelines and the established upper limit in an international pharmacopoeia, respectively. Four other quality control tests commonly used for a commercially available 99mTc pertechnetate solution also demonstrated to meet the United States Pharmacopeia requirements. The results strongly support that the thermochromatographic separation method used to separate 99mTc from 99Mo can be a promising substitute for the fission product 99Mo.

Quality control: can compounding pharmacy learn from the automotive industry?

PubMed

Dillon, L Rad

2014-01-01

The healthcare system is vast in scope, with constant concerns of how the system's major changes will affect the quality of future patient care. This article concerns only one small corner of the healthcare system--pharmaceutical compounding. Despite our best efforts, we are not going to single-handedly change all of the grim statistics, no matter how many years we are given or how much assistance Americans obtain from their international colleagues. Yet, the "good" news is that although in my opinion the overall quality of America's healthcare system has declined, perhaps the modest niche of compounding pharmacy can become a role model of what actually works and can offer immense opportunities to improve the efficiency and effectiveness of health care.

Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets.

PubMed

Fonteyne, Margot; Wickström, Henrika; Peeters, Elisabeth; Vercruysse, Jurgen; Ehlers, Henrik; Peters, Björn-Hendrik; Remon, Jean Paul; Vervaet, Chris; Ketolainen, Jarkko; Sandler, Niklas; Rantanen, Jukka; Naelapää, Kaisa; De Beer, Thomas

2014-07-01

Continuous manufacturing gains more and more interest within the pharmaceutical industry. The International Conference of Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product performance over a range of raw material attributes, manufacturing process options and process parameters. This fits further into the Process Analytical Technology (PAT) and Quality by Design (QbD) framework. The present study evaluates the effect of variation in critical raw material properties on the critical quality attributes of granules and tablets, produced by a continuous from-powder-to-tablet wet granulation line. The granulation process parameters were kept constant to examine the differences in the end product quality caused by the variability of the raw materials properties only. Theophylline-Lactose-PVP (30-67.5-2.5%) was used as model formulation. Seven different grades of theophylline were granulated. Afterward, the obtained granules were tableted. Both the characteristics of granules and tablets were determined. The results show that differences in raw material properties both affect their processability and several critical quality attributes of the resulting granules and tablets. Copyright © 2014 Elsevier B.V. All rights reserved.

Factors to consider in developing individual pharmaceutical product quality risk profiles useful to government procurement agencies

PubMed Central

Xu, Wei; Boehm, Garth; Zheng, Qiang

2015-01-01

Governments that procure pharmaceutical products from an Essential Medicine List (EML) bear special responsibility for the quality of these products. In this article we examine the possibility of developing a pharmaceutical product quality risk assessment scheme for use by government procurement officials. We use the Chinese EML as a basis, and US recall data is examined as it is publically available.This is justified as the article is only concerned with inherent product quality risks. After establishing a link between Chinese essential medicines and those available in the US, we examine US recall data to separate product specific recalls. We conclude that, in addition to existing manufacturing based risks, there are two other product specific risks that stand out from all others, degradation and dissolution failure. Methodology for relative product risk for degradation is needed to be developed and further work is required to better understand dissolution failures which largely occur with modified-release solid oral products. We conclude that a product specific quality risk profile would be enhanced by including a risk assessment for degradation for all products, and in the case of solid oral products, dissolution. PMID:26904402

Factors to consider in developing individual pharmaceutical product quality risk profiles useful to government procurement agencies.

PubMed

Xu, Wei; Boehm, Garth; Zheng, Qiang

2016-01-01

Governments that procure pharmaceutical products from an Essential Medicine List (EML) bear special responsibility for the quality of these products. In this article we examine the possibility of developing a pharmaceutical product quality risk assessment scheme for use by government procurement officials. We use the Chinese EML as a basis, and US recall data is examined as it is publically available.This is justified as the article is only concerned with inherent product quality risks. After establishing a link between Chinese essential medicines and those available in the US, we examine US recall data to separate product specific recalls. We conclude that, in addition to existing manufacturing based risks, there are two other product specific risks that stand out from all others, degradation and dissolution failure. Methodology for relative product risk for degradation is needed to be developed and further work is required to better understand dissolution failures which largely occur with modified-release solid oral products. We conclude that a product specific quality risk profile would be enhanced by including a risk assessment for degradation for all products, and in the case of solid oral products, dissolution.

Qualitative insights into promotion of pharmaceutical products in Bangladesh: how ethical are the practices?

PubMed

Mohiuddin, Mahrukh; Rashid, Sabina Faiz; Shuvro, Mofijul Islam; Nahar, Nahitun; Ahmed, Syed Masud

2015-12-01

The pharmaceutical market in Bangladesh is highly concentrated (top ten control around 70 % of the market). Due to high competition aggressive marketing strategies are adopted for greater market share, which sometimes cross limit. There is lack of data on this aspect in Bangladesh. This exploratory study aimed to fill this gap by investigating current promotional practices of the pharmaceutical companies including the role of their medical representatives (MR). This qualitative study was conducted as part of a larger study to explore the status of governance in health sector in 2009. Data were collected from Dhaka, Chittagong and Bogra districts through in-depth interview (healthcare providers and MRs), observation (physician-MR interaction), and round table discussion (chief executives and top management of the pharmaceutical companies). Findings reveal a highly structured system geared to generate prescriptions and ensure market share instituted by the pharmaceuticals. A comprehensive training curriculum for the MRs prepares the newly recruited science graduates for generating enough prescriptions by catering to the identified needs and demands of the physicians expressed or otherwise, and thus grab higher market-share for the companies they represent. Approaches such as inducements, persuasion, emotional blackmail, serving family members, etc. are used. The type, quantity and quality of inducements offered to the physicians depend upon his/her capacity to produce prescriptions. The popular physicians are cultivated meticulously by the MRs to establish brand loyalty and fulfill individual and company targets. The physicians, willingly or unwillingly, become part of the system with few exceptions. Neither the regulatory authority nor the professional or consumer rights bodies has any role to control or ractify the process. The aggressive marketing of the pharmaceutical companies compel their MRs, programmed to maximize market share, to adopt unethical means if and when necessary. When medicines are prescribed and dispensed more for financial interests than for needs of the patients, it reflects system's failed ability to hold individuals and entities accountable for adhering to basic professional ethics, code of conduct, and statutory laws.

MEMS tunable grating micro-spectrometer

NASA Astrophysics Data System (ADS)

Tormen, Maurizio; Lockhart, R.; Niedermann, P.; Overstolz, T.; Hoogerwerf, A.; Mayor, J.-M.; Pierer, J.; Bosshard, C.; Ischer, R.; Voirin, G.; Stanley, R. P.

2017-11-01

The interest in MEMS based Micro-Spectrometers is increasing due to their potential in terms of flexibility as well as cost, low mass, small volume and power savings. This interest, especially in the Near-Infrared and Mid- Infrared, ranges from planetary exploration missions to astronomy, e.g. the search for extra solar planets, as well as to many other terrestrial fields of application such as, industrial quality and surface control, chemical analysis of soil and water, detection of chemical pollutants, exhausted gas analysis, food quality control, process control in pharmaceuticals, to name a few. A compact MEMS-based Spectrometer for Near- Infrared and Mid-InfraRed operation have been conceived, designed and demonstrated. The design based on tunable MEMS blazed grating, developed in the past at CSEM [1], achieves state of the art results in terms of spectral resolution, operational wavelength range, light throughput, overall dimensions, and power consumption.

[Comparison and review on specifications of fermented Cordyceps sinensis products].

PubMed

Yang, Ping; Zhao, Xiao-Xia; Zhang, Yong-Wen

2018-02-01

There are five kinds of fermented Cordyceps crude drug and their preparations that have been approved as medicine on the market. Since the initial strains of the crude drug were all isolated from natural Cordyceps sinensis， they have similar names， chemical components and even clinical applications. However， because of the different strain species and fermentation processes， there was significant difference in quality. As a result， they should be clearly distinguished in clinical use. Most of the products were researched and developed during the 1980s and 1990s， so there was difference in quality standards for different products， and their quality control levels of some products were not perfect. At present， some of the products are approved as Chinese medicine， others are approved as chemical drugs， with a confusion in products name， management and clinical application. In this paper， the approval numbers， quality standards and clinical applications， and current problems of these products were summarized and compared; some suggestions were put forward， such as standardizing the product name， unifying the management of approval number category， and increasing the specific quality control attributes， in order to provide reference for standard implementation， quality control and drug regulation for fermented Cordyceps crude drugs and their preparations. Copyright© by the Chinese Pharmaceutical Association.

Screening for the anti-inflammation quality markers of Xiaojin Pills based on HPLC-MS/MS method, COX-2 inhibition test and protein interaction network.

PubMed

Xiong, Xi; He, Ya-Nan; Feng, Bi; Pan, Yuan; Zhang, Hai-Zhu; Ke, Xiu-Mei; Zhang, Yi; Yang, Ming; Han, Li; Zhang, Ding-Kun

2018-05-10

Nowadays, breast disorders seriously affect women's health in an increasing number. In China, Xiaojin Pills are commonly used in the treatment of breast diseases. Doctors have concluded that the combined use of Xiaojin Pills with conventional therapy can significantly improve the efficacy with fewer side effects. However, the prescription of Xiaojin Pills is complicated and their quality control methods cannot completely ensure the quality of Xiaojin Pills. On the basis of its mechanism, our study combined chemical evaluation and biological evaluation to identify the anti-inflammatory markers of Xiaojin Pills. In this manuscript, 13 compounds in Xiaojin Pills were quantified. At the same time, the cyclooxygenase-2 inhibition rates of different Xiaojin Pills were measured and the possible markers were screened by spectrum-effect relationship. Further, anti-inflammatory activities of markers were verified and protein interaction network was analyzed, identifying the components of Protocatechuate, Beta-Boswellic acid and Levistilide A as the anti-inflammatory quality markers of Xiaojin Pills. We hope our studies can provide a scientific theoretical basis for accurately quality control of Xiaojin Pills and reasonable suggestions for pharmaceutical companies and new ideas for the quality control of other medicines.

Association between physicians’ interaction with pharmaceutical companies and their clinical practices: A systematic review and meta-analysis

PubMed Central

Al-Khaled, Lina; Kahale, Lara A.; Nas, Hala; El-Jardali, Fadi

2017-01-01

Background Pharmaceutical company representatives likely influence the prescribing habits and professional behaviors of physicians. The objective of this study was to systematically review the association between physicians’ interactions with pharmaceutical companies and their clinical practices. Methods We used the standard systematic review methodology. Observational and experimental study designs examining any type of targeted interaction between practicing physicians and pharmaceutical companies were eligible. The search strategy included a search of MEDLINE and EMBASE databases up to July 2016. Two reviewers selected studies, abstracted data, and assessed risk of bias in duplicate and independently. We assessed the quality of evidence using the GRADE approach. Results Twenty articles reporting on 19 studies met our inclusion criteria. All of these studies were conducted in high-income countries and examined different types of interactions, including detailing, industry-funded continuing medical education, and receiving free gifts. While all included studies assessed prescribing behaviors, four studies also assessed financial outcomes, one assessed physicians’ knowledge, and one assessed their beliefs. None of the studies assessed clinical outcomes. Out of the 19 studies, 15 found a consistent association between interactions promoting a medication, and inappropriately increased prescribing rates, lower prescribing quality, and/or increased prescribing costs. The remaining four studies found both associations and lack of significant associations for the different types of exposures and drugs examined in the studies. A meta-analysis of six of these studies found a statistically significant association between exposure and physicians’ prescribing behaviors (OR = 2.52; 95% CI 1.82–3.50). The quality of evidence was downgraded to moderate for risk of bias and inconsistency. Sensitivity analysis excluding studies at high risk of bias did not substantially change these results. A subgroup analysis did not find a difference by type of exposure. Conclusion There is moderate quality evidence that physicians’ interactions with pharmaceutical companies are associated with their prescribing patterns and quality. PMID:28406971

A quality by design study applied to an industrial pharmaceutical fluid bed granulation.

PubMed

Lourenço, Vera; Lochmann, Dirk; Reich, Gabriele; Menezes, José C; Herdling, Thorsten; Schewitz, Jens

2012-06-01

The pharmaceutical industry is encouraged within Quality by Design (QbD) to apply science-based manufacturing principles to assure quality not only of new but also of existing processes. This paper presents how QbD principles can be applied to an existing industrial pharmaceutical fluid bed granulation (FBG) process. A three-step approach is presented as follows: (1) implementation of Process Analytical Technology (PAT) monitoring tools at the industrial scale process, combined with multivariate data analysis (MVDA) of process and PAT data to increase the process knowledge; (2) execution of scaled-down designed experiments at a pilot scale, with adequate PAT monitoring tools, to investigate the process response to intended changes in Critical Process Parameters (CPPs); and finally (3) the definition of a process Design Space (DS) linking CPPs to Critical to Quality Attributes (CQAs), within which product quality is ensured by design, and after scale-up enabling its use at the industrial process scale. The proposed approach was developed for an existing industrial process. Through enhanced process knowledge established a significant reduction in product CQAs, variability already within quality specifications ranges was achieved by a better choice of CPPs values. The results of such step-wise development and implementation are described. Copyright © 2012 Elsevier B.V. All rights reserved.

Assessing the quality of pharmacoeconomic studies in India: a systematic review.

PubMed

Desai, Pooja R; Chandwani, Hitesh S; Rascati, Karen L

2012-09-01

The aim of the study was to evaluate the quality of pharmacoeconomic studies based in India. A literature search was conducted using PubMed, MEDLINE, EconLit, PsycInfo and Google Scholar to identify published work on pharmacoeconomics studies based in India. Articles were included if they were original studies that evaluated pharmaceuticals, were based in India and were conducted between 1990 and 2010. Two reviewers independently reviewed the articles using a subjective 10-point quality scale in addition to the 100-point Quality of Health Economic Studies (QHES) questionnaire. Twenty-nine articles published between 1998 and May 2010 were included in the review. The included articles were published in 23 different journals. Each article was written by an average of five authors. The mean subjective quality score of the 29 articles was 7.8 (standard deviation [SD] = 1.3) and the mean QHES scores for the complete pharmacoeconomic studies (n = 24) was 86 (SD = 6). The majority of authors resided in India (62%) at the time of publication and had a medical background (90%). The quality score was significantly (p ≤ 0.05) related to the country of residence of the primary author (non-India = higher) and the study design (randomized controlled trials = higher). Although the overall quality scores were comparable to (e.g. Nigeria) or higher than (e.g. Zimbabwe) similar studies in other developing countries, key features such as an explicit study perspective and the use of sensitivity analyses were missing in about 40% of the articles. The need for economic evaluation of pharmaceuticals is imperative, especially in developing countries such as India as this helps decision makers allocate scarce resources in a justifiable manner.

WHO Expert Committee on Specifications for Pharmaceutical Preparations. Fiftieth report.

PubMed

2016-01-01

The Expert Committee on Specifications for Pharmaceutical Preparations works towards clear, independent and practical standards and guidelines for the quality assurance of medicines. Standards are developed by the Committee through worldwide consultation and an international consensus-building process. The following new guidelines were adopted and recommended for use. Good pharmacopoeial practices; FIP-WHO technical guidelines: points to consider in the provision by health-care professionals of children-specific preparations that are not available as authorized products; Guidance on good manufacturing practices for biological products; Guidance on good manufacturing practices: inspection report, including Appendix 1: Model inspection report; Guidance on good data and record management practices; Good trade and distribution practices for starting materials; Guidelines on the conduct of surveys of the quality of medicines; Collaborative procedure between the World Health Organization (WHO) prequalification team and national regulatory authorities in the assessment and accelerated national registration of WHO-prequalified pharmaceutical products and vaccines; Guidance for organizations performing in vivo bioequivalence studies; and World Health Organization (WHO) general guidance on variations to multisource pharmaceutical products.

Quality by design in the chiral separation strategy for the determination of enantiomeric impurities: development of a capillary electrophoresis method based on dual cyclodextrin systems for the analysis of levosulpiride.

PubMed

Orlandini, S; Pasquini, B; Del Bubba, M; Pinzauti, S; Furlanetto, S

2015-02-06

Quality by design (QbD) concepts, in accordance with International Conference on Harmonisation Pharmaceutical Development guideline Q8(R2), represent an innovative strategy for the development of analytical methods. In this paper QbD principles have been comprehensively applied in the set-up of a capillary electrophoresis method aimed to quantify enantiomeric impurities. The test compound was the chiral drug substance levosulpiride (S-SUL) and the developed method was intended to be used for routine analysis of the pharmaceutical product. The target of analytical QbD approach is to establish a design space (DS) of critical process parameters (CPPs) where the critical quality attributes (CQAs) of the method have been assured to fulfil the desired requirements with a selected probability. QbD can improve the understanding of the enantioseparation process, including both the electrophoretic behavior of enantiomers and their separation, therefore enabling its control. The CQAs were represented by enantioresolution and analysis time. The scouting phase made it possible to select a separation system made by sulfated-β-cyclodextrin and a neutral cyclodextrin, operating in reverse polarity mode. The type of neutral cyclodextrin was included among other CPPs, both instrumental and related to background electrolyte composition, which were evaluated in a screening phase by an asymmetric screening matrix. Response surface methodology was carried out by a Doehlert design and allowed the contour plots to be drawn, highlighting significant interactions between some of the CPPs. DS was defined by applying Monte-Carlo simulations, and corresponded to the following intervals: sulfated-β-cyclodextrin concentration, 9-12 mM; methyl-β-cyclodextrin concentration, 29-38 mM; Britton-Robinson buffer pH, 3.24-3.50; voltage, 12-14 kV. Robustness of the method was examined by a Plackett-Burman matrix and the obtained results, together with system repeatability data, led to define a method control strategy. The method was validated and was finally applied to determine the enantiomeric purity of S-SUL in pharmaceutical dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

The PEDro scale had acceptably high convergent validity, construct validity, and interrater reliability in evaluating methodological quality of pharmaceutical trials.

PubMed

Yamato, Tie Parma; Maher, Chris; Koes, Bart; Moseley, Anne

2017-06-01

The Physiotherapy Evidence Database (PEDro) scale has been widely used to investigate methodological quality in physiotherapy randomized controlled trials; however, its validity has not been tested for pharmaceutical trials. The aim of this study was to investigate the validity and interrater reliability of the PEDro scale for pharmaceutical trials. The reliability was also examined for the Cochrane Back and Neck (CBN) Group risk of bias tool. This is a secondary analysis of data from a previous study. We considered randomized placebo controlled trials evaluating any pain medication for chronic spinal pain or osteoarthritis. Convergent validity was evaluated by correlating the PEDro score with the summary score of the CBN risk of bias tool. The construct validity was tested using a linear regression analysis to determine the degree to which the total PEDro score is associated with treatment effect sizes, journal impact factor, and the summary score for the CBN risk of bias tool. The interrater reliability was estimated using the Prevalence and Bias Adjusted Kappa coefficient and 95% confidence interval (CI) for the PEDro scale and CBN risk of bias tool. Fifty-three trials were included, with 91 treatment effect sizes included in the analyses. The correlation between PEDro scale and CBN risk of bias tool was 0.83 (95% CI 0.76-0.88) after adjusting for reliability, indicating strong convergence. The PEDro score was inversely associated with effect sizes, significantly associated with the summary score for the CBN risk of bias tool, and not associated with the journal impact factor. The interrater reliability for each item of the PEDro scale and CBN risk of bias tool was at least substantial for most items (>0.60). The intraclass correlation coefficient for the PEDro score was 0.80 (95% CI 0.68-0.88), and for the CBN, risk of bias tool was 0.81 (95% CI 0.69-0.88). There was evidence for the convergent and construct validity for the PEDro scale when used to evaluate methodological quality of pharmacological trials. Both risk of bias tools have acceptably high interrater reliability. Copyright © 2017 Elsevier Inc. All rights reserved.

Food and Drug Administration: Helping pharmacists ensure that patients receive high-quality medicines.

PubMed

Kremzner, Mary

2016-01-01

Ensuring that the drugs patients take are safe and effective is critical to the Food and Drug Administration (FDA) mission and a major reason for testing an active pharmaceutical ingredient or currently marketed drug product. To address gaps in the assessment of drug quality, FDA's Center for Drug Evaluation and Research (CDER) has created the Office of Pharmaceutical Quality (OPQ). This newly formed "super-office" within CDER launched a concerted new strategy that enhances the surveillance of drug manufacturing and will bring a comprehensive approach to quality oversight. With OPQ and these new performance measures in place, FDA can sharpen its focus on issues critical to quality and can identify and respond to manufacturing issues before they become major systemic problems. Published by Elsevier Inc.

Development and validation of a reversed-phase ion-pair high-performance liquid chromatographic method for the determination of risedronate in pharmaceutical preparations.

PubMed

Kyriakides, Demetra; Panderi, Irene

2007-02-12

A stability indicating, reversed-phase ion-pair high-performance liquid chromatographic method was developed and validated for the determination of risedronate in pharmaceutical dosage forms. The determination was performed on a BDS C(18) analytical column (250 mm x 4.6 mm i.d., 5 microm particle size); the mobile phase consisted of 0.005 M tetrabutylammonium hydroxide and 0.005 M pyrophosphate sodium (pH 7.0) mixed with acetonitrile in a ratio (78:22, v/v) and pumped at a flow rate 1.00 mL min(-1). The ultraviolet (UV) detector was operated at 262 nm. The retention times of magnesium ascorbyl phosphate, which was used as internal standard and risedronate were 4.94 and 5.95 min, respectively. The calibration graph was ranged from 2.50 to 20.00 microg mL(-1), while detection and quantitation limits were found to be 0.48 and 1.61 microg mL(-1), respectively. The intra- and inter-day percentage relative standard deviations, %R.S.D., were less than 5.9%, while the relative percentage error, %E(r), was less than 0.4%. The method was applied to the quality control of commercial tablets and content uniformity test and proved to be suitable for rapid and reliable quality control.

Time trends and determinants of pharmaceutical expenditure in China (1990-2009).

PubMed

Shi, Lizheng; Yang, Heidi Y; Cheng, Gang; Meng, Qingyue

2014-03-01

Pharmaceutical policy reform is currently one of the primary areas of health reform in China. The national pharmaceutical policy of China has multiple objectives: to develop the domestic pharmaceutical industry and encourage innovation, to control escalation of total pharmaceutical expenditures (TPE) which constitute a substantial component of total health expenditures (THE), and to ensure access to essential medicines for poor and uninsured patients. The current pharmaceutical system has been criticized for its high costs, questionable prescribing practices, and poor regulation of drug quality. This study aims to examine the time trends and influential factors of TPE in China. Data from the 2010 China National Health Accounts Report and the 2010 China Health Statistics Year Book were used in the analysis. Time trends of TPE as a share of THE (TPE/THE), of gross domestic product [GDP] (TPE/GDP), and the relationship between TPE/THE and GDP were examined. The growth of TPE was examined after adjusting for health care utilization and GDP. The determinants of the TPE/THE and the TPE/GDP between 1990 and 2009 were investigated by two time-series regression models including the amount of prescriptions dispensed (using proxy variables of health utilization), the price indices of medical services, and the price indices of pharmaceuticals during that time period. Descriptive analyses showed that TPE and THE grew consistently during the years 1990-2009. The ratio of the THE/GDP increased more rapidly in recent years than the TPE/GDP. Furthermore, outpatient pharmaceutical expenditures (PEs) per visit and hospital PEs per admission grew throughout the study period. The amount of outpatient visits did not show a significant growth pattern during the 1990s, despite rapid GDP growth during that period. The time-series models showed that the TPE/THE was negatively associated with GDP during the same year (p = 0.039), as well as the medical consumer price index [CPI] (p = 0.021). The TPE/GDP was influenced by the price index of prescriptions (p < 0.001) and the amount of health services utilization, including inpatient admissions (p = 0.012) and outpatient visits (p = 0.003). The cost escalations in PEs and health expenditures were concurrent with GDP growth. TPE has been the major source of financial burden for patients. Even though the rapid growth in China's economy may ameliorate the overall TPE burden, control of PEs is still a key for successful health system reform.

Pharmaceuticals and Controlled Substances and Demolition

EPA Pesticide Factsheets

Pharmaceuticals and controlled substances found during residential demolition, such as prescription medications or illegal drugs, may require special treatment for disposal or recycling before demolition.

Establishing the pharmaceutical quality of Chinese herbal medicine: a provisional BCS classification.

PubMed

Fong, Sophia Y K; Liu, Mary; Wei, Hai; Löbenberg, Raimar; Kanfer, Isadore; Lee, Vincent H L; Amidon, Gordon L; Zuo, Zhong

2013-05-06

The Biopharmaceutical Classification System (BCS), which is a scientific approach to categorize active drug ingredient based on its solubility and intestinal permeability into one of the four classes, has been used to set the pharmaceutical quality standards for drug products in western society. However, it has received little attention in the area of Chinese herbal medicine (CHM). This is likely, in part, due to the presence of multiple active components as well as lack of standardization of CHM. In this report, we apply BCS classification to CHMs provisionally as a basis for establishing improved in vitro quality standards. Based on a top-200 drugs selling list in China, a total of 31 CHM products comprising 50 official active marker compounds (AMCs) were provisionally classified according to BCS. Information on AMC content and doses of these CHM products were retrieved from the Chinese Pharmacopoeia. BCS parameters including solubility and permeability of the AMCs were predicted in silico (ACD/Laboratories). A BCS classification of CHMs according to biopharmaceutical properties of their AMCs is demonstrated to be feasible in the current study and can be used to provide a minimum set of quality standards. Our provisional results showed that 44% of the included AMCs were classified as Class III (high solubility, low permeability), followed by Class II (26%), Class I (18%), and Class IV (12%). A similar trend was observed when CHMs were classified in accordance with the BCS class of AMCs. Most (45%) of the included CHMs were classified as Class III, followed by Class II (16%), Class I (10%), and Class IV (6%); whereas 23% of the CHMs were of mixed class due to the presence of multiple individual AMCs with different BCS classifications. Moreover, about 60% of the AMCs were classified as high-solubility compounds (Class I and Class III), suggesting an important role for an in vitro dissolution test in setting quality control standards ensuring consistent biopharmaceutical quality for the commercially available CHM products. That is, provisionally, more than half of the AMCs of the top-selling CHMs included in this study would be candidates for a bioequivalence (BE) biowaiver, based on WHO recommendations and EMEA guidelines. Thus a dissolution requirement on these AMCs would represent a significant advance in the pharmaceutical quality of CHM today.

[PICS: pharmaceutical inspection cooperation scheme].

PubMed

Morénas, J

2009-01-01

The pharmaceutical inspection cooperation scheme (PICS) is a structure containing 34 participating authorities located worldwide (October 2008). It has been created in 1995 on the basis of the pharmaceutical inspection convention (PIC) settled by the European free trade association (EFTA) in1970. This scheme has different goals as to be an international recognised body in the field of good manufacturing practices (GMP), for training inspectors (by the way of an annual seminar and experts circles related notably to active pharmaceutical ingredients [API], quality risk management, computerized systems, useful for the writing of inspection's aide-memoires). PICS is also leading to high standards for GMP inspectorates (through regular crossed audits) and being a room for exchanges on technical matters between inspectors but also between inspectors and pharmaceutical industry.

Enabling ICH Q10 Implementation--Part 1. Striving for Excellence by Embracing ICH Q8 and ICH Q9.

PubMed

Calnan, Nuala; O'Donnell, Kevin; Greene, Anne

2013-01-01

This article is the first in a series of articles that will focus on understanding the implementation essentials necessary to deliver operational excellence through a International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) Q10-based pharmaceutical quality system (PQS). The authors examine why, despite the fact that the ICH Q10 guideline has been with us since 2008, the transformation of the traditional Quality Management Systems QMS in use within the pharmaceutical industry is a work in progress for only a few forward-thinking organisations. Unfortunately, this transformation remains a mere aspiration for the majority of organisations. We explore the apparent lack of progress by the pharmaceutical sector in adopting six sigma and related quality management techniques to ensure the availability of high-quality medicines worldwide. The authors propose that the desired progress can be delivered through two key shifts in our current practices; by embodying the principles of operational excellence in every aspect of our business and by learning how to unlock the scientific and tacit knowledge within our organisations. It has been ten years since The Wall Street Journal revealed the pharmaceutical industry's "little secret" comparing the perceived level of manufacturing expertise in the industry as lagging far behind those of potato-chip and laundry-soap makers. Would you consider the quality and manufacturing strategies in place today in your organisation to be more efficient and scientifically based than those of 2003? If so, what evidence exists for you to draw any conclusion regarding enhanced performance? Do your current practices drive innovation and facilitate continual improvement and if so, how? Ultimately, can you confidently affirm that patient-related risks associated with the product(s) manufactured by your organisation have been reduced due to the quality assurance program now applied within your organisation? This article asks you to question if you have truly embraced Q8(R2), Q9, and Q10, and in doing so can you demonstrate that you have made the necessary changes that would warrant reduced regulatory oversight?

Interactions between physicians and the pharmaceutical industry: what does the literature say?

PubMed Central

Lexchin, J

1993-01-01

OBJECTIVE: To determine the effect of three types of interaction between physicians and the pharmaceutical industry--company-funded clinical trials, company-sponsored continuing medical education (CME) and information for physicians supplied by pharmaceutical detailers--on orientation and quality of clinical trials, content of CME courses and physicians' prescribing behaviour. DATA SOURCES: MEDLINE and HEALTH searches for English-language articles published from 1978 to 1993, supplemented by material from the author's personal collection. STUDY SELECTION: A total of 227 papers from the MEDLINE and HEALTH searches and about 2000 items from the author's library were initially reviewed. The following selection criteria were used: studies conducted in Australia, Canada, New Zealand, Britain and the United States; studies conducted after 1977; quantitative surveys containing details of the survey methods; studies on the orientation and quality of company-funded clinical trials and on the content of CME courses giving explicit criteria used in the evaluation; and reports on the outcome of interactions stating how the outcomes were assessed. Thirty-six studies met these criteria. DATA EXTRACTION: Information was extracted on five topics: physicians' attitudes toward drug industry interactions, frequency with which physicians participate in the interactions, orientation and quality of company-funded clinical trials, content of company-sponsored CME courses and changes in physicians' prescribing behaviour as a result of an interaction. DATA SYNTHESIS: Although most physicians participate only occasionally in company-sponsored clinical trials, most see detailers and attend company-sponsored CME courses. However, physicians do not have a very high opinion of the information from detailers or of company-sponsored CME events. Many doctors regard pharmaceutical companies as an important source of funding for clinical trials, but they also have concerns about accepting money from this source. Company funding of clinical trials may affect the quality of the trials and the types of research that physicians undertake. Company-sponsored CME courses may have a commercial bias even if conducted under guidelines designed to ensure the independence of the event. All three types of interactions affect physicians' prescribing behaviour and, in the case of obtaining information from detailers, physicians' prescribing practices are less appropriate as a result of the interaction. CONCLUSIONS: Physicians are affected by their interactions with the pharmaceutical industry. Further research needs to be done in most cases to determine whether such interactions lead to more or less appropriate prescribing practices. The CMA's guidelines on this topic should be evaluated to see whether they are effective in controlling physician-industry interactions. Further measures may be necessary if the guidelines fail to prevent negative effects on prescribing practices. PMID:8221424

Sickle cell disease

PubMed Central

2011-01-01

Introduction Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises. It also increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion. In sub-Saharan Africa, up to a third of adults are carriers of the defective sickle cell gene, and 1% to 2% of babies are born with the disease. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: what are the effects of pharmaceutical and non-pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? What are the effects of pharmaceutical and non-pharmaceutical interventions to treat pain in people with sickle cell crisis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to March 2010 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 38 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, antibiotic prophylaxis in children <5 years of age, antibiotic prophylaxis in children >5 years of age, aspirin, avoidance of cold environment, blood transfusion, codeine, corticosteroid (with narcotic analgesics), diflunisal, hydration, hydroxyurea, ibuprofen, ketorolac, limiting physical exercise, malaria chemoprophylaxis, morphine (controlled-release oral after initial intravenous bolus, repeated intravenous doses), oxygen, paracetamol, patient-controlled analgesia, pneumococcal vaccines, and rehydration. PMID:21718552

Sickle cell disease

PubMed Central

2009-01-01

Introduction Sickle cell disease causes chronic haemolytic anaemia, dactylitis, and painful acute crises, and increases the risk of stroke, organ damage, bacterial infections, and complications of blood transfusion. In sub-Saharan Africa, up to a third of adults are carriers of the defective sickle cell gene, and 1-2% of babies are born with the disease. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of pharmaceutical and non-pharmaceutical interventions to prevent sickle cell crisis and other acute complications in people with sickle cell disease? What are the effects of pharmaceutical and non-pharmaceutical interventions to treat pain in people with sickle cell crisis? We searched: Medline, Embase, The Cochrane Library, and other important databases up to September 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 38 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: acupuncture, antibiotic prophylaxis in children under 5 years of age, aspirin, avoidance of cold environment, blood transfusion, codeine, corticosteroid (with narcotic analgesics), diflunisal, hydration, hydroxyurea, ibuprofen, ketorolac, limiting physical exercise, malaria chemoprophylaxis, morphine (controlled-release oral after initial intravenous bolus, repeated intravenous doses), oxygen, paracetamol, patient-controlled analgesia, penicillin prophylaxis in children over 5 years of age, piracetam, pneumococcal vaccines, rehydration, and zinc sulphate. PMID:19445751

Paper analytical devices for detection of low-quality pharmaceuticals

NASA Astrophysics Data System (ADS)

Weaver, A.; Lieberman, M.

2014-03-01

There is currently no global screening system to detect low quality pharmaceuticals, despite widespread recognition of the public health problems caused by substandard and falsified medicines. In order to fill this void, we designed a rapid field screening test that is interfaced with the mobile phone network. The user scrapes a pill over several reaction areas on a paper test card, and then dips one edge of the card into water to activate dried reagents stored on the paper. These reagents carry out multiple color tests and result in a pattern of colored stripes that give information about the chemical content of the pill. The test cards are inexpensive and instrument-free, and we think they will be a scalable testing option in low resource settings. Studies on falsified drugs archived at the FDA show that the test cards are effective at detecting a wide variety of low-quality formulations of many classes of pharmaceuticals, and field tests are currently under way in Kenya.

Drug policy and administration affecting quality of life of the poor in Thailand.

PubMed

Prutipinyo, Chardsumon; Sirichotiratana, Nithat

2011-09-01

This study aims to analyze drug policy and administration affecting quality of life of the poor in Thailand. Review of official reports and related documents, for the past 10 years (from 2000-2010). By imposing compulsory licensing, the Thai government maintains negotiating power over the price of pharmaceutical products with the patent holders of the original drugs. This gives an opportunity for relevant government agencies to produce or import patented drugs. At present, there are many problems and obstacles. The findings show that developing countries need to strengthen their negotiating power so that the pharmaceutical manufacturers cannot take advantage through mechanisms provided for such as compulsory licensing and provisions for flexibility in Trade-Related Intellectual Property Rights (TRIPS) agreement. Furthermore, these countries must support and empower the local pharmaceutical manufacturers to produce generic drugs. Developing countries should ensure that their populations have confidence in universal coverage service and medical systems regarding the quality of generic drugs.

Economic Evaluations of Pharmaceuticals Granted a Marketing Authorisation Without the Results of Randomised Trials: A Systematic Review and Taxonomy.

PubMed

Hatswell, Anthony J; Freemantle, Nick; Baio, Gianluca

2017-02-01

Pharmaceuticals are usually granted a marketing authorisation on the basis of randomised controlled trials (RCTs). Occasionally the efficacy of a treatment is assessed without a randomised comparator group (either active or placebo). To identify and develop a taxonomic account of economic modelling approaches for pharmaceuticals licensed without RCT data. We searched PubMed, the websites of UK health technology assessment bodies and the International Society for Pharmacoeconomics and Outcomes Research Scientific Presentations Database for assessments of treatments granted a marketing authorisation by the US Food and Drug Administration or European Medicines Agency from January 1999 to May 2014 without RCT data (74 indications). The outcome of interest was the approach to modelling efficacy data. Fifty-one unique models were identified in 29 peer-reviewed articles, 30 health technology appraisals, and 15 International Society for Pharmacoeconomics and Outcomes Research abstracts concerning 30 indications (44 indications had not been modelled). We noted the high rate of non-submission to health technology assessment agencies (28/98). The majority of models (43/51) were based on 'historical controls'-comparisons to previous meta-analysis or pooling of trials (5), individual trials (16), registries/case series (15), or expert opinion (7). Other approaches used the patient as their own control, performed threshold analysis, assumed time on treatment was added to overall survival, or performed cost-minimisation analysis. There is considerable variation in the quality and approach of models constructed for drugs granted a marketing authorisation without a RCT. The most common approach is of a naive comparison to historical data (using other trials/registry data as a control group), which has considerable scope for bias.

Orientation to determine quality attributes of flavoring excipients containing volatile molecules.

PubMed

Kiene, Florian E; Pein, Miriam; Thommes, Markus

2015-06-10

Pharmaceutical excipients containing volatile odor-active molecules can be used in pharmaceutical development to increase patients' compliance. However, capturing the molecular composition of these odor-active substances is challenging. Therefore, guidance for the analytical investigation of these excipients should be developed. Using a model flavor, lead molecules were chosen and a gas chromatographic method was validated according to pharmaceutical guidelines. Changes during storage as well as batch homogeneity and conformity were investigated. The knowledge gained could be used to understand molecular differences between batches caused by aging. A suitable attempt to capture the volatile molecular composition of flavoring substance was presented and the found results could be used for the determination and interpretation of quality attributes. Copyright © 2015 Elsevier B.V. All rights reserved.

Framework for industry engagement and quality principles for industry-provided medical education in Europe

PubMed Central

Allen, Tamara; Donde, Nina; Hofstädter-Thalmann, Eva; Keijser, Sandra; Moy, Veronique; Murama, Jean-Jacques; Kellner, Thomas

2017-01-01

ABSTRACT Lifelong learning through continuing professional development (CPD) and medical education is critical for healthcare professionals to stay abreast of knowledge and skills and provide an optimal standard of care to patients. In Europe, CPD and medical education are fragmented as there are numerous models, providers and national regulations and a lack of harmonisation of qualitative criteria. There is continued debate on the appropriate role of pharmaceutical companies in the context of medical education. Accrediting bodies such as European Accreditation Council for Continuing Medical Education do not permit active involvement of the pharmaceutical industry due to concerns around conflicts of interest and potential for bias. However, many examples of active collaboration between pharmaceutical companies and medical societies and scientific experts exist, demonstrating high integrity, clear roles and responsibilities, and fair and balanced content. Medical education experts from 16 pharmaceutical companies met to develop a set of quality principles similar to standards that have been established for clinical trials and in alignment with existing principles of accrediting bodies. This paper outlines their proposal for a framework to improve and harmonise medical education quality standards in Europe, and is also an invitation for all stakeholders to join a discussion on this integrative model. PMID:29644135

Comprehensive taxonomy and worldwide trends in pharmaceutical policies in relation to country income status.

PubMed

Maniadakis, N; Kourlaba, G; Shen, J; Holtorf, A

2017-05-25

Rapidly evolving socioeconomic and technological trends make it challenging to improve access, effectiveness and efficiency in the use of pharmaceuticals. This paper identifies and systematically classifies the prevailing pharmaceutical policies worldwide in relation to a country's income status. A literature search was undertaken to identify and taxonomize prevailing policies worldwide. Countries that apply those policies and those that do not were then grouped by income status. Pharmaceutical policies are linked to a country's socioeconomics. Developed countries have universal coverage and control pharmaceuticals with external and internal price referencing systems, and indirect price-cost controls; they carry out health technology assessments and demand utilization controls. Price-volume and risk-sharing agreements are also evolving. Developing countries are underperforming in terms of coverage and they rely mostly on restrictive state controls to regulate prices and expenditure. There are significant disparities worldwide in the access to pharmaceuticals, their use, and the reimbursement of costs. The challenge in high-income countries is to maintain access to care whilst dealing with trends in technology and aging. Essential drugs should be available to all; however, many low- and middle-income countries still provide most of their population with only poor access to medicines. As economies grow, there should be greater investment in pharmaceutical care, looking to the policies of high-income countries to increase efficiency. Pharmaceutical companies could also develop special access schemes with low prices to facilitate coverage in low-income countries.

Real-time feedback control of twin-screw wet granulation based on image analysis.

PubMed

Madarász, Lajos; Nagy, Zsombor Kristóf; Hoffer, István; Szabó, Barnabás; Csontos, István; Pataki, Hajnalka; Démuth, Balázs; Szabó, Bence; Csorba, Kristóf; Marosi, György

2018-06-04

The present paper reports the first dynamic image analysis-based feedback control of continuous twin-screw wet granulation process. Granulation of the blend of lactose and starch was selected as a model process. The size and size distribution of the obtained particles were successfully monitored by a process camera coupled with an image analysis software developed by the authors. The validation of the developed system showed that the particle size analysis tool can determine the size of the granules with an error of less than 5 µm. The next step was to implement real-time feedback control of the process by controlling the liquid feeding rate of the pump through a PC, based on the real-time determined particle size results. After the establishment of the feedback control, the system could correct different real-life disturbances, creating a Process Analytically Controlled Technology (PACT), which guarantees the real-time monitoring and controlling of the quality of the granules. In the event of changes or bad tendencies in the particle size, the system can automatically compensate the effect of disturbances, ensuring proper product quality. This kind of quality assurance approach is especially important in the case of continuous pharmaceutical technologies. Copyright © 2018 Elsevier B.V. All rights reserved.

Opportunities and challenges of real-time release testing in biopharmaceutical manufacturing.

PubMed

Jiang, Mo; Severson, Kristen A; Love, John Christopher; Madden, Helena; Swann, Patrick; Zang, Li; Braatz, Richard D

2017-11-01

Real-time release testing (RTRT) is defined as "the ability to evaluate and ensure the quality of in-process and/or final drug product based on process data, which typically includes a valid combination of measured material attributes and process controls" (ICH Q8[R2]). This article discusses sensors (process analytical technology, PAT) and control strategies that enable RTRT for the spectrum of critical quality attributes (CQAs) in biopharmaceutical manufacturing. Case studies from the small-molecule and biologic pharmaceutical industry are described to demonstrate how RTRT can be facilitated by integrated manufacturing and multivariable control strategies to ensure the quality of products. RTRT can enable increased assurance of product safety, efficacy, and quality-with improved productivity including faster release and potentially decreased costs-all of which improve the value to patients. To implement a complete RTRT solution, biologic drug manufacturers need to consider the special attributes of their industry, particularly sterility and the measurement of viral and microbial contamination. Continued advances in on-line and in-line sensor technologies are key for the biopharmaceutical manufacturing industry to achieve the potential of RTRT. Related article: http://onlinelibrary.wiley.com/doi/10.1002/bit.26378/full. © 2017 Wiley Periodicals, Inc.

Elemental Impurities in Pharmaceutical Excipients.

PubMed

Li, Gang; Schoneker, Dave; Ulman, Katherine L; Sturm, Jason J; Thackery, Lisa M; Kauffman, John F

2015-12-01

Control of elemental impurities in pharmaceutical materials is currently undergoing a transition from control based on concentrations in components of drug products to control based on permitted daily exposures in drug products. Within the pharmaceutical community, there is uncertainty regarding the impact of these changes on manufactures of drug products. This uncertainty is fueled in part by a lack of publically available information on elemental impurity levels in common pharmaceutical excipients. This paper summarizes a recent survey of elemental impurity levels in common pharmaceutical excipients as well as some drug substances. A widely applicable analytical procedure was developed and was shown to be suitable for analysis of elements that are subject to United States Pharmacopoeia Chapter <232> and International Conference on Harmonization's Q3D Guideline on Elemental Impurities. The procedure utilizes microwave-assisted digestion of pharmaceutical materials and inductively coupled plasma mass spectrometry for quantitative analysis of these elements. The procedure was applied to 190 samples from 31 different excipients and 15 samples from eight drug substances provided through the International Pharmaceutical Excipient Council of the Americas. The results of the survey indicate that, for the materials included in the study, relatively low levels of elemental impurities are present. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association.

Qualitative and Semiquantitative Analysis of Doping Products Seized at the Swiss Border.

PubMed

Weber, Christina; Krug, Oliver; Kamber, Matthias; Thevis, Mario

2017-05-12

Substances developed for therapeutic use are also known to be misused by athletes as doping agents and, outside of regulated sport, for image-enhancement. This has generated a market for counterfeit doping substances. Counterfeit doping agents may be of poor pharmaceutical quality and therefore constitute health risks to consumers. This study aims to investigate the pharmaceutical quality of 1,190 doping products seized at the Swiss border. Swiss customs authorities seize incoming shipments potentially containing doping agents. Qualitative and semiquantitative analyses were performed in order to test for prohibited doping substances. The main analytical methods utilized for characterizing confiscated compounds were liquid chromatography-high resolution mass spectrometry, polyacrylamide gel electrophoresis with subsequent in-gel tryptic digestion and identification of peptidic compounds using nanoliquid chromatography-tandem mass spectrometry, and electrochemiluminescence immuno assay. For 889 (75%) of the analyzed products, the label suggested the content of anabolic agents, for 146 samples (12%) peptide hormones or growth factors, and for 113 items (9%) antiestrogens, aromatase inhibitors or other metabolic modulators. For the majority of the investigated products, the pharmaceutical quality was an unsatisfactory standard: nonapproved substances were detected and less than 20% of the products contained the claimed substance in the respective amount. A comprehensive sample of confiscated doping products was analyzed, allowing for monitoring of developments regarding the use of doping substances in Switzerland and for anticipating future trends and challenges in sports drug testing. An alarming number of tested products was of substandard pharmaceutical quality.

21 CFR 26.20 - Alert system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Alert system. 26.20 Section 26.20 Food and Drugs... PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN... Provisions for Pharmaceutical Good Manufacturing Practices § 26.20 Alert system. (a) The details of an alert...

21 CFR 26.20 - Alert system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Alert system. 26.20 Section 26.20 Food and Drugs... PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN... Provisions for Pharmaceutical Good Manufacturing Practices § 26.20 Alert system. (a) The details of an alert...

21 CFR 26.20 - Alert system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Alert system. 26.20 Section 26.20 Food and Drugs... Provisions for Pharmaceutical Good Manufacturing Practices § 26.20 Alert system. (a) The details of an alert...

Integration of Pharmacy Practice and Pharmaceutical Analysis: Quality Assessment of Laboratory Performance.

ERIC Educational Resources Information Center

McGill, Julian E.; Holly, Deborah R.

1996-01-01

Laboratory portions of courses in pharmacy practice and pharmaceutical analysis at the Medical University of South Carolina are integrated and coordinated to provide feedback on student performance in compounding medications. Students analyze the products they prepare, with early exposure to compendia requirements and other references. Student…

A Case Study in Experiential Learning: Pharmaceutical Cold Chain Management on Wheels

ERIC Educational Resources Information Center

Vesper, James; Kartoglu, Umit; Bishara, Rafik; Reeves, Thomas

2010-01-01

Introduction: People who handle and regulate temperature-sensitive pharmaceutical products require the knowledge and skills to ensure those products maintain quality, integrity, safety, and efficacy throughout their shelf life. People best acquire such knowledge and skills through "experiential learning" that involves working with other…

[Not Available].

PubMed

Medina, Yves

2015-01-01

To date, work on health democracy has never dealt with relationships between patient associations and the pharmaceutical industry. The emergence of a genuine health citizenship depends, however, to a great extent on the quality of such a relationship. This communication, which is based on a survey of 1742 patient associations and 270 French-pharmaceutical companies, conducted by BVA upon request of the Ethics Commitee of the French association of pharmaceutical companies (CODEEM) highlights the significance of the ethical issues. Beyond the financial issue, the relationship between patient associations and pharmaceutical companies raises the issue of associations governance, and reveals the limits of "association expertise" but also a high expectations for effective partnerships.

Pharmaceutical industry research and cost savings in community-acquired pneumonia.

PubMed

Kessler, Lori A; Waterer, Grant W; Barca, Robin; Wunderink, Richard G

2002-09-01

To provide financial justification for continuing pharmaceutical research in an environment that has met with increasing resistance from insurance carriers to paying for the care of patients enrolled in research studies. Matched case-control study of patients enrolled into inpatient community-acquired pneumonia (CAP) pharmaceutical research protocols. Case patients were enrolled into a CAP pharmaceutical research trial. Control patients were obtained from a prospective cohort study of CAP. Cases were matched to controls on the basis of age, sex, pneumonia severity index (PSI) grade, and comorbid illnesses as measured by the PSI and Acute Physiologic and Chronic Health Evaluation II (APACHE II) scoring systems. Financial data were obtained from hospital billing records. Twenty-five cases were identified and matched to appropriate controls. There was no statistically significant difference in mean PSI and APACHE II scores between cases and controls. There was a significant reduction in the total charges for hospital care of patients enrolled into a pharmaceutical industry trial ($6267 vs $9979; P = .03). As expected, the most dramatic reduction was in pharmacy charges ($642 vs $1797; P = .002), but there were trends toward lower charges in all cost subgroups. Interestingly, there was also a strong trend toward reduced length of hospital stay associated with enrollment in a pharmaceutical trial (4.5 vs 6.0 days; P = .06). Enrollment in a pharmaceutical research protocol results in significant cost savings in patients admitted to the hospital with CAP and may lead to earlier hospital discharge.

Review on fate and mechanism of removal of pharmaceutical pollutants from wastewater using biological approach.

PubMed

Tiwari, Bhagyashree; Sellamuthu, Balasubramanian; Ouarda, Yassine; Drogui, Patrick; Tyagi, Rajeshwar D; Buelna, Gerardo

2017-01-01

Due to research advancement and discoveries in the field of medical science, maintains and provides better human health and safer life, which lead to high demand for production of pharmaceutical compounds with a concomitant increase in population. These pharmaceutical (biologically active) compounds were not fully metabolized by the body and excreted out in wastewater. This micro-pollutant remains unchanged during wastewater treatment plant operation and enters into the receiving environment via the discharge of treated water. Persistence of pharmaceutical compounds in both surface and ground waters becomes a major concern due to their potential eco-toxicity. Pharmaceuticals (emerging micro-pollutants) deteriorate the water quality and impart a toxic effect on living organisms. Therefore, from last two decades, plenty of studies were conducted on the occurrence, impact, and removal of pharmaceutical residues from the environment. This review provides an overview on the fate and removal of pharmaceutical compounds via biological treatment process. Copyright © 2016 Elsevier Ltd. All rights reserved.

Acoustic Sample Deposition MALDI-MS (ASD-MALDI-MS): A Novel Process Flow for Quality Control Screening of Compound Libraries.

PubMed

Chin, Jefferson; Wood, Elizabeth; Peters, Grace S; Drexler, Dieter M

2016-02-01

In the early stages of drug discovery, high-throughput screening (HTS) of compound libraries against pharmaceutical targets is a common method to identify potential lead molecules. For these HTS campaigns to be efficient and successful, continuous quality control of the compound collection is necessary and crucial. However, the large number of compound samples and the limited sample amount pose unique challenges. Presented here is a proof-of-concept study for a novel process flow for the quality control screening of small-molecule compound libraries that consumes only minimal amounts of samples and affords compound-specific molecular data. This process employs an acoustic sample deposition (ASD) technique for the offline sample preparation by depositing nanoliter volumes in an array format onto microscope glass slides followed by matrix-assisted laser desorption/ionization mass spectrometric (MALDI-MS) analysis. An initial study of a 384-compound array employing the ASD-MALDI-MS workflow resulted in a 75% first-pass positive identification rate with an analysis time of <1 s per sample. © 2015 Society for Laboratory Automation and Screening.

Higher pharmaceutical public expenditure after direct price control: improved access or induced demand? The Colombian case.

PubMed

Prada, Sergio I; Soto, Victoria E; Andia, Tatiana S; Vaca, Claudia P; Morales, Álvaro A; Márquez, Sergio R; Gaviria, Alejandro

2018-01-01

High pharmaceutical expenditure is one of the main concerns for policymakers worldwide. In Colombia, a middle-income country, outpatient prescription represents over 10% of total health expenditure in the mandatory benefits package (POS), and close to 90% in the complementary government fund (No POS). In order to control expenditure, since 2011, the Ministry of Health introduced price caps on inpatient drugs reimbursements by active ingredient. By 2013, more than 400 different products, covering 80% of public pharmaceutical expenditure were controlled. This paper investigates the effects of the Colombian policy efforts to control expenditure by controlling prices. Using SISMED data, the official database for prices and quantities sold in the domestic market, we estimate a Laspeyres price index for 90 relevant markets in the period 2011-2015, and, then, we estimate real pharmaceutical expenditure. Results show that, after direct price controls were enacted, price inflation decreased almost - 43%, but real pharmaceutical expenditure almost doubled due mainly to an increase in units sold. Such disproportionate increase in units sold maybe attributable to better access to drugs due to lower prices, and/or to an increase in marketing efforts by the pharmaceutical industry to maintain profits. We conclude that pricing interventions should be implemented along with a strong market monitoring to prevent market distortions such as inappropriate and unnecessary drug use.

77 FR 30326 - Importer of Controlled Substances; Notice Of Registration; Mylan Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-22

... Registration; Mylan Pharmaceuticals, Inc. By Notice dated February 23, 2012, and published in the Federal Register on March 1, 2012, 77 FR 12620, Mylan Pharmaceuticals, Inc., 781 Chestnut Ridge Road, Morgantown...), and determined that the registration of Mylan Pharmaceuticals, Inc. to import the basic classes of...

78 FR 46373 - Manufacturer of Controlled Substances; Notice of Registration; Johnson Matthey Pharmaceutical...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

...; Notice of Registration; Johnson Matthey Pharmaceutical Materials, Inc. By Notice dated March 20, 2013, and published in the Federal Register on March 28, 2013, 78 FR 19017, Johnson Matthey Pharmaceutical Materials, Inc., Pharmaceutical Services, 25 Patton Road, Devens, Massachusetts 01434, made application by...

78 FR 33441 - Importer of Controlled Substances; Notice of Registration; Caraco Pharmaceutical Laboratories, LTD

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-04

... Registration; Caraco Pharmaceutical Laboratories, LTD By Notice dated February 8, 2013, and published in the Federal Register on February 21, 2013, 78 FR 12101, Caraco Pharmaceutical Laboratories, Ltd., 270 Prospect... 952(a), and determined that the registration of Caraco Pharmaceutical Laboratories, Ltd., to import...

The good pharmacy practice on Einstein Program at Paraisópolis Community

PubMed Central

de Oliveira, Lara Tânia de Assumpção Domingues Gonçalves; da Silva, Camila Pontes; Guedes, Maria das Vitorias; Sousa, Ana Célia de Oliveira; Sarno, Flávio

2016-01-01

ABSTRACT Objectives: To describe indicators and processes developed and implemented for pharmaceutical assistance at the Einstein Program at Paraisópolis Community pharmacy. Methods: This was a descriptive study of retrospective data from January 2012 to December 2015. Data were obtained from spreadsheets developed for monitoring the productivity and care quality provided at the pharmacy. The evaluated variables were pharmaceutical assistance to prescription, pharmaceutical intervention, orientation (standard and pharmaceutical) and pharmaceutical orientation rate. Results: The pharmacy assisted, on average, 2,308 prescriptions monthly, dispensing 4,871 items, including medications, materials and food supplements. Since March 2015, virtually, the pharmacist analyzed all prescriptions, prior to dispensing. In the analyzed period, there was an increase in monthly pharmaceutical interventions from 7 to 32 on average, and, although there was a decrease in the number of standard orientation, the pharmaceutical orientation had an increase, causing a rise of pharmaceutical orientation rate from 4 to 11%. Conclusion: The processes developed and implemented at the program pharmacy sought to follow the good pharmacy practice, and help patients to make the best use of their medications. PMID:27759833

The application of uniplex, duplex, and multiplex PCR for the absence of specified microorganism testing of pharmaceutical excipients and drug products.

PubMed

Ragheb, Suzan M; Yassin, Aymen S; Amin, Magdy A

2012-01-01

Notable progress has been made in methods that encourage the use of polymerase chain reaction (PCR) as a rapid and accurate tool in microbiological testing of pharmaceuticals. In this study, the detection of the four main specified microorganisms according to the pharmacopeial recommendations, Salmonella spp, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, was optimized in different pharmaceutical dosage forms and raw materials. Uniplex PCR was performed for the detection of each microorganism individually targeting the conserved region in each bacterial genome. Further optimizations were done to perform duplex and multiplex PCR assays considering relative concentrations of competitor primers used in the reaction. The uniplex PCR amplicons were successfully sequenced, confirming the conservation of used primers. Other validation parameters such as specificity, sensitivity, and robustness were examined closely. The method provides a high-throughput screening method to test different pharmaceutical preparations for specified microorganisms for the detection of microbiological contamination. Strict regulations govern the production of pharmaceutical products whether they are sterile or nonsterile. Certain official tests are carried out in microbiology testing laboratory in any pharmaceutical production facility to ensure the pharmaceuticals microbiological quality according to the standard pharmacopeial recommendations. Nonsterile products must be free of specified microorganisms that are used as a check for their quality. Topical preparations must be free of Pseudomonas aeruginosa and Staphylococcus aureus, and oral preparations must be free of Salmonella spp and Escherichia coli. Conventional microbiological methods are time-consuming, labor-intensive, and require long incubation times, resulting in delaying the release of the products. In this study, we tested and validated a polymerase chain reaction identification approach to detect indicator bacteria in pharmaceutical preparations. The method depends on amplification of certain conserved genes located in the four specified bacteria. The method is optimized to be carried out individually or collectively to detect all indicator bacteria in a single reaction in different forms of pharmaceutical products.

[Effectiveness and economic impact of a program of integrated care with telemedicine support on insulin-treated type 2 diabetic patients (Study GITDIABE)].

PubMed

Inoriza, Jose M; Ibañez, Annabel; Pérez-Berruezo, Xavier; Inoriza-Nadal, Cristina; Coderch, Jordi

2017-03-01

To evaluate if insulin-treated type 2 diabetic patients with blood glucose self-monitoring (DIA), included in a program of integrated management of diabetes mellitus (DM), achieve a better level of metabolic control with telemedicine support than with conventional support, after 12 months follow-up. The impact on the use and cost of healthcare services, pharmaceutical expenditure, and consumption of test strips for blood glucose, was also assessed. A prospective parallel cohorts study. Four basic health areas of an integrated healthcare organisation. The study included 126 DIA patients aged 15 or more years, treated with rapid or intermediate Insulin and blood glucose self-monitoring, grouped into 42 cases and 84 controls, matched according to age, sex, level of metabolic control, and morbidity profile. Telematics physician-patient communication and download of blood glucose self-monitoring data through the Emminens eConecta ® platform; test strips home delivered according to consumption. Hidden controls with usual follow-up. Glycosylated haemoglobin (%HbA1c); perception of quality of life (EuroQol-5 and EsDQOL); cardiovascular risk; use of healthcare resources; consumption of test strips; pharmaceutical and healthcare expenditure. Reduction of 0.38% in HbA1c in the cases (95% CI:-0.89% to 0.12%). No significant differences with regard to any of the activities registered, or any significant change in the quality of life. The results obtained are similar to other equivalent studies. The profile of the patient is elderly and with multiple morbidities, who still have technological limitations. To surpass these barriers, it would be necessary to devote more time to the training and to the resolution of possible technological problems. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

[Drug-promoting advertisements in the Dutch Journal of Medicine and Pharmaceutical Weekly: not always evidence based].

PubMed

van Eeden, Annelies E; Roach, Rachel E J; Halbesma, Nynke; Dekker, Friedo W

2012-01-01

To determine and compare the foundation of claims in drug-promoting advertisements in a Dutch journal for physicians and a Dutch journal for pharmacists. A cross-sectional study. We included all the drug-promoting advertisements referring to a randomized controlled trial (RCT) we could find on Medline from 2 volumes of the Dutch Journal of Medicine (Nederlands Tijdschrift voor Geneeskunde; NTvG) and the (also Dutch) Pharmaceutical Weekly (Pharmaceutisch Weekblad; PW). The validity of the advertisements (n = 54) and the methodological quality of the referenced RCTs (n = 150) were independently scored by 250 medical students using 2 standardised questionnaires. The advertisements' sources were concealed from the students. Per journal, the percentage of drug-promoting advertisements having a valid claim and the percentage of high-quality RCT references were determined. Average scores on quality and validity were compared between the 2 journals. On a scale of 0-18 points, the mean quality scores of the RCTs differed 0.3 (95% CI: -0.1-0.7) between the NTvG (score: 14.8; SD: 2.2) and the PW (score: 14.5; SD: 2.6). The difference between the validity scores of drug-promoting advertisements in the NTvG (score: 5.8; SD: 3.3) and the PW (score: 5.6; SD: 3.6) was 0.3 (95% CI: -0.3-0.9) on a scale of 0-10 points. For both journals, an average of 15% of drug-promoting advertisements was valid (defined as a validity score of > 8 points); 35% of the RCTs referred to was of good methodological quality (defined as a quality score of > 16 points). The substantiation of many claims in drug-promoting advertisements in the NTvG and the PW was mediocre. There was no difference between the 2 journals.

21 CFR 26.31 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-04-01

... PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN... under which a party will accept the results of quality system-related evaluations and inspections and...

[Witch hunt and hypotheses loss].

PubMed

Köhler, Dieter

2015-12-01

At this time randomized controlled studies (RCT) in clinical trials usually have high quality. But this quality is only true for the included patients (intrinsic validity). It is common to generalize the results to more or less similar patients. This inductive method is prohibited in epistemology what is known for 250 years (D Hume, K R Popper). Therefore the external validity for the data of RCT is low. To solve this problem additional clinical and pathophysiological based data are necessary to generalize the results. Unfortunately RCT show less quality in their premises. This is partly due to the influence of the pharmaceutical industry. A loss of universality of the hypothesis for RCT decreases basically the extrinsic validity. The articles describe this problem with examples. © Georg Thieme Verlag KG Stuttgart · New York.

Paper Test Cards for Presumptive Testing of Very Low Quality Antimalarial Medications

PubMed Central

Weaver, Abigail A.; Lieberman, Marya

2015-01-01

Carrying out chemical analysis of antimalarials to detect low-quality medications before they reach a patient is a costly venture. Here, we show that a library of chemical color tests embedded on a paper card can presumptively identify formulations corresponding to very low quality antimalarial drugs. The presence or absence of chloroquine (CQ), doxycycline (DOX), quinine, sulfadoxine, pyrimethamine, and primaquine antimalarial medications, in addition to fillers used in low-quality pharmaceuticals, are indicated by patterns of colors that are generated on the test cards. Test card sensitivity for detection of these pure components ranges from 90% to 100% with no false positives in the absence of pharmaceutical. The color intensities from reactions characteristic of CQ or DOX allowed visual detection of formulations of these medications cut with 60% or 100% filler, although samples cut with 30% filler could not be reliably detected colorimetrically. However, the addition of unexpected fillers, even in 30% quantities, or substitute pharmaceuticals, could sometimes be detected by other color reactions on the test cards. Tests are simple and inexpensive enough to be carried out in clinics, pharmacies, and ports of entry and could provide a screening method to presumptively indicate very low quality medicines throughout the supply chain. PMID:25897064

Supercritical carbon dioxide processing of active pharmaceutical ingredients for polymorphic control and for complex formation.

PubMed

Moribe, Kunikazu; Tozuka, Yuichi; Yamamoto, Keiji

2008-02-14

Supercritical fluid technique have been exploited in extraction, separation and crystallization processes. In the field of pharmaceutics, supercritical carbon dioxide (scCO(2)) has been used for the purpose of micronization, polymorphic control, and preparation of solid dispersion and complexes. Particle design of active pharmaceutical ingredients is important to make the solid dosage forms with suitable physicochemical properties. Control of the characteristic properties of particles, such as size, shape, crystal structure and morphology is required to optimize the formulation. For solubility enhancement of poorly water-soluble drugs, preparation of the solid dispersion or the complexation with proper drugs or excipients should be a promising approach. This review focuses on aspects of polymorphic control and complexation behavior of active pharmaceutical ingredients by scCO(2) processing.

How we make cell therapy in Italy.

PubMed

Montemurro, Tiziana; Viganò, Mariele; Budelli, Silvia; Montelatici, Elisa; Lavazza, Cristiana; Marino, Luigi; Parazzi, Valentina; Lazzari, Lorenza; Giordano, Rosaria

2015-01-01

In the 21st century scenario, new therapeutic tools are needed to take up the social and medical challenge posed by the more and more frequent degenerative disorders and by the aging of population. The recent category of advanced therapy medicinal products has been created to comprise cellular, gene therapy, and tissue engineered products, as a new class of drugs. Their manufacture requires the same pharmaceutical framework as for conventional drugs and this means that industrial, large-scale manufacturing process has to be adapted to the peculiar characteristics of cell-containing products. Our hospital took up the challenge of this new path in the early 2000s; and herein we describe the approach we followed to set up a pharmaceutical-grade facility in a public hospital context, with the aim to share the solutions we found to make cell therapy compliant with the requirements for the production and the quality control of a high-standard medicinal product.

Pharmaceutical development of a parenteral formulation of the novel anti-tumor agent carzelesin (U-80,244).

PubMed

Jonkman-de Vries, J D; de Graaff-Teulen, M J; Henrar, R E; Kettenes-van den Bosch, J J; Bult, A; Beijnen, J H

1994-01-01

The aim of this study was to design a parenteral dosage form for the investigational cytotoxic drug carzelesin. A stable formulation in PET (Polyethylene glycol 400/absolute ethanol/Tween 80, 6:3:1, v/v/v) was developed. The prototype, containing 0.50 mg carzelesin in 2.0 ml PET formulation, was found to be the optimal formulation in terms of solubility, stability and dosage requirements in phase I clinical trials. Quality control of the formulation showed that the pharmaceutical preparation of carzelesin in PET is not negatively influenced by the manufacturing process. Shelf life studies demonstrated that the formulation is stable for at least 1 year, when stored at -30 degrees C in the dark. In addition, the stability of carzelesin in the PET formulation is discussed as a function of temperature, additives and after dilution in infusion fluids.

ICP-MS: Analytical Method for Identification and Detection of Elemental Impurities.

PubMed

Mittal, Mohini; Kumar, Kapil; Anghore, Durgadas; Rawal, Ravindra K

2017-01-01

Aim of this article is to review and discuss the currently used quantitative analytical method ICP-MS, which is used for quality control of pharmaceutical products. ICP-MS technique has several applications such as determination of single elements, multi element analysis in synthetic drugs, heavy metals in environmental water, trace element content of selected fertilizers and dairy manures. ICP-MS is also used for determination of toxic and essential elements in different varieties of food samples and metal pollutant present in the environment. The pharmaceuticals may generate impurities at various stages of development, transportation and storage which make them risky to be administered. Thus, it is essential that these impurities must be detected and quantified. ICP-MS plays an important function in the recognition and revealing of elemental impurities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Pharmaceutical considerations of nitroglycerin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yacobi, A.; Amann, A.H.; Baaske, D.M.

1983-04-01

During the past few years, there have been rapid changes in the pharmaceutical uses of nitroglycerin. New dosage forms and new delivery systems have become available, which have resulted in potential confusion to all concerned with the proper use of these systems. The goal of this review is to prevent confusion and to bring all the relevant information together. The various analytical techniques available for quality control of the dosage forms and for the study of the pharmacokinetics are reviewed, with the intent of enabling the reader to identify pertinent references rapidly. The interaction of nitroglycerin with packaging and plasticmore » delivery devices is also reviewed so that the reader can make informed choices. Finally, the clinical pharmacy and pharmacokinetics are reviewed so as to bring the reader up to date in that area. After reading this article, the areas of nitroglycerin research that still need to be explored should be apparent.« less

Practice of Regulatory Science (Drug Development).

PubMed

Kawanishi, Toru

2017-01-01

The practice of regulatory science (RS) for drug development is described. In the course material for education in pharmaceutical sciences drafted by the RS Division of the Pharmaceutical Society of Japan, RS for pharmaceuticals is defined as the science of predicting, assessing, and judging the quality, efficacy, and safety of pharmaceutical products throughout their lifespan. RS is also described as an integrated science based on basic and applied biomedical sciences, including analytical chemistry, biochemistry, pharmacology, toxicology, genetics, biostatistics, epidemiology, and clinical trial methodology, and social sciences such as decision science, risk assessment, and communication science. The involvement of RS in drug development generally starts after the optimization of lead compounds. RS plays important roles governing pharmaceuticals during their entire life cycle management phase as well as the drug development phase.

Development and validation of chromatographic methods (HPLC and GC) for the determination of the active components (benzocaine, tyrothricin and menthol) of a pharmaceutical preparation.

PubMed

Ortiz-Boyer, F; Tena, M T; Luque de Castro, M D; Valcárcel, M

1995-10-01

Methods are reported for the determination of tyrothricin and benzocaine by HPLC and menthol by GC in the analysis of throat lozenges (tablets) containing all three compounds. After optimization of the variables involved in both HPLC and GC the methods have been characterized and validated according to the guidelines of the Spanish Pharmacopoeia, and applied to both the monitoring of the manufacturing process and the quality control of the final product.

Recent Regulatory Trends in Pharmaceutical Manufacturing and their Impact on the Industry.

PubMed

Tabersky, Daniel; Woelfle, Michael; Ruess, Juan-Antonio; Brem, Simon; Brombacher, Stephan

2018-03-30

The pharmaceutical industry is one of the most regulated industries in Switzerland. Though the concept of good manufacturing practises (GMP) was implemented for chemical production in the early 1990s, the rules and regulations for our industry are in constant evolution. In this article we will highlight the impact of these changes to the industry using three recent guideline up-dates as examples: the implementation of ICH Q3D 'Guideline for elemental impurities', the EU-GMP Guideline Part III Chapter 'Guideline on setting health based exposure limits for use in risk identification in the manufacture of different medicinal products in shared facilities' from 01. June 2015, and the new guidelines to data integrity such as 'PIC/S 041-1 Good Practices for Data Management and Integrity in regulated GMP/GDP environments'. These examples show how scientific approaches help to modernize the control strategies for our products and increase product quality for a better patient safety. The requirements of data integrity regulations are also of interest to industries and universities not working under GxP requirements as they also support the business to improve data quality (traceability) for patent applications, and reduce risk of data falsification.

Minimizing variability of cascade impaction measurements in inhalers and nebulizers.

PubMed

Bonam, Matthew; Christopher, David; Cipolla, David; Donovan, Brent; Goodwin, David; Holmes, Susan; Lyapustina, Svetlana; Mitchell, Jolyon; Nichols, Steve; Pettersson, Gunilla; Quale, Chris; Rao, Nagaraja; Singh, Dilraj; Tougas, Terrence; Van Oort, Mike; Walther, Bernd; Wyka, Bruce

2008-01-01

The purpose of this article is to catalogue in a systematic way the available information about factors that may influence the outcome and variability of cascade impactor (CI) measurements of pharmaceutical aerosols for inhalation, such as those obtained from metered dose inhalers (MDIs), dry powder inhalers (DPIs) or products for nebulization; and to suggest ways to minimize the influence of such factors. To accomplish this task, the authors constructed a cause-and-effect Ishikawa diagram for a CI measurement and considered the influence of each root cause based on industry experience and thorough literature review. The results illustrate the intricate network of underlying causes of CI variability, with the potential for several multi-way statistical interactions. It was also found that significantly more quantitative information exists about impactor-related causes than about operator-derived influences, the contribution of drug assay methodology and product-related causes, suggesting a need for further research in those areas. The understanding and awareness of all these factors should aid in the development of optimized CI methods and appropriate quality control measures for aerodynamic particle size distribution (APSD) of pharmaceutical aerosols, in line with the current regulatory initiatives involving quality-by-design (QbD).

21 CFR 26.19 - Information relating to quality aspects.

Code of Federal Regulations, 2010 CFR

2010-04-01

... MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS, AND CERTAIN MEDICAL DEVICE PRODUCT EVALUATION REPORTS: UNITED STATES AND THE EUROPEAN...

Application of a tablet film coating model to define a process-imposed transition boundary for robust film coating.

PubMed

van den Ban, Sander; Pitt, Kendal G; Whiteman, Marshall

2018-02-01

A scientific understanding of interaction of product, film coat, film coating process, and equipment is important to enable design and operation of industrial scale pharmaceutical film coating processes that are robust and provide the level of control required to consistently deliver quality film coated product. Thermodynamic film coating conditions provided in the tablet film coating process impact film coat formation and subsequent product quality. A thermodynamic film coating model was used to evaluate film coating process performance over a wide range of film coating equipment from pilot to industrial scale (2.5-400 kg). An approximate process-imposed transition boundary, from operating in a dry to a wet environment, was derived, for relative humidity and exhaust temperature, and used to understand the impact of the film coating process on product formulation and process control requirements. This approximate transition boundary may aid in an enhanced understanding of risk to product quality, application of modern Quality by Design (QbD) based product development, technology transfer and scale-up, and support the science-based justification of critical process parameters (CPPs).

High Speed Video Applications In The Pharmaceutical Industry

NASA Astrophysics Data System (ADS)

Stapley, David

1985-02-01

The pursuit of quality is essential in the development and production of drugs. The pursuit of excellence is relentless, a never ending search. In the pharmaceutical industry, we all know and apply wide-ranging techniques to assure quality production. We all know that in reality none of these techniques are perfect for all situations. We have all experienced, the damaged foil, blister or tube, the missing leaflet, the 'hard to read' batch code. We are all aware of the need to supplement the traditional techniques of fault finding. This paper shows how high speed video systems can be applied to fully automated filling and packaging operations as a tool to aid the company's drive for high quality and productivity. The range of products involved totals some 350 in approximately 3,000 pack variants, encompassing creams, ointments, lotions, capsules, tablets, parenteral and sterile antibiotics. Pharmaceutical production demands diligence at all stages, with optimum use of the techniques offered by the latest technology. Figure 1 shows typical stages of pharmaceutical production in which quality must be assured, and highlights those stages where the use of high speed video systems have proved of value to date. The use of high speed video systems begins with the very first use of machine and materials: commissioning and validation, (the term used for determining that a process is capable of consistently producing the requisite quality) and continues to support inprocess monitoring, throughout the life of the plant. The activity of validation in the packaging environment is particularly in need of a tool to see the nature of high speed faults, no matter how infrequently they occur, so that informed changes can be made precisely and rapidly. The prime use of this tool is to ensure that machines are less sensitive to minor variations in component characteristics.

Investigation into the use of microwave sensors to monitor particulate manufacturing processes

NASA Astrophysics Data System (ADS)

Austin, John Samuel, III

Knowledge of a material's properties in-line during manufacture is of critical importance to many industries, including the pharmaceutical industry, and can be used for either process or quality control. Different microwave sensor configurations were tested to determine both the moisture content and the bulk density in pharmaceutical powders during processing on-line. Although these parameters can significantly affect a material's flowability, compressibility, and cohesivity, in the presence of blends, the picture is incomplete. Due to the ease with which particulate blends tend to segregate, blend uniformity and chemical composition are two critical parameters in nearly all solids manufacturing industries. The prevailing wisdom has been that microwave sensors are not capable of or sensitive enough to measure the relative concentrations of components in a blend. Consequently, it is common to turn to near infrared sensing to determine material composition on-line. In this study, a novel microwave sensor was designed and utilized to determine, separately, the concentrations of different components in a blend of pharmaceutical powders. This custom microwave sensor was shown to have comparable accuracy to the state-of-the-art for both chemical composition and moisture content determination.

Absolutely nondestructive discrimination of Huoshan Dendrobium nobile species with miniature near-infrared (NIR) spectrometer engine.

PubMed

Hu, Tian; Yang, Hai-Long; Tang, Qing; Zhang, Hui; Nie, Lei; Li, Lian; Wang, Jin-Feng; Liu, Dong-Ming; Jiang, Wei; Wang, Fei; Zang, Heng-Chang

2014-10-01

As one very precious traditional Chinese medicine (TCM), Huoshan Dendrobium has not only high price, but also significant pharmaceutical efficacy. However, different species of Huoshan Dendrobium exhibit considerable difference in pharmaceutical efficacy, so rapid and absolutely non-destructive discrimination of Huoshan Dendrobium nobile according to different species is crucial to quality control and pharmaceutical effect. In this study, as one type of miniature near-infrared (NIR) spectrometer, MicroNIR 1700 was used for absolutely nondestructive determination of NIR spectra of 90 batches of Dendrobium from five species of differ- ent commodity grades. The samples were intact and not smashed. Soft independent modeling of class analogy (SIMCA) pattern recognition based on principal component analysis (PCA) was used to classify and recognize different species of Dendrobium samples. The results indicated that the SIMCA qualitative models established with pretreatment method of standard normal variate transformation (SNV) in the spectra range selected by Qs method had 100% recognition rates and 100% rejection rates. This study demonstrated that a rapid and absolutely non-destructive analytical technique based on MicroNIR 1700 spectrometer was developed for successful discrimination of five different species of Huoshan Dendrobium with acceptable accuracy.

Micro Computer Tomography for medical device and pharmaceutical packaging analysis.

PubMed

Hindelang, Florine; Zurbach, Raphael; Roggo, Yves

2015-04-10

Biomedical device and medicine product manufacturing are long processes facing global competition. As technology evolves with time, the level of quality, safety and reliability increases simultaneously. Micro Computer Tomography (Micro CT) is a tool allowing a deep investigation of products: it can contribute to quality improvement. This article presents the numerous applications of Micro CT for medical device and pharmaceutical packaging analysis. The samples investigated confirmed CT suitability for verification of integrity, measurements and defect detections in a non-destructive manner. Copyright © 2015 Elsevier B.V. All rights reserved.

Description of the Protocols for Randomized Controlled Trials on Cancer Drugs Conducted in Spain (1999–2003)

PubMed Central

Bonfill, Xavier; Ballesteros, Mónica; Gich, Ignasi; Serrano, María Antonia; García López, Fernando; Urrútia, Gerard

2013-01-01

Objective To describe the characteristics of randomized controlled clinical trials (RCT) on cancer drugs conducted in Spain between 1999 and 2003 based on their protocols. Methods We conducted an observational retrospective cohort study to identify the protocols of RCTs on cancer drugs authorized by the Agencia Española del Medicamento y Productos Sanitarios (AEMPS) (Spanish Agency for Medicines and Medical Devices) during 1999-2003. A descriptive analysis was completed and the association between variables based on the study setting and sponsorship were assessed. Results We identified a total of 303 protocols, which included 176,835 potentially eligible patients. Three-quarter of the studies were internationally-based, 61.7% were phase III, and 76.2% were sponsored by pharmaceutical companies. The most frequently assessed outcomes were response rate (24.7%), overall survival (20.7%), and progression-free survival (14.5%). Of all protocols, 10.6% intended to include more than 1000 patients (mean: 2442, SD: 2724). Compared with their national counterparts, internationally-based studies were significantly larger (p<0.001) and were more likely to implement centralized randomization (p<0.001), blinding of the intervention (p<0.001), and survival as primary outcome (p<0.001). Additionally, most internationally-based studies were sponsored by pharmaceutical companies (p<0.01). In a high percentage of protocols, the available information was not explicit enough to assess the validity of each trial. Compared to other European countries, the proportion of Spanish cancer drugs protocols registered at www.clinicaltrials.gov (7%) was lower. Conclusion RCTs on cancer drugs conducted in Spain between 1999 and 2003 were more likely to be promoted by pharmaceutical companies rather than by non-profit national groups. The former were more often part of international studies, which generally had better methodological quality than national ones. There are some worldwide on-going initiatives that aim to increase the transparency and quality of future research. PMID:24236154

Validated spectroscopic methods for determination of anti-histaminic drug azelastine in pure form: Analytical application for quality control of its pharmaceutical preparations

NASA Astrophysics Data System (ADS)

El-Masry, Amal A.; Hammouda, Mohammed E. A.; El-Wasseef, Dalia R.; El-Ashry, Saadia M.

2018-02-01

Two simple, sensitive, rapid, validated and cost effective spectroscopic methods were established for quantification of antihistaminic drug azelastine (AZL) in bulk powder as well as in pharmaceutical dosage forms. In the first method (A) the absorbance difference between acidic and basic solutions was measured at 228 nm, whereas in the second investigated method (B) the binary complex formed between AZL and Eosin Y in acetate buffer solution (pH 3) was measured at 550 nm. Different criteria that have critical influence on the intensity of absorption were deeply studied and optimized so as to achieve the highest absorption. The proposed methods obeyed Beer's low in the concentration range of (2.0-20.0 μg·mL- 1) and (0.5-15.0 μg·mL- 1) with % recovery ± S.D. of (99.84 ± 0.87), (100.02 ± 0.78) for methods (A) and (B), respectively. Furthermore, the proposed methods were easily applied for quality control of pharmaceutical preparations without any conflict with its co-formulated additives, and the analytical results were compatible with those obtained by the comparison one with no significant difference as insured by student's t-test and the variance ratio F-test. Validation of the proposed methods was performed according the ICH guidelines in terms of linearity, limit of quantification, limit of detection, accuracy, precision and specificity, where the analytical results were persuasive. The absorption spectrum of AZL (16 μg·mL- 1) in 0.1 M HCl. The absorption spectrum of AZL (16 μg·mL- 1) in 0.1 M NaOH. The difference absorption spectrum of AZL (16 μg·mL- 1) in 0.1 M NaOH vs 0.1 M HCl. The absorption spectrum of eosin binary complex with AZL (10 μg·mL- 1).

Application of quality risk management to set viable environmental monitoring frequencies in biotechnology processing and support areas.

PubMed

Sandle, Tim

2012-01-01

Environmental monitoring programs are essential for pharmaceutical facilities in order to assess the level of environmental control. For biotechnology facilities there is little advice as to the frequency at which viable environmental monitoring should be conducted. This paper outlines an approach, based on the principles of quality risk management, for the development of a framework from which monitoring frequencies can be determined. This involved the identification of common hazards and the evaluation those hazards in terms of the severity of contamination and the probability of contamination occurring. These elements of risk were evaluated for different cleanrooms and the relative risks ranked. Once the risk scores were calculated, the methods for detecting risks within the cleanrooms were assessed. Risk filtering was then used to group different cleanrooms based on their relative risks and detection methods against predetermined monitoring frequencies. Through use of case study examples, the paper presents the model and describes how appropriate frequencies for the environmental monitoring of cleanrooms can be set. Cleanrooms in which biotechnology pharmaceutical processing takes place are subject to environmental monitoring. The frequency at which such monitoring should be performed can be difficult to determine. This paper uses quality risk assessment methods to construct a framework for determining monitoring frequencies and illustrates the suitability of the framework through a case study.

Quality assessment of pharmaceutical tablet samples using Fourier transform near infrared spectroscopy and multivariate analysis

NASA Astrophysics Data System (ADS)

Kandpal, Lalit Mohan; Tewari, Jagdish; Gopinathan, Nishanth; Stolee, Jessica; Strong, Rick; Boulas, Pierre; Cho, Byoung-Kwan

2017-09-01

Determination of the content uniformity, assessed by the amount of an active pharmaceutical ingredient (API), and hardness of pharmaceutical materials is important for achieving a high-quality formulation and to ensure the intended therapeutic effects of the end-product. In this work, Fourier transform near infrared (FT-NIR) spectroscopy was used to determine the content uniformity and hardness of a pharmaceutical mini-tablet and standard tablet samples. Tablet samples were scanned using an FT-NIR instrument and tablet spectra were collected at wavelengths of 1000-2500 nm. Furthermore, multivariate analysis was applied to extract the relationship between the FT-NIR spectra and the measured parameters. The results of FT-NIR spectroscopy for API and hardness prediction were as precise as the reference high-performance liquid chromatography and mechanical hardness tests. For the prediction of mini-tablet API content, the highest coefficient of determination for the prediction (R2p) was found to be 0.99 with a standard error of prediction (SEP) of 0.72 mg. Moreover, the standard tablet hardness measurement had a R2p value of 0.91 with an SEP of 0.25 kg. These results suggest that FT-NIR spectroscopy is an alternative and accurate nondestructive measurement tool for the detection of the chemical and physical properties of pharmaceutical samples.

78 FR 52802 - Manufacturer of Controlled Substances; Notice of Registration; Morton Grove Pharmaceuticals

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-26

...; Notice of Registration; Morton Grove Pharmaceuticals By Notice dated March 12, 2013, and published in the Federal Register on March 20, 2013, 78 FR 17231, Morton Grove Pharmaceuticals, 6451 Main Street, Morton... 21 U.S.C. 823(a), and determined that the registration of Morton Grove Pharmaceuticals to manufacture...

78 FR 46371 - Importer of Controlled Substances; Notice of Registration; Meda Pharmaceuticals, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-31

... Registration; Meda Pharmaceuticals, Inc. By Notice dated February 8, 2013, and published in the Federal Register on February 21, 2013, 78 FR 12101, Meda Pharmaceuticals, Inc., 705 Eldorado Street, Decatur... 21 U.S.C. 823(a) and 952(a), and determined that the registration of Meda Pharmaceuticals Inc., to...

78 FR 5503 - Manufacturer of Controlled Substances, Notice of Registration; Morton Grove Pharmaceuticals

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

..., Notice of Registration; Morton Grove Pharmaceuticals By Notice dated September 25, 2012, and published in the Federal Register on October 2, 2012, 77 FR 60144, Morton Grove Pharmaceuticals, 6451 Main Street... the factors in 21 U.S.C. 823(a), and determined that the registration of Morton Grove Pharmaceuticals...

77 FR 75672 - Manufacturer of Controlled Substances, Notice of Registration, Halo Pharmaceutical, Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-21

..., Notice of Registration, Halo Pharmaceutical, Inc. By Notice dated July 30, 2012, and published in the Federal Register on August 7, 2012, 77 FR 47114, Halo Pharmaceutical, Inc., 30 North Jefferson Road... 21 U.S.C. 823(a), and determined that the registration of Halo Pharmaceutical, Inc., to manufacture...

77 FR 47078 - 2012 Parenteral Drug Association/Food and Drug Administration Joint Regulatory Conference...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-07

... of today's leading pharmaceutical companies present case studies on how they employ global strategies... Through Quality Systems: Implementing and Advancing a Sustainable Global Quality Culture AGENCY: Food and... entitled ``Compliance Through Quality Systems: Implementing and Advancing a Sustainable Global Quality...

21 CFR 26.19 - Information relating to quality aspects.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Information relating to quality aspects. 26.19... relating to quality aspects. The authorities will establish an appropriate means of exchanging information... MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM...

21 CFR 26.19 - Information relating to quality aspects.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Information relating to quality aspects. 26.19... relating to quality aspects. The authorities will establish an appropriate means of exchanging information... MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM...

21 CFR 26.19 - Information relating to quality aspects.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Information relating to quality aspects. 26.19... relating to quality aspects. The authorities will establish an appropriate means of exchanging information... MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM...

21 CFR 26.19 - Information relating to quality aspects.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Information relating to quality aspects. 26.19... relating to quality aspects. The authorities will establish an appropriate means of exchanging information... MUTUAL RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM...

The antidepressant fluoxetine alters mechanisms of pre- and post-copulatory sexual selection in the eastern mosquitofish (Gambusia holbrooki).

PubMed

Bertram, Michael G; Ecker, Tiarne E; Wong, Bob B M; O'Bryan, Moira K; Baumgartner, John B; Martin, Jake M; Saaristo, Minna

2018-03-19

Contamination of aquatic habitats with pharmaceuticals is a major environmental concern. Recent studies have detected pharmaceutical pollutants in a wide array of ecosystems and organisms, with many of these contaminants being highly resistant to biodegradation and capable of eliciting sub-lethal effects in non-target species. One such pollutant is fluoxetine, a widely prescribed antidepressant, which is frequently detected in surface waters globally and can alter physiology and behaviour in aquatic organisms. Despite this, relatively little is known about the potential for fluoxetine to disrupt mechanisms of sexual selection. Here, we investigate the impacts of 30-day exposure to two environmentally realistic levels of fluoxetine (low and high) on mechanisms of pre- and post-copulatory sexual selection in the eastern mosquitofish (Gambusia holbrooki). We tested 1) male mating behaviour in the absence or presence of a competitor male, and 2) sperm quality and quantity. We found that high-fluoxetine exposure increased male copulatory behaviour in the absence of a competitor, while no effect was detected under male-male competition. Further, fluoxetine exposure at both concentrations increased total sperm count relative to males from the control group, while no significant change in sperm quality was observed. Lastly, low-fluoxetine males showed a significant reduction in condition index (mass relative to length). Our study is the first to show altered mechanisms of both pre- and post-copulatory sexual selection in an aquatic species resulting from environmentally realistic fluoxetine exposure, highlighting the capacity of pharmaceutical pollution to interfere with sensitive reproductive processes in wildlife. Copyright © 2018 Elsevier Ltd. All rights reserved.

Regulatory Science in Practice (Pharmaceuticals and Medical Devices Agency).

PubMed

Hojo, Taisuke

2017-01-01

Review, safety, and relief services of the Pharmaceuticals and Medical Devices Agency are primarily focused on scientifically evaluating pharmaceuticals, medical devices, and cellular and tissue-based products referring to their quality, efficacy, and safety, which requires a variety of scientific knowledge and methods. Pharmaceutical regulation should be established based on the most advanced scientific expertise at all times. In order to evaluate products that use cutting-edge technology such as induced pluripotent stem cells and information and communication technology adequately, since fiscal year 2012 the Science Committee has been established as a platform to exchange opinions among members from top-ranking domestic and international academia and to enhance personnel exchanges through the Initiative to Facilitate Development of Innovative Drugs. In addition, the Regulatory Science Center will be established in 2018 to increase the integrity of our services for product reviews and safety measures. In particular, requiring electronic data submissions for clinical trial applications followed by an advanced approach to analysis should not only enhance the quality of reviews of individual products but should also support the development of pharmaceuticals and medical devices by providing pharmaceutical affairs consultations on research and development strategies with various guidelines based on new insights resulting from product-bridging data analysis. Moreover, a database including electronic health records with comprehensive medical information collected mainly from 10 cooperating medical institutions will be developed with the aim of developing safety measures in a more timely manner using methods of pharmacoepidemiological analysis.

[An example of self-evaluation of a sense of achievement by students in 6-year pharmacy school with the model core curriculum of pharmaceutical education].

PubMed

Shingaki, Tomoteru; Koyanagi, Jyunichi; Nakamura, Hiroshi; Hirata, Takahiro; Ohta, Atsutane; Akimoto, Masayuki; Shirahata, Akira; Mitsumoto, Atsushi

2013-01-01

In March 2012, the first students, finishing the newly introduced 6-year-course of pharmaceutical education, have graduated and gone out into the world. At this point, the Ministry of Education, Culture, Sports, Science and Technology (MEXT) is going to revise the model core curriculum of pharmaceutical education to be more suited for educating students to achieve their goal of becoming the clinical pharmacist standard defined by the revised School Education Act. Here we report the self-evaluation study based on the survey using questionnaire about a sense of achievement with Visual Analog Scales, regarding the fundamental quality as a pharmacist standard proposed by the Professional Activities Committee in the MEXT. The sample size of survey was about 600 of students studying in the Faculty of Pharmaceutical Sciences in Josai International University (JIU) and the survey was carried out during the period of March-April in 2012. The study suggested that the majority of graduates were satisfied with the new education system and marked as a well-balanced quality to be a pharmacist standard, after completing the 6-year pharmaceutical education based on "the model core-curriculum". It would be worthwhile to perform this kind of survey continuously to monitor the student's self-evaluation of a sense of achievement to verify the effectiveness of 6-year-course pharmaceutical education based on the newly establishing core curriculum in Japan.

Quantitative structure-activity relationship models that stand the test of time.

PubMed

Davis, Andrew M; Wood, David J

2013-04-01

The pharmaceutical industry is in a period of intense change. While this has many drivers, attrition through the development process continues to be an important pressure. The emerging definitions of "compound quality" that are based on retrospective analyses of developmental attrition have highlighted a new direction for medicinal chemistry and the paradigm of "quality at the point of design". The time has come for retrospective analyses to catalyze prospective action. Quality at the point of design places pressure on the quality of our predictive models. Empirical QSAR models when built with care provide true predictive control, but their accuracy and precision can be improved. Here we describe AstraZeneca's experience of automation in QSAR model building and validation, and how an informatics system can provide a step-change in predictive power to project design teams, if they choose to use it.

Systematic review and quality assessment of cost-effectiveness analysis of pharmaceutical therapies for advanced colorectal cancer.

PubMed

Leung, Henry W C; Chan, Agnes L F; Leung, Matthew S H; Lu, Chin-Li

2013-04-01

To systematically review and assess the quality of cost-effectiveness analyses (CEAs) of pharmaceutical therapies for metastatic colorectal cancer (mCRC). The MEDLINE, EMBASE, Cochrane, and EconLit databases were searched for the Medical Subject Headings or text key words quality-adjusted, QALY, life-year gained (LYG), and cost-effectiveness (January 1, 1999-December 31, 2009). Original CEAs of mCRC pharmacotherapy published in English were included. CEAs that measured health effects in units other than quality-adjusted life years or LYG and letters to the editor, case reports, posters, and editorials were excluded. Each article was independently assessed by 2 trained reviewers according to a quality checklist created by the Panel on Cost-Effectiveness in Health and Medicine. Twenty-four CEA studies pertaining to pharmaceutical therapies for mCRC were identified. All studies showed a wide variation in methodologic approaches, which resulted in a different range of incremental cost-effectiveness ratios reported for each regimen. We found common methodologic flaws in a significant number of CEA studies, including lack of clear description for critique of data quality; lack of method for adjusting costs for inflation and methods for obtaining expert judgment; no results of model validation; wide differences in the types of perspective, time horizon, study design, cost categories, and effect outcomes; and no quality assessment of data (cost and effectiveness) for the interventions evaluation. This study has shown a wide variation in the methodology and quality of cost-effectiveness analysis for mCRC. Improving quality and harmonization of CEA for cancer treatment is needed. Further study is suggested to assess the quality of CEA methodology outside the mCRC disease state.

Importance and globalization status of good manufacturing practice (GMP) requirements for pharmaceutical excipients

PubMed Central

Abdellah, Abubaker; Noordin, Mohamed Ibrahim; Wan Ismail, Wan Azman

2013-01-01

Pharmaceutical excipients are no longer inert materials but it is effective and able to improve the characteristics of the products’ quality, stability, functionality, safety, solubility and acceptance of patients. It can interact with the active ingredients and alter the medicament characteristics. The globalization of medicines’ supply enhances the importance of globalized good manufacturing practice (GMP) requirements for pharmaceutical excipients. This review was intended to assess the globalization status of good manufacturing practice (GMP) requirements for pharmaceutical excipients. The review outcomes demonstrate that there is a lack of accurately defined methods to evaluate and measure excipients’ safety. Furthermore good manufacturing practice requirements for excipients are not effectively globalized. PMID:25685037

Real time monitoring of powder blend bulk density for coupled feed-forward/feed-back control of a continuous direct compaction tablet manufacturing process.

PubMed

Singh, Ravendra; Román-Ospino, Andrés D; Romañach, Rodolfo J; Ierapetritou, Marianthi; Ramachandran, Rohit

2015-11-10

The pharmaceutical industry is strictly regulated, where precise and accurate control of the end product quality is necessary to ensure the effectiveness of the drug products. For such control, the process and raw materials variability ideally need to be fed-forward in real time into an automatic control system so that a proactive action can be taken before it can affect the end product quality. Variations in raw material properties (e.g., particle size), feeder hopper level, amount of lubrication, milling and blending action, applied shear in different processing stages can affect the blend density significantly and thereby tablet weight, hardness and dissolution. Therefore, real time monitoring of powder bulk density variability and its incorporation into the automatic control system so that its effect can be mitigated proactively and efficiently is highly desired. However, real time monitoring of powder bulk density is still a challenging task because of different level of complexities. In this work, powder bulk density which has a significant effect on the critical quality attributes (CQA's) has been monitored in real time in a pilot-plant facility, using a NIR sensor. The sensitivity of the powder bulk density on critical process parameters (CPP's) and CQA's has been analyzed and thereby feed-forward controller has been designed. The measured signal can be used for feed-forward control so that the corrective actions on the density variations can be taken before they can influence the product quality. The coupled feed-forward/feed-back control system demonstrates improved control performance and improvements in the final product quality in the presence of process and raw material variations. Copyright © 2015 Elsevier B.V. All rights reserved.

The Impact of Granule Density on Tabletting and Pharmaceutical Product Performance.

PubMed

van den Ban, Sander; Goodwin, Daniel J

2017-05-01

The impact of granule densification in high-shear wet granulation on tabletting and product performance was investigated, at pharmaceutical production scale. Product performance criteria need to be balanced with the need to deliver manufacturability criteria to assure robust industrial scale tablet manufacturing processes. A Quality by Design approach was used to determine in-process control specifications for tabletting, propose a design space for disintegration and dissolution, and to understand the permitted operating limits and required controls for an industrial tabletting process. Granules of varying density (filling density) were made by varying water amount added, spray rate, and wet massing time in a design of experiment (DoE) approach. Granules were compressed into tablets to a range of thicknesses to obtain tablets of varying breaking force. Disintegration and dissolution performance was evaluated for the tablets made. The impact of granule filling density on tabletting was rationalised with compressibility, tabletability and compactibility. Tabletting and product performance criteria provided competing requirements for porosity. An increase in granule filling density impacted tabletability and compactability and limited the ability to achieve tablets of adequate mechanical strength. An increase in tablet solid fraction (decreased porosity) impacted disintegration and dissolution. An attribute-based design space for disintegration and dissolution was specified to achieve both product performance and manufacturability. The method of granulation and resulting granule filling density is a key design consideration to achieve both product performance and manufacturability required for modern industrial scale pharmaceutical product manufacture and distribution.

Systematic screening of common wastewater-marking pharmaceuticals in urban aquatic environments: implications for environmental risk control.

PubMed

Zhou, Haidong; Zhang, Qingjun; Wang, Xuelian; Zhang, Qianqian; Ma, Lixin; Zhan, Yong

2014-01-01

In this report, we refer to pharmaceuticals that are widespread in the urban aquatic environment and that mainly originate from wastewater treatment plants or non-point source sewage as "wastewater-marking pharmaceuticals" (WWMPs). To some extent, they reflect the condition or trend of water contamination and also contribute to aquatic environmental risk assessment. The method reported here for screening typical WWMPs was proposed based on academic concerns about them and their concentrations present in the urban aquatic environment, as well as their properties of accumulation, persistence, eco-toxicity and related environmental risks caused by them. The screening system consisted of an initial screening system and a further screening system. In the former, pharmaceuticals were categorised into different evaluation levels, and in the latter, each pharmaceutical was given a normalised final evaluation score, which was the sum of every score for its properties of accumulation, persistence, eco-toxicity and environmental risk in the aquatic environment. The system was applied to 126 pharmaceuticals frequently detected in the aquatic environment. In the initial screening procedure, five pharmaceuticals were classified into the "high" category, 16 pharmaceuticals into the "medium" category, 15 pharmaceuticals into the "low" category and 90 pharmaceuticals into the "very low" category. Subsequently, further screening were conducted on 36 pharmaceuticals considered as being of "high", "medium" and "low" categories in the former system. We identified 7 pharmaceuticals with final evaluation scores of 1-10, 10 pharmaceuticals with scores of 11-15, 15 pharmaceuticals with scores from 16 to 20 and 4 pharmaceuticals with scores above 21. The results showed that this screening system could contribute to the effective selection of target WWMPs, which would be important for spatial-temporal dynamics, transference and pollution control of pharmaceuticals in the urban aquatic environment. However, there remains a number of pharmaceutical parameters with measured data gaps, such as organic carbon adsorption coefficients and bioconcentration factors, which, if filled, would improve the accuracy of the screening system.

Pharmaceutical supply chain risk assessment in Iran using analytic hierarchy process (AHP) and simple additive weighting (SAW) methods.

PubMed

Jaberidoost, Mona; Olfat, Laya; Hosseini, Alireza; Kebriaeezadeh, Abbas; Abdollahi, Mohammad; Alaeddini, Mahdi; Dinarvand, Rassoul

2015-01-01

Pharmaceutical supply chain is a significant component of the health system in supplying medicines, particularly in countries where main drugs are provided by local pharmaceutical companies. No previous studies exist assessing risks and disruptions in pharmaceutical companies while assessing the pharmaceutical supply chain. Any risks affecting the pharmaceutical companies could disrupt supply medicines and health system efficiency. The goal of this study was the risk assessment in pharmaceutical industry in Iran considering process's priority, hazard and probability of risks. The study was carried out in 4 phases; risk identification through literature review, risk identification in Iranian pharmaceutical companies through interview with experts, risk analysis through a questionnaire and consultation with experts using group analytic hierarchy process (AHP) method and rating scale (RS) and risk evaluation of simple additive weighting (SAW) method. In total, 86 main risks were identified in the pharmaceutical supply chain with perspective of pharmaceutical companies classified in 11 classes. The majority of risks described in this study were related to the financial and economic category. Also financial management was found to be the most important factor for consideration. Although pharmaceutical industry and supply chain were affected by current political conditions in Iran during the study time, but half of total risks in the pharmaceutical supply chain were found to be internal risks which could be fixed by companies, internally. Likewise, political status and related risks forced companies to focus more on financial and supply management resulting in less attention to quality management.

Real-time determination of critical quality attributes using near-infrared spectroscopy: a contribution for Process Analytical Technology (PAT).

PubMed

Rosas, Juan G; Blanco, Marcel; González, Josep M; Alcalà, Manel

2012-08-15

Process Analytical Technology (PAT) is playing a central role in current regulations on pharmaceutical production processes. Proper understanding of all operations and variables connecting the raw materials to end products is one of the keys to ensuring quality of the products and continuous improvement in their production. Near infrared spectroscopy (NIRS) has been successfully used to develop faster and non-invasive quantitative methods for real-time predicting critical quality attributes (CQA) of pharmaceutical granulates (API content, pH, moisture, flowability, angle of repose and particle size). NIR spectra have been acquired from the bin blender after granulation process in a non-classified area without the need of sample withdrawal. The methodology used for data acquisition, calibration modelling and method application in this context is relatively inexpensive and can be easily implemented by most pharmaceutical laboratories. For this purpose, Partial Least-Squares (PLS) algorithm was used to calculate multivariate calibration models, that provided acceptable Root Mean Square Error of Predictions (RMSEP) values (RMSEP(API)=1.0 mg/g; RMSEP(pH)=0.1; RMSEP(Moisture)=0.1%; RMSEP(Flowability)=0.6 g/s; RMSEP(Angle of repose)=1.7° and RMSEP(Particle size)=2.5%) that allowed the application for routine analyses of production batches. The proposed method affords quality assessment of end products and the determination of important parameters with a view to understanding production processes used by the pharmaceutical industry. As shown here, the NIRS technique is a highly suitable tool for Process Analytical Technologies. Copyright © 2012 Elsevier B.V. All rights reserved.

77 FR 16264 - Manufacturer of Controlled Substances, Notice of Registration; Halo Pharmaceutical Inc.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-20

..., Notice of Registration; Halo Pharmaceutical Inc. By Notice dated December 2, 2011, and published in the Federal Register on December 14, 2011, 76 FR 77850, Halo Pharmaceutical Inc., 30 North Jefferson Road... considered the factors in 21 U.S.C. 823(a) and determined that the registration of Halo Pharmaceutical Inc...

Defining pharmaceutical systems strengthening: concepts to enable measurement

PubMed Central

Hafner, Tamara; Lee, David; Aboagye-Nyame, Francis

2017-01-01

Abstract Pharmaceutical products are indispensable for improving health outcomes. An extensive body of work on access to and use of medicines has resulted in an assortment of tools measuring various elements of pharmaceutical systems. Until now however, there has been little attempt to conceptualize a pharmaceutical system as an entity and define its strengthening in a way that allows for measuring systems strengthening. The narrow focus of available tools limits their value in ascertaining which interventions result in stronger, more resilient systems. We sought to address this shortcoming by revisiting the current definitions, frameworks and assessment tools related to pharmaceutical systems. We conducted a comprehensive literature review and consulted with select pharmaceutical experts. On the basis of our review, we propose that a pharmaceutical system consists of all structures, people, resources, processes, and their interactions within the broader health system that aim to ensure equitable and timely access to safe, effective, quality pharmaceutical products and related services that promote their appropriate and cost-effective use to improve health outcomes. We further propose that pharmaceutical systems strengthening is the process of identifying and implementing strategies and actions that achieve coordinated and sustainable improvements in the critical components of a pharmaceutical system to make it more responsive and resilient and to enhance its performance for achieving better health outcomes. Finally, we established that, in addition to system performance and resilience, seven components of the pharmaceutical system are critical for measuring pharmaceutical systems strengthening: pharmaceutical products and related services; policy, laws and governance; regulatory systems; innovation, research and development, manufacturing, and trade; financing; human resources; and information. This work adds clarity to the concept of pharmaceutical systems and their strengthening by proposing holistic definitions on the basis of systems thinking. It provides a practical starting point for measuring the progress of pharmaceutical systems strengthening. PMID:28025324

Recent trends and future of pharmaceutical packaging technology

PubMed Central

Zadbuke, Nityanand; Shahi, Sadhana; Gulecha, Bhushan; Padalkar, Abhay; Thube, Mahesh

2013-01-01

The pharmaceutical packaging market is constantly advancing and has experienced annual growth of at least five percent per annum in the past few years. The market is now reckoned to be worth over $20 billion a year. As with most other packaged goods, pharmaceuticals need reliable and speedy packaging solutions that deliver a combination of product protection, quality, tamper evidence, patient comfort and security needs. Constant innovations in the pharmaceuticals themselves such as, blow fill seal (BFS) vials, anti-counterfeit measures, plasma impulse chemical vapor deposition (PICVD) coating technology, snap off ampoules, unit dose vials, two-in-one prefilled vial design, prefilled syringes and child-resistant packs have a direct impact on the packaging. The review details several of the recent pharmaceutical packaging trends that are impacting packaging industry, and offers some predictions for the future. PMID:23833515

Quality of Diabetes Care: The Challenges of an Increasing Epidemic in Mexico. Results from Two National Health Surveys (2006 and 2012)

PubMed Central

Flores-Hernández, Sergio; Saturno-Hernández, Pedro J.; Reyes-Morales, Hortensia; Barrientos-Gutiérrez, Tonatiuh; Villalpando, Salvador; Hernández-Ávila, Mauricio

2015-01-01

Background The quality of diabetes care remains suboptimal according to numerous studies assessing the achievement of quality indicators for diabetes care in various healthcare settings. We report about global and specific quality indicators for diabetes care and their association to glycemic control at the population level in two national health surveys in Mexico. Methods We conducted a cross-sectional analysis of the 2006 and 2012 National Health Surveys in Mexico. We examined quality of care for 2,965 and 4,483 adults (≥ 20 years) with diagnosed type 2 diabetes using fourteen simple and two composite indicators derived from self-reported information. In a subsample for both surveys, glycated hemoglobin (HbA1c) was measured at the time of the interview. We obtained survey weight-adjusted estimators using multiple regression models (logistic and linear) with combined data files, including survey year as covariate to assess change. Results Global quality of care in 2012 was 40.8%, with a relative improvement of 11.7% between 2006 and 2012. Detections of cardiovascular disease risk factors (dyslipidemia and hypertension) were the indicators with the highest improvement, while non-pharmaceutical treatment and diabetic foot exams showed minor changes. We found a significant association between the quality of the process of diabetes care and glycemic control (OR 2.53, 95% CI 1.63-3.94). Age more than 65 years old, the type of health subsystem, gender (males), and high socio-economic status were also significantly associated to glycemic control. Conclusions Quality diabetes care and glycemic control improved and are significantly associated. However, according to international standards, the current situation remains suboptimal. A more holistic approach is needed, with an emphasis on improving quality in outpatient care. PMID:26230991

Quality of Diabetes Care: The Challenges of an Increasing Epidemic in Mexico. Results from Two National Health Surveys (2006 and 2012).

PubMed

Flores-Hernández, Sergio; Saturno-Hernández, Pedro J; Reyes-Morales, Hortensia; Barrientos-Gutiérrez, Tonatiuh; Villalpando, Salvador; Hernández-Ávila, Mauricio

2015-01-01

The quality of diabetes care remains suboptimal according to numerous studies assessing the achievement of quality indicators for diabetes care in various healthcare settings. We report about global and specific quality indicators for diabetes care and their association to glycemic control at the population level in two national health surveys in Mexico. We conducted a cross-sectional analysis of the 2006 and 2012 National Health Surveys in Mexico. We examined quality of care for 2,965 and 4,483 adults (≥ 20 years) with diagnosed type 2 diabetes using fourteen simple and two composite indicators derived from self-reported information. In a subsample for both surveys, glycated hemoglobin (HbA1c) was measured at the time of the interview. We obtained survey weight-adjusted estimators using multiple regression models (logistic and linear) with combined data files, including survey year as covariate to assess change. Global quality of care in 2012 was 40.8%, with a relative improvement of 11.7% between 2006 and 2012. Detections of cardiovascular disease risk factors (dyslipidemia and hypertension) were the indicators with the highest improvement, while non-pharmaceutical treatment and diabetic foot exams showed minor changes. We found a significant association between the quality of the process of diabetes care and glycemic control (OR 2.53, 95% CI 1.63-3.94). Age more than 65 years old, the type of health subsystem, gender (males), and high socio-economic status were also significantly associated to glycemic control. Quality diabetes care and glycemic control improved and are significantly associated. However, according to international standards, the current situation remains suboptimal. A more holistic approach is needed, with an emphasis on improving quality in outpatient care.

Maintaining quality in blood banking.

PubMed

Harvey, E; Hewison, C; Nevalainen, D E; Lloyd, H L

1995-03-01

Regulation of transfusion or blood banking facilities has followed, rather than preceded the regulation of the pharmaceutical industry and today we find, in Europe and the United States, the basic regulations developed for the pharmaceutical industry being extended to blood transfusion centres (BTC)*. In this article we explore the role of voluntary accreditation or registration to quality systems standards such as ISO 9000 and discuss how these can be used to advantage and how these standards can provide a substantial base for meeting legislative requirements. In the UK there is also a voluntary accreditation procedure available for all clinical laboratories, known as Clinical Pathology Accreditation (CPA). Comparisons between ISO 9000, CPA and other standards are made. We also discuss how voluntary registration, particularly to ISO 9000 can provide an excellent basis for moving into more extensive and progressive Total Quality Management (TQM) programmes which in turn bring a variety of benefits, not least of which is increased staff involvement in your organisation. Experience of the route to quality through voluntary accreditation suggests that external assessment delivers new insights into the organisation that cannot easily be supplanted by internal audit. In Europe legislation relating to pharmaceuticals has steadily increased in scope and in detailed requirements from those set out in the 1965 Directive 65/65/EEC. The legislative framework has steadily increased, bringing plasma and plasma products as well as others such as radiopharmaceuticals, into the product licensing requirements. The progression of legislation seems unlikely to cease and it is debatable how long the Medicines Control Agency (MCA) and its Inspectorate will accept that BTCs can operate at a level which is different from that of the majority of pharmaceutical manufacturers. The change in emphasis in legislation particularly in Europe means that harm that is caused to a patient by a blood component will warrant redress. The degree of fault attributed to the producer will in part depend on whether they have met the best available standards at all stages in the preparation of the product. If a Transfusion Service can show that it's operation has external accreditation, particularly to an internationally recognised standard such as ISO 9000 and they can show that staff have been properly trained, that equipment is properly supplied and maintained and that the facility is appropriate to the work being carried out, then the liability that exists when something goes wrong will be reduced.(ABSTRACT TRUNCATED AT 400 WORDS)

Industry's efforts: devices and pharmaceuticals.

PubMed

Sanders, C A

1995-11-01

The pharmaceutical industry has been irreversibly affected by the changes occurring in healthcare. Despite the obvious contributions of pharmaceuticals to human health, our customers are demanding that we help the patient and contribute to value, whether it be in terms of cost, clinical outcomes, or quality of life. We are learning to balance the variables to ensure that cost plus quality equals value in the marketplace in three ways: by focusing on the needs of the customers and demonstrating value through outcomes research, by maintaining an emphasis on innovation, and by taking an active role in the public arena to direct the course of our future. Outcomes research proves the value of what we do. Economic data will have to be correlated with clinical data. In addition to standard clinical and economic parameters, we must also provide quality of life data. Collaboration between the academic and the practicing community produces a win-win situation for both parties. Industry and practitioners are bonded together ineluctably in the service of the patient. Working together we can shape our future and the future of our patients.

Innovative Technologies for Efficient Pharmacotherapeutic Management in Space

NASA Technical Reports Server (NTRS)

Putcha, Lakshmi; Daniels, Vernie

2014-01-01

Current and future Space exploration missions and extended human presence in space aboard the ISS will expose crew to risks that differ both quantitatively and qualitatively from those encountered before by space travelers and will impose an unknown risk of safety and crew health. The technology development challenges for optimizing therapeutics in space must include the development of pharmaceuticals with extended stability, optimal efficacy and bioavailability with minimal toxicity and side effects. Innovative technology development goals may include sustained/chronic delivery preventive health care products and vaccines, low-cost high-efficiency noninvasive, non-oral dosage forms with radio-protective formulation matrices and dispensing technologies coupled with self-reliant tracking technologies for quality assurance and quality control assessment. These revolutionary advances in pharmaceutical technology will assure human presence in space and healthy living on Earth. Additionally, the Joint Commission on Accreditation of Healthcare Organizations advocates the use of health information technologies to effectively execute all aspects of medication management (prescribing, dispensing, and administration). The advent of personalized medicine and highly streamlined treatment regimens stimulated interest in new technologies for medication management. Intelligent monitoring devices enhance medication accountability compliance, enable effective drug use, and offer appropriate storage and security conditions for dangerous drug and controlled substance medications in remote sites where traditional pharmacies are unavailable. These features are ideal for Exploration Medical Capabilities. This presentation will highlight current novel commercial off-the-shelf (COTS) intelligent medication management devices for the unique dispensing, therapeutic drug monitoring, medication tracking, and drug delivery demands of exploration space medical operations.

Occurrence of selected pharmaceutical and non-pharmaceutical compounds, and stable hydrogen and oxygen isotope ratios in a riverbank filtration study, Platte River, Nebraska, 2002 to 2005, Volume 2

USGS Publications Warehouse

Vogel, J.R.; Barber, L.B.; Furlong, E.T.; Coplen, T.B.; Verstraeten, Ingrid M.; Meyer, M.T.

2005-01-01

This document is the second volume of a data series report that describes the data collected during a study conducted during 2001 through 2005 by the U.S. Geological Survey, in cooperation with the U.S. Environmental Protection Agency and the City of Lincoln, at an established riverbank-filtration well field with horizontal collector wells and vertical wells. The data were collected as part of a study designed to help researchers better understand the efficiency of riverbank filtration with respect to endocrine disrupting compounds and to evaluate the use of riverbank filtration as an effective means of drinking-water treatment. This study provides information that will be useful for (1) increased understanding of the processes and factors controlling the transport of endocrine disrupters, such as pesticides and pharmaceuticals during riverbank filtration, (2) better understanding of the physical and chemical processes that affect riverbank-filtration efficiency, and (3) managing the water resources of the eastern Platte River Basin. This report presents analytical methods and additional data for pharmaceuticals, dissolved organic carbon (DOC), ultraviolet absorbance at 254 nanometer (nm) wavelength (UV254), specific ultraviolet absorbance (SUVA), nitrilotriacetic acid (NTA), ethylenediaminetetraacetic acid (EDTA), nonylphenol ethoxycarboxylates (NPECs), and stable hydrogen and oxygen isotope ratios that were not available at the time of publication of Volume 1 in the data series. Data are presented as generalized statistics and in figures showing temporal variations. Sites from which water-quality samples were collected for this study included wastewater sites (a cattle feedlot lagoon, a hog confinement lagoon, and wastewater-treatment plant effluent), surface-water sites (Platte River, Salt Creek, and Loup Power Canal), ground-water sites (one collector well and five vertical wells), and drinking-water sites (raw and finished). Field water-quality properties also were measured in samples from these sites. Pharmaceuticals detected at least once in samples collected from the Platte River included 1,7-dimethylxanthine, acetaminophen, caffeine, carbamazapine, and cotinine. Among the ground-water samples, pharmaceutical compounds detected at low concentrations in at least one sample included 1,7-dimethylxanthine, acetaminophen, carbamazapine, and trimethoprim. When analyzing for non-pharmaceutical compounds in samples from the wastewater sites, the wastewater-treatment plant effluent samples had the highest concentrations of each of NTA, EDTA, and NPECs compounds. Surface-water samples from Salt Creek had higher concentrations of EDTA and NPECs than samples from the Platte River. NTA was not detected in any samples from the ground-water sites. EDTA was detected in all samples from all wells. Detectable concentrations of EDTA were also observed in all samples from the raw water and finished water.

Regulatory aspects of pharmaceuticals' exports in gulf cooperation council countries.

PubMed

Pateriya, S; Janodia, Md; Deshpande, Pb; Ligade, Vs; Talole, Kb; Kulshrestha, T; Kamariya, Y; Musmade, Pb; Udupa, N

2011-04-01

The Gulf cooperation council (GCC) region is considered as "Emerging market" for pharmaceutical export and bilateral trade. The understanding of the regulatory requirements of this region can be beneficial for pharmaceutical export. Some incidents of the year 2008-09, like recession or economic slowdown in highly well-off and regulated market of the EU and US, raised the demand for alternate destinations for business. The regulations of Gulf countries are encouraging the import of quality generic products, which can be good news to the Indian drug manufacturers.

The view of the pharmaceutical industry.

PubMed

Roche, G; Helenport, J P

1994-06-01

Rhône-Poulenc Rorer has committed itself to the development of artemether because we believe the drug will be of considerable benefit to sufferers from severe falciparum malaria, and because it is a stable, effective and economical compound that can be given by intramuscular injection. The quality of the pharmaceutical product meets international regulatory standards. Artemether is unlikely to yield big profits, but we believe that major pharmaceutical companies have a responsibility to develop such much-needed products. To develop this project further, we will need the assistance of academic institutions, research organizations and international bodies.

Modeling in the quality by design environment: Regulatory requirements and recommendations for design space and control strategy appointment.

PubMed

Djuris, Jelena; Djuric, Zorica

2017-11-30

Mathematical models can be used as an integral part of the quality by design (QbD) concept throughout the product lifecycle for variety of purposes, including appointment of the design space and control strategy, continual improvement and risk assessment. Examples of different mathematical modeling techniques (mechanistic, empirical and hybrid) in the pharmaceutical development and process monitoring or control are provided in the presented review. In the QbD context, mathematical models are predominantly used to support design space and/or control strategies. Considering their impact to the final product quality, models can be divided into the following categories: high, medium and low impact models. Although there are regulatory guidelines on the topic of modeling applications, review of QbD-based submission containing modeling elements revealed concerns regarding the scale-dependency of design spaces and verification of models predictions at commercial scale of manufacturing, especially regarding real-time release (RTR) models. Authors provide critical overview on the good modeling practices and introduce concepts of multiple-unit, adaptive and dynamic design space, multivariate specifications and methods for process uncertainty analysis. RTR specification with mathematical model and different approaches to multivariate statistical process control supporting process analytical technologies are also presented. Copyright © 2017 Elsevier B.V. All rights reserved.

Endocrine-Active Pharmaceuticals: An Environmental Concern?

EPA Science Inventory

Recently, there has been growing interest in pharmaceuticals that are specifically designed to have endocrine activity, such as the estrogens used in birth control pills, exerting unintended effects on fish and other aquatic organisms. These pharmaceuticals may not be persistent...

Pharmaceutical cost control in primary care: opinion and contributions by healthcare professionals

PubMed Central

2009-01-01

Background Strategies adopted by health administrations and directed towards drug cost control in primary care (PC) can, according to earlier studies, generate tension between health administrators and healthcare professionals. This study collects and analyzes the opinions of general practitioners (GPs) regarding current cost control measures as well as their proposals for improving the effectiveness of these measures. Methods A qualitative exploratory study was carried out using 11 focus groups composed of GPs from the Spanish regions of Aragon, Catalonia and the Balearic Islands. A semi-structured guide was applied in obtaining the GPs' opinions. The transcripts of the dialogues were analyzed by two investigators who independently considered categorical and thematic content. The results were supervised by other members of the team, with overall responsibility assigned to the team leader. Results GPs are conscious of their public responsibility with respect to pharmaceutical cost, but highlight the need to spread responsibility for cost control among the different actors of the health system. They insist on implementing measures to improve the quality of prescriptions, avoiding mere quantitative evaluations of prescription costs. They also suggest moving towards the self-management of the pharmaceutical budget by each health centre itself, as a means to design personalized incentives to improve their outcomes. These proposals need to be considered by the health administration in order to pre-empt the feelings of injustice, impotence, frustration and lack of motivation that currently exist among GPs as a result of the implemented measures. Conclusion Future investigations should be oriented toward strategies that involve GPs in the planning and management of drug cost control mechanisms. The proposals in this study may be considered by the health administration as a means to move toward the rational use of drugs while avoiding concerns about injustice and feelings of impotence on the part of the GPs, which can lead to lack of interest in and disaffection with the current measures. PMID:19922620

Pharmaceuticals, hormones, pesticides, and other bioactive contaminants in water, sediment, and tissue from Rocky Mountain National Park, 2012–2013

USGS Publications Warehouse

Battaglin, William A.; Bradley, Paul M.; Iwanowicz, Luke R.; Journey, Celeste A.; Walsh, Heather L.; Blazer, Vicki S.

2018-01-01

Pharmaceuticals, hormones, pesticides, and other bioactive contaminants (BCs) are commonly detected in surface water and bed sediment in urban and suburban areas, but these contaminants are understudied in remote locations. In Rocky Mountain National Park (RMNP), Colorado, USA, BCs may threaten the reproductive success and survival of native aquatic species, benthic communities, and pelagic food webs. In 2012–2013, 67 water, 57 sediment, 63 fish, 10 frog, and 12 quality-control samples (8 water and 4 sediment) were collected from 20 sites in RMNP. Samples were analyzed for 369 parameters including 149 pharmaceuticals, 22 hormones, 137 pesticides, and 61 other chemicals or conditions to provide a representative assessment of BC occurrence within RMNP. Results indicate that BCs were detected in water and/or sediment from both remote and more accessible locations in RMNP. The most commonly detected BCs in water were caffeine, camphor, para-cresol, and DEET; and the most commonly detected BCs in sediment were indole, 3-methyl-1H-indole, para-cresol, and 2,6-dimethyl-naphthalene. Some detected contaminants, including carbaryl, caffeine, and oxycodone, are clearly attributable to direct local human input, whereas others may be transported into the park atmospherically (e.g., atrazine) or have local natural sources (e.g., para-cresol). One or more pharmaceuticals were detected in at least 1 sample from 15 of 20 sites. Most of the 29 detected pharmaceuticals are excreted primarily in human urine, not feces. Elevated net estrogenicity was observed in 18% of water samples, and elevated vitellogenin in blood was observed in 12% of male trout, both evidence of potential endocrine disruption. Hormone concentrations in sediment tended to be greater than concentrations in water. Most BCs were observed at concentrations below those not expected to pose adverse effects to aquatic life. Results indicate that even in remote locations aquatic wildlife can be exposed to pharmaceuticals, hormones, pesticides, and other bioactive contaminants.

Quality survey of natural mineral water and spring water sold in France: Monitoring of hormones, pharmaceuticals, pesticides, perfluoroalkyl substances, phthalates, and alkylphenols at the ultra-trace level.

PubMed

Le Coadou, Laurine; Le Ménach, Karyn; Labadie, Pierre; Dévier, Marie-Hélène; Pardon, Patrick; Augagneur, Sylvie; Budzinski, Hélène

2017-12-15

The aim of the present study, one of the most complete ever performed in France, was to carry out an extensive survey on the potential presence of a large amount of emerging contaminants in 40 French bottled waters, including parent compounds and metabolites. The studied samples represented 70% of the French bottled water market in volume. Six classes of compounds were investigated, most of them being unregulated in bottled waters: pesticides and their transformation products (118), pharmaceutical substances (172), hormones (11), alkylphenols (APs) (8), phthalates (11) and perfluoroalkyl substances (PFAS) (10). One of the objectives of this work was to achieve low and reliable limits of quantification (LOQs) (87% of the LOQs were below 10ng/L) using advanced analytical technologies and reliable sample preparation methodologies, including stringent quality controls. Among the 14,000 analyses performed, 99.7% of the results were below the LOQs. None of the hormones, pharmaceutical substances and phthalates were quantified. Nineteen compounds out of the 330 investigated were quantified in 11 samples. Eleven were pesticides including 7 metabolites, 6 were PFAS and 2 were APs. As regards pesticides, their sum was at least twice lower than the quality standards applicable for bottled waters in France. The presence of a majority of pesticide metabolites suggested a former use in the recharge areas of the exploited aquifers. The quantification of a few unregulated emerging compounds at the nano-trace level, such as PFAS, raised the issue of their potential sources, including long-range atmospheric transport and deposition. This study confirmed that the groundwater aquifers exploited for bottling were well-preserved from chemicals, as compared to less geologically protected groundwaters, and also underlined the need to pursue the protection policies implemented in recharge areas in order to limit the anthropogenic pressure. Copyright © 2016. Published by Elsevier B.V.

New protocol for αAstree electronic tongue enabling full performance qualification according to ICH Q2.

PubMed

Pein, Miriam; Eckert, Carolin; Preis, Maren; Breitkreutz, Jörg

2013-09-01

Performance qualification (PQ) of taste sensing systems is mandatory for their use in pharmaceutical industry. According to ICH Q2 (R1) and a recent adaptation for taste sensing systems, non-specificity, log-linear relationships between the concentration of analytes and the sensor signal as well as a repeatability with relative standard deviation (RSD) values <4% were defined as basic requirements to pass a PQ. In the present work, the αAstree taste sensing system led to a successful PQ procedure by the use of recent sensor batches for pharmaceutical applications (sensor set #2) and a modified measurement protocol. Log-linear relationships between concentration and responses of each sensor were investigated for different bitter tasting active pharmaceutical ingredients (APIs). Using the new protocol, RSD values <2.1% were obtained in the repeatability study. Applying the visual evaluation approach, detection and quantitation limit could be determined for caffeine citrate with every sensor (LOD 0.05-0.5 mM, LOQ: 0.1-0.5 mM). In addition, the sensor set marketed for food applications (sensor set #5) was proven to show beneficial effects regarding the log-linear relationship between the concentration of quinine hydrochloride and the sensor signal. By the use of our proposed protocol, it is possible to implement the αAstree taste sensing system as a tool to assure quality control in the pharmaceutical industry. Copyright © 2013 Elsevier B.V. All rights reserved.

Purity Analysis of the Pharmaceuticals Naproxen and Propranolol: A Guided-Inquiry Laboratory Experiment in the Analytical Chemistry Laboratory

ERIC Educational Resources Information Center

Fakayode, Sayo O.

2015-01-01

Counterfeiting and adulteration of prescription drugs, herbal products, and food supplements are a global challenge, causing serious economic loss to drug marketers and health implications for humans. Accordingly, accurate determination of the purity of pharmaceuticals is critical for the quality assurance of prescription drugs. Herein, the first…

Pharmaceutical Equivalence of Distributed Generic Antiretroviral (ARV) in Asian Settings: The Cross-Sectional Surveillance Study - PEDA Study.

PubMed

Sapsirisavat, Vorapot; Vongsutilers, Vorasit; Thammajaruk, Narukjaporn; Pussadee, Kanitta; Riyaten, Prakit; Kerr, Stephen; Avihingsanon, Anchalee; Phanuphak, Praphan; Ruxrungtham, Kiat

2016-01-01

Ensuring that medicines meet quality standards is mandatory for ensuring safety and efficacy. There have been occasional reports of substandard generic medicines, especially in resource-limiting settings where policies to control quality may be less rigorous. As HIV treatment in Thailand depends mostly on affordable generic antiretrovirals (ARV), we performed quality assurance testing of several generic ARV available from different sources in Thailand and a source from Vietnam. We sampled Tenofovir 300mg, Efavirenz 600mg and Lopinavir/ritonavir 200/50mg from 10 primary hospitals randomly selected from those participating in the National AIDS Program, 2 non-government organization ARV clinics, and 3 private drug stores. Quality of ARV was analyzed by blinded investigators at the Faculty of Pharmaceutical Science, Chulalongkorn University. The analysis included an identification test for drug molecules, a chemical composition assay to quantitate the active ingredients, a uniformity of mass test and a dissolution test to assess in-vitro drug release. Comparisons were made against the standards described in the WHO international pharmacopeia. A total of 42 batches of ARV from 15 sources were sampled from January-March 2015. Among those generics, 23, 17, 1, and 1 were Thai-made, Indian-made, Vietnamese-made and Chinese-made, respectively. All sampled products, regardless of manufacturers or sources, met the International Pharmacopeia standards for composition assay, mass uniformity and dissolution. Although local regulations restrict ARV supply to hospitals and clinics, samples of ARV could be bought from private drug stores even without formal prescription. Sampled generic ARVs distributed within Thailand and 1 Vietnamese pharmacy showed consistent quality. However some products were illegally supplied without prescription, highlighting the importance of dispensing ARV for treatment or prevention in facilities where continuity along the HIV treatment and care cascade is available.

Comparison of Rheological and Sedimentation Behavior of Commercially Available Suspending Vehicles for Oral Pharmaceutical Preparations.

PubMed

Visser, J Carolina; Ten Seldam, Inge E J; van der Linden, Isabella J; Hinrichs, Wouter L J; Veenendaal, Reinier F H; Dijkers, Eli C F; Woerdenbag, Herman J

2018-01-01

A pharmaceutical suspension is a semi-liquid dosage form suitable for patients being unable to swallow solid medicines such as tablets and capsules. A vehicle used for the preparation of pharmaceutical oral suspensions preferably shows pseudo-plastic behavior. In a product that gets thinner with agitation and thicker upon standing, slow settlement of the suspended active pharmaceutical ingredient is combined with good pourability and rehomogenization. This gives the best guarantee of uniformity of dose for oral suspensions. In this study, the rheological behavior of commercially available ready-to-use vehicles for oral pharmaceutical preparations was compared, and the sedimentation of paracetamol dispersed in these vehicles was investigated. With SuspendIt and SyrSpend SF PH4 (Liquid), both pseudoplastic vehicles, very stable paracetamol suspensions were obtained. Of these two vehicles, SyrSpend SF PH4 (Liquid) displayed somewhat higher viscosity, which is a favorable quality characteristic for suspensions. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Creating a new class of pharmaceutical services provider for underserved areas: the Tanzania accredited drug dispensing outlet experience.

PubMed

Rutta, Edmund; Senauer, Katie; Johnson, Keith; Adeya, Grace; Mbwasi, Romuald; Liana, Jafary; Kimatta, Suleiman; Sigonda, Margareth; Alphonce, Emmanuel

2009-01-01

In developing countries, the most accessible source of treatment for common conditions is often an informal drug shop, where drug sellers are untrained and operations are unmonitored. We sought to describe a public-private initiative in Tanzania that created a new class of provider in government-accredited drug outlets, which improved the quality of medicines and pharmaceutical services in previously underserved areas. The accredited drug-dispensing outlet program combines changing behavior and expectations of community members who use, own, regulate, and work in drug shops. Success resulted from including community stakeholders from the beginning of the process. Addressing shortages in qualified health care providers by training and accrediting private sector drug dispensers to recognize common conditions and provide quality pharmaceutical products and services is feasible in a developing country, when supported by an appropriate policy and regulatory environment. Scaling up and sustaining the program will be a challenge.

Regional medicine use in the Rhine basin and its implication on water quality

NASA Astrophysics Data System (ADS)

Hut, R. W.; Houtman, C. J.; van de Giesen, N. C.; de Jong, S. A. P.

2012-04-01

Do Germans use more painkillers than the French? Pharmaceuticals used in our Western society form an important group of contaminants found in the river Rhine. As this river is the drinking water source for millions of Europeans, methods to investigate relations between drug use and their penetration in the watercycle are of great importance. An analysis is presented relating medicine residue in the river Rhine to the number of people living in its watershed. An extensive measuring campaign was carried out, sampling river Rhine at 42 locations from its source to the start of its delta (Dutch-German border). The samples were analyzed for 40 common pharmaceuticals. Using discharge data, digital elevation models and demographic data from Eurostat, the relation between total load of drug residue and population was analyzed. Results show regional differences in drug use as well as implications for (down)stream water quality concerning contamination with pharmaceuticals.

Inline UV/Vis spectroscopy as PAT tool for hot-melt extrusion.

PubMed

Wesholowski, Jens; Prill, Sebastian; Berghaus, Andreas; Thommes, Markus

2018-01-11

Hot-melt extrusion on co-rotating twin screw extruders is a focused technology for the production of pharmaceuticals in the context of Quality by Design. Since it is a continuous process, the potential for minimizing product quality fluctuation is enhanced. A typical application of hot-melt extrusion is the production of solid dispersions, where an active pharmaceutical ingredient (API) is distributed within a polymer matrix carrier. For this dosage form, the product quality is related amongst others to the drug content. This can be monitored on- or inline as critical quality attribute by a process analytical technology (PAT) in order to meet the specific requirements of Quality by Design. In this study, an inline UV/Vis spectrometer from ColVisTec was implemented in an early development twin screw extruder and the performance tested in accordance to the ICH Q2 guideline. Therefore, two API (carbamazepine and theophylline) and one polymer matrix (copovidone) were considered with the main focus on the quantification of the drug load. The obtained results revealed the suitability of the implemented PAT tool to quantify the drug load in a typical range for pharmaceutical applications. The effort for data evaluation was minimal due to univariate data analysis, and in combination with a measurement frequency of 1 Hz, the system is sufficient for real-time data acquisition.

Stability studies needed to define the handling and transport conditions of sensitive pharmaceutical or biotechnological products.

PubMed

Ammann, Claude

2011-12-01

Many pharmaceutical or biotechnological products require transport using temperature-controlled systems to keep their therapeutic properties. There are presently no official guidelines for testing pharmaceutical products in order to define suitable transport specifications. After reviewing the current guidance documents, this paper proposes a methodology for testing pharmaceutical products and defining appropriate transport conditions.

A high efficiency, high quality and low cost internal regulated bioanalytical laboratory to support drug development needs.

PubMed

Song, Yan; Dhodda, Raj; Zhang, Jun; Sydor, Jens

2014-05-01

In the recent past, we have seen an increase in the outsourcing of bioanalysis in pharmaceutical companies in support of their drug development pipeline. This trend is largely driven by the effort to reduce internal cost, especially in support of late-stage pipeline assets where established bioanalytical assays are used to analyze a large volume of samples. This article will highlight our perspective of how bioanalytical laboratories within pharmaceutical companies can be developed into the best partner in the advancement of drug development pipelines with high-quality support at competitive cost.

Drug-usage evaluation and the patient-care pharmacist: a synergistic combination.

PubMed

Gayman, J; Tapley, D J

1991-07-01

The Joint Commission requires a continuous monitoring program to assure quality pharmaceutical care. The only way to achieve compliance with this standard is to enlist the help of the patient-care pharmacists. Equally important to the pharmacy manager is the way a DUE program can benefit the patient-care pharmacists. The key to an effective program is to assist the patient-care pharmacists in taking responsibility for the quality of drug therapy provided to their patients. Through education, encouragement, and recognition, the DUE Coordinator can elevate the practice of the patient-care pharmacists. The outcome is a synergistic program that enriches the practice of the patient-care pharmacists who, in turn, enrich the quality of pharmaceutical care received by their patients.

Continuous improvement and TQM in health care: an emerging operational paradigm becomes a strategic imperative.

PubMed

Swinehart, K; Green, R F

1995-01-01

Argues that US health care is in a state of crisis. Escalating costs account for 13 per cent of GNP, making health care the third largest industry in the USA, and spending is expected to increase. Claims health-care providers need to control rising costs, improve productivity and flexibility, adopt appropriate technologies, and maintain competitive levels of quality and value. States that TQM may provide an environment that will focus on quality of patient care and continuous quality improvement at all levels of the organization including the governing body, the administrative, managerial, and clinical areas. Any new national or state health-care plan will force providers to be more efficient while maintaining quality standards. Concludes that it will be strategically imperative that health-care providers ranging from family physicians to major medical centres and suppliers ranging from laboratories to pharmaceutical firms establish methods for making rapid continuous improvement and total quality management the cornerstone of the strategic planning process.

Implications of external price referencing of pharmaceuticals in Middle East countries.

PubMed

Kaló, Zoltán; Alabbadi, Ibrahim; Al Ahdab, Ola Ghaleb; Alowayesh, Maryam; Elmahdawy, Mahmoud; Al-Saggabi, Abdulaziz H; Tanzi, Vito Luigi; Al-Badriyeh, Daoud; Alsultan, Hamad S; Ali, Faleh Mohamed Hussain; Elsisi, Gihan H; Akhras, Kasem S; Vokó, Zoltán; Kanavos, Panos

2015-01-01

External price referencing (EPR) is applied frequently to control pharmaceutical prices. Our objective was to analyse how EPR is used in Middle Eastern (ME) countries and to compare the price corridor for original pharmaceuticals to non-pharmaceutical services not subjected to EPR. We conducted a survey on EPR regulations and collected prices of 16 patented pharmaceuticals and 14 non-pharmaceutical services in seven Middle Eastern (ME) countries. Maximum and minimum prices of each pharmaceutical and non-pharmaceutical technology were compared to mean prices in the countries studied by using market exchange rates. Influencing factors of pharmaceutical prices were assessed by multivariate linear regression analysis. The average price corridor is narrower for pharmaceuticals (-39.8%; +35.9%) than for outpatient and hospital services (-81.7%; +96.3%). Our analysis revealed the importance of population size and EPR implementation on drug price levels; however, EPR results in higher pharmaceutical prices in lower-income countries compared to non-pharmaceutical services.

Quality assessment of the visits of pharmaceutical company representatives to hospital pharmacists.

PubMed

Fonzo-Christe, Caroline; Herrmann, François; Bonnabry, Pascal

2005-11-19

To evaluate whether the quality of pharmaceutical company representatives' (PCRs) visits to hospital pharmacists can be improved by written communication of the results of an evaluation of their visits. Pilot study with prospective evaluation of overall visit quality and strength of request for adding drugs to the hospital formulary, and of the scientific quality of products presentations using a standardized form. Two one-year study periods (59 vs. 61 visits) separated by the intervention (global results of the first period sent to each drug company). No difference was observed between both periods in overall visit quality (VAS 0 = null, 10 = excellent: mean 4.7 (2.1 SD) vs. 5.2 (2.1) or strength of request for adding drug to hospital formulary (VAS 0 = null, 10 = extreme: 7.0 [2.6] vs. 7.2 [2.7]). Clarity and scientific value of products' presentations and scientific value of responses were better during the second study period, as a sign of quality improvement. This study suggests that systematic quality evaluation of PCRs visits and communication of results to drug companies may improve the scientific quality of products' presentation.

Environmental management practices in the Lebanese pharmaceutical industries: implementation strategies and challenges.

PubMed

Massoud, May A; Makarem, N; Ramadan, W; Nakkash, R

2015-03-01

This research attempts to provide an understanding of the Lebanese pharmaceutical industries' environmental management strategies, priorities, and perceptions as well as drivers, barriers, and incentives regarding the implementation of the voluntary ISO 14001 Environmental Management System. Accordingly, a semistructured in-depth interview was conducted with the pharmaceutical industries. The findings revealed a significant lack of knowledge about the standard among the industries. The main perceived drivers for adopting the ISO 14001 are improving the companies' image and overcoming international trade. The main perceived barriers for acquiring the standard are the lack of government support and the fact that ISO 14001 is not being legally required or enforced by the government. Moreover, results revealed that adopting the ISO 14001 standard is not perceived as a priority for the Lebanese pharmaceutical industries. Although the cost of certification was not considered as a barrier for the implementation of ISO 14001, the majority of the pharmaceutical industries are neither interested nor willing to adopt the Standard if they are not exposed to any regulatory pressure or external demand. They are more concerned with quality and safety issues with the most adopted international standard among the industries being the ISO 9001 quality management system. This study highlights the aspect that financial barriers are not always the hurdles for implementing environmental management strategies in developing countries and underscores the need for regulatory frameworks and enforcement.

Principles of pharmacoeconomics and their impact on strategic imperatives of pharmaceutical research and development.

PubMed

Bodrogi, József; Kaló, Zoltán

2010-04-01

The importance of evidence-based health policy is widely acknowledged among health care professionals, patients and politicians. Health care resources available for medical procedures, including pharmaceuticals, are limited all over the world. Economic evaluations help to alleviate the burden of scarce resources by improving the allocative efficiency of health care financing. Reimbursement of new medicines is subject to their cost-effectiveness and affordability in more and more countries. There are three major approaches to calculate the cost-effectiveness of new pharmaceuticals. Economic analyses alongside pivotal clinical trials are often inconclusive due to the suboptimal collection of economic data and protocol-driven costs. The major limitation of observational naturalistic economic evaluations is the selection bias and that they can be conducted only after registration and reimbursement. Economic modelling is routinely used to predict the cost-effectiveness of new pharmaceuticals for reimbursement purposes. Accuracy of cost-effectiveness estimates depends on the quality of input variables; validity of surrogate end points; and appropriateness of modelling assumptions, including model structure, time horizon and sophistication of the model to differentiate clinically and economically meaningful outcomes. These economic evaluation methods are not mutually exclusive; in practice, economic analyses often combine data collection alongside clinical trials or observational studies with modelling. The need for pharmacoeconomic evidence has fundamentally changed the strategic imperatives of research and development (R&D). Therefore, professionals in pharmaceutical R&D have to be familiar with the principles of pharmacoeconomics, including the selection of health policy-relevant comparators, analytical techniques, measurement of health gain by quality-adjusted life-years and strategic pricing of pharmaceuticals.

Principles of pharmacoeconomics and their impact on strategic imperatives of pharmaceutical research and development

PubMed Central

Bodrogi, József; Kaló, Zoltán

2010-01-01

The importance of evidence-based health policy is widely acknowledged among health care professionals, patients and politicians. Health care resources available for medical procedures, including pharmaceuticals, are limited all over the world. Economic evaluations help to alleviate the burden of scarce resources by improving the allocative efficiency of health care financing. Reimbursement of new medicines is subject to their cost-effectiveness and affordability in more and more countries. There are three major approaches to calculate the cost-effectiveness of new pharmaceuticals. Economic analyses alongside pivotal clinical trials are often inconclusive due to the suboptimal collection of economic data and protocol-driven costs. The major limitation of observational naturalistic economic evaluations is the selection bias and that they can be conducted only after registration and reimbursement. Economic modelling is routinely used to predict the cost-effectiveness of new pharmaceuticals for reimbursement purposes. Accuracy of cost-effectiveness estimates depends on the quality of input variables; validity of surrogate end points; and appropriateness of modelling assumptions, including model structure, time horizon and sophistication of the model to differentiate clinically and economically meaningful outcomes. These economic evaluation methods are not mutually exclusive; in practice, economic analyses often combine data collection alongside clinical trials or observational studies with modelling. The need for pharmacoeconomic evidence has fundamentally changed the strategic imperatives of research and development (R&D). Therefore, professionals in pharmaceutical R&D have to be familiar with the principles of pharmacoeconomics, including the selection of health policy-relevant comparators, analytical techniques, measurement of health gain by quality-adjusted life-years and strategic pricing of pharmaceuticals. PMID:20132213

Discovery, innovation and the cyclical nature of the pharmaceutical business.

PubMed

Schmid, Esther F; Smith, Dennis A

2002-05-15

Unlike many recent articles, which paint the future of the pharmaceutical industry in gloomy colours, this article provides an optimistic outlook. It explores the foundations on which the pharmaceutical industry has based its outstanding successes. Case studies of important drug classes underpin the arguments made and provide the basis for the authors' argument that recent technological breakthroughs and the unravelling of the human genome will provide a new wave of high quality targets (substrate) on which the industry can build. The article suggests that in a conducive environment that understands the benefits that pharmaceuticals provide to healthcare, those players who can base their innovation on a sufficient scale and from a large capital base will reshape the industry.

Pharmaceutical company influences on medication prescribing and their potential impact on quality use of medicines.

PubMed

Kyle, G J; Nissen, L M; Tett, S E

2008-10-01

Pharmaceuticals are big business, reporting strong market growth year after year. The 'gatekeepers' of this market are prescribers of medicines, who are the major target of pharmaceutical companies, utilizing direct and indirect influences. This paper draws on previous research investigating pharmaceutical company prescribing influences to develop a qualitative model demonstrating the synergism between commercial influences on prescribing. The generic model was used to explore a realistic but hypothetical scenario to ascertain the applicability of the model. A generic influence model was developed. The model was readily able to be adapted to reflect a realistic practice scenario. Prescriber awareness of the linkages between various seemingly separate marketing techniques could potentially improve medicines usage in an evidence-based practice paradigm.

In-vitro tomography and non-destructive imaging at depth of pharmaceutical solid dosage forms.

PubMed

Zeitler, J Axel; Gladden, Lynn F

2009-01-01

Tomographic imaging techniques offer new prospects for a better understanding of the quality, performance and release mechanisms of pharmaceutical solid dosage forms. It is only over the last fifteen years that tomography has been applied for the in-vitro characterisation of dosage forms. This review aims to introduce the concept of tomography in a pharmaceutical context, and describes the current state-of-the-art of the four most promising techniques: X-ray computed microtomography, magnetic resonance imaging, terahertz imaging and optical coherence tomography. The basic working principles of the techniques are introduced and the current pharmaceutical applications of the technologies are discussed, together with a comparison of their specific strengths and weaknesses. Possible future developments in these fields are also discussed.

Medicines Information and the Regulation of the Promotion of Pharmaceuticals.

PubMed

Leonardo Alves, Teresa; Lexchin, Joel; Mintzes, Barbara

2018-05-02

Many factors contribute to the inappropriate use of medicines, including not only a lack of information but also inaccurate and misleading promotional information. This review examines how the promotion of pharmaceuticals directly affects the prescribing and use of medicines. We define promotion broadly as all actions taken directly by pharmaceutical companies with the aim of enhancing product sales. We look in greater detail at promotion techniques aimed at prescribers, such as sales representatives, pharmaceutical advertisements in medical journals and use of key opinion leaders, along with the quality of information provided and the effects thereof. We also discuss promotion to the public, through direct-to-consumer advertising, and its effects. Finally, we consider initiatives to regulate promotion that come from industry, government and nongovernmental organizations.

Total Health-Related Costs Due to Absenteeism, Presenteeism, and Medical and Pharmaceutical Expenses in Japanese Employers

PubMed Central

Nagata, Tomohisa; Mori, Koji; Ohtani, Makoto; Nagata, Masako; Kajiki, Shigeyuki; Fujino, Yoshihisa; Matsuda, Shinya; Loeppke, Ronald

2018-01-01

Objective: This study aimed to examine a detailed breakdown of costs (absenteeism, presenteeism, and medical/pharmaceutical expenses), of the employees in four pharmaceutical companies in Japan. Methods: This is a cross-sectional study. Absenteeism and presenteeism were measured by a self-administered questionnaire for workers, and their costs were estimated using the human capital approach. Presenteeism was evaluated by the degree affected quality and quantity of work. Medical and pharmaceutical expenses were obtained by insurance claims. Results: The monetary value due to absenteeism was $520 per person per year (11%), that of presenteeism was $3055 (64%), and medical/pharmaceutical expenses were $1165 (25%). Two of the highest total cost burdens from chronic illness were related to mental (behavioral) health conditions and musculoskeletal disorders. Conclusion: A total cost approach can help employers set priorities for occupational health, safety, and population health management initiatives. PMID:29394196

21 CFR 26.39 - Equivalence assessment.

Code of Federal Regulations, 2010 CFR

2010-04-01

... RECOGNITION OF PHARMACEUTICAL GOOD MANUFACTURING PRACTICE REPORTS, MEDICAL DEVICE QUALITY SYSTEM AUDIT REPORTS... perform any type of quality system or product evaluation covered by this subpart and with regard to any... any type of quality system or product evaluation. (b) The parties shall allow CAB's not listed for...

Quality assurance of medicines supplied to low-income and middle-income countries: poor products in shiny boxes?

PubMed Central

Schiavetti, B; Meessen, B; Pouget, C; Caudron, J M; Marchal, B; Massat, P; Thys, S; Ravinetto, R

2017-01-01

Objective In today's context of globalisation of pharmaceutical production and distribution, international and national procurement agencies play a de facto key role in defining the quality of medicines available in sub-Saharan Africa. We evaluated the compliance of a sample of pharmaceutical distributors active in sub-Saharan Africa with the standards of the WHO guideline ‘Model Quality Assurance System (WHO MQAS) for procurement agencies’, and we investigated factors favouring or hindering the adequate implementation of the guideline. Methods We used mixed-methods methodology to analyse quantitative and qualitative data. The quantitative study consisted of a retrospective secondary analysis of data collected by QUAMED (Quality Medicines for all), a partnership that pleads for universal access to quality-assured medicines. The qualitative survey consisted of formal and informal interviews with key informants. We adopted an embedded multiple-case study design. Findings Our analysis suggests that international distributors based in Europe perform, on average, better than sub-Saharan African distributors. However, some weaknesses are ubiquitous and concern critical processes, such as the initial selection of the products and the ongoing reassessment of their quality. This is due to several different factors: weak regulatory oversight, insufficient human/financial resources, weak negotiating power, limited judicial autonomy and/or lack of institutional commitment to quality. Conclusions Our findings suggest that pharmaceutical distributors active in sub-Saharan Africa generally do not apply stringent criteria for selecting products and suppliers. Therefore, product quality is not consistently assured but depends on the requirements of purchasers. While long-term solutions are awaited, the WHO MQAS guideline should be used as an evaluation and training tool to upgrade current standards. PMID:28589013

Analysis of Cl and Na in Hyperimmune Sera by NAA

NASA Astrophysics Data System (ADS)

Baptista, T. S.; Zamboni, C. B.; Marcelino, J. R.

2011-08-01

The Cl and Na concentration values in four types of hyperimmune sera (anti-Bothrops, anti-Diphtheria, anti-Rabies and anti-Tetanus) used for immunological therapy were determined using Neutron Activation Analysis (NAA). These data were compatible with the specifications established by the Word Health Organization (WHO-OMS) and with the Brazilian Official Pharmacopea (Pharmaceutical Code Official of the Country). These data are an important support for quality control of hyperimmune sera production at Butantan Institute (São Paulo city, Brazil), responsible for supplying the Brazilian market.

Quality by design for herbal drugs: a feedforward control strategy and an approach to define the acceptable ranges of critical quality attributes.

PubMed

Yan, Binjun; Li, Yao; Guo, Zhengtai; Qu, Haibin

2014-01-01

The concept of quality by design (QbD) has been widely accepted and applied in the pharmaceutical manufacturing industry. There are still two key issues to be addressed in the implementation of QbD for herbal drugs. The first issue is the quality variation of herbal raw materials and the second issue is the difficulty in defining the acceptable ranges of critical quality attributes (CQAs). To propose a feedforward control strategy and a method for defining the acceptable ranges of CQAs for the two issues. In the case study of the ethanol precipitation process of Danshen (Radix Salvia miltiorrhiza) injection, regression models linking input material attributes and process parameters to CQAs were built first and an optimisation model for calculating the best process parameters according to the input materials was established. Then, the feasible material space was defined and the acceptable ranges of CQAs for the previous process were determined. In the case study, satisfactory regression models were built with cross-validated regression coefficients (Q(2) ) all above 91 %. The feedforward control strategy was applied successfully to compensate the quality variation of the input materials, which was able to control the CQAs in the 90-110 % ranges of the desired values. In addition, the feasible material space for the ethanol precipitation process was built successfully, which showed the acceptable ranges of the CQAs for the concentration process. The proposed methodology can help to promote the implementation of QbD for herbal drugs. Copyright © 2013 John Wiley & Sons, Ltd.

Media portrayal of herbal remedies versus pharmaceutical clinical trials: impacts on decision.

PubMed

Bubela, T; Koper, M; Boon, H; Caulfield, T

2007-06-01

The use of Complementary and Alternative Medicines (CAM) in Europe and North America is increasing significantly with a concomitant growth in business interest. Users are educated and self-empowered and rely on information sources beyond mainstream medical practitioners. Not surprisingly, media coverage, much of dubious quality, has increased to meet demand for information. Here we present data from a study that explores how knowledge is translated in the socioeconomic-political context of CAM as compared to conventional pharmaceuticals. Specifically, we are interested in the nature of the information provided by clinical trials and the media and how this might impact decision-making regarding the use of CAM versus conventional pharmaceuticals and the reporting of conflicts of interest and industry funding of research. Our results suggest that, in the media, there were significant errors of omission in describing clinical trial quality and a serious under-reporting of risks of herbal remedies. Consumers, who often self-administer CAM are not being provided with information sufficient to make informed choices about treatment alternatives. The next step in the research is to determine whether these reporting dynamics in describing CAM clinical trials differ from those of reporting on pharmaceutical clinical trials.

Present Conditions and Problems of Home Care Education in Pharmaceutical Education: Through the Activities of "the Working Group to Create Home Clinical Cases for Education".

PubMed

Kobuke, Yuko

2017-01-01

In the pharmaceutical education model core curriculums revision, "basic qualities required as a pharmacist" are clearly shown, and "the method based on learning outcomes" has been adopted. One of the 10 qualities (No. 7) is "Practical ability of the health and medical care in the community". In the large item "F. Pharmaceutical clinical" of the model core curriculums, "participation in the home (visit) medical care and nursing care" is written in "participation in the health, medical care, and welfare of the community", and it is an important problem to offer opportunities of home medical care education at university. In our university, we launched a working group to create "home clinical cases for education" from the educational point of view to pharmacy students to learn home medical care, in collaboration with university faculty members and pharmacists, who are practitioners of home care. Through its working group activities, we would like to organize the present conditions and problems of home care education in pharmaceutical education and to examine the possibility of using "home clinical case studies" in home care education at university.

In-line Raman spectroscopic monitoring and feedback control of a continuous twin-screw pharmaceutical powder blending and tableting process.

PubMed

Nagy, Brigitta; Farkas, Attila; Gyürkés, Martin; Komaromy-Hiller, Szofia; Démuth, Balázs; Szabó, Bence; Nusser, Dávid; Borbás, Enikő; Marosi, György; Nagy, Zsombor Kristóf

2017-09-15

The integration of Process Analytical Technology (PAT) initiative into the continuous production of pharmaceuticals is indispensable for reliable production. The present paper reports the implementation of in-line Raman spectroscopy in a continuous blending and tableting process of a three-component model pharmaceutical system, containing caffeine as model active pharmaceutical ingredient (API), glucose as model excipient and magnesium stearate as lubricant. The real-time analysis of API content, blend homogeneity, and tablet content uniformity was performed using a Partial Least Squares (PLS) quantitative method. The in-line Raman spectroscopic monitoring showed that the continuous blender was capable of producing blends with high homogeneity, and technological malfunctions can be detected by the proposed PAT method. The Raman spectroscopy-based feedback control of the API feeder was also established, creating a 'Process Analytically Controlled Technology' (PACT), which guarantees the required API content in the produced blend. This is, to the best of the authors' knowledge, the first ever application of Raman-spectroscopy in continuous blending and the first Raman-based feedback control in the formulation technology of solid pharmaceuticals. Copyright © 2017 Elsevier B.V. All rights reserved.

[50 years of the Institute for Research in Pharmacy and Biochemistry].

PubMed

Trcka, V

2003-05-01

After the nationalization of pharmaceutical industry and establishment of the United Pharmaceutical Enterprises in 1946, the Research and Control Institute (VKU) was established in Prague in 1947 to support the development of research, manufacture, and control of drugs. After other measures of nationalization and unification of research, in 1951 the research sections of the VKU and the pharmaceutical sections of the Research Institute of CCHZ were fused to form the Research Institute for Pharmacy and Biochemistry (VUFB). The section the VUFB taking care of the quality of production was transformed into the Pharmaceutical Control Institute (KUF). Each of the institutes had its own farm for breeding experimental animals outside Prague. In 1958, KUF was transformed into the Research Institute of Medicinal Plants (VULERO) and later, in 1960, into the Research Institute of Natural Substances (VUPL), which eventually fused with VUFB in 1967. During the years of increasing activities of VUFB, a chemical pilot plant was established in Olomouc, and a department of clinical pharmacology in Plzen. Research activities of VUFB were aimed to search for original drugs and to develop non-proprietary medicines in the field of the central and vegetative nervous systems, blood circulation, inflammatory processes, microbial infections, carcinostatic drugs, etc. In natural substances, the greatest attention was paid to ergot alkaloids, but the extent of research also included the constituents of the poppy, periwinkle, and other plants. An important part of the programme was also the breeding and cultivation of selected medicinal plants. The results of research were continuously published in both inland and foreign scholarly journals and at conferences and congresses. Every year, usually more than 100 papers were published and 40-50 for patents applications were submitted. The activity of the Institute resulted in the production of 30 original substances which were introduced into therapeutic practice. Twenty of them are still commonly prescribed. Some of these original substances got into foreign markets, particularly Prothiaden and Trimepranol represented important exports. In addition, 83 non-proprietary drugs were introduced into the inland market.

Hollow-fiber flow field-flow fractionation with multi-angle laser scattering detection for aggregation studies of therapeutic proteins.

PubMed

Reschiglian, P; Roda, B; Zattoni, A; Tanase, M; Marassi, V; Serani, S

2014-02-01

The rapid development of protein-based pharmaceuticals highlights the need for robust analytical methods to ensure their quality and stability. Among proteins used in pharmaceutical applications, an important and ever increasing role is represented by monoclonal antibodies and large proteins, which are often modified to enhance their activity or stability when used as drugs. The bioactivity and the stability of those proteins are closely related to the maintenance of their complex structure, which however are influenced by many external factors that can cause degradation and/or aggregation. The presence of aggregates in these drugs could reduce their bioactivity and bioavailability, and induce immunogenicity. The choice of the proper analytical method for the analysis of aggregates is fundamental to understand their (size) dimensional range, their amount, and if they are present in the sample as generated by an aggregation or as an artifact due to the method itself. Size exclusion chromatography is one of the most important techniques for the quality control of pharmaceutical proteins; however, its application is limited to relatively low molar mass aggregates. Among the techniques for the size characterization of proteins, field-flow fractionation (FFF) represents a competitive choice because of its soft mechanism due to the absence of a stationary phase and application in a broader size range, from nanometer- to micrometer-sized analytes. In this paper, the microcolumn variant of FFF, the hollow-fiber flow FFF, was online coupled with multi-angle light scattering, and a method for the characterization of aggregates with high reproducibility and low limit of detection was demonstrated employing an avidin derivate as sample model.

Water Quality in the Blue River Basin, Kansas City Metropolitan Area, Missouri and Kansas, July 1998 to October 2004

USGS Publications Warehouse

Wilkison, Donald H.; Armstrong, Daniel J.; Norman, Richard D.; Polton, Barry C.; Furlong, Edward T.; Zaugg, Steven D.

2006-01-01

Water-quality data were collected from sites in the Blue River Basin from July 1998 to October. Sites upstream from wastewater-treatment plants or the combined sewer system area had lower concentrations of total nitrogen, phosphorus, organic wastewater compounds, and pharmaceuticals, and more diverse aquatic communities. Sites downstream from wastewater-treatment plants had the largest concentrations and loads of nutrients, organic wastewater compounds, and pharmaceuticals. Approximately 60 percent of the total nitrogen and phosphorus in Blue River originated from the Indian Creek, smaller amounts from the upper Blue River (from 28 to 16 percent), and less than 5 percent from Brush Creek. Nutrient yields from the Indian Creek and the middle Blue River were significantly greater than yields from the upper Blue River, lower Brush Creek, the outside control site, and other U.S. urban sites. Large concentrations of nutrients led to eutrophication of impounded Brush Creek reaches. Bottom sediment samples collected from impoundments generally had concentrations of organic wastewater and pharmaceutical compounds equivalent to or greater than, concentrations observed in streambed sediments downstream from wastewater-treatment plants. Bacteria in streams largely was the result of nonpoint-source contributions during storms. Based on genetic source-tracking, average contributions of in-stream Esherichia coli bacteria in the basin from dogs ranged from 26-32 percent of the total concentration, and human sources ranged from 28-42 percent. Macro invertebrate diversity was highest at sites with the largest percentage of upstream land use devoted to forests and grasslands. Declines in macro invertebrate community metrics were correlated strongly with increases in several, inter-related urbanization factors.

Water quality in the Blue River basin, Kansas City metropolitan area, Missouri and Kansas, July 1998 to October 2004

USGS Publications Warehouse

Wilkison, Donald H.; Armstrong, Daniel J.; Norman, Richard D.; Poulton, Barry C.; Furlong, Edward T.; Zaugg, Steven D.

2006-01-01

Water-quality data were collected from sites in the Blue River Basin from July 1998 to October. Sites upstream from wastewater-treatment plants or the combined sewer system area had lower concentrations of total nitrogen, phosphorus, organic wastewater compounds, and pharmaceuticals, and more diverse aquatic communities. Sites downstream from wastewater-treatment plants had the largest concentrations and loads of nutrients, organic wastewater compounds, and pharmaceuticals. Approximately 60 percent of the total nitrogen and phosphorus in Blue River originated from the Indian Creek, smaller amounts from the upper Blue River (from 28 to 16 percent), and less than 5 percent from Brush Creek. Nutrient yields from the Indian Creek and the middle Blue River were significantly greater than yields from the upper Blue River, lower Brush Creek, the outside control site, and other U.S. urban sites. Large concentrations of nutrients led to eutrophication of impounded Brush Creek reaches. Bottom sediment samples collected from impoundments generally had concentrations of organic wastewater and pharmaceutical compounds equivalent to or greater than, concentrations observed in streambed sediments downstream from wastewater-treatment plants. Bacteria in streams largely was the result of nonpoint-source contributions during storms. Based on genetic source-tracking, average contributions of in-stream Esherichia coli bacteria in the basin from dogs ranged from 26-32 percent of the total concentration, and human sources ranged from 28-42 percent. Macro invertebrate diversity was highest at sites with the largest percentage of upstream land use devoted to forests and grasslands. Declines in macro invertebrate community metrics were correlated strongly with increases in several, inter-related urbanization factors.

Automated Dissolution for Enteric-Coated Aspirin Tablets: A Case Study for Method Transfer to a RoboDis II.

PubMed

Ibrahim, Sarah A; Martini, Luigi

2014-08-01

Dissolution method transfer is a complicated yet common process in the pharmaceutical industry. With increased pharmaceutical product manufacturing and dissolution acceptance requirements, dissolution testing has become one of the most labor-intensive quality control testing methods. There is an increased trend for automation in dissolution testing, particularly for large pharmaceutical companies to reduce variability and increase personnel efficiency. There is no official guideline for dissolution testing method transfer from a manual, semi-automated, to automated dissolution tester. In this study, a manual multipoint dissolution testing procedure for an enteric-coated aspirin tablet was transferred effectively and reproducibly to a fully automated dissolution testing device, RoboDis II. Enteric-coated aspirin samples were used as a model formulation to assess the feasibility and accuracy of media pH change during continuous automated dissolution testing. Several RoboDis II parameters were evaluated to ensure the integrity and equivalency of dissolution method transfer from a manual dissolution tester. This current study provides a systematic outline for the transfer of the manual dissolution testing protocol to an automated dissolution tester. This study further supports that automated dissolution testers compliant with regulatory requirements and similar to manual dissolution testers facilitate method transfer. © 2014 Society for Laboratory Automation and Screening.

Microbiological assay for the analysis of certain macrolides in pharmaceutical dosage forms.

PubMed

Mahmoudi, A; Fourar, R E-A; Boukhechem, M S; Zarkout, S

2015-08-01

Clarithromycin (CLA) and roxithromycin (ROX) are macrolide antibiotics with an expanded spectrum of activity that are commercially available as tablets. A microbiological assay, applying the cylinder-plate method and using a strain of Micrococcus luteus ATCC 9341 as test organism, has been used and validated for the quantification of two macrolide drugs; CLA and ROX in pure and pharmaceutical formulations. The validation of the proposed method was carried out for linearity, precision, accuracy and specificity. The linear dynamic ranges were from 0.1 to 0.5μg/mL for both compounds. Logarithmic calibration curve was obtained for each macrolide (r>0.989) with statistically equal slopes varying from 3.275 to 4.038, and a percentage relative standard deviation in the range of 0.24-0.92%. Moreover, the method was applied successfully for the assay of the studied drugs in pharmaceutical tablet dosage forms. Recovery from standard addition experiments in commercial products was 94.71-96.91% regarding clarithromycin and 93.94-98.12% regarding roxithromycin, with a precision (%RSD) 1.32-2.11%. Accordingly, this microbiological assay can be used for routine quality control analysis of titled drugs in tablet formulations. Copyright © 2015 Elsevier B.V. All rights reserved.

Thermal Analysis by Structural Characterization as a Method for Assessing Heterogeneity in Complex Solid Pharmaceutical Dosage Forms.

PubMed

Alhijjaj, Muqdad; Reading, Mike; Belton, Peter; Qi, Sheng

2015-11-03

Characterizing inter- and intrasample heterogeneity of solid and semisolid pharmaceutical products is important both for rational design of dosage forms and subsequent quality control during manufacture; however, most pharmaceutical products are multicomponent formulations that are challenging in this regard. Thermal analysis, in particular differential scanning calorimetry, is commonly used to obtain structural information, such as degree of crystallinity, or identify the presence of a particular polymorph, but the results are an average over the whole sample; it cannot directly provide information about the spatial distribution of phases. This study demonstrates the use of a new thermo-optical technique, thermal analysis by structural characterization (TASC), that can provide spatially resolved information on thermal transitions by applying a novel algorithm to images acquired by hot stage microscopy. We determined that TASC can be a low cost, relatively rapid method of characterizing heterogeneity and other aspects of structure. In the examples studied, it was found that high heating rates enabled screening times of 3-5 min per sample. In addition, this study demonstrated the higher sensitivity of TASC for detecting the metastable form of polyethylene glycol (PEG) compared to conventional differential scanning calorimetry (DSC). This preliminary work suggests that TASC will be a worthwhile additional tool for characterizing a broad range of materials.

Study of formulation of mild pharmaceutical forms of paracetamol in medical practice.

PubMed

Abdullahu, Bedri; Morina, Naim; Islami, Hilmi

2012-01-01

Paracetamol is one of the most used antipyretic- analgesic preparation, which can be found in different pharmaceutical forms and in different doses. Due to its wide utilization in the clinical practice, determination of paracetamol in pharmaceutical formulation is of a great importance since that over dosage with paracetamol may cause the hepatic fulminant necroses and other toxic effects. Study has included two formulations of paracetamol suppositories with doses of 125 mg widely used in the paediatric practice. Suppositories prepared according to these two formulations by the melting method and spilling into forms was subject to the quality control by implementing a series of trials and analyses for that aim, such are: reactions of identification, average mass, disintegration time, and homogeneity whilst quantitative determination was performed by applying two methods of instrumental analyze: spectrophotometry in UV zone and cromatography in liquid phase with high pressure. Results of these analyses, performed immediately following the preparation and 3 months after the preparation, showed that content of paracetamol in both of two formulations is within the norms of Pharmacopoeia. Suppositories of paracetamol in doses of 125 mg prepared as per formulation 1 are to be considered as more appropriate because it contains semi synthetic glycerides as excipient which has better features than other suppository excipients.

How Deformation Behavior Controls Product Performance After Twin Screw Granulation With High Drug Loads and Crospovidone as Disintegrant.

PubMed

Meier, Robin; Moll, Klaus-Peter; Krumme, Markus; Kleinebudde, Peter

2017-01-01

This study addresses the quantitative influence of 12 different materials (active pharmaceutical ingredients and excipients as surrogate active pharmaceutical ingredients) on the critical quality attributes of twin screw granulated products and subsequently produced tablets. Prestudies demonstrated the significant influence of the chosen model materials (in combination with crospovidone) on the disintegration behavior of the resulting tablets, despite comparable tablet porosities. This study elucidates possible reasons for the varying disintegration behavior by investigating raw material, granule, and tablet properties. An answer could be found in the mechanical properties of the raw materials and the produced granules. Through compressibility studies, the materials could be classified into materials with high compressibility, which deform rather plastically under compression stress, and low compressibility, which display breakages under compression stress. In general, and apart from (pseudo)-polymorphic transformations, brittle materials featured excellent disintegration performance, even at low resulting tablet porosities <8%, whereas plastically deformable materials mostly did not reveal any disintegration. These findings must be considered in the development of simplified formulations with high drug loads, in which the active pharmaceutical ingredient predominantly defines the deformation behavior of the granule. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Taste sensing systems (electronic tongues) for pharmaceutical applications.

PubMed

Woertz, Katharina; Tissen, Corinna; Kleinebudde, Peter; Breitkreutz, Jörg

2011-09-30

Electronic tongues are sensor array systems able to detect single substances as well as complex mixtures by means of particular sensor membranes and electrochemical techniques. Two systems are already commercially available, the Insent taste sensing system and the αAstree electronic tongue. In addition, various laboratory prototype versions exist. Besides the successful use in food industry, the implementation for pharmaceutical purposes has strongly grown within the recent years. A reason for this is the increased interest of developing palatable formulations, especially for children. As taste assessment of drugs comes along with challenges due to possible toxicity and subjectivity of the taste assessors, electronic tongues could offer a safe and objective alternative. In order to provide guidance on the use of these systems, possible fields of interest are presented in this review, as for example, system qualification, quality control, formulation development, comparison between marketed drug products, and the validation of the methods used. Further, different approaches for solid and liquid dosage forms are summarized. But, also the difficulty to obtain absolute statements regarding taste was identified and the need of more validated data was discussed to offer guidance for the next years of research and application of electronic tongues for pharmaceutical applications. Copyright © 2010 Elsevier B.V. All rights reserved.

Identifying and assessing highly hazardous drugs within quality risk management programs.

PubMed

Sussman, Robert G; Schatz, Anthony R; Kimmel, Tracy A; Ader, Allan; Naumann, Bruce D; Weideman, Patricia A

2016-08-01

Historically, pharmaceutical industry regulatory guidelines have assigned certain active pharmaceutical ingredients (APIs) to various categories of concern, such as "cytotoxic", "hormones", and "steroids". These categories have been used to identify APIs requiring segregation or dedication in order to prevent cross-contamination and protect the quality and safety of drug products. Since these terms were never defined by regulatory authorities, and many novel pharmacological mechanisms challenge these categories, there is a recognized need to modify the historical use of these terms. The application of a risk-based approach using a health-based limit, such as an acceptable daily exposure (ADE), is more appropriate for the development of a Quality Risk Management Program (QRMP) than the use of categories of concern. The toxicological and pharmacological characteristics of these categories are discussed to help identify and prioritize compounds requiring special attention. Controlling airborne concentrations and the contamination of product contact surfaces in accordance with values derived from quantitative risk assessments can prevent adverse effects in workers and patients, regardless of specific categorical designations to which these APIs have been assigned. The authors acknowledge the movement away from placing compounds into categories and, while not yet universal, the importance of basing QRMPs on compound-specific ADEs and risk assessments. Based on the results of a risk assessment, segregation and dedication may also be required for some compounds to prevent cross contamination during manufacture of APIs. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of Pharmaceutical, Psychological, and Exercise Treatments for Cancer-Related Fatigue: A Meta-analysis.

PubMed

Mustian, Karen M; Alfano, Catherine M; Heckler, Charles; Kleckner, Amber S; Kleckner, Ian R; Leach, Corinne R; Mohr, David; Palesh, Oxana G; Peppone, Luke J; Piper, Barbara F; Scarpato, John; Smith, Tenbroeck; Sprod, Lisa K; Miller, Suzanne M

2017-07-01

Cancer-related fatigue (CRF) remains one of the most prevalent and troublesome adverse events experienced by patients with cancer during and after therapy. To perform a meta-analysis to establish and compare the mean weighted effect sizes (WESs) of the 4 most commonly recommended treatments for CRF-exercise, psychological, combined exercise and psychological, and pharmaceutical-and to identify independent variables associated with treatment effectiveness. PubMed, PsycINFO, CINAHL, EMBASE, and the Cochrane Library were searched from the inception of each database to May 31, 2016. Randomized clinical trials in adults with cancer were selected. Inclusion criteria consisted of CRF severity as an outcome and testing of exercise, psychological, exercise plus psychological, or pharmaceutical interventions. Studies were independently reviewed by 12 raters in 3 groups using a systematic and blinded process for reconciling disagreement. Effect sizes (Cohen d) were calculated and inversely weighted by SE. Severity of CRF was the primary outcome. Study quality was assessed using a modified 12-item version of the Physiotherapy Evidence-Based Database scale (range, 0-12, with 12 indicating best quality). From 17 033 references, 113 unique studies articles (11 525 unique participants; 78% female; mean age, 54 [range, 35-72] years) published from January 1, 1999, through May 31, 2016, had sufficient data. Studies were of good quality (mean Physiotherapy Evidence-Based Database scale score, 8.2; range, 5-12) with no evidence of publication bias. Exercise (WES, 0.30; 95% CI, 0.25-0.36; P < .001), psychological (WES, 0.27; 95% CI, 0.21-0.33; P < .001), and exercise plus psychological interventions (WES, 0.26; 95% CI, 0.13-0.38; P < .001) improved CRF during and after primary treatment, whereas pharmaceutical interventions did not (WES, 0.09; 95% CI, 0.00-0.19; P = .05). Results also suggest that CRF treatment effectiveness was associated with cancer stage, baseline treatment status, experimental treatment format, experimental treatment delivery mode, psychological mode, type of control condition, use of intention-to-treat analysis, and fatigue measures (WES range, -0.91 to 0.99). Results suggest that the effectiveness of behavioral interventions, specifically exercise and psychological interventions, is not attributable to time, attention, and education, and specific intervention modes may be more effective for treating CRF at different points in the cancer treatment trajectory (WES range, 0.09-0.22). Exercise and psychological interventions are effective for reducing CRF during and after cancer treatment, and they are significantly better than the available pharmaceutical options. Clinicians should prescribe exercise or psychological interventions as first-line treatments for CRF.

Enhancing cell and gene therapy manufacture through the application of advanced fluorescent optical sensors (Review).

PubMed

Harrison, Richard P; Chauhan, Veeren M

2017-12-15

Cell and gene therapies (CGTs) are examples of future therapeutics that can be used to cure or alleviate the symptoms of disease, by repairing damaged tissue or reprogramming defective genetic information. However, despite the recent advancements in clinical trial outcomes, the path to wide-scale adoption of CGTs remains challenging, such that the emergence of a "blockbuster" therapy has so far proved elusive. Manufacturing solutions for these therapies require the application of scalable and replicable cell manufacturing techniques, which differ markedly from the existing pharmaceutical incumbent. Attempts to adopt this pharmaceutical model for CGT manufacture have largely proved unsuccessful. The most significant challenges facing CGT manufacturing are process analytical testing and quality control. These procedures would greatly benefit from improved sensory technologies that allow direct measurement of critical quality attributes, such as pH, oxygen, lactate and glucose. In turn, this would make manufacturing more robust, replicable and standardized. In this review, the present-day state and prospects of CGT manufacturing are discussed. In particular, the authors highlight the role of fluorescent optical sensors, focusing on their strengths and weaknesses, for CGT manufacture. The review concludes by discussing how the integration of CGT manufacture and fluorescent optical sensors could augment future bioprocessing approaches.

Price competition in the Chinese pharmaceutical market.

PubMed

Wang, Y Richard

2006-06-01

We study price competition between high-quality global products and low-quality local products in a developing country, i.e., China, Nearly all previous studies on pharmaceutical price competition focused on developed countries with bioequivalent generics. In China, local generic products are not bioequivalent and are deemed of lower quality, while global products in the same class are considered similar in quality and better substitutes. We hypothesize that local generic competition drives down local product price but not global product price. In addition, we hypothesize that therapeutic competition among similar global products lowers global product price. Our empirical results support both hypotheses. Number of local generic competitors has a significantly negative effect on local product price but no effect on global product price, while number of global therapeutic competitors has a significantly negative effect on global product price. Policy changes that encourage bioequivalent local products and accelerate global product approvals will enhance price competition in China.

Pharmaceutical Raw Material Identification Using Miniature Near-Infrared (MicroNIR) Spectroscopy and Supervised Pattern Recognition Using Support Vector Machine

PubMed Central

Hsiung, Chang; Pederson, Christopher G.; Zou, Peng; Smith, Valton; von Gunten, Marc; O’Brien, Nada A.

2016-01-01

Near-infrared spectroscopy as a rapid and non-destructive analytical technique offers great advantages for pharmaceutical raw material identification (RMID) to fulfill the quality and safety requirements in pharmaceutical industry. In this study, we demonstrated the use of portable miniature near-infrared (MicroNIR) spectrometers for NIR-based pharmaceutical RMID and solved two challenges in this area, model transferability and large-scale classification, with the aid of support vector machine (SVM) modeling. We used a set of 19 pharmaceutical compounds including various active pharmaceutical ingredients (APIs) and excipients and six MicroNIR spectrometers to test model transferability. For the test of large-scale classification, we used another set of 253 pharmaceutical compounds comprised of both chemically and physically different APIs and excipients. We compared SVM with conventional chemometric modeling techniques, including soft independent modeling of class analogy, partial least squares discriminant analysis, linear discriminant analysis, and quadratic discriminant analysis. Support vector machine modeling using a linear kernel, especially when combined with a hierarchical scheme, exhibited excellent performance in both model transferability and large-scale classification. Hence, ultra-compact, portable and robust MicroNIR spectrometers coupled with SVM modeling can make on-site and in situ pharmaceutical RMID for large-volume applications highly achievable. PMID:27029624

A Review of Herbal and Pharmaceutical Galactagogues for Breast-Feeding

PubMed Central

Bazzano, Alessandra N.; Hofer, Rebecca; Thibeau, Shelley; Gillispie, Veronica; Jacobs, Marni; Theall, Katherine P.

2016-01-01

Background: Therapeutic approaches to addressing insufficient lactation are available but remain poorly understood. Current trends in maternal health, such as increasing rates of obesity, delayed age at childbearing, and high rates of cesarean section, may be associated with physiological challenges for lactation that cannot be managed by counseling alone. Women who have not had success with counseling alone, including adoptive mothers seeking to induce lactation, may use galactagogues (pharmaceutical and herbal compounds used to increase lactation). We present a review of selected studies of galactagogues and data indicating popular demand for such products. Methods: A systematic search was conducted for published studies on the use of galactagogues for breast-feeding. The following databases were searched: MEDLINE (PubMed), EBSCO (Academic Search Complete), and EMBASE. The search was conducted between July 15, 2015, and August 18, 2015; only English language articles were included, and we imposed no restrictions on publication date. Two authors independently reviewed the studies and extracted data. Results: Blinded, placebo-controlled clinical trials of 2 pharmaceutical galactagogues (domperidone and metoclopramide) and 5 popular herbal galactagogues (shatavari, fenugreek, silymarin, garlic, and malunggay) were identified. All of the studies identified for domperidone showed a significant difference in milk production between the treatment and placebo groups. Of the 6 trials of metoclopramide, only 1 study showed a significant difference in milk production compared to placebo. Results of the clinical trials on herbal galactagogues were mixed. Our review of the evidence for the efficacy of popular pharmaceutical and herbal galactagogues revealed a dearth of high-quality clinical trials and mixed results. Conclusion: Health providers face the challenge of prescribing or recommending galactagogues without the benefit of robust evidence. Given the suboptimal rates of exclusive breast-feeding worldwide and the availability and demand for medical and herbal lactation therapies, controlled trials and analyses investigating these medicines are urgently warranted. PMID:27999511

A Review of Herbal and Pharmaceutical Galactagogues for Breast-Feeding.

PubMed

Bazzano, Alessandra N; Hofer, Rebecca; Thibeau, Shelley; Gillispie, Veronica; Jacobs, Marni; Theall, Katherine P

2016-01-01

Therapeutic approaches to addressing insufficient lactation are available but remain poorly understood. Current trends in maternal health, such as increasing rates of obesity, delayed age at childbearing, and high rates of cesarean section, may be associated with physiological challenges for lactation that cannot be managed by counseling alone. Women who have not had success with counseling alone, including adoptive mothers seeking to induce lactation, may use galactagogues (pharmaceutical and herbal compounds used to increase lactation). We present a review of selected studies of galactagogues and data indicating popular demand for such products. A systematic search was conducted for published studies on the use of galactagogues for breast-feeding. The following databases were searched: MEDLINE (PubMed), EBSCO (Academic Search Complete), and EMBASE. The search was conducted between July 15, 2015, and August 18, 2015; only English language articles were included, and we imposed no restrictions on publication date. Two authors independently reviewed the studies and extracted data. Blinded, placebo-controlled clinical trials of 2 pharmaceutical galactagogues (domperidone and metoclopramide) and 5 popular herbal galactagogues (shatavari, fenugreek, silymarin, garlic, and malunggay) were identified. All of the studies identified for domperidone showed a significant difference in milk production between the treatment and placebo groups. Of the 6 trials of metoclopramide, only 1 study showed a significant difference in milk production compared to placebo. Results of the clinical trials on herbal galactagogues were mixed. Our review of the evidence for the efficacy of popular pharmaceutical and herbal galactagogues revealed a dearth of high-quality clinical trials and mixed results. Health providers face the challenge of prescribing or recommending galactagogues without the benefit of robust evidence. Given the suboptimal rates of exclusive breast-feeding worldwide and the availability and demand for medical and herbal lactation therapies, controlled trials and analyses investigating these medicines are urgently warranted.

Sample size and number of outcome measures of veterinary randomised controlled trials of pharmaceutical interventions funded by different sources, a cross-sectional study.

PubMed

Wareham, K J; Hyde, R M; Grindlay, D; Brennan, M L; Dean, R S

2017-10-04

Randomised controlled trials (RCTs) are a key component of the veterinary evidence base. Sample sizes and defined outcome measures are crucial components of RCTs. To describe the sample size and number of outcome measures of veterinary RCTs either funded by the pharmaceutical industry or not, published in 2011. A structured search of PubMed identified RCTs examining the efficacy of pharmaceutical interventions. Number of outcome measures, number of animals enrolled per trial, whether a primary outcome was identified, and the presence of a sample size calculation were extracted from the RCTs. The source of funding was identified for each trial and groups compared on the above parameters. Literature searches returned 972 papers; 86 papers comprising 126 individual trials were analysed. The median number of outcomes per trial was 5.0; there were no significant differences across funding groups (p = 0.133). The median number of animals enrolled per trial was 30.0; this was similar across funding groups (p = 0.302). A primary outcome was identified in 40.5% of trials and was significantly more likely to be stated in trials funded by a pharmaceutical company. A very low percentage of trials reported a sample size calculation (14.3%). Failure to report primary outcomes, justify sample sizes and the reporting of multiple outcome measures was a common feature in all of the clinical trials examined in this study. It is possible some of these factors may be affected by the source of funding of the studies, but the influence of funding needs to be explored with a larger number of trials. Some veterinary RCTs provide a weak evidence base and targeted strategies are required to improve the quality of veterinary RCTs to ensure there is reliable evidence on which to base clinical decisions.

Trends in Process Analytical Technology: Present State in Bioprocessing.

PubMed

Jenzsch, Marco; Bell, Christian; Buziol, Stefan; Kepert, Felix; Wegele, Harald; Hakemeyer, Christian

2017-08-04

Process analytical technology (PAT), the regulatory initiative for incorporating quality in pharmaceutical manufacturing, is an area of intense research and interest. If PAT is effectively applied to bioprocesses, this can increase process understanding and control, and mitigate the risk from substandard drug products to both manufacturer and patient. To optimize the benefits of PAT, the entire PAT framework must be considered and each elements of PAT must be carefully selected, including sensor and analytical technology, data analysis techniques, control strategies and algorithms, and process optimization routines. This chapter discusses the current state of PAT in the biopharmaceutical industry, including several case studies demonstrating the degree of maturity of various PAT tools. Graphical Abstract Hierarchy of QbD components.

Defining pharmaceutical systems strengthening: concepts to enable measurement.

PubMed

Hafner, Tamara; Walkowiak, Helena; Lee, David; Aboagye-Nyame, Francis

2017-05-01

Pharmaceutical products are indispensable for improving health outcomes. An extensive body of work on access to and use of medicines has resulted in an assortment of tools measuring various elements of pharmaceutical systems. Until now however, there has been little attempt to conceptualize a pharmaceutical system as an entity and define its strengthening in a way that allows for measuring systems strengthening. The narrow focus of available tools limits their value in ascertaining which interventions result in stronger, more resilient systems. We sought to address this shortcoming by revisiting the current definitions, frameworks and assessment tools related to pharmaceutical systems. We conducted a comprehensive literature review and consulted with select pharmaceutical experts. On the basis of our review, we propose that a pharmaceutical system consists of all structures, people, resources, processes, and their interactions within the broader health system that aim to ensure equitable and timely access to safe, effective, quality pharmaceutical products and related services that promote their appropriate and cost-effective use to improve health outcomes. We further propose that pharmaceutical systems strengthening is the process of identifying and implementing strategies and actions that achieve coordinated and sustainable improvements in the critical components of a pharmaceutical system to make it more responsive and resilient and to enhance its performance for achieving better health outcomes. Finally, we established that, in addition to system performance and resilience, seven components of the pharmaceutical system are critical for measuring pharmaceutical systems strengthening: pharmaceutical products and related services; policy, laws and governance; regulatory systems; innovation, research and development, manufacturing, and trade; financing; human resources; and information. This work adds clarity to the concept of pharmaceutical systems and their strengthening by proposing holistic definitions on the basis of systems thinking. It provides a practical starting point for measuring the progress of pharmaceutical systems strengthening. © The Author 2016. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.

Aspects of research and development contract terms in the bio/pharmaceutical sector.

PubMed

Banerjee, Tannista

2012-01-01

The cost of new drug development is increasing every year. Pharmaceutical companies use R&D joint ventures, mergers, and outsource different stages of pharmaceutical R&D activities for a faster and cost minimizing method of innovation. Pharmaceutical companies outsource R&D activities to independent small biotech or pharmaceutical companies that specialize in different stages of pharmaceutical R&D. This chapter examines the determinants of the payment structure of research contracts between large bio/pharmaceutical companies and specialized research firms. Determinants of R&D contracts are analyzed using detailed R&D contract data between bio/pharmaceutical companies and independent research firms for 10 years. A multinomial logit model is used in order to understand the determinants of three different types of contracts; royalty contracts, fixed payment contracts, and the mixed contracts. Under uncertainty, the likelihood of a royalty contract rises for the early stages of the research and with the patent stock of the research firm. It is more likely to observe both royalty and fixed payment if the pharmaceutical client has past contracts with the same research firm. The results also suggest that if Food and Drug Administration (FDA) is more stringent in any disease area in reviewing the new drug application, then the likelihood of signing pure royalty contract decreases. Understanding the nature of R&D contracts and the effects of FDA's behavior on the pharmaceutical R&D contract is important because these contracts not only affect the cost of new drug invention but also the quality and the rate of invention. VALUE: Results are useful for both the pharmaceutical companies and the economic/business researchers.

[Function and structure of the Federal Joint Committee and the Institute for Quality and Efficiency in Health Care in consideration of patient involvement].

PubMed

Mühlbauer, V; Teupen, S

2014-01-01

The Federal Joint Committee and the Institute for Quality and Efficiency in Health Care have become important players in the German health care system, not only since the benefit assessment of pharmaceuticals and the Act on the Reform of the Market for Medicinal Products (AMNOG) were established. However, the manifold tasks and duties these institutions have besides the benefit assessment of pharmaceuticals is less known, just as the role the patient's representatives play. The function and structure of the Federal Joint Committee and the Institute for Quality and Efficiency in Health Care as well as their collaboration in consideration of patient involvement will be explained in this article. © Georg Thieme Verlag KG Stuttgart · New York.

Creative compliance in pharmaceutical markets: the case of profit controls.

PubMed

Bradley, James; Vandoros, Sotiris

2012-02-01

This article discusses the issue of creative compliance in pharmaceutical markets. In particular, we explore the case of profit controls in the UK as an indirect way of regulating prices of in-patent originators. We study creative compliance in the presence of profit controls, rather than price controls or the Pharmaceutical Price Regulation Scheme in general. We use lessons from the accounting literature to explain firm behavior and reveal potential weaknesses in profit control regulation and use data to show changes in trends following the introduction of this policy. We demonstrate that in the presence of profit controls there is an incentive for producers to increase costs (leading to inefficiencies) or to inflate reported costs. We find some evidence that the behavior of pharmaceutical firms in the UK may have changed as a result of the introduction of profit controls. Although the evidence is in line with what we would expect to occur as a result of creative compliance, establishing a concrete causal relationship between such a pricing policy and costs is not possible. As institutions or organizations look to achieve legitimacy for their actions, they will use the tools they have, whether accounting or regulatory, to best represent themselves.

A novel reporter gene assay for recombinant human erythropoietin (rHuEPO) pharmaceutical products.

PubMed

Yang, Yushuai; Zhou, Yong; Yu, Lei; Li, Xiang; Shi, Xinchang; Qin, Xi; Rao, Chunming; Wang, Junzhi

2014-11-01

Accurate determination of in vitro biological activity of therapeutic erythropoietin is essential in quality control of recombinant human erythropoietin (rHuEPO) pharmaceutical products. However, most of currently-used methods leave much to be desired so that a simpler, quicker and more accurate method is urgently needed. The bioassay described here utilizes a sub clone of UT-7/epo cell line stably transfected with luciferase gene under the control of sis inducible element and interferon γ-activated sequence element promoter. Active erythropoietin could induce the expression of luciferase by signaling through the erythropoietin receptor and the dose-response curve showed good linearity, yielding a coefficient of determination of 0.99 or higher. The optimized assay was simpler with the operation completed within 24h and more sensitive with EC50 being 0.077IU/mL. The accuracy estimates ranged from 81.7% to 102.4%, and both intra-assay and inter-assay precision was below 15.0%. The robustness of the assay was demonstrated by no effect of passage levels of the cells on the performance of the assay (p values: 0.772 for sample 1 and 0.943 for sample 2). Besides, Bland-Altman analysis showed a high consistency of the new assay with in vivo reticulocyte assay in results. These results suggested that the new reporter gene assay can be a viable supplement to the traditional reticulocyte assay and employed in potency determination of rHuEPO pharmaceutical products. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Extension of quality-by-design concept to the early development phase of pharmaceutical R&D processes.

PubMed

Csóka, Ildikó; Pallagi, Edina; Paál, Tamás L

2018-03-27

Here, we propose the extension of the quality-by-design (QbD) concept to also fit the early development phases of pharmaceuticals by adding elements that are currently widely applied, but not yet included in the QbD model in a structured way. These are the introduction of a 'zero' preformulation phase (i.e., selection of drug substance, possible dosage forms and administration routes based on the evaluated therapeutic need); building in stakeholders' (industry, patient, and regulatory) requirements into the quality target product profile (QTTP); and the use of modern quality management tools during the composition and process design phase [collecting critical quality attributes (CQAs) and selection of CPPs) for (still laboratory-scale) design space (DS) development. Moreover, during industrial scale-up, CQAs (as well as critical process parameters; CPPs) can be changed; however, we recommend that the existing QbD elements are reconsidered and updated after this phase. Copyright © 2018 Elsevier Ltd. All rights reserved.

Design of experiments (DoE) in pharmaceutical development.

PubMed

N Politis, Stavros; Colombo, Paolo; Colombo, Gaia; M Rekkas, Dimitrios

2017-06-01

At the beginning of the twentieth century, Sir Ronald Fisher introduced the concept of applying statistical analysis during the planning stages of research rather than at the end of experimentation. When statistical thinking is applied from the design phase, it enables to build quality into the product, by adopting Deming's profound knowledge approach, comprising system thinking, variation understanding, theory of knowledge, and psychology. The pharmaceutical industry was late in adopting these paradigms, compared to other sectors. It heavily focused on blockbuster drugs, while formulation development was mainly performed by One Factor At a Time (OFAT) studies, rather than implementing Quality by Design (QbD) and modern engineering-based manufacturing methodologies. Among various mathematical modeling approaches, Design of Experiments (DoE) is extensively used for the implementation of QbD in both research and industrial settings. In QbD, product and process understanding is the key enabler of assuring quality in the final product. Knowledge is achieved by establishing models correlating the inputs with the outputs of the process. The mathematical relationships of the Critical Process Parameters (CPPs) and Material Attributes (CMAs) with the Critical Quality Attributes (CQAs) define the design space. Consequently, process understanding is well assured and rationally leads to a final product meeting the Quality Target Product Profile (QTPP). This review illustrates the principles of quality theory through the work of major contributors, the evolution of the QbD approach and the statistical toolset for its implementation. As such, DoE is presented in detail since it represents the first choice for rational pharmaceutical development.

[Bacteriological quality of air in a ward for sterile pharmaceutical preparations].

PubMed

Caorsi P, Beatriz; Sakurada Z, Andrea; Ulloa F, M Teresa; Pezzani V, Marcela; Latorre O, Paz

2011-02-01

An extremely clean area is required for preparation of sterile pharmaceutical compounds, in compliance with international standards, to minimize the probability of microbial contamination. To evaluate the bacteriological quality of the air in the Sterile Pharmaceutical Preparation Unit of the University of Chile's Clinical Hospital and to set up alerts and action levels of bacterial growth. We studied eight representative sites of our Unit on a daily basis from January to February 2005 and twice a week from June 2005 to February 2006. We collected 839 samples of air by impact in the Petri dish. 474 (56.5%) samples were positive; 17 (3.5%) of them had an inappropriate bacterial growth (2% of total samples). The samples from sites 1 and 2 (big and small biosafety cabinets) were negative. The countertop and transfer area occasionally exceeded the bacterial growth limits. The most frequently isolated bacteria were coagulase-negative staphylococci, Micrococcus spp and Corynebacterium spp, from skin microbiota, and Bacillus spp, an environmental bacteria. From a microbiological perspective, the air quality in our sterile preparation unit complied with international standards. Setting institutional alerts and action levels and appropriately identifying bacteria in sensitive areas permits quantification of the microbial load and application of preventive measures.

Male enhancement Nutraceuticals in the Middle East market: Claim, pharmaceutical quality and safety assessments.

PubMed

ElAgouri, Ghada; ElAmrawy, Fatema; ElYazbi, Ahmed; Eshra, Ahmed; Nounou, Mohamed I

2015-08-15

The global market is invaded by male enhancement nutraceuticals claimed to be of natural origin sold with a major therapeutic claim. Most of these products have been reported by international systems like the Food and Drug Administration (FDA). We hypothesize that these products could represent a major threat to the health of the consumers. In this paper, pharmaceutical evaluation of some of these nutraceutical products sold in Egypt under the therapeutic claim of treating erectile dysfunction, are discussed along with pharmacological evaluation to investigate their safety and efficacy parameters. Samples were analyzed utterly using conventional methods, i.e.: HPLC, HPTLC, NIR, content uniformity and weight variation and friability. The SeDeM system was used for quality assessment. On the basis of the results of this research, the sampled products are adulterated and totally heterogeneous in their adulterant drug content and pharmaceutical quality. These products represent a major safety threat for the consumers in Egypt and the Middle East, especially; the target audience is mostly affected with heart and blood pressure problems seeking natural and safe alternatives to the well-established Phosphodiesterase 5 Inhibitors (PDE-5Is). Copyright © 2015 Elsevier B.V. All rights reserved.

Pharmaceutical policies: effects of financial incentives for prescribers.

PubMed

Rashidian, Arash; Omidvari, Amir-Houshang; Vali, Yasaman; Sturm, Heidrun; Oxman, Andrew D

2015-08-04

The proportion of total healthcare expenditures spent on drugs has continued to grow in countries of all income categories. Policy-makers are under pressure to control pharmaceutical expenditures without adversely affecting quality of care. Financial incentives seeking to influence prescribers' behaviour include budgetary arrangements at primary care and hospital settings (pharmaceutical budget caps or targets), financial rewards for target behaviours or outcomes (pay for performance interventions) and reduced benefit margin for prescribers based on medicine sales and prescriptions (pharmaceutical reimbursement rate reduction policies). This is the first update of the original version of this review. To determine the effects of pharmaceutical policies using financial incentives to influence prescribers' practices on drug use, healthcare utilisation, health outcomes and costs (expenditures). We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (searched 29/01/2015); MEDLINE, Ovid SP (searched 29/01/2015); EMBASE, Ovid SP (searched 29/01/2015); International Network for Rational Use of Drugs (INRUD) Bibliography (searched 29/01/2015); National Health Service (NHS) Economic Evaluation Database (searched 29/01/2015); EconLit - ProQuest (searched 02/02/2015); and Science Citation Index and Social Sciences Citation Index, Institute for Scientific Information (ISI) Web of Knowledge (citation search for included studies searched 10/02/2015). We screened the reference lists of relevant reports and contacted study authors and organisations to identify additional studies. We included policies that intend to affect prescribing by means of financial incentives for prescribers. Included in this category are pharmaceutical budget caps or targets, pay for performance and drug reimbursement rate reductions and other financial policies, if they were specifically targeted at prescribing or drug utilisation. Policies in this review were defined as laws, rules, regulations and financial and administrative orders made or implemented by payers such as national or local governments, non-government organisations, private or social insurers and insurance-like organisations. One of the following outcomes had to be reported: drug use, healthcare utilisation, health outcomes or costs. The study had to be a randomised or non-randomised trial, an interrupted time series (ITS) analysis, a repeated measures study or a controlled before-after (CBA) study. At least two review authors independently assessed eligibility for inclusion of studies and risks of bias using Cochrane Effective Practice and Organisation of Care (EPOC) criteria and extracted data from the included studies. For CBA studies, we reported relative effects (e.g. adjusted relative change). The review team re-analysed all ITS results. When possible, the review team also re-analysed CBA data as ITS data. Eighteen evaluations (six new studies) of pharmaceutical policies from six high-income countries met our inclusion criteria. Fourteen studies evaluated pharmaceutical budget policies in the UK (nine studies), two in Germany and Ireland and one each in Sweden and Taiwan. Three studies assessed pay for performance policies in the UK (two) and the Netherlands (one). One study from Taiwan assessed a reimbursement rate reduction policy. ITS analyses had some limitations. All CBA studies had serious limitations. No study from low-income or middle-income countries met the inclusion criteria.Pharmaceutical budgets may lead to a modest reduction in drug use (median relative change -2.8%; low-certainty evidence). We are uncertain of the effects of the policy on drug costs or healthcare utilisation, as the certainty of such evidence has been assessed as very low. Effects of this policy on health outcomes were not reported. Effects of pay for performance policies on drug use and health outcomes are uncertain, as the certainty of such evidence has been assessed as very low. Effects of this policy on drug costs and healthcare utilisation have not been measured. Effects of the reimbursement rate reduction policy on drug use and drug costs are uncertain, as the certainty of such evidence has been assessed as very low. No included study assessed the effects of this policy on healthcare utilisation or health outcomes. Administration costs of the policies were not reported in any of the included studies. Although financial incentives are considered an important element in strategies to change prescribing patterns, limited evidence of their effects can be found. Effects of policies, including pay for performance policies, in improving quality of care and health outcomes remain uncertain. Because pharmaceutical policies have uncertain effects, and because they might cause harm as well as benefit, proper evaluation of these policies is needed. Future studies should consider the impact of these policies on health outcomes, drug use and overall healthcare expenditures, as well as on drug expenditures.

Unhealthy marketing of pharmaceutical products: An international public health concern.

PubMed

Mulinari, Shai

2016-05-01

I consider the current state of pharmaceutical marketing vis-à-vis ethical and legal standards and advocate measures to improve it. There is abundant evidence of unethical or illicit marketing. It fuels growing concerns about undue corporate influence over pharmaceutical research, education, and consumption. The most extensive evidence of industry transgressions comes from the United States (US), where whistle-blowers are encouraged by financial rewards to help uncover illicit marketing and fraud. Outside the US increasing evidence of transgressions exists. Recently I have observed a range of new measures to align pharmaceutical marketing practices with ethical and legal standards. In the interest of public health, I highlight the need for additional and more profound reforms to ensure that information about medicines supports quality and resource-efficient care.

Herbal Products in Italy: The Thin Line between Phytotherapy, Nutrition and Parapharmaceuticals; A Normative Overview of the Fastest Growing Market in Europe

PubMed Central

Biagi, Marco; Pecorari, Rita; Appendino, Giovanni; Miraldi, Elisabetta; Magnano, Anna Rosa; Governa, Paolo; Cettolin, Giulia; Giachetti, Daniela

2016-01-01

The Italian herbal products market is the most prosperous in Europe. The proof is represented by the use of these products in several marketing categories, ranging from medicine to nutrition and cosmetics. Market and legislation in Italy are at the same time cause and consequence of this peculiar situation. In fact, the legislation on botanical food supplements in Italy is very permissive and at the same time the market shows an overall satisfaction of users and strong feedback in terms of consumption, which brings a widening use of medicinal plants, formerly the prerogative of pharmaceuticals, to other fields such as nutrition. This review summarizes the market and normative panorama of herbal products in Italy, highlighting the blurred boundaries of health indications, marketing authorizations and quality controls between herbal medicines and non pharmaceutical products, such as food supplements, cosmetics and other herbal-based “parapharmaceuticals”. PMID:27801865

Commercialism, choice and consumer protection: regulation of complementary medicines in Australia.

PubMed

Harvey, Ken J; Korczak, Viola S; Marron, Loretta J; Newgreen, David B

2008-01-07

Controls on the supply and promotion of complementary medicines in Australia are weak. We used weight-loss products as an example to compare the regulation in Australia of listed complementary medicines and registered pharmaceutical products. Complementary medicines are listed without evaluation for efficacy, while conventional pharmaceutical products are registered after evaluation for quality, safety and efficacy. From 1996 to 2006, over 1000 "weight-loss" products were listed on the Australian Register of Therapeutic Goods; most contained multiple unevaluated ingredients (herbs, vitamins, minerals) of dubious efficacy. Over the same period, 10 conventional medicines were registered; each contained one evaluated ingredient of proven efficacy. The number of listed weight-loss products (and complaints about their promotion) is increasing. These appear to be a direct consequence of the decision not to evaluate listed products for efficacy and the lower fees for listing a product, compared with registration. Complaint procedures (now overloaded) are no substitute for adequate regulation at the time of market entry. Regulatory reform of listed and homoeopathic products is required.

A new technique for spectrophotometric determination of pseudoephedrine and guaifenesin in syrup and synthetic mixture.

PubMed

Riahi, Siavash; Hadiloo, Farshad; Milani, Seyed Mohammad R; Davarkhah, Nazila; Ganjali, Mohammad R; Norouzi, Parviz; Seyfi, Payam

2011-05-01

The accuracy in predicting different chemometric methods was compared when applied on ordinary UV spectra and first order derivative spectra. Principal component regression (PCR) and partial least squares with one dependent variable (PLS1) and two dependent variables (PLS2) were applied on spectral data of pharmaceutical formula containing pseudoephedrine (PDP) and guaifenesin (GFN). The ability to derivative in resolved overlapping spectra chloropheniramine maleate was evaluated when multivariate methods are adopted for analysis of two component mixtures without using any chemical pretreatment. The chemometrics models were tested on an external validation dataset and finally applied to the analysis of pharmaceuticals. Significant advantages were found in analysis of the real samples when the calibration models from derivative spectra were used. It should also be mentioned that the proposed method is a simple and rapid way requiring no preliminary separation steps and can be used easily for the analysis of these compounds, especially in quality control laboratories. Copyright © 2011 John Wiley & Sons, Ltd.

E-tongue: a tool for taste evaluation.

PubMed

Gupta, Himanshu; Sharma, Aarti; Kumar, Suresh; Roy, Saroj K

2010-01-01

Taste has an important role in the development of oral pharmaceuticals. With respect to patient acceptability and compliance, taste is one of the prime factors determining the market penetration and commercial success of oral formulations, especially in pediatric medicine. Taste assessment is one important quality-control parameter for evaluating taste-masked formulations. Hence, pharmaceutical industries invest time, money and resources into developing palatable and pleasant-tasting products. The primary method for the taste measurement of a drug substance or a formulation is by human sensory evaluation, in which tasting a sample is relayed to inspectors. However, this method is impractical for early stage drug development because the test in humans is expensive and the taste of a drug candidate may not be important to the final product. Therefore, taste-sensing analytical devices, which can detect tastes, have been replacing the taste panelists. In the present review we are presenting different aspect of electronic tongue. The review article also discussed some useful patents and instrument with respect to E-tongue.