Sample records for drug quality control

  1. 21 CFR 111.117 - What quality control operations are required for equipment, instruments, and controls?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What quality control operations are required for equipment, instruments, and controls? 111.117 Section 111.117 Food and Drugs FOOD AND DRUG ADMINISTRATION... and Process Control System: Requirements for Quality Control § 111.117 What quality control operations...

  2. 21 CFR 864.8625 - Hematology quality control mixture.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... quality control mixture. (a) Identification. A hematology quality control mixture is a device used to...

  3. The effects of perceived quality on the behavioural economics of alcohol, amphetamine, cannabis, cocaine, and ecstasy purchases.

    PubMed

    Cole, Jon C; Goudie, Andrew J; Field, Matt; Loverseed, Anne-Claire; Charlton, Sarah; Sumnall, Harry R

    2008-04-01

    Previous research has indicated that non-dependent polydrug users are willing to pay more money to buy good quality drugs as their income increased. This study sought to examine whether altering the perceived quality of controlled drugs would affect drug purchases if the monetary price remained fixed. A random sample of 80 polydrug users were recruited. All participants were administered an anonymous questionnaire consisting of the Drug Abuse Screening Test for Adolescents (DAST-A), the Severity of Dependence Scale for cannabis (SDS), the Alcohol Use Disorders Identification Test (AUDIT), the Hospital Anxiety and Depression Scale (HADS), and questions about their drug use. Participants then completed a simulation of controlled drug purchases where the price of alcohol, amphetamine, cannabis, cocaine, and ecstasy remained the same but their perceived quality changed (i.e. unit price increased as the perceived quality decreased). The demand for alcohol was quality inelastic and alcohol quality had no effects on the purchase of any other controlled drug. Demand for cannabis was quality elastic and alcohol substituted for cannabis as its unit price increased. Demand for cocaine was quality elastic and alcohol, cannabis, and ecstasy substituted for cocaine as its unit price increased. Demand for ecstasy was quality elastic and alcohol and cocaine both substituted for ecstasy as its unit price increased. These results suggest that perceived quality influences the demand for controlled drugs and that monitoring the perceived quality of controlled drugs may provide a warning of potential public health problems in the near future.

  4. 21 CFR 866.2480 - Quality control kit for culture media.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Quality control kit for culture media. 866.2480 Section 866.2480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2480 Quality...

  5. 21 CFR 866.2480 - Quality control kit for culture media.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Quality control kit for culture media. 866.2480 Section 866.2480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2480 Quality...

  6. 21 CFR 866.2480 - Quality control kit for culture media.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Quality control kit for culture media. 866.2480 Section 866.2480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2480 Quality...

  7. 21 CFR 866.2480 - Quality control kit for culture media.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Quality control kit for culture media. 866.2480 Section 866.2480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2480 Quality...

  8. 21 CFR 866.2480 - Quality control kit for culture media.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Quality control kit for culture media. 866.2480 Section 866.2480 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2480 Quality...

  9. [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.

  10. 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...

  11. 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...

  12. 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...

  13. The effects of price and perceived quality on the behavioural economics of alcohol, amphetamine, cannabis, cocaine, and ecstasy purchases.

    PubMed

    Goudie, Andrew J; Sumnall, Harry R; Field, Matt; Clayton, Hannah; Cole, Jon C

    2007-07-10

    Behavioural economic models of substance use describe the relationship between changes in unit price and consumption. However, these models rarely take account of the perceived quality (i.e. potency) of controlled drugs. Therefore we investigated the effects of both price and quality on the decision to purchase controlled drugs by polysubstance misusers. Forty current polysubstance misusers (29 males, 11 females; mean age 23.8) were recruited into the study. Participants were asked to hypothetically purchase drugs from a price list of alcohol, amphetamine, cannabis, cocaine and ecstasy at different levels of quality and price (i.e. better quality drugs cost more money). The disposable income available for those purchases was systematically varied in order to determine the impact of income on the decision to purchase drugs. Demand for both normal and strong alcohol was income inelastic. Demand for both poor and average quality cannabis and ecstasy was income inelastic, but demand for good quality cannabis and ecstasy was income elastic. The demand for poor quality cocaine was income inelastic, with the demand for both average and good quality cocaine being income elastic. Participants reported too few purchases of amphetamine, which precluded behavioural economic analysis. These results suggest that, like other goods, controlled drugs are purchased based upon the consumer's interpretations of their relative value. Therefore, it is probable that the purchase and subsequent use of controlled drugs by polysubstance misusers will be heavily influenced by the economic environment.

  14. 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.

  15. 21 CFR 106.90 - Coding.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Coding. 106.90 Section 106.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES Quality Control Procedures for Assuring Nutrient Content...

  16. 21 CFR 106.90 - Coding.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Coding. 106.90 Section 106.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES Quality Control Procedures for Assuring Nutrient Content...

  17. 21 CFR 106.90 - Coding.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Coding. 106.90 Section 106.90 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES Quality Control Procedures for Assuring Nutrient Content...

  18. 21 CFR 864.8625 - Hematology quality control mixture.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8625 Hematology...

  19. 21 CFR 864.8625 - Hematology quality control mixture.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8625 Hematology...

  20. 21 CFR 864.8625 - Hematology quality control mixture.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Hematology quality control mixture. 864.8625 Section 864.8625 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8625 Hematology...

  1. 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)

  2. 21 CFR 640.56 - Quality control test for potency.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., Center for Biologics Evaluation and Research, Food and Drug Administration. Such testing shall not be... Evaluation and Research, Food and Drug Administration. (d) If the average potency level of antihemophilic... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Quality control test for potency. 640.56 Section...

  3. 42 CFR 423.153 - Drug utilization management, quality assurance, and medication therapy management programs (MTMPs).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement Requirements § 423.153 Drug utilization... 42 Public Health 3 2010-10-01 2010-10-01 false Drug utilization management, quality assurance, and medication therapy management programs (MTMPs). 423.153 Section 423.153 Public Health CENTERS FOR MEDICARE...

  4. 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.

  5. 21 CFR 111.105 - What must quality control personnel do?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false What must quality control personnel do? 111.105... for Quality Control § 111.105 What must quality control personnel do? Quality control personnel must... manufacturing record. To do so, quality control personnel must perform operations that include: (a) Approving or...

  6. 21 CFR 111.105 - What must quality control personnel do?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What must quality control personnel do? 111.105..., LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control System: Requirements for Quality Control § 111.105 What must quality control personnel do? Quality control personnel must...

  7. 75 FR 68364 - Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-05

    ... European Protocol for the Quality Control of the Physical and Technical Aspects of Mammography Screening... entitled ``Physical Laboratory Testing, Breast Compression System'' to follow the Mammography Quality...] Guidance for Industry and Food and Drug Administration Staff; Class II Special Controls Guidance Document...

  8. 21 CFR 111.127 - What quality control operations are required for packaging and labeling operations?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What quality control operations are required for packaging and labeling operations? 111.127 Section 111.127 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION CURRENT GOOD MANUFACTURING...

  9. QUALITY CONTROL OF PHARMACEUTICALS.

    PubMed

    LEVI, L; WALKER, G C; PUGSLEY, L I

    1964-10-10

    Quality control is an essential operation of the pharmaceutical industry. Drugs must be marketed as safe and therapeutically active formulations whose performance is consistent and predictable. New and better medicinal agents are being produced at an accelerated rate. At the same time more exacting and sophisticated analytical methods are being developed for their evaluation. Requirements governing the quality control of pharmaceuticals in accordance with the Canadian Food and Drugs Act are cited and discussed.

  10. Quality Control of Pharmaceuticals

    PubMed Central

    Levi, Leo; Walker, George C.; Pugsley, L. I.

    1964-01-01

    Quality control is an essential operation of the pharmaceutical industry. Drugs must be marketed as safe and therapeutically active formulations whose performance is consistent and predictable. New and better medicinal agents are being produced at an accelerated rate. At the same time more exacting and sophisticated analytical methods are being developed for their evaluation. Requirements governing the quality control of pharmaceuticals in accordance with the Canadian Food and Drugs Act are cited and discussed. PMID:14199105

  11. 21 CFR 866.5910 - Quality control material for cystic fibrosis nucleic acid assays.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Quality control material for cystic fibrosis... Test Systems § 866.5910 Quality control material for cystic fibrosis nucleic acid assays. (a) Identification. Quality control material for cystic fibrosis nucleic acid assays. A quality control material for...

  12. 21 CFR 866.5910 - Quality control material for cystic fibrosis nucleic acid assays.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Quality control material for cystic fibrosis... Test Systems § 866.5910 Quality control material for cystic fibrosis nucleic acid assays. (a) Identification. Quality control material for cystic fibrosis nucleic acid assays. A quality control material for...

  13. 21 CFR 866.5910 - Quality control material for cystic fibrosis nucleic acid assays.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Quality control material for cystic fibrosis... Test Systems § 866.5910 Quality control material for cystic fibrosis nucleic acid assays. (a) Identification. Quality control material for cystic fibrosis nucleic acid assays. A quality control material for...

  14. 21 CFR 866.5910 - Quality control material for cystic fibrosis nucleic acid assays.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Quality control material for cystic fibrosis... Test Systems § 866.5910 Quality control material for cystic fibrosis nucleic acid assays. (a) Identification. Quality control material for cystic fibrosis nucleic acid assays. A quality control material for...

  15. 21 CFR 211.22 - Responsibilities of quality control unit.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Responsibilities of quality control unit. 211.22... Personnel § 211.22 Responsibilities of quality control unit. (a) There shall be a quality control unit that... have been fully investigated. The quality control unit shall be responsible for approving or rejecting...

  16. 21 CFR 211.22 - Responsibilities of quality control unit.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Responsibilities of quality control unit. 211.22... Personnel § 211.22 Responsibilities of quality control unit. (a) There shall be a quality control unit that... have been fully investigated. The quality control unit shall be responsible for approving or rejecting...

  17. 21 CFR 862.1660 - Quality control material (assayed and unassayed).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Quality control material (assayed and unassayed... Test Systems § 862.1660 Quality control material (assayed and unassayed). (a) Identification. A quality... that may arise from reagent or analytical instrument variation. A quality control material (assayed and...

  18. 21 CFR 226.40 - Production and control procedures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Production and control procedures. 226.40 Section 226.40 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES Product Quality Control...

  19. 21 CFR 111.130 - What quality control operations are required for returned dietary supplements?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... returned dietary supplements? 111.130 Section 111.130 Food and Drugs FOOD AND DRUG ADMINISTRATION... PRACTICE IN MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production... are required for returned dietary supplements? Quality control operations for returned dietary...

  20. 21 CFR 111.130 - What quality control operations are required for returned dietary supplements?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... returned dietary supplements? 111.130 Section 111.130 Food and Drugs FOOD AND DRUG ADMINISTRATION... PRACTICE IN MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production... are required for returned dietary supplements? Quality control operations for returned dietary...

  1. 21 CFR 111.130 - What quality control operations are required for returned dietary supplements?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... returned dietary supplements? 111.130 Section 111.130 Food and Drugs FOOD AND DRUG ADMINISTRATION... PRACTICE IN MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production... are required for returned dietary supplements? Quality control operations for returned dietary...

  2. 21 CFR 111.130 - What quality control operations are required for returned dietary supplements?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... returned dietary supplements? 111.130 Section 111.130 Food and Drugs FOOD AND DRUG ADMINISTRATION... PRACTICE IN MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production... are required for returned dietary supplements? Quality control operations for returned dietary...

  3. 21 CFR 111.130 - What quality control operations are required for returned dietary supplements?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... returned dietary supplements? 111.130 Section 111.130 Food and Drugs FOOD AND DRUG ADMINISTRATION... PRACTICE IN MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production... are required for returned dietary supplements? Quality control operations for returned dietary...

  4. [Advances in the use of instrumental measurement of colour in the development, production and quality control of drugs, medicinal preparations and pharmaceutical auxiliary substances I ].

    PubMed

    Subert, Jan; Cižmárik, Jozef

    2013-04-01

    Colour is one of the important indices of the quality of drugs, medicinal preparations and pharmaceutical auxiliary substances. The paper summarizes the development and use of instrumental measurement of colour in pharmacy in recent ten years focusing on the drugs of synthetic origin and pharmaceutical auxiliary substances including their control.

  5. Root Cause Analysis of Quality Defects Using HPLC-MS Fingerprint Knowledgebase for Batch-to-batch Quality Control of Herbal Drugs.

    PubMed

    Yan, Binjun; Fang, Zhonghua; Shen, Lijuan; Qu, Haibin

    2015-01-01

    The batch-to-batch quality consistency of herbal drugs has always been an important issue. To propose a methodology for batch-to-batch quality control based on HPLC-MS fingerprints and process knowledgebase. The extraction process of Compound E-jiao Oral Liquid was taken as a case study. After establishing the HPLC-MS fingerprint analysis method, the fingerprints of the extract solutions produced under normal and abnormal operation conditions were obtained. Multivariate statistical models were built for fault detection and a discriminant analysis model was built using the probabilistic discriminant partial-least-squares method for fault diagnosis. Based on multivariate statistical analysis, process knowledge was acquired and the cause-effect relationship between process deviations and quality defects was revealed. The quality defects were detected successfully by multivariate statistical control charts and the type of process deviations were diagnosed correctly by discriminant analysis. This work has demonstrated the benefits of combining HPLC-MS fingerprints, process knowledge and multivariate analysis for the quality control of herbal drugs. Copyright © 2015 John Wiley & Sons, Ltd.

  6. 21 CFR 111.135 - What quality control operations are required for product complaints?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What quality control operations are required for... MANUFACTURING, PACKAGING, LABELING, OR HOLDING OPERATIONS FOR DIETARY SUPPLEMENTS Production and Process Control System: Requirements for Quality Control § 111.135 What quality control operations are required for...

  7. 21 CFR 111.65 - What are the requirements for quality control operations?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 2 2010-04-01 2010-04-01 false What are the requirements for quality control... Process Control System § 111.65 What are the requirements for quality control operations? You must implement quality control operations in your manufacturing, packaging, labeling, and holding operations for...

  8. 21 CFR 864.9650 - Quality control kit for blood banking reagents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Quality control kit for blood banking reagents... Manufacture Blood and Blood Products § 864.9650 Quality control kit for blood banking reagents. (a) Identification. A quality control kit for blood banking reagents is a device that consists of sera, cells...

  9. 21 CFR 864.9650 - Quality control kit for blood banking reagents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Quality control kit for blood banking reagents... Manufacture Blood and Blood Products § 864.9650 Quality control kit for blood banking reagents. (a) Identification. A quality control kit for blood banking reagents is a device that consists of sera, cells...

  10. 21 CFR 864.9650 - Quality control kit for blood banking reagents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Quality control kit for blood banking reagents... Manufacture Blood and Blood Products § 864.9650 Quality control kit for blood banking reagents. (a) Identification. A quality control kit for blood banking reagents is a device that consists of sera, cells...

  11. 21 CFR 864.9650 - Quality control kit for blood banking reagents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Quality control kit for blood banking reagents... Manufacture Blood and Blood Products § 864.9650 Quality control kit for blood banking reagents. (a) Identification. A quality control kit for blood banking reagents is a device that consists of sera, cells...

  12. 21 CFR 640.56 - Quality control test for potency.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... quality control test for potency may be performed by a clinical laboratory which meets the standards of... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Quality control test for potency. 640.56 Section...) BIOLOGICS ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Cryoprecipitate § 640.56 Quality control...

  13. [The Scope, Quality and Safety Requirements of Drug Abuse Testing].

    PubMed

    Küme, Tuncay; Karakükcü, Çiğdem; Pınar, Aslı; Coşkunol, Hakan

    2017-01-01

    The aim of this review is to inform about the scopes and requirements of drug abuse testing. Drug abuse testing is one of the tools for determination of drug use. It must fulfill the quality and safety requirements in judgmental legal and administrative decisions. Drug abuse testing must fulfill some requirements like selection of the appropriate test matrix, appropriate screening test panel, sampling in detection window, patient consent, identification of the donor, appropriate collection site, sample collection with observation, identification and control of the sample, specimen custody chain in preanalytical phase; analysis in authorized laboratories, specimen validity tests, reliable testing METHODS, strict quality control, two-step analysis in analytical phase; storage of the split specimen, confirmation of the split specimen in the objection, result custody chain, appropriate cut-off concentration, the appropriate interpretation of the result in postanalytical phase. The workflow and analytical processes of drug abuse testing are explained in last regulation of the Department of Medical Laboratory Services, Ministry of Health in Turkey. The clinical physicians have to know and apply the quality and safety requirements in drug abuse testing according to last regulations in Turkey.

  14. Aberrant use and poor quality of trypanocides: a risk for drug resistance in south western Ethiopia.

    PubMed

    Tekle, T; Terefe, G; Cherenet, T; Ashenafi, H; Akoda, K G; Teko-Agbo, A; Van Den Abbeele, J; Gari, G; Clausen, P-H; Hoppenheit, A; Mattioli, R C; Peter, R; Marcotty, T; Cecchi, G; Delespaux, V

    2018-01-05

    Trypanocidal drugs have been used to control African animal trypanosomosis for several decades. In Ethiopia, these drugs are available from both authorized (legal) and unauthorized (illegal) sources but documentation on utilization practices and quality of circulating products is scanty. This study looked at the practices of trypanocidal drug utilization by farmers and the integrity of active ingredient in trypanocides sold in Gurage zone, south western Ethiopia. The surveys were based on a structured questionnaire and drug quality determination of commonly used brands originating from European and Asian companies and sold at both authorized and unauthorized markets. One hundred farmers were interviewed and 50 drug samples were collected in 2013 (Diminazene aceturate = 33 and Isometamidium chloride = 17; 25 from authorized and 25 from unauthorized sources). Samples were tested at the OIE-certified Veterinary Drug Control Laboratory (LACOMEV) in Dakar, Senegal, by using galenic standards and high performance liquid chromatography. Trypanosomosis was found to be a major threat according to all interviewed livestock keepers in the study area. Diminazene aceturate and isometamidium chloride were preferred by 79% and 21% of the respondents respectively, and 85% of them indicated that an animal receives more than six treatments per year. About 60% of these treatments were reported to be administered by untrained farmers. Trypanocidal drug sources included both unauthorized outlets (56%) and authorized government and private sources (44%). A wide availability and usage of substandard quality drugs was revealed. Twenty eight percent of trypanocidal drugs tested failed to comply with quality requirements. There was no significant difference in the frequency of non-compliance between diminazene-based and isometamidium chloride products (P = 0.87) irrespective of the marketing channel (official and unofficial). However, higher rates of non-compliant trypanocides were detected for drugs originating from Asia than from Europe (P = 0.029). The findings revealed the presence of risk factors for the development of drug resistance, i.e. wide distribution of poor quality drugs as well as substandard administration practices. Therefore, it is strongly recommended to enforce regulatory measures for quality control of veterinary drugs, to expand and strengthen veterinary services and to undertake trypanocidal drug efficacy studies of wider coverage.

  15. 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.

  16. Effects of controlled-release formulations of atypical antipsychotics on functioning and quality of life of schizophrenic individuals.

    PubMed

    Ruiu, Stefania; Casu, Maria Antonietta; Casu, Gianluca; Piras, Sara; Marchese, Giorgio

    2012-08-01

    Controlled-release formulations of atypical antipsychotics have recently been introduced into clinical practice. Clinical studies have indicated that these new therapies induce meaningful improvements in the functioning and quality of life of schizophrenic individuals. The present analysis makes an attempt to address the clinical relevance of these studies and their contribution to the understanding of the mechanisms of action of these new drugs. A Medline search was done using the keywords 'antipsychotic', 'plasma level', 'quality of life' and 'functioning'. After reviewing the literature, it seems that symptom control and side effects may play a role in modulating the functioning and quality of life of schizophrenic individuals treated with controlled-release formulations of atypical antipsychotics. The analysis also highlights that these new drugs may possess peculiarities and similarities in regulating patient functioning. However, the low number of clinical analyses that have focused on these aspects of antipsychotic therapy limits the interpretation of the results. Additional comparative clinical trials are needed to evaluate how the pharmacokinetic/pharmacodynamic properties of antipsychotic drugs may modulate the functioning and quality of life of schizophrenic individuals, as well as to establish whether new clinical benefits may come from the use of these drugs in schizophrenia therapy.

  17. [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.

  18. 21 CFR 864.9650 - Quality control kit for blood banking reagents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Quality control kit for blood banking reagents... SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Products Used In Establishments That Manufacture Blood and Blood Products § 864.9650 Quality control kit for blood banking reagents. (a...

  19. A QRM Discussion of Microbial Contamination of Non-sterile Drug Products, Using FDA and EMA Warning Letters Recorded between 2008 and 2016.

    PubMed

    Santos, Ana M C; Doria, Mara S; Meirinhos-Soares, Luís; Almeida, António J; Menezes, José C

    2018-01-01

    Microbial quality control of non-sterile drug products has been a concern to regulatory agencies and the pharmaceutical industry since the 1960s. Despite being an old challenge to companies, microbial contamination still affects a high number of manufacturers of non-sterile products. Consequences go well beyond the obvious direct costs related to batch rejections or product recalls, as human lives and a company's reputation are significantly impacted if such events occur. To better manage risk and establish effective mitigation strategies, it is necessary to understand the microbial hazards involved in non-sterile drug products manufacturing, be able to evaluate their potential impact on final product quality, and apply mitigation actions. Herein we discuss the most likely root causes involved in microbial contaminations referenced in warning letters issued by US health authorities and non-compliance reports issued by European health authorities over a period of several years. The quality risk management tools proposed were applied to the data gathered from those databases, and a generic risk ranking was provided based on a panel of non-sterile drug product manufacturers that was assembled and given the opportunity to perform the risk assessments. That panel identified gaps and defined potential mitigation actions, based on their own experience of potential risks expected for their processes. Major findings clearly indicate that the manufacturers affected by the warning letters should focus their attention on process improvements and microbial control strategies, especially those related to microbial analysis and raw material quality control. Additionally, the WLs considered frequently referred to failures in quality-related issues, which indicates that the quality commitment should be reinforced at most companies to avoid microbiological contaminations. LAY ABSTRACT: Microbial contamination of drug products affects the quality of non-sterile drug products produced by numerous manufacturers, representing a major risk to patients. It is necessary to understand the microbial hazards involved in the manufacturing process and evaluate their impact on final product quality so that effective prevention strategies can be implemented. A risk-based classification of most likely root causes for microbial contamination found in the warning letters issued by the US Food and Drug Administration and the European Medicines Agency is proposed. To validate the likely root causes extracted from the warning letters, a subject matter expert panel made of several manufacturers was formed and consulted. A quality risk management approach to assess microbiological contamination of non-sterile drug products is proposed for the identification of microbial hazards involved in the manufacturing process. To enable ranking of microbial contamination risks, quality risk management metrics related to criticality and overall risk were applied. The results showed that manufacturers of non-sterile drug products should improve their microbial control strategy, with special attention to quality controls of raw materials, primary containers, and closures. Besides that, they should invest in a more robust quality system and culture. As a start, manufacturers may consider investigating their specific microbiological risks, adressing their sites' own microbial ecology, type of manufacturing processes, and dosage form characteristics, as these may lead to increased contamination risks. Authorities should allow and enforce innovative, more comprehensive, and more effective approaches to in-process contamination monitoring and controls. © PDA, Inc. 2018.

  20. HPTLC Fingerprint Analysis: A Quality Control for Authentication of Herbal Phytochemicals

    NASA Astrophysics Data System (ADS)

    Ram, Mauji; Abdin, M. Z.; Khan, M. A.; Jha, Prabhakar

    Authentication and consistent quality are the basic requirement for Indian traditional medicine (TIM), Chinese traditional herbal medicine (TCHM), and their commercial products, regardless of the kind of research conducted to modernize the TIM and TCHM. The complexities of TIM and TCHM challenge the current official quality control mode, for which only a few biochemical markers were selected for identification and quantitative assay. Referring too many unknown factors existed in TIM and TCHM, it is impossible and unnecessary to pinpoint qualitatively and quantitatively every single component contained in the herbal drug. Chromatographic fingerprint is a rational option to meet the need for more effective and powerful quality assessment to TIM and TCHM. The optimized chromatographic fingerprint is not only an alternative analytical tool for authentication, but also an approach to express the various pattern of chemical ingredients distribution in the herbal drugs and preserve such "database" for further multifaced sustainable studies. Analytical separation techniques, for example, high-performance liquid chromatography (HPLC), gas chromatography (GC) and mass spectrometry (MS) were among the most popular methods of choice used for quality control of raw material and finished herbal product. Fingerprint analysis approach using high-performance thin-layer chromatography (HPTLC) has become the most potent tool for quality control of herbal medicines because of its simplicity and reliability. It can serve as a tool for identification, authentication, and quality control of herbal drugs. In this chapter, attempts are being made to expand the use of HPTLC and at the same time create interest among prospective researcher in herbal analysis. The developed method can be used as a quality control tool for rapid authentication from a wide variety of herbal samples. Some examples demonstrated the role of fingerprinting in quality control and assessment.

  1. 21 CFR 225.58 - Laboratory controls.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Laboratory controls. 225.58 Section 225.58 Food...: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR MEDICATED FEEDS Product Quality Control § 225.58 Laboratory controls. (a) The periodic assay of medicated feeds for drug components provides a measure of...

  2. 21 CFR 225.58 - Laboratory controls.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Laboratory controls. 225.58 Section 225.58 Food...: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR MEDICATED FEEDS Product Quality Control § 225.58 Laboratory controls. (a) The periodic assay of medicated feeds for drug components provides a measure of...

  3. 21 CFR 225.58 - Laboratory controls.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Laboratory controls. 225.58 Section 225.58 Food...: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR MEDICATED FEEDS Product Quality Control § 225.58 Laboratory controls. (a) The periodic assay of medicated feeds for drug components provides a measure of...

  4. Drug Addiction

    MedlinePlus

    ... harm it causes. Drug addiction can start with experimental use of a recreational drug in social situations, ... and interests K2, Spice and bath salts Two groups of synthetic drugs ... is no quality control and some ingredients may not be known. Synthetic ...

  5. 21 CFR 210.3 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... holding of a drug product includes packaging and labeling operations, testing, and quality control of drug... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Definitions. 210.3 Section 210.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL...

  6. 21 CFR 210.3 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... holding of a drug product includes packaging and labeling operations, testing, and quality control of drug... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Definitions. 210.3 Section 210.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL...

  7. 21 CFR 210.3 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... holding of a drug product includes packaging and labeling operations, testing, and quality control of drug... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Definitions. 210.3 Section 210.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL...

  8. 21 CFR 210.3 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... holding of a drug product includes packaging and labeling operations, testing, and quality control of drug... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Definitions. 210.3 Section 210.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL...

  9. [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.

  10. [Use of the MS2 automated system in the determination of the activity of 5 antiseptic drugs: quality control].

    PubMed

    Vincent, F; Guyomard, S; Goury, V; Darbord, J C

    1987-06-01

    The study of growth curves of Klebsiella pneumoniae and Staphylococcus aureus in presence of five antiseptics, established using a MS2 Abbott system is presented. From our results, the advantages of automation after the adaptation of the method for the determination of bactericidal properties are examined. This technique may be proposed for the quality control of such drugs.

  11. Integrated Application of Quality-by-Design Principles to Drug Product Development: A Case Study of Brivanib Alaninate Film-Coated Tablets.

    PubMed

    Badawy, Sherif I F; Narang, Ajit S; LaMarche, Keirnan R; Subramanian, Ganeshkumar A; Varia, Sailesh A; Lin, Judy; Stevens, Tim; Shah, Pankaj A

    2016-01-01

    Modern drug product development is expected to follow quality-by-design (QbD) paradigm. At the same time, although there are several issue-specific examples in the literature that demonstrate the application of QbD principles, a holistic demonstration of the application of QbD principles to drug product development and control strategy, is lacking. This article provides an integrated case study on the systematic application of QbD to product development and demonstrates the implementation of QbD concepts in the different aspects of product and process design for brivanib alaninate film-coated tablets. Using a risk-based approach, the strategy for development entailed identification of product critical quality attributes (CQAs), assessment of risks to the CQAs, and performing experiments to understand and mitigate identified risks. Quality risk assessments and design of experiments were performed to understand the quality of the input raw materials required for a robust formulation and the impact of manufacturing process parameters on CQAs. In addition to the material property and process parameter controls, the proposed control strategy includes use of process analytical technology and conventional analytical tests to control in-process material attributes and ensure quality of the final product. Copyright © 2016. Published by Elsevier Inc.

  12. 21 CFR 106.20 - Ingredient control.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 2 2013-04-01 2013-04-01 false Ingredient control. 106.20 Section 106.20 Food and... CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES Quality Control Procedures for Assuring Nutrient Content of Infant Formulas § 106.20 Ingredient control. (a) Except as provided in § 106.20(b), no analysis...

  13. 21 CFR 106.20 - Ingredient control.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Ingredient control. 106.20 Section 106.20 Food and... CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES Quality Control Procedures for Assuring Nutrient Content of Infant Formulas § 106.20 Ingredient control. (a) Except as provided in § 106.20(b), no analysis...

  14. 21 CFR 106.20 - Ingredient control.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 2 2011-04-01 2011-04-01 false Ingredient control. 106.20 Section 106.20 Food and... CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES Quality Control Procedures for Assuring Nutrient Content of Infant Formulas § 106.20 Ingredient control. (a) Except as provided in § 106.20(b), no analysis...

  15. [How to adapt to the requirements of "clinical value-oriented drug innovation" for pharmaceutical research in application process of new traditional Chinese medicine].

    PubMed

    Jin, Fang

    2017-05-01

    On August 9, 2015, the State Council promulgated the "Opinions of the State Council on the reform of drug and medical device review and approval system" (Guofa 2015 No. 44), and established the "clinical value-oriented drug innovation" model to encourage the research and development of new drugs. Following that, China Food and Drug Administration (CFDA) promulgated the "Notice on several policies for drug registration review and approval" (2015 No. 230 ) on November 11, 2015, clearly specifying that CFDA would "implement one-time approval for clinical trials application of the new drugs, and no longer take a phased declaration, review and approval system; for the new drugs that apply for clinical trials, mainly review the scientific natureof the clinical protocols and the risk control of the new drugs to guarantee the safety of subjects". Accordingly, the evaluation ideas and forms of new drug registration have also been adjusted greatly. For example, issues like the rationality of the drug manufacturing process, whether the scale can reflect the stability of the process, whether the preparation process is sufficient, and whether the choice of dosage form is reasonable are no longer the focus of evaluation before clinical trials. Issues regarding whether the preparation process design is reasonable, whether the effective components can be transferred to the preparation to a maximum extent, whether the process parameters determined in small and middle pilot trials can adapt to the requirements of mass production, no longer act as the reasons for refusing the clinical trials. The corresponding risks shall be borne by the applicant as the subject of liability. The focus in registration evaluation is mainly transferred to how to ensure the consistence of quality between clinical trial samples and the samples already available on market by guaranteeing stable sources of drug raw materials and stable quality of medicines as well as control of the whole preparation process. These issues run through the whole process of new drug development, but also have different focuses in different stages. According to the "Measures on communicating about drug research and development and technical review" (2016 No. 94) (On Trial) issued by CFDA on June 2, 2016, the applicants may communicate with the drug evaluation center in different phases in the process of new drugs registration in respects of medicine material problems, technological problems, and quality control of the preparations. In this paper, the transformation of Chinese medicine research model was described mainly in the following aspects: how to control the quality of medicines from origins, technology design of the preparation and technology process research, and how to establish whole-process quality system. The paper also reflects the concept that the quality of new Chinese drugs research and development comes from design. Copyright© by the Chinese Pharmaceutical Association.

  16. [Study thought of pharmaceutical preparations quality standards by dynamic quality control technology].

    PubMed

    Yu, Dan-Hong; Mao, Chen-Mei; Lv, Cheng-Zhe; Jin, Hui-Zhen; Yao, Xin; Jia, Xiao-Bin

    2014-07-01

    Pharmaceutical preparations, particularly as a "secret recipe" of traditional Chinese medicine in medical institutions, are the product of China's medical and health industry, and they are also an important means of competing of different medical institutions. Although pharmaceutical preparations have advantages and characteristics than institutes for drug and pharmaceutical companies, the quality standards of pharmaceutical preparations in medical institutions has not reached the desired level over the years. As we all know, the quality of pharmaceutical preparations is important to ensure the efficacy, especially under the environment of people pay more sttention on drug safety and effectiveness and contry increase emphasis on the stste of pharmaceutical preparations. In view of this, we will improve the grade, stability, and clinical efficacy of pharmaceutical preparations by the advanced equipment, testing instruments and the process dynamic quality control technology. Finally, we hope we can provide new ideas for the quality control of pharmaceutical preparations.

  17. Drug procurement and management.

    PubMed

    Salhotra, V S

    2003-03-01

    A strong drug procurement and management system under the RNTCP is critical to programme success. Significant improvements in manufacturing, inspection, supply, storage and quality control practices and procedures have been achieved due to an intensive RNTCP network. Drugs used in RNTCP are rifampicin, isoniazid, ethambutol, pyrazinamide and streptomycin. Patients of TB are categorised into I, II and III and each category has a different standarised treatment. Procurement, distribution system and quality assurance of drugs are narrated in brief in this article.

  18. Indicators for the automated analysis of drug prescribing quality.

    PubMed

    Coste, J; Séné, B; Milstein, C; Bouée, S; Venot, A

    1998-01-01

    Irrational and inconsistent drug prescription has considerable impact on morbidity, mortality, health service utilization, and community burden. However, few studies have addressed the methodology of processing the information contained in these drug orders used to study the quality of drug prescriptions and prescriber behavior. We present a comprehensive set of quantitative indicators for the quality of drug prescriptions which can be derived from a drug order. These indicators were constructed using explicit a priori criteria which were previously validated on the basis of scientific data. Automatic computation is straightforward, using a relational database system, such that large sets of prescriptions can be processed with minimal human effort. We illustrate the feasibility and value of this approach by using a large set of 23,000 prescriptions for several diseases, selected from a nationally representative prescriptions database. Our study may result in direct and wide applications in the epidemiology of medical practice and in quality control procedures.

  19. Quality control of antibiotics before the implementation of an STD program in Northern Myanmar.

    PubMed

    Prazuck, Thierry; Falconi, Isabelle; Morineau, Guy; Bricard-Pacaud, Véronique; Lecomte, Antoine; Ballereau, Francoise

    2002-11-01

    The ready availability of poor-quality drugs in developing countries leads to treatment failure and, consequently, excess mortality and morbidity. Moreover, the widespread availability of substandard drugs plays a key role in increasing the resistance to antimicrobial drugs.GOAL As a prerequisite to the establishment of a sexually transmitted disease (STD) control program, this study aimed to evaluate the quality of antibiotics recommended for treatment of STDs that were locally available in the capital of a province of Northern Myanmar. In addition to the hospital pharmacy, we selected at random 5 of the 41 drug sellers and 5 of the 40 general practitioners who sell antibiotics in the city of Myitkyina. Twenty-one marketing products corresponding to nine different antibiotics used for STD treatment were purchased (benzathine benzylpenicillin, benzylpenicillin, ceftriaxone, chlortetracycline, ciprofloxacin, clotrimazole, co-trimoxazole, doxycycline, and erythromycin). Drugs were sent to France, where they were analyzed according to the WHO guidelines. Drugs were considered to be standard if their dosage remained in the 10% range of the expected value. Among the 21 different specialty products, only three displayed the official "registered" label. Three drugs were expired and the expiration date was not available for six others. One product did not contain the active drug declared (chlortetracycline; Lombisin, Unicorn, China) and did not show any in vitro activity against bacteria. Seven of 21 products (33%) did not contain the stated dosage (1, more than stated dosage; 6, less than stated dosage). The highest deficit observed was 48% in two products (co-trimoxazole, Yong Fong, Myanmar; benzylpenicillin, China [city and manufacturer unknown]). The dosage was not available for five drugs. As a result, only 8 of 21 products (38%) did not contain the stated dosage of active drug. These findings suggest that public health policies based on national treatment guidelines should rigorously include the monitoring of quality control of available antimicrobial products. In the absence of such measures, specific treatment strategies are likely to fail and to generate drug resistance.

  20. 21 CFR 106.20 - Ingredient control.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Ingredient control. 106.20 Section 106.20 Food and... CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES (Eff. until 7-10-14) Quality Control Procedures for Assuring Nutrient Content of Infant Formulas § 106.20 Ingredient control. (a) Except as provided in § 106...

  1. Data available on the impact of drug use on transportation safety

    DOT National Transportation Integrated Search

    1988-05-01

    The report assesses the available data on drug use in transportation, the relevant experimental research on the impacts of drugs, and the state-of-the-art in drug analysis and toxicological quality control. The report describes and evaluates: informa...

  2. 42 CFR 423.159 - Electronic prescription drug program.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Electronic prescription drug program. 423.159... SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement Requirements § 423.159 Electronic prescription drug program. (a) Definitions...

  3. 42 CFR 423.159 - Electronic prescription drug program.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Electronic prescription drug program. 423.159... SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement Requirements § 423.159 Electronic prescription drug program. (a) Definitions...

  4. 42 CFR 423.159 - Electronic prescription drug program.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 3 2013-10-01 2013-10-01 false Electronic prescription drug program. 423.159... SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement Requirements § 423.159 Electronic prescription drug program. (a) Definitions...

  5. Multidrug-resistant bacteria infection and nursing quality management application in the department of physical examination.

    PubMed

    Xu, Li; Luo, Qiang; Chen, Liangzhen; Jiao, Lingmei

    2017-09-01

    The main problem of clinical prevention and control of multi drug resistant bacteria infection is to strengthen the monitoring of pathogenic bacteria spectrum, this study research on the multi drug-resistant bacteria infection and nursing quality management application in the department of physical examination. The results of this study showed that the number of patients with multiple drug resistant infections showed an increasing trend. Therefore, once the patients with multiple drug-resistant bacteria infection are found, the prevention and control of the patients with multiple drug-resistant bacteria should be strictly followed, and the patient's medication care should be highly valued. Also, the nurses need to be classified based on the knowledge and skill characteristics of the nurses in the department of physical examination, and compare the nursing effect before and after classification and grouping. The physicians and individuals receiving physical examinations in the department of physical examination had a higher degree of satisfaction for nursing effect after classification compared with those before classification. Classification and grouping management helps improve the nursing quality and overall quality of the nurses in the department of physical examination.

  6. 42 CFR 423.159 - Electronic prescription drug program.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Electronic prescription drug program. 423.159... SERVICES (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement Requirements § 423.159 Electronic prescription drug program. (a) Definitions. For purposes of this...

  7. Access to orphan drugs despite poor quality of clinical evidence

    PubMed Central

    Dupont, Alain G; Van Wilder, Philippe B

    2011-01-01

    AIM We analysed the Belgian reimbursement decisions of orphan drugs as compared with those of innovative drugs for more common but equally severe diseases, with special emphasis on the quality of clinical evidence. METHODS Using the National Health Insurance Agency administrative database, we evaluated all submitted orphan drug files between 2002 and 2007. A quality analysis of the clinical evidence in the orphan reimbursement files was performed. The evaluation reports of the French ‘Haute Autorité de Santé’, including the five-point scale parameter ‘Service Médical Rendu (SMR), were examined to compare disease severity. Chi-squared tests (at P < 0.05 significance level) were used to compare the outcome of the reimbursement decisions between orphan and non-orphan innovative medicines. RESULTS Twenty-five files of orphan drugs and 117 files of non-orphan drugs were evaluated. Twenty-two of 25 (88%) submissions of orphan drugs were granted reimbursement as opposed to 74 of the 117 (63%) non-orphan innovative medicines (P = 0.02). Only 52% of the 25 orphan drug files included a randomized controlled trial as opposed to 84% in a random control sample of 25 non-orphan innovative submissions (P < 0.01). The duration of drug exposure was in most cases far too short in relation to the natural history of the disease. CONCLUSIONS Orphan drug designation predicts reimbursement despite poor quality of clinical evidence. The evidence gap at market authorization should be reduced by post-marketing programmes, in which the centralized regulatory and the local reimbursement authorities collaborate in an efficient way across the European Union member states. PMID:21395641

  8. Refractometry for quality control of anesthetic drug mixtures.

    PubMed

    Stabenow, Jennifer M; Maske, Mindy L; Vogler, George A

    2006-07-01

    Injectable anesthetic drugs used in rodents are often mixed and further diluted to increase the convenience and accuracy of dosing. We evaluated clinical refractometry as a simple and rapid method of quality control and mixing error detection of rodent anesthetic or analgesic mixtures. Dilutions of ketamine, xylazine, acepromazine, and buprenorphine were prepared with reagent-grade water to produce at least 4 concentration levels. The refraction of each concentration then was measured with a clinical refractometer and plotted against the percentage of stock concentration. The resulting graphs were linear and could be used to determine the concentration of single-drug dilutions or to predict the refraction of drug mixtures. We conclude that refractometry can be used to assess the concentration of dilutions of single drugs and can verify the mixing accuracy of drug combinations when the components of the mixture are known and fall within the detection range of the instrument.

  9. Effects of a clinical pharmacist service on health-related quality of life and prescribing of drugs: a randomised controlled trial.

    PubMed

    Bladh, Lina; Ottosson, Ellinor; Karlsson, John; Klintberg, Lars; Wallerstedt, Susanna M

    2011-09-01

    OBJECTIVE To evaluate the effects of a clinical pharmacist service on health-related quality of life (HRQL) and prescribing of drugs. METHODS A randomised controlled study was performed in two internal medicine wards. The intervention consisted of medication reviews with feedback to the physicians, drug treatment discussion with patients at discharge and medication reports. HRQL was evaluated at inclusion and after six months by self-rated global health (1: very poor; 5: very good) and by the EuroQol 5-dimension questionnaire (EQ-5D). Prescribing of drugs was analysed regarding three established drug-specific quality indicators (intervention and control patients) and potential drug-related problems (DRPs) during in-hospital care (intervention patients). RESULTS 345 patients (61% female; median age: 82) were analysed, 204 of whom (59%) completed the six-month HRQL follow-up. A total of 87 patients (53% of the intervention patients) received all parts of the intervention. Intention-to-treat analysis revealed no significant findings for any of the HRQL measures. Per-protocol analysis revealed significantly better HRQL in the intervention group at six-month follow-up as measured by global health (mean: 3.14 (SD: 0.87) vs 2.77 (0.94), p=0.020), but not as measured by summarised EQ-5D index (0.48 (0.36) vs 0.43 (0.37), p=0.57). The number of potentially inappropriate prescribings per patient according to the quality indicators (admission vs discharge) was 0.35 (0.73) versus 0.38 (0.72), p=0.47 (control patients), and 0.39 (0.83) versus 0.26 (0.56), p=0.039 (intervention patients who received the intervention). In the intervention group, 133 relevant potential DRPs were identified in 81 patients, 55 of which (41%) were acted upon by the attending physician. CONCLUSION A clinical pharmacist service during inpatient care may improve quality of prescribing and patients' HRQL. Trial registration clinicaltrials.gov Identifier: NCT01016301.

  10. 21 CFR 212.70 - What controls and acceptance criteria must I have for my finished PET drug products?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... for my finished PET drug products? 212.70 Section 212.70 Food and Drugs FOOD AND DRUG ADMINISTRATION... acceptance criteria must I have for my finished PET drug products? (a) Specifications. You must establish specifications for each PET drug product, including criteria for determining identity, strength, quality, purity...

  11. 21 CFR 212.70 - What controls and acceptance criteria must I have for my finished PET drug products?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... for my finished PET drug products? 212.70 Section 212.70 Food and Drugs FOOD AND DRUG ADMINISTRATION... acceptance criteria must I have for my finished PET drug products? (a) Specifications. You must establish specifications for each PET drug product, including criteria for determining identity, strength, quality, purity...

  12. 21 CFR 212.70 - What controls and acceptance criteria must I have for my finished PET drug products?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... for my finished PET drug products? 212.70 Section 212.70 Food and Drugs FOOD AND DRUG ADMINISTRATION... acceptance criteria must I have for my finished PET drug products? (a) Specifications. You must establish specifications for each PET drug product, including criteria for determining identity, strength, quality, purity...

  13. 21 CFR 212.70 - What controls and acceptance criteria must I have for my finished PET drug products?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... for my finished PET drug products? 212.70 Section 212.70 Food and Drugs FOOD AND DRUG ADMINISTRATION... acceptance criteria must I have for my finished PET drug products? (a) Specifications. You must establish specifications for each PET drug product, including criteria for determining identity, strength, quality, purity...

  14. 21 CFR 211.100 - Written procedures; deviations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Process Controls § 211.100 Written procedures; deviations. (a) There shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality... approved by the appropriate organizational units and reviewed and approved by the quality control unit. (b...

  15. 21 CFR 211.100 - Written procedures; deviations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Process Controls § 211.100 Written procedures; deviations. (a) There shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality... approved by the appropriate organizational units and reviewed and approved by the quality control unit. (b...

  16. 21 CFR 211.100 - Written procedures; deviations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Process Controls § 211.100 Written procedures; deviations. (a) There shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality... approved by the appropriate organizational units and reviewed and approved by the quality control unit. (b...

  17. 21 CFR 211.100 - Written procedures; deviations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Process Controls § 211.100 Written procedures; deviations. (a) There shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality... approved by the appropriate organizational units and reviewed and approved by the quality control unit. (b...

  18. 21 CFR 211.100 - Written procedures; deviations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Process Controls § 211.100 Written procedures; deviations. (a) There shall be written procedures for production and process control designed to assure that the drug products have the identity, strength, quality... approved by the appropriate organizational units and reviewed and approved by the quality control unit. (b...

  19. 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.

  20. 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

  1. Patients’ perceived value of pharmacy quality measures: a mixed-methods study

    PubMed Central

    Shiyanbola, Olayinka O; Mort, Jane R

    2015-01-01

    Objective To describe patients’ perceived value and use of quality measures in evaluating and choosing community pharmacies. Design Focus group methodology was combined with a survey tool. During the focus groups, participants assessed the value of the Pharmacy Quality Alliance's quality measures in evaluating and choosing a pharmacy. Also, participants completed questionnaires rating their perceived value of quality measures in evaluating a pharmacy (1 being low value and 5 being high) or choosing a pharmacy (yes/no). Thematic analysis and descriptive statistics were used to analyse the focus groups and surveys, respectively. Setting Semistructured focus groups were conducted in a private meeting space of an urban and a rural area of a Mid-western State in the USA. Participants Thirty-four adults who filled prescription medications in community pharmacies for a chronic illness were recruited in community pharmacies, senior centres and public libraries. Results While comments indicated that all measures were important, medication safety measures (eg, drug-drug interactions) were valued more highly than others. Rating of quality measure utility in evaluating a pharmacy ranged from a mean of 4.88 (‘drug-drug interactions’) to a mean of 4.0 (‘absence of controller therapy for patients with asthma’). Patients were hesitant to use quality information in choosing a pharmacy (depending on the participant's location) but might consider if moving to a new area or having had a negative pharmacy experience. Use of select quality measures to choose a pharmacy ranged from 97.1% of participants using ‘drug-drug interactions’ (medication safety measure) to 55.9% using ‘absence of controller therapy for patients with asthma’. Conclusions The study participants valued quality measures in evaluating and selecting a community pharmacy, with medication safety measures valued highest. The participants reported that the quality measures would not typically cause a switch in pharmacy but might influence their selection in certain situations. PMID:25600253

  2. Major achievements of evidence-based traditional Chinese medicine in treating major diseases.

    PubMed

    Chao, Jung; Dai, Yuntao; Verpoorte, Robert; Lam, Wing; Cheng, Yung-Chi; Pao, Li-Heng; Zhang, Wei; Chen, Shilin

    2017-09-01

    A long history of use and extensive documentation of the clinical practices of traditional Chinese medicine resulted in a considerable number of classical preparations, which are still widely used. This heritage of our ancestors provides a unique resource for drug discovery. Already, a number of important drugs have been developed from traditional medicines, which in fact form the core of Western pharmacotherapy. Therefore, this article discusses the differences in drug development between traditional medicine and Western medicine. Moreover, the article uses the discovery of artemisinin as an example that illustrates the "bedside-bench-bedside" approach to drug discovery to explain that the middle way for drug development is to take advantage of the best features of these two distinct systems and compensate for certain weaknesses in each. This article also summarizes evidence-based traditional medicines and discusses quality control and quality assessment, the crucial steps in botanical drug development. Herbgenomics may provide effective tools to clarify the molecular mechanism of traditional medicines in the botanical drug development. The totality-of-the-evidence approach used by the U.S. Food and Drug Administration for botanical products provides the directions on how to perform quality control from the field throughout the entire production process. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. 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.

  4. Psychological distress and substance use by adolescent mothers: associations with parenting attitudes and the quality of mother-child interaction.

    PubMed

    Spieker, S J; Gillmore, M R; Lewis, S M; Morrison, D M; Lohr, M J

    2001-01-01

    This study examines associations between psychological distress and alcohol and drug use across the first five years of raising a child and parenting quality at child age six for 185 adolescent mothers. Overall, alcohol and other drug use in this sample was relatively low, but drug use was associated with more mother-reported unrealistic expectations of child behavior and more attributions of child intent to annoy parent by misbehaving. Maternal psychological distress was associated with maternal reports of negative control (yelling, pushing, spanking, etc.), and alcohol use moderated the association between psychological distress and negative control. At low levels of alcohol use, more maternal distress was associated with greater negative control; at higher levels of alcohol use, maternal distress was not related to negative control, but the absolute level of negative control was similar to that reported by more distressed mothers. Neither psychological distress nor alcohol and other drug use were related to maternal behavior during an interaction task. Overall, much stronger associations with parenting outcomes were found for an index of maternal vocabulary, compared with maternal psychological distress or maternal alcohol and other drug use.

  5. Liposomal Drug Product Development and Quality: Current US Experience and Perspective.

    PubMed

    Kapoor, Mamta; Lee, Sau L; Tyner, Katherine M

    2017-05-01

    Research in the area of liposomes has grown substantially in the past few decades. Liposomes are lipid bilayer structures that can incorporate drug substances to modify the drug's pharmacokinetic profile thereby improving drug delivery. The agency has received over 400 liposomal drug product submissions (excluding combination therapies), and there are currently eight approved liposomal drug products on the US market. In order to identify the pain points in development and manufacturing of liposomal drug products, a retrospective analysis was performed from a quality perspective on submissions for new and generic liposomal drug products. General analysis on liposomal drug product submissions was also performed. Results indicated that 96% of the submissions were Investigational New Drug (IND) applications, 3% were New Drug Applications (NDAs), and the remaining 1% was Abbreviated New Drug Applications (ANDAs). Doxorubicin hydrochloride was the most commonly used drug substance incorporated into the liposomes (31%). The majority of the liposomal products were administered via intravenous route (84%) with cancer (various types) being the most common indication (63%). From a quality perspective, major challenges during the development of liposomal drug products included identification and (appropriate) characterization of critical quality attributes of liposomal drug products and suitable control strategies during product development. By focusing on these areas, a faster and more efficient development of liposomal drug products may be achieved. Additionally, in this way, the drug review process for such products can be streamlined.

  6. 21 CFR 211.160 - General requirements.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false General requirements. 211.160 Section 211.160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... drafted by the appropriate organizational unit and reviewed and approved by the quality control unit. The...

  7. Comprehensive HPTLC Fingerprinting for Quality Control of an Herbal Drug - The Case of Angelica gigas Root.

    PubMed

    Frommenwiler, Débora Arruda; Kim, Jonghwan; Yook, Chang-Soo; Tran, Thi Thu Trang; Cañigueral, Salvador; Reich, Eike

    2018-04-01

    The quality of herbal drugs is usually controlled using several tests recommended in a monograph. HPTLC is the method of choice for identification in many pharmacopoeias. If combined with a suitable reference material for comparison, HPTLC can provide information beyond identification and thus may simplify quality control. This paper describes, as a proof of concept, how HPTLC can be applied to define specifications for an herbal reference material and to control the quality of an herbal drug according to these specifications. Based on multiple batches of cultivated Angelica gigas root, a specific HPTLC method for identification was optimized. This method can distinguish 27 related species. It also can detect the presence of mixtures of A. gigas with two other Angelica species traded as "Dang gui" and is suitable as well for quantitative assessment of samples in a test for minimum content of the sum of decursin and decursinol angelate. The new concept of "comprehensive HPTLC fingerprinting" is proposed: HPTLC fingerprints (images), which are used for identification, are converted into peak profiles and the intensities of selected zones are quantitatively compared to those of the corresponding zones of the reference material. Following a collaborative trial involving three laboratories in three countries, the method was applied to check the quality of further candidates for establishing an appropriate reference material. In conclusion, this case demonstrates that a single HPTLC analysis can provide information about identity, purity, and minimum content of markers of an herbal drug. Georg Thieme Verlag KG Stuttgart · New York.

  8. Quality of life in children with adverse drug reactions: a narrative and systematic review.

    PubMed

    Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro

    2015-10-01

    Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn's disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases. © 2014 The British Pharmacological Society.

  9. Quality of life in children with adverse drug reactions: a narrative and systematic review

    PubMed Central

    Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro

    2015-01-01

    Aims Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. Methods We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Results Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn’s disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. Conclusions To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases. PMID:24833305

  10. [The Contribution of GMP-grade Hospital Preparation to Translational Research].

    PubMed

    Yonezawa, Atsushi; Kajiwara, Moto; Minami, Ikuko; Omura, Tomohiro; Nakagawa, Shunsaku; Matsubara, Kazuo

    2015-01-01

    Translational research is important for applying the outcomes of basic research studies to practical medical treatments. In exploratory early-phase clinical trials for an innovative therapy, researchers should generally manufacture investigational agents by themselves. To provide investigational agents with safety and high quality in clinical studies, appropriate production management and quality control are essential. In the Department of Pharmacy of Kyoto University Hospital, a manufacturing facility for sterile drugs was established, independent of existing manufacturing facilities. Manuals on production management and quality control were developed according to Good Manufacturing Practices (GMP) for Investigational New Drugs (INDs). Advanced clinical research has been carried out using investigational agents manufactured in our facility. These achievements contribute to both the safety of patients and the reliability of clinical studies. In addition, we are able to do licensing-out of our technique for the manufacture of investigational drugs. In this symposium, we will introduce our GMP grade manufacturing facility for sterile drugs and discuss the role of GMP grade hospital preparation in translational research.

  11. 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

  12. Antiretroviral therapy supply chain quality control and assurance in improving people living with HIV therapeutic outcomes in Cameroon.

    PubMed

    Djobet, M P Ngogang; Singhe, David; Lohoue, Julienne; Kuaban, Christopher; Ngogang, Jeanne; Tambo, Ernest

    2017-04-04

    Evaluation of medication efficacy and safety is an essential guarantee to successful therapeutic outcome in public health practices. However, larger distribution chain supply in developing countries such as Cameroon is often challenged by counterfeit drugs, poor manufacturing, storage and degradation leading to health and patient adverse consequences. Yet, access to supply chain management in strengthening ARVs quality assurance and outcomes remains poorly documented. More than 53,000 patients have been enrolled on free ARVs medications, but little is documented on quality assurance and validity of safety for affected populations along the supply chain management since 2008. The cross sectional study was conducted in ARVs distribution units and centers in central, littoral and south west regions of Cameroon. ARVs drugs samples included Nevirapine, Efavirenz, and fixed dose combinations of Zidovudine + Lamivudine, Lamivudine + Stavudine and Zidovudine + Lamivudine + Nevirapine. Drugs packaging and labeling was assessed and galenic assays were performed at National Laboratory of quality Control of Medications and Expertise (LANACOME), Yaoundé, Cameroon. The study covered 16 structures located in eight different towns including the central ARVs store, two regional pharmaceutical procurement centers and thirteen HIV approved treatment centers and management units. A total of 35 ARVs products were collected. Only eight ARVs drugs containing Lamivudine and Stavudine presented with white stains on tablets, however these drugs were standard for all other tests performed. The others 28 ARVs products were standards to all assays performed. We concluded that ARVs drugs freely accessible and distributed to PLWHA are of good quality in Cameroon. However, with the increase number of patients under HAART since 2013, adoption of "Test and Treat" approach to reach the 90-90-90 goals and with the implementation of new national antiretroviral regimen guidelines and molecules such as boosted protease inhibitors, continuous quality control and assurance surveillance, monitoring and evaluation is recommended. Assessment of quality of formulations that are more susceptible to degradation such as pediatric formulations for averting the rising multidrug resistance trend is also desired.

  13. Does price reveal poor-quality drugs? Evidence from 17 countries.

    PubMed

    Bate, Roger; Jin, Ginger Zhe; Mathur, Aparna

    2011-12-01

    Focusing on 8 drug types on the WHO-approved medicine list, we constructed an original dataset of 899 drug samples from 17 low- and median-income countries and tested them for visual appearance, disintegration, and analyzed their ingredients by chromatography and spectrometry. Fifteen percent of the samples fail at least one test and can be considered substandard. After controlling for local factors, we find that failing drugs are priced 13.6-18.7% lower than non-failing drugs but the signaling effect of price is far from complete, especially for non-innovator brands. The look of the pharmacy, as assessed by our covert shoppers, is weakly correlated with the results of quality tests. These findings suggest that consumers are likely to suspect low quality from market price, non-innovator brand and the look of the pharmacy, but none of these signals can perfectly identify substandard and counterfeit drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Application of the quality by design approach to the drug substance manufacturing process of an Fc fusion protein: towards a global multi-step design space.

    PubMed

    Eon-duval, Alex; Valax, Pascal; Solacroup, Thomas; Broly, Hervé; Gleixner, Ralf; Strat, Claire L E; Sutter, James

    2012-10-01

    The article describes how Quality by Design principles can be applied to the drug substance manufacturing process of an Fc fusion protein. First, the quality attributes of the product were evaluated for their potential impact on safety and efficacy using risk management tools. Similarly, process parameters that have a potential impact on critical quality attributes (CQAs) were also identified through a risk assessment. Critical process parameters were then evaluated for their impact on CQAs, individually and in interaction with each other, using multivariate design of experiment techniques during the process characterisation phase. The global multi-step Design Space, defining operational limits for the entire drug substance manufacturing process so as to ensure that the drug substance quality targets are met, was devised using predictive statistical models developed during the characterisation study. The validity of the global multi-step Design Space was then confirmed by performing the entire process, from cell bank thawing to final drug substance, at its limits during the robustness study: the quality of the final drug substance produced under different conditions was verified against predefined targets. An adaptive strategy was devised whereby the Design Space can be adjusted to the quality of the input material to ensure reliable drug substance quality. Finally, all the data obtained during the process described above, together with data generated during additional validation studies as well as manufacturing data, were used to define the control strategy for the drug substance manufacturing process using a risk assessment methodology. Copyright © 2012 Wiley-Liss, Inc.

  15. Cardiac Valve Noise Reduction by Non-Drug Interventions Improves the Sleep Quality of Patients after Mechanical Cardiac Valve Implantation.

    PubMed

    Lin, Yanjuan; Xu, Le; Huang, Xizhen; Jiang, Fei; Lin, Fen; Ye, Qingyang; Lin, Jianling

    2016-01-01

    To investigate the effects of non-drug interventions on the sleep quality of patients after mechanical cardiac valve implantation. In this prospective, randomized, controlled trial, 64 patients scheduled for mechanical mitral valve replacement were recruited. Patients underwent cognitive behavioral therapy and wore noise cancelling earplugs and eye mask. Sleep quality was evaluated on the 4th after admission and the 5th days after operation. The primary outcome was the total sleep quality score differences between the 4th day after admission and the 5th day after operation. All patients had been suffering from poor sleep quality for a month before admission. There was no difference between both groups on the 4th day after admission. Overall sleep quality in the intervention group was better than in the control group on the 5th day after operation. The subjective sleep quality of the patients in each group was significantly lower on the 5th day after the operation than on the 4th day after admission (P <0.05). Non-drug intervention could improve the sleep quality of patients after mechanical cardiac valve implantation and help the postoperative recovery of the patients. ( ChiCTR-TRC-14004405, 21 March 2014.).

  16. 42 CFR 423.159 - Electronic prescription drug program.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Electronic prescription drug program. 423.159 Section 423.159 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality...

  17. 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.

  18. Medical Devices; Immunology and Microbiology Devices; Classification of the Assayed Quality Control Material for Clinical Microbiology Assays. Final order.

    PubMed

    2017-07-27

    The Food and Drug Administration (FDA, Agency, or we) is classifying the assayed quality control material for clinical microbiology assays into class II (special controls). The special controls that will apply to the device are identified in this order and will be part of the codified language for the assayed quality control material for clinical microbiology assays' classification. The Agency is classifying the device into class II (special controls) to provide a reasonable assurance of safety and effectiveness of the device.

  19. Modulated evaluation metrics for drug-based ontologies.

    PubMed

    Amith, Muhammad; Tao, Cui

    2017-04-24

    Research for ontology evaluation is scarce. If biomedical ontological datasets and knowledgebases are to be widely used, there needs to be quality control and evaluation for the content and structure of the ontology. This paper introduces how to effectively utilize a semiotic-inspired approach to ontology evaluation, specifically towards drug-related ontologies hosted on the National Center for Biomedical Ontology BioPortal. Using the semiotic-based evaluation framework for drug-based ontologies, we adjusted the quality metrics based on the semiotic features of drug ontologies. Then, we compared the quality scores before and after tailoring. The scores revealed a more precise measurement and a closer distribution compared to the before-tailoring. The results of this study reveal that a tailored semiotic evaluation produced a more meaningful and accurate assessment of drug-based ontologies, lending to the possible usefulness of semiotics in ontology evaluation.

  20. Affective symptoms and determinants of health-related quality of life in Mexican people with epilepsy.

    PubMed

    Camara-Lemarroy, Carlos R; Hoyos, Mariana; Ibarra-Yruegas, Beatriz E; Díaz-Torres, Marco A; De León, Rolando

    2017-10-01

    Epilepsy is known to be associated with multiple psychiatric comorbidities, such as depression, sleep-disorders, and anxiety. The objective of this study was to determine the prevalence and impact of affective symptoms over health-related quality of life (QOL) in Mexican people with epilepsy (PWE). We performed a cross-sectional observational study on 73 consecutive PWE and corresponding age- and sex-matched controls. HrQOL was assessed using the QOLIE-10 (QOL in Epilepsy-10) instrument. Clinical and demographic characteristics were recorded, and instruments evaluating depressive/anxiety symptoms, sleep quality, and insomnia were completed. PWE had more depressive/anxiety symptoms when compared with controls. QOLIE-10 scores were significantly inversely correlated with poor sleep quality, insomnia symptoms, depressive/anxiety symptoms, and number of anti-epileptic drugs used, but not with seizure type or number of seizures per month. A poor QOL was independently associated only with anti-epileptic drug polytherapy. PWE are burdened with depressive/anxiety symptoms at alarming rates. The presence of depressive symptoms along with sleep disturbances and more significantly, anti-epileptic drug polytherapy, appears to negatively impact QOL, to a greater degree than short-term seizure control.

  1. 21 CFR 820.130 - Device packaging.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Device packaging. 820.130 Section 820.130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES QUALITY SYSTEM REGULATION Labeling and Packaging Control § 820.130 Device packaging. Each manufacturer...

  2. 21 CFR 820.120 - Device labeling.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Device labeling. 820.120 Section 820.120 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES QUALITY SYSTEM REGULATION Labeling and Packaging Control § 820.120 Device labeling. Each manufacturer...

  3. Substandard drugs: a potential crisis for public health

    PubMed Central

    Johnston, Atholl; Holt, David W

    2014-01-01

    Poor-quality medicines present a serious public health problem, particularly in emerging economies and developing countries, and may have a significant impact on the national clinical and economic burden. Attention has largely focused on the increasing availability of deliberately falsified drugs, but substandard medicines are also reaching patients because of poor manufacturing and quality-control practices in the production of genuine drugs (either branded or generic). Substandard medicines are widespread and represent a threat to health because they can inadvertently lead to healthcare failures, such as antibiotic resistance and the spread of disease within a community, as well as death or additional illness in individuals. This article reviews the different aspects of substandard drug formulation that can occur (for example, pharmacological variability between drug batches or between generic and originator drugs, incorrect drug quantity and presence of impurities). The possible means of addressing substandard manufacturing practices are also discussed. A concerted effort is required on the part of governments, drug manufacturers, charities and healthcare providers to ensure that only drugs of acceptable quality reach the patient. PMID:24286459

  4. Application of miniaturized near-infrared spectroscopy for quality control of extemporaneous orodispersible films.

    PubMed

    Foo, Wen Chin; Widjaja, Effendi; Khong, Yuet Mei; Gokhale, Rajeev; Chan, Sui Yung

    2018-02-20

    Extemporaneous oral preparations are routinely compounded in the pharmacy due to a lack of suitable formulations for special populations. Such small-scale pharmacy preparations also present an avenue for individualized pharmacotherapy. Orodispersible films (ODF) have increasingly been evaluated as a suitable dosage form for extemporaneous oral preparations. Nevertheless, as with all other extemporaneous preparations, safety and quality remain a concern. Although the United States Pharmacopeia (USP) recommends analytical testing of compounded preparations for quality assurance, pharmaceutical assays are typically not routinely performed for such non-sterile pharmacy preparations, due to the complexity and high cost of conventional assay methods such as high performance liquid chromatography (HPLC). Spectroscopic methods including Raman, infrared and near-infrared spectroscopy have been successfully applied as quality control tools in the industry. The state-of-art benchtop spectrometers used in those studies have the advantage of superior resolution and performance, but are not suitable for use in a small-scale pharmacy setting. In this study, we investigated the application of a miniaturized near infrared (NIR) spectrometer as a quality control tool for identification and quantification of drug content in extemporaneous ODFs. Miniaturized near infrared (NIR) spectroscopy is suitable for small-scale pharmacy applications in view of its small size, portability, simple user interface, rapid measurement and real-time prediction results. Nevertheless, the challenge with miniaturized NIR spectroscopy is its lower resolution compared to state-of-art benchtop equipment. We have successfully developed NIR spectroscopy calibration models for identification of ODFs containing five different drugs, and quantification of drug content in ODFs containing 2-10mg ondansetron (OND). The qualitative model for drug identification produced 100% prediction accuracy. The quantitative model to predict OND drug content in ODFs was divided into two calibrations for improved accuracy: Calibration I and II covered the 2-4mg and 4-10mg ranges respectively. Validation was performed for method accuracy, linearity and precision. In conclusion, this study demonstrates the feasibility of miniaturized NIR spectroscopy as a quality control tool for small-scale, pharmacy preparations. Due to its non-destructive nature, every dosage unit can be tested thus affording positive impact on patient safety. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. [Does implementation of benchmarking in quality circles improve the quality of care of patients with asthma and reduce drug interaction?].

    PubMed

    Kaufmann-Kolle, Petra; Szecsenyi, Joachim; Broge, Björn; Haefeli, Walter Emil; Schneider, Antonius

    2011-01-01

    The purpose of this cluster-randomised controlled trial was to evaluate the efficacy of quality circles (QCs) working either with general data-based feedback or with an open benchmark within the field of asthma care and drug-drug interactions. Twelve QCs, involving 96 general practitioners from 85 practices, were randomised. Six QCs worked with traditional anonymous feedback and six with an open benchmark. Two QC meetings supported with feedback reports were held covering the topics "drug-drug interactions" and "asthma"; in both cases discussions were guided by a trained moderator. Outcome measures included health-related quality of life and patient satisfaction with treatment, asthma severity and number of potentially inappropriate drug combinations as well as the general practitioners' satisfaction in relation to the performance of the QC. A significant improvement in the treatment of asthma was observed in both trial arms. However, there was only a slight improvement regarding inappropriate drug combinations. There were no relevant differences between the group with open benchmark (B-QC) and traditional quality circles (T-QC). The physicians' satisfaction with the QC performance was significantly higher in the T-QCs. General practitioners seem to take a critical perspective about open benchmarking in quality circles. Caution should be used when implementing benchmarking in a quality circle as it did not improve healthcare when compared to the traditional procedure with anonymised comparisons. Copyright © 2011. Published by Elsevier GmbH.

  6. Assessing Lymphatic Filariasis Data Quality in Endemic Communities in Ghana, Using the Neglected Tropical Diseases Data Quality Assessment Tool for Preventive Chemotherapy.

    PubMed

    de Souza, Dziedzom K; Yirenkyi, Eric; Otchere, Joseph; Biritwum, Nana-Kwadwo; Ameme, Donne K; Sackey, Samuel; Ahorlu, Collins; Wilson, Michael D

    2016-03-01

    The activities of the Global Programme for the Elimination of Lymphatic Filariasis have been in operation since the year 2000, with Mass Drug Administration (MDA) undertaken yearly in disease endemic communities. Information collected during MDA-such as population demographics, age, sex, drugs used and remaining, and therapeutic and geographic coverage-can be used to assess the quality of the data reported. To assist country programmes in evaluating the information reported, the WHO, in collaboration with NTD partners, including ENVISION/RTI, developed an NTD Data Quality Assessment (DQA) tool, for use by programmes. This study was undertaken to evaluate the tool and assess the quality of data reported in some endemic communities in Ghana. A cross sectional study, involving review of data registers and interview of drug distributors, disease control officers, and health information officers using the NTD DQA tool, was carried out in selected communities in three LF endemic Districts in Ghana. Data registers for service delivery points were obtained from District health office for assessment. The assessment verified reported results in comparison with recounted values for five indicators: number of tablets received, number of tablets used, number of tablets remaining, MDA coverage, and population treated. Furthermore, drug distributors, disease control officers, and health information officers (at the first data aggregation level), were interviewed, using the DQA tool, to determine the performance of the functional areas of the data management system. The results showed that over 60% of the data reported were inaccurate, and exposed the challenges and limitations of the data management system. The DQA tool is a very useful monitoring and evaluation (M&E) tool that can be used to elucidate and address data quality issues in various NTD control programmes.

  7. 21 CFR 820.72 - Inspection, measuring, and test equipment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Inspection, measuring, and test equipment. 820.72 Section 820.72 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES QUALITY SYSTEM REGULATION Production and Process Controls § 820.72 Inspection...

  8. 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.

  9. QbD-Enabled Development of Novel Stimuli-Responsive Gastroretentive Systems of Acyclovir for Improved Patient Compliance and Biopharmaceutical Performance.

    PubMed

    Singh, Bhupinder; Kaur, Anterpreet; Dhiman, Shashi; Garg, Babita; Khurana, Rajneet Kaur; Beg, Sarwar

    2016-04-01

    The current studies entail systematic quality by design (QbD)-based development of stimuli-responsive gastroretentive drug delivery systems (GRDDS) of acyclovir using polysaccharide blends for attaining controlled drug release profile and improved patient compliance. The patient-centric quality target product profile was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies, carried out through Ishikawa fish bone diagram and failure mode, effect, and criticality analysis, helped in identifying the plausible risks or failure modes affecting the quality attributes of the drug product. A face-centered cubic design was employed for systematic development and optimization of the concentration of sodium alginate (X 1) and gellan (X 2) as the critical material attributes (CMAs) in the stimuli-responsive formulations, which were evaluated for CQAs viz. viscosity, gel strength, onset of floatation, and drug release characteristics. Mathematical modeling was carried out for generation of design space, and optimum formulation was embarked upon, exhibiting formulation characteristics marked by excellent floatation and bioadhesion characteristics along with promising drug release control up to 24 h. Drug-excipient compatibility studies through FTIR and DSC revealed absence of any interaction(s) among the formulation excipients. In vivo pharmacokinetic studies in Wistar rats corroborated extension in the drug absorption profile from the optimized stimuli-responsive GR formulations vis-à-vis the marketed suspension (ZOVIRAX®). Establishment of in vitro/in vivo correlation (IVIVC) revealed a high degree of correlation between the in vitro and in vivo data. In a nutshell, the present investigations report the successful development of stimuli-responsive GRDDS of acyclovir, which can be applicable as a platform approach for other drugs too.

  10. [Investigation on pattern of quality control for Chinese materia medica based on famous-region drug and bioassay--the work reference].

    PubMed

    Yan, Dan; Xiao, Xiaohe

    2011-05-01

    Selection and standardization of the work reference are the technical issues to be faced with in the bioassay of Chinese materia medica. Taking the bioassay of Coptis chinensis. as an example, the manufacture process of the famous-region drugs extraction was explained from the aspects of original identification, routine examination, component analysis and bioassay. The common technologies were extracted, and the selection and standardization procedures of the work reference for the bioassay of Chinese materia medica were drawn up, so as to provide technical support for constructing a new mode and method of the quality control of Chinese materia medica based on the famous-region drugs and bioassay.

  11. Emerging anti-insomnia drugs: tackling sleeplessness and the quality of wake time.

    PubMed

    Wafford, Keith A; Ebert, Bjarke

    2008-06-01

    Sleep is essential for our physical and mental well being. However, when novel hypnotic drugs are developed, the focus tends to be on the marginal and statistically significant increase in minutes slept during the night instead of the effects on the quality of wakefulness. Recent research on the mechanisms underlying sleep and the control of the sleep-wake cycle has the potential to aid the development of novel hypnotic drugs; however, this potential has not yet been realized. Here, we review the current understanding of how hypnotic drugs act, and discuss how new, more effective drugs and treatment strategies for insomnia might be achieved by taking into consideration the daytime consequences of disrupted sleep.

  12. Drug pricing reform in China: analysis of piloted approaches and potential impact of the reform.

    PubMed

    Chen, Yixi; Hu, Shanlian; Dong, Peng; Kornfeld, Åsa; Jaros, Patrycja; Yan, Jing; Ma, Fangfang; Toumi, Mondher

    2016-01-01

    In 2009, the Chinese government launched a national healthcare reform programme aiming to control healthcare expenditure and increase the quality of care. As part of this programme, a new drug pricing reform was initiated on 1 June 2015. The objective of this study was to describe the changing landscape of drug pricing policy in China and analyse the potential impact of the reform. The authors conducted thorough research on the drug pricing reform using three Chinese databases (CNKI, Wanfang, and Weipu), Chinese health authority websites, relevant press releases, and pharmaceutical blogs and discussion forums. This research was complemented with qualitative research based on targeted interviews with key Chinese opinion leaders representing the authorities' and prescribers' perspectives. With the current reform, the government has attempted to replace its direct control over the prices of reimbursable drugs with indirect, incentive-driven influence. Although the exact implementation of the reform remains unclear at the moment, the changes introduced so far and the pilot project designs indicate that China is considering adaptation of some form of internal and external reference pricing policies, commonly used in the Organisation for Economic Co-operation and Development countries. Several challenges related to the potential new mechanism were identified: 1) the risk of hospital underfunding, if hospital funding reform is not prioritised; 2) the risk of promoting the use of cheap, low-quality drugs, if a reliable quality control system is not in place and discrepancy between the available drugs is present; 3) the risk of increasing disparity in access to care between poor and rich regions, in case of country-wide price convergence; and 4) the risk of industry underinvestment, resulting in reduced competition, issues with quality and sustainability of supply, and potentially negative social impact. Foreign pricing policies cannot be transferred to China without prioritising historical, cultural, and economic contextualisation. Otherwise, the new policy may be counterproductive and affect the whole healthcare chain, as well as the health outcomes of Chinese patients.

  13. Chemistry, manufacturing and controls in passive transdermal drug delivery systems.

    PubMed

    Goswami, Tarun; Audett, Jay

    2015-01-01

    Transdermal drug delivery systems (TDDS) are used for the delivery of the drugs through the skin into the systemic circulation by applying them to the intact skin. The development of TDDS is a complex and multidisciplinary affair which involves identification of suitable drug, excipients and various other components. There have been numerous problems reported with respect to TDDS quality and performance. These problems can be reduced by appropriately addressing chemistry, manufacturing and controls requirements, which would thereby result in development of robust TDDS product and processes. This article provides recommendations on the chemistry, manufacturing and controls focusing on the unique technical aspects of TDDS.

  14. RELATIONSHIP OF ASSESS SELF-ESTEEM AND LOCUS OF CONTROL WITH QUALITY OF LIFE DURING TREATMENT STAGES IN PATIENTS REFERRING TO DRUG ADDICTION REHABILITATION CENTERS

    PubMed Central

    Heidari, Mohammad; Ghodusi, Mansureh

    2016-01-01

    Objective: Thus, the present research was carried out aimed at determining the relationship between self-esteem and locus of control and quality of life during treatment stages in the patients referring to drug addiction rehabilitation centers of Borujen city, Iran. Methods: The current study was a sectional research of descriptive correlation type. The research sample was 150 individuals of patients referring to addiction rehabilitation centers of Borujen city. For data gathering, Rosenberg Self-esteem Scale, Rotter’s Locus of Control Scale, and SF36 Quality of Life Questionnaire were used. Following collection of questionnaires, the data were analyzed using SPSS/16 software. Results: According to the results, in the 12th day of treatment, 96 patients exhibited moderate self-esteem, 102 patients had internal locus of control, and the score of their overall quality of life was 40.43±12.71. Furthermore, Pearson’s correlation coefficient indicated that a significant and positive relationship was observed between locus of control and quality of life during different treatment stages. Conclusion: It seems that quality of life improves during addiction treatment stages due to improvement of personality traits including locus of control and self-esteem. Therefore, consultation methods as a very crucial priority in addiction rehabilitation centers shall be taken into account by the health sector authorities and managers and can play an essential role in enhancing quality of life. PMID:27698598

  15. Surveillance of drug resistance for tuberculosis control: why and how?

    PubMed

    Chaulet, P; Boulahbal, F; Grosset, J

    1995-12-01

    The resistance of Mycobacterium tuberculosis to antibiotics, which reflects the quality of the chemotherapy applied in the community, is one of the elements of epidemiological surveillance used in national tuberculosis programmes. Measurement of drug resistance poses problems for biologists in standardization of laboratory methods and quality control. The definition of rates of acquired and primary drug resistance also necessitates standardization in the methods used to collect information transmitted by clinicians. Finally, the significance of the rates calculated depends on the choice of the patients sample on which sensitivity tests have been performed. National surveys of drug resistance therefore require multidisciplinary participation in order to select the only useful indicators: rates of primary resistance and of acquired resistance. These indicators, gathered in representative groups of patients over a long period, are a measurement of the impact of modern chemotherapy regimens on bacterial ecology.

  16. C-A4-01: Computerized Clinical Decision Support During Drug Ordering for Long-term Care Residents With Renal Insufficiency

    PubMed Central

    Field, Terry S; Rochon, Paula; Lee, Monica; Gavendo, Linda; Baril, Joann L; Gurwitz, Jerry H

    2010-01-01

    Objective: To determine whether a computerized clinical decision support system (CDSS) providing patient specific recommendations in real- time improves the quality of prescribing for long-term care residents with renal insufficiency. Design: A randomized trial within the long-stay units of a large long-term care facility. Randomization was within blocks by unit type. Alerts related to medication prescribing for residents with renal insufficiency were displayed to prescribers in the intervention units and hidden but tracked in control units. Measurement: The proportions of final drug orders that were appropriate were compared between intervention and control units within alert categories: recommended medication doses; recommended administration frequencies; recommendations to avoid the drug; 4) warnings of missing information. Results: The rates of alerts were nearly equal in the intervention and control units: 2.5 per 1000 resident days in the intervention units and 2.4 in the control units. The proportions of dose alerts for which the final drug orders were appropriate were similar between the intervention and control units (relative risk 0.95, 95% confidence interval 0.83, 1.1). For the remaining alert categories significantly higher proportions of final drug orders were appropriate in the intervention units: relative risk 2.4 for maximum frequency (1.4, 4.4); 2.6 for drugs that should be avoided (1.4, 5.0); and 1.8 for alerts to acquire missing information (1.1, 3.4). Overall, final drug orders were appropriate significantly more often than a relative risk 1.2 (1.0, 1.4). By tracking personnel time and expenditures, we estimated the cost of developing the CDSS as $48,668.57. Drug costs saved during the 12 months of the trial are estimated at $2,137. Conclusion: Clinical decision support for physicians prescribing medications for long-term care residents with renal insufficiency can improve the quality of prescribing decisions. However, patient well-being and quality of care rather than the business case related to cost savings are likely to be the key drivers for adoption of this HIT application.

  17. A Systematic Review of Physicians' and Pharmacists' Perspectives on Generic Drug Use: What are the Global Challenges?

    PubMed

    Toverud, Else-Lydia; Hartmann, Katrin; Håkonsen, Helle

    2015-08-01

    Generic substitution has been introduced in most countries in order to reduce costs and improve access to drugs. However, regulations and the generic drugs available vary between countries. It is the prescriber or dispenser of the drug who is the final decision maker. Nevertheless, physicians' and pharmacists' perceptions of generic drug use are not well documented to date. This study presents a systematic review of physicians' and pharmacists' perspectives on generic drug use worldwide. A systematic literature search was performed to retrieve all articles published between 2002 and 2012 regarding physicians' and/or pharmacists' experiences with generic drugs and generic substitution. Of 1322 publications initially identified, 24 were eligible for inclusion. Overall, the studies revealed that physicians and pharmacists were aware of the cost-saving function of generic drugs and their role in improving global access to drugs. Nevertheless, marked differences were observed between countries when studying physicians' and pharmacists' perceptions of the available generic drugs. In less mature healthcare systems, large variations regarding, for example, control routines, bioequivalence requirements, and manufacturer standards were reported. A lack of reliable information and mistrust in the efficacy and quality were also mentioned by these participants. In the most developed healthcare systems, the participants trusted the quality of the generic drugs and did not hesitate to offer them to all patients regardless of socioeconomic status. In general, pharmacists seemed to have better knowledge of the concept of bioequivalence and generic drug aspects than physicians. The present study indicates that physicians and pharmacists are aware of the role of generic drugs in the improvement of global access to drugs. However, there are marked differences regarding how these health professionals view the quality of generic drugs depending on the maturity of their country's healthcare system. This can be attributed to the fact that developed healthcare systems have more reliable public control routines for drugs in general as well as better bioequivalence requirements concerning generics in particular.

  18. E-learning in order to improve drug prescription for hospitalized older patients: a cluster-randomized controlled study.

    PubMed

    Franchi, Carlotta; Tettamanti, Mauro; Djade, Codjo Dgnefa; Pasina, Luca; Mannucci, Pier Mannuccio; Onder, Graziano; Gussoni, Gualberto; Manfellotto, Dario; Bonassi, Stefano; Salerno, Francesco; Nobili, Alessandro

    2016-07-01

    The aim of the study was to evaluate the effect of an e-learning educational program meant to foster the quality of drug prescription in hospitalized elderly patients. Twenty geriatric and internal medicine wards were randomized to intervention (e-learning educational program) or control (basic geriatric pharmacology notions). Logistic regression analysis was used in order to assess the effect of the intervention on the use of potentially inappropriate medication (PIM, primary outcome) at hospital discharge. Secondary outcomes were a reduced prevalence of at least one potential drug-drug interaction (DDI) and potentially severe DDI at discharge. Mortality rate and incidence of re-hospitalizations were other secondary outcomes assessed at the 12-month follow-up. A total of 697 patients (347 in the intervention and 350 in the control arms) were enrolled. No difference in the prevalence of PIM at discharge was found between arms (OR 1.29 95%CI 0.87-1.91). We also found no decrease in the prevalence of DDI (OR 0.67 95%CI 0.34-1.28) and potentially severe DDI (OR 0.86 95%CI 0.63-1.15) at discharge, nor in mortality rates and incidence of re-hospitalization at 12-month follow-up. This e-learning educational program had no clear effect on the quality of drug prescription and clinical outcomes in hospitalized elderly patients. Given the high prevalence of PIMs and potential DDIs recorded in the frame of this study, other approaches should be developed in order to improve the quality of drug prescription in this population. © 2016 The British Pharmacological Society.

  19. 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.

  20. Psychosocial interventions for pregnant women in outpatient illicit drug treatment programs compared to other interventions

    PubMed Central

    Terplan, Mishka; Ramanadhan, Shaalini; Locke, Abigail; Longinaker, Nyaradzo; Lui, Steve

    2016-01-01

    Background Illicit drug use in pregnancy is a complex social and public health problem. The consequences of drug use in pregnancy are high for both the woman and her child. Therefore, it is important to develop and evaluate effective treatments. There is evidence for the effectiveness of psychosocial interventions in drug treatment but it is unclear whether they are effective in pregnant women. This is an update of a Cochrane review originally published in 2007. Objectives To evaluate the effectiveness of psychosocial interventions in pregnant women enrolled in illicit drug treatment programmes on birth and neonatal outcomes, on attendance and retention in treatment, as well as on maternal and neonatal drug abstinence. In short, do psychosocial interventions translate into less illicit drug use, greater abstinence, better birth outcomes, or greater clinic attendance? Search methods We conducted the original literature search in May 2006 and performed the search update up to January 2015. For both review stages (original and update), we searched the Cochrane Drugs and Alcohol Group Trial's register (May 2006 and January 2015); the Cochrane Central Register of Trials (CENTRAL; the Cochrane Library 2015, Issue 1); PubMed (1996 to January 2015); EMBASE (1996 to January 2015); and CINAHL (1982 to January 2015). Selection criteria We included randomized controlled trials comparing any psychosocial intervention vs. a control intervention that could include pharmacological treatment, such as methadone maintenance, a different psychosocial intervention, counselling, prenatal care, STD counselling and testing, transportation, or childcare. Data collection and analysis We used standard methodological procedures expected by the Cochrane Collaboration. We performed analyses based on three comparisons: any psychosocial intervention vs. control, contingency management (CM) interventions vs. control, and motivational interviewing based (MIB) interventions vs. control. Main results In total, we included 14 studies with 1298 participants: nine studies (704 participants) compared CM vs. control, and five studies (594 participants) compared MIB interventions vs. control. We did not find any studies that assessed other types of psychosocial interventions. For the most part, it was unclear if included studies adequately controlled for biases within their studies as such information was not often reported. We assessed risk of bias in the included studies relating to participant selection, allocation concealment, personnel and outcome assessor blinding, and attrition. The included trials rarely captured maternal and neonatal outcomes. For studies that did measure such outcomes, no difference was observed in pre-term birth rates (RR 0.71, 95% confidence interval (CI) 0.34 to 1.51; three trials, 264 participants, moderate quality evidence), maternal toxicity at delivery (RR 1.18, 95% CI 0.52 to 2.65; two trials, 217 participants, moderate quality evidence), or low birth weight (RR 0.72, 95% CI 0.36 to 1.43; one trial, 160 participants, moderate quality evidence). However, the results did show that neonates remained in hospital for fewer days after delivery in CM intervention groups (RR -1.27, 95% CI -2.52 to -0.03; two trials, 103 participants, moderate quality evidence). There were no differences observed at the end of studies in retention or abstinence (as assessed by positive drug test at the end of treatment) in any psychosocial intervention group compared to control (Retention: RR 0.99, 95% CI 0.93 to 1.06, nine trials, 743 participants, low quality evidence; and Abstinence: RR 1.14, 95% CI 0.75 to 1.73, three trials, 367 participants, low quality evidence). These results held for both CM and MIB combined. Overall, the quality of the evidence was low to moderate. Authors’ conclusions The present evidence suggests that there is no difference in treatment outcomes to address drug use in pregnant women with use of psychosocial interventions, when taken in the presence of other comprehensive care options. However, few studies evaluated obstetrical or neonatal outcomes and rarely did so in a systematic way, making it difficult to assess the effect of psychosocial interventions on these clinically important outcomes. It is important to develop a better evidence base to evaluate psychosocial modalities of treatment in this important population. PMID:25835053

  1. Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents).

    PubMed

    Calixto, J B

    2000-02-01

    This review highlights the current advances in knowledge about the safety, efficacy, quality control, marketing and regulatory aspects of botanical medicines. Phytotherapeutic agents are standardized herbal preparations consisting of complex mixtures of one or more plants which contain as active ingredients plant parts or plant material in the crude or processed state. A marked growth in the worldwide phytotherapeutic market has occurred over the last 15 years. For the European and USA markets alone, this will reach about $7 billion and $5 billion per annum, respectively, in 1999, and has thus attracted the interest of most large pharmaceutical companies. Insufficient data exist for most plants to guarantee their quality, efficacy and safety. The idea that herbal drugs are safe and free from side effects is false. Plants contain hundreds of constituents and some of them are very toxic, such as the most cytotoxic anti-cancer plant-derived drugs, digitalis and the pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic agents are less frequent compared with synthetic drugs, but well-controlled clinical trials have now confirmed that such effects really exist. Several regulatory models for herbal medicines are currently available including prescription drugs, over-the-counter substances, traditional medicines and dietary supplements. Harmonization and improvement in the processes of regulation is needed, and the general tendency is to perpetuate the German Commission E experience, which combines scientific studies and traditional knowledge (monographs). Finally, the trend in the domestication, production and biotechnological studies and genetic improvement of medicinal plants, instead of the use of plants harvested in the wild, will offer great advantages, since it will be possible to obtain uniform and high quality raw materials which are fundamental to the efficacy and safety of herbal drugs.

  2. Quality assurance: Importance of systems and standard operating procedures

    PubMed Central

    Manghani, Kishu

    2011-01-01

    It is mandatory for sponsors of clinical trials and contract research organizations alike to establish, manage and monitor their quality control and quality assurance systems and their integral standard operating procedures and other quality documents to provide high-quality products and services to fully satisfy customer needs and expectations. Quality control and quality assurance systems together constitute the key quality systems. Quality control and quality assurance are parts of quality management. Quality control is focused on fulfilling quality requirements, whereas quality assurance is focused on providing confidence that quality requirements are fulfilled. The quality systems must be commensurate with the Company business objectives and business model. Top management commitment and its active involvement are critical in order to ensure at all times the adequacy, suitability, effectiveness and efficiency of the quality systems. Effective and efficient quality systems can promote timely registration of drugs by eliminating waste and the need for rework with overall financial and social benefits to the Company. PMID:21584180

  3. Quality assurance: Importance of systems and standard operating procedures.

    PubMed

    Manghani, Kishu

    2011-01-01

    It is mandatory for sponsors of clinical trials and contract research organizations alike to establish, manage and monitor their quality control and quality assurance systems and their integral standard operating procedures and other quality documents to provide high-quality products and services to fully satisfy customer needs and expectations. Quality control and quality assurance systems together constitute the key quality systems. Quality control and quality assurance are parts of quality management. Quality control is focused on fulfilling quality requirements, whereas quality assurance is focused on providing confidence that quality requirements are fulfilled. The quality systems must be commensurate with the Company business objectives and business model. Top management commitment and its active involvement are critical in order to ensure at all times the adequacy, suitability, effectiveness and efficiency of the quality systems. Effective and efficient quality systems can promote timely registration of drugs by eliminating waste and the need for rework with overall financial and social benefits to the Company.

  4. Fixed-dose combination drugs for tuberculosis: application in standardised treatment regimens.

    PubMed

    Blomberg, Bjørn; Fourie, Bernard

    2003-01-01

    Short-course chemotherapy is highly efficacious in treating tuberculosis (TB). However, the length (>/=6 months) and complexity (three or four different drugs) of the treatment makes adherence difficult. Erratic treatment not only fails to cure patients but also creates chronically contagious cases, who may excrete drug-resistant TB bacteria. The Directly Observed Treatment Short-course (DOTS) strategy recommended by WHO provides a comprehensive organisational and infrastructural framework for the rational use of diagnosis, drug supply, as well as case and programme management services, in TB control. WHO and other organisations recommend fixed-dose combination formulations (FDCs) as a further step to facilitate the optimal drug treatment of TB. Using FDCs in TB control will simplify the doctor's prescription and patient's drug intake, as well as the drug supply management of the programme. By preventing monotherapy and facilitating the ingestion of adequate doses of the constituent anti-TB drugs, FDCs are expected to help prevent the emergence of drug resistance. This article presents the international recommendations for the use of FDCs in TB programmes. The fundamental issue is to obtain drug supplies of good quality. A laboratory network for quality testing, including bioavailability testing of FDCs exists, and the recently established Global TB Drug Facility (GDF) supplies quality TB drugs, including 4-drug FDCs, to countries requesting assistance. This articles deals with the requirements for a successful transition to FDC-based treatment. It emphasises the need for appropriately revised programme documentation (programme manual, training modules, treatment guidelines and forms), training of staff at all levels, carefully calculated drug needs, and a plan for the exhaustion of existing stocks of loose tablets and the phasing-in of FDCs at all levels of the programme at the same time. Loose drugs for individualised treatment of patients with adverse effects should be kept at district or central health institutions.

  5. 42 CFR 423.150 - Scope.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... PROGRAM (CONTINUED) VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement... utilization management programs, quality assurance measures and systems, and medication therapy management... organization (QIO) activities. (f) Compliance deemed on the basis of accreditation. (g) Accreditation...

  6. 42 CFR 423.150 - Scope.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... PROGRAM (CONTINUED) VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement... utilization management programs, quality assurance measures and systems, and medication therapy management... organization (QIO) activities. (f) Compliance deemed on the basis of accreditation. (g) Accreditation...

  7. 42 CFR 423.150 - Scope.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement Requirements... utilization management programs, quality assurance measures and systems, and medication therapy management... organization (QIO) activities. (f) Compliance deemed on the basis of accreditation. (g) Accreditation...

  8. 42 CFR 423.150 - Scope.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... PROGRAM (CONTINUED) VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement... utilization management programs, quality assurance measures and systems, and medication therapy management... organization (QIO) activities. (f) Compliance deemed on the basis of accreditation. (g) Accreditation...

  9. [Preparation of freeze - drying control materials of IgG antibody against Schistosoma japonicum for immunodetection kits].

    PubMed

    Jin, Huang; Chun-Lian, Tang; Zu-Wu, Tu; Li, Tang; Ke-Hui, Zhang; Qian, Li; Jun, Ye

    2018-04-18

    To prepare freeze-drying control materials of IgG antibody against Schistosoma japonicum for detection kits. The serum samples of schistosomiasis patients from endemic areas and normal people without history of schistosome infection or contact with infested water in Hubei Province were collected. All the sera were detected by the method approved by China Food and Drug Administration and selected for preparation of quality control samples. Totally twelve positive quality control materials, ten negative quality control materials, and one sensitive and one precision quality control materials were screened. According to the positive serum level, the positive degrees of quality control materials were divided into strong, medium and weak levels. The stability could be valid for one year. The freeze-drying quality control materials of IgG antibody against S. japonicum for detection kits are prepared. They are easy to use and have good stability, and therefore, they may meet the requirement of quality control for the detection of schistosomiasis diagnostics kits.

  10. Donor support for quality assurance and pharmacovigilance of anti-malarials in malaria-endemic countries.

    PubMed

    Kovacs, Stephanie D; Mills, Brianna M; Stergachis, Andy

    2017-07-11

    Malaria control efforts have been strengthened by funding from donor groups and government agencies. The Global Fund to Fight AIDS, Tuberculosis and the Malaria (Global Fund), the US President's Malaria Initiative (PMI) account for the majority of donor support for malaria control and prevention efforts. Pharmacovigilance (PV), which encompasses all activities relating to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problem, is a necessary part of efforts to reduce drug resistance and improve treatment outcomes. This paper reports on an analysis of PV plans in the Global Fund and PMI and World Bank's grants for malaria prevention and control. All active malaria grants as of September 2015 funded by the Global Fund and World Bank, and fiscal year 2015 and 2016 PMI Malaria Operational Plans (MOP) were identified. The total amount awarded for PV-related activities and drug quality assurance was abstracted. A Key-Word-in-Context (KWIC) analysis was conducted for the content of each grant. Specific search terms consisted of pharmacovigilance, pregn*, registry, safety, adverse drug, mass drug administration, primaquine, counterfeit, sub-standard, and falsified. Grants that mentioned PV activities identified in the KWIC search, listed PV in their budgets, or included the keywords: counterfeit, sub-standard, falsified, mass drug administration, or adverse event were thematically coded using Dedoose software version 7.0. The search identified 159 active malaria grants including 107 Global Fund grants, 39 fiscal year 2015 and 2016 PMI grants and 13 World Bank grants. These grants were primarily awarded to low-income countries (57.2%) and in sub-Saharan Africa (SSA) (70.4%). Thirty-seven (23.3%) grants included a budget line for PV- or drug quality assurance-related activities, including 21 PMI grants and 16 Global Fund grants. Only 23 (14.5%) grants directly mentioned PV. The primary focus area was improving drug quality monitoring, especially among the PMI grants. The results of the analysis demonstrate that funding for PV has not been sufficiently prioritized by either the key malaria donor organizations or by the recipient countries, as reflected in their grant proposal submissions and MOPs.

  11. Short Communication - Study on quality and efficacy of commercial tylosin and doxycycline products against local isolates of mycoplasma in broilers.

    PubMed

    Riazuddin, -; Khan, Sarzamin; Imtiaz, Naila; Aslam, Saima; Ahmad, Shakoor; Khan, Hamayun; Rabbani, Masood; Muhammad, Javed; Tanveer, Zafar Iqbal; Ali, Sakhawat

    2017-03-01

    The present study was conducted to investigate the quality and efficacy of commercially available preparations of tylosin and doxycycline available in the local market at Peshawar for poultry. In vitro and in vivo, tests were conducted to check the quality of these antimicrobial drugs. In vitro quality control test was performed by High performance liquid chromatographic (HPLC) and micro dilution method. In vivo, efficacy of the test drugs was checked in broilers infected with Mycoplasma gallisepticum. Results of HPLC indicated that test drug-2 contains doxycycline hydrochloride within specified limits but contain high quantity of active ingredient (Tylosin tartrate 120%). Recovery percentage of test drugs (3, 4, 5) were below the pharmacopoeial limit, which contained low quantity of tylosin tartrate (85%, 87.5%, 85%) respectively however, percent recovery of doxycycline were in the appropriate limits. All the tested drugs were effective against Mycoplasma gallisepticum and showed minimum inhibitory concentration (MIC) at 1.9μg/ml. The in vivo result indicated that all tested drugs decreased morbidity and mortality in infected chicks. The birds treated with test drugs (3 and 5) showed mortality of 9.5%, which was slightly higher than the other test groups. The current study suggested that there are incidences of substandard drugs in Pakistan and the drug regularity authorities should take strict actions against the manufacturing companies.

  12. [Post-marketing reevaluation for potential quality risk and quality control in clinical application of traditional Chinese medicines].

    PubMed

    Li, Hong-jiao; He, Li-yun; Liu, Bao-yan

    2015-06-01

    The effective quality control in clinical practices is an effective guarantee for the authenticity and scientificity of the findings. The post-marketing reevaluation for traditional Chinese medicines (TCM) focuses on the efficacy, adverse reaction, combined medication and effective dose of drugs in the market by expanded clinical trials, and requires a larger sample size and a wider range of patients. Therefore, this increases the difficulty of quality control in clinical practices. With the experience in quality control in clinical practices for the post-marketing reevaluation for Kangbingdu oral for cold, researchers in this study reviewed the study purpose, project, scheme design and clinical practice process from an overall point of view, analyzed the study characteristics of the post-marketing reevaluation for TCMs and the quality control risks, designed the quality control contents with quality impacting factors, defined key review contents and summarized the precautions in clinical practices, with the aim to improve the efficiency of quality control of clinical practices. This study can provide reference to clinical units and quality control-related personnel in the post-marketing reevaluation for TCMs.

  13. The use of Minilabs to improve the testing capacity of regulatory authorities in resource limited settings: Tanzanian experience.

    PubMed

    Risha, Peter Gasper; Msuya, Zera; Clark, Malcolm; Johnson, Keith; Ndomondo-Sigonda, Margareth; Layloff, Thomas

    2008-08-01

    The Tanzania Food and Drugs Authority piloted the use of Minilab kits, a thin-layer-chromatographic based drug quality testing technique, in a two-tier quality assurance program. The program is intended to improve testing capacity with timely screening of the quality of medicines as they enter the market. After 1 week training of inspectors on Minilab screening techniques, they were stationed at key Ports-of-Entry (POE) to screen the quality of imported medicines. In addition, three non-Ports-of-Entry centres were established to screen samples collected during Post-Marketing-Surveillance. Standard operating procedures (SOPs) were developed to structure and standardize the implementation process. Over 1200 samples were tested using the Minilab outside the central quality control laboratory (QCL), almost doubling the previous testing capacity. The program contributed to increased regulatory reach and visibility of the Authority throughout the country, serving as a deterrent against entry of substandard medicines into market. The use of Minilab for quality screening was inexpensive and provided a high sample throughput. However, it suffers from the limitation that it can reliably detect only grossly substandard or wrong drug samples and therefore, it should not be used as an independent testing resource but in conjunction with a full-service quality control laboratory capable of auditing reported substandard results.

  14. Results of drug screening from a producer's view.

    PubMed

    Adams, J B

    1994-07-01

    The dairy industry is faced with increasing governmental and public concern about the safety of the nation's milk supply. New regulations under the Grade A Pasteurized Milk Ordinance require that prescription drugs be properly labeled and that all tanker loads of milk be tested for beta-lactam antimicrobial residues. Concern over the use of animal drugs in an extralabel manner has prompted the National Milk Producers Federation and the American Veterinary Medical Association to develop a quality assurance program for on-farm residue prevention known as the Dairy Quality Assurance 10-Point Milk and Dairy Beef Residue Prevention Protocol. The program promotes the concept of Hazard Analysis Critical Control Points, applied to a pre-harvest farm environment. Screening limitations at point of milk receipt necessitates widespread adoption of the Dairy Quality Assurance protocol to address controlled use of all animal medications under a valid relationship among veterinarian, client, and animals, thus minimizing the potential for violative residues in the milk and meat supply.

  15. 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.

  16. Correlation of dissolution and disintegration results for an immediate-release tablet.

    PubMed

    Nickerson, Beverly; Kong, Angela; Gerst, Paul; Kao, Shangming

    2018-02-20

    The drug release rate of a rapidly dissolving immediate-release tablet formulation with a highly soluble drug is proposed to be controlled by the disintegration rate of the tablet. Disintegration and dissolution test methods used to evaluate the tablets were shown to discriminate manufacturing process differences and compositionally variant tablets. In addition, a correlation was established between disintegration and dissolution. In accordance with ICH Q6A, this work demonstrates that disintegration in lieu of dissolution is suitable as the drug product quality control method for evaluating this drug product. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. 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.

  18. Does bargaining affect Medicare prescription drug plan reimbursements to independent pharmacies?

    PubMed

    Tang, Yuexin; Xie, Yang; Urmie, Julie M; Doucette, William R

    2011-01-01

    To examine how pharmacy bargaining activities affect reimbursement rates in Medicare Part D prescription drug plan (PDP) contracts, controlling for pharmacy quality attributes, market structures, and area socioeconomic status. Cross-sectional study. Six Medicare regions throughout the United States between October and December 2009. Random sample of 1,650 independent pharmacies; 321 returned surveys containing sufficient responses for analysis. Pharmacies were surveyed regarding PDP reimbursement rates, costs, and cash prices of two popular prescription drugs (atorvastatin calcium [Lipitor-Pfizer] and lisinopril, 1-month supply of a common strength), as well as pharmacy bargaining activities and quality attributes. Data also were used from the National Council for Prescription Drug Programs pharmacy database, the 2000 U. S. Census, and the 2006 Economic Census on local market structures and area socio-economic status. PDP reimbursement rates. For the brand-name drug atorvastatin calcium, the PDP reimbursement was positively related to a pharmacy's request for a contract change (β = 0.887, P < 0.05), whereas other bargaining activities were not significantly related to PDP reimbursement. However, for the generic drug lisinopril, no bargaining activities were found to be significantly related to the PDP reimbursement. Pharmacy request for a contract change was associated with higher reimbursement rates for the brand-name drug atorvastatin calcium in PDP contracts, after controlling for pharmacy quality attributes, local market structures, and area socioeconomic status; this finding likely applies to other brand-name drugs because of the structure of the contracts. Our results suggest that independent pharmacies are more likely to acquire higher reimbursement rates by engaging in active bargaining with third-party payers.

  19. The association between fear of falling and quality of life for balance impairments based on hip and ankle strategies in the drug On- and Off-phase of patients with idiopathic Parkinson' disease.

    PubMed

    Mehdizadeh, Maryam; Lajevardi, Laleh; Habibi, Seyed Amir Hassan; ArabBaniasad, Mina; Baghoori, Delaram; Daneshjoo, Fatemeh; Taghizadeh, Ghorban

    2016-01-01

    Background: Despite the negative effect of fear of falling during functioning and social participation of patients with Parkinson' disease, so far, only few studies have investigated its effect on the quality of life in these patients. We aimed to investigate the association between fear of falling and quality of life controlling for balance impairments based on hip and ankle strategy in drug On- and Off-phase of patients with idiopathic Parkinson' disease. Methods: In this non-experimental cross-sectional study, 139 patients with idiopathic Parkinson' disease (100 male, 39 female) by mean± SD age of 60.2±12.27 years, mean±SD time since diagnosis of 6.7±5.53 years and mean±SD Hoehn and Yahr stage of 2.8±1.49 were selected by a simple non-probability method. Balance function was measured by a functional reach test with hip and ankle strategy. The Persian version of the selfcompleted Fall Efficacy Scale-International and Parkinson's disease quality of life questionnaire was used to evaluate fear of falling and quality of life, respectively. Results: The results showed that the score of all dimensions of quality of life (i.e., mobility, activities of daily living, emotional wellbeing, stigma, social support, cognition, communication and bodily discomfort) were significantly affected by the intensity of fear of falling. Multiple regression analysis indicated a significant association between fear of falling and quality of life in a way that fear of falling explained 11% to 47% and 12% to 43% of variance in drug On-phase, as well as 8% to 45% and 9% to 48% of variance in the drug Off-phase in dimensions of quality of life after controlling for balance function based on hip and ankle strategy, respectively. In the drug On-phase, the strongest association (R=0.85, p<0.001) was found between fear of falling and mobility dimension of quality of life. In the drug Off-phase, the strongest relation was observed between fear of falling and mobility (R=0.82, p<0.001) as well as activities of daily living (R=0.78-0.79, p<0.001) dimensions. Conclusion: This study found that fear of falling affects the quality of life of patients with Parkinson' disease beyond its relationship with balance impairments based on the hip and ankle strategy in both drug On- and Off-phase.

  20. Audits of radiopharmaceutical formulations

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

    Castronovo, F.P. Jr.

    A procedure for auditing radiopharmaceutical formulations is described. To meet FDA guidelines regarding the quality of radiopharmaceuticals, institutional radioactive drug research committees perform audits when such drugs are formulated away from an institutional pharmacy. All principal investigators who formulate drugs outside institutional pharmacies must pass these audits before they can obtain a radiopharmaceutical investigation permit. The audit team meets with the individual who performs the formulation at the site of drug preparation to verify that drug formulations meet identity, strength, quality, and purity standards; are uniform and reproducible; and are sterile and pyrogen free. This team must contain an expertmore » knowledgeable in the preparation of radioactive drugs; a radiopharmacist is the most qualified person for this role. Problems that have been identified by audits include lack of sterility and apyrogenicity testing, formulations that are open to the laboratory environment, failure to use pharmaceutical-grade chemicals, inadequate quality control methods or records, inadequate training of the person preparing the drug, and improper unit dose preparation. Investigational radiopharmaceutical formulations, including nonradiolabeled drugs, must be audited before they are administered to humans. A properly trained pharmacist should be a member of the audit team.« less

  1. Assessment of Efficacy and Quality of Two Albendazole Brands Commonly Used against Soil-Transmitted Helminth Infections in School Children in Jimma Town, Ethiopia

    PubMed Central

    Suleman, Sultan; Mohammed, Tesfaye; Deti, Habetewold; D'Hondt, Matthias; Wynendaele, Evelien; Mekonnen, Zeleke; Vercruysse, Jozef; Duchateau, Luc; De Spiegeleer, Bart; Levecke, Bruno

    2015-01-01

    Background There is a worldwide upscale in mass drug administration (MDA) programs to control the morbidity caused by soil-transmitted helminths (STHs): Ascaris lumbricoides, Trichuris trichiura and hookworm. Although anthelminthic drugs which are used for MDA are supplied by two pharmaceutical companies through donation, there is a wide range of brands available on local markets for which the efficacy against STHs and quality remain poorly explored. In the present study, we evaluated the drug efficacy and quality of two albendazole brands (Bendex and Ovis) available on the local market in Ethiopia. Methodology/Principal Findings A randomized clinical trial was conducted according to the World Health Organization (WHO) guidelines to assess drug efficacy, by means of egg reduction rate (ERR), of Bendex and Ovis against STH infections in school children in Jimma, Ethiopia. In addition, the chemical and physicochemical quality of the drugs was assessed according to the United States and European Pharmacopoeia, encompassing mass uniformity of the tablets, amount of active compound and dissolution profile. Both drugs were highly efficacious against A. lumbricoides (>97%), but showed poor efficacy against T. trichiura (~20%). For hookworms, Ovis was significantly (p < 0.05) more efficacious compared to Bendex (98.1% vs. 88.7%). Assessment of the physicochemical quality of the drugs revealed a significant difference in dissolution profile, with Bendex having a slower dissolution than Ovis. Conclusion/Significance The study revealed that differences in efficacy between the two brands of albendazole (ABZ) tablets against hookworm are linked to the differences in the in-vitro drug release profile. Differences in uptake and metabolism of this benzimidazole drug among different helminth species may explain that this efficacy difference was only observed in hookworms and not in the two other species. The results of the present study underscore the importance of assessing the chemical and physicochemical quality of drugs before conducting efficacy assessment in any clinical trials to ensure appropriate therapeutic efficacy and to exclude poor drug quality as a factor of reduced drug efficacy other than anthelminthic resistance. Overall, this paper demonstrates that “all medicines are not created equal”. PMID:26406600

  2. Assessment of Efficacy and Quality of Two Albendazole Brands Commonly Used against Soil-Transmitted Helminth Infections in School Children in Jimma Town, Ethiopia.

    PubMed

    Belew, Sileshi; Getachew, Mestawet; Suleman, Sultan; Mohammed, Tesfaye; Deti, Habetewold; D'Hondt, Matthias; Wynendaele, Evelien; Mekonnen, Zeleke; Vercruysse, Jozef; Duchateau, Luc; De Spiegeleer, Bart; Levecke, Bruno

    2015-09-01

    There is a worldwide upscale in mass drug administration (MDA) programs to control the morbidity caused by soil-transmitted helminths (STHs): Ascaris lumbricoides, Trichuris trichiura and hookworm. Although anthelminthic drugs which are used for MDA are supplied by two pharmaceutical companies through donation, there is a wide range of brands available on local markets for which the efficacy against STHs and quality remain poorly explored. In the present study, we evaluated the drug efficacy and quality of two albendazole brands (Bendex and Ovis) available on the local market in Ethiopia. A randomized clinical trial was conducted according to the World Health Organization (WHO) guidelines to assess drug efficacy, by means of egg reduction rate (ERR), of Bendex and Ovis against STH infections in school children in Jimma, Ethiopia. In addition, the chemical and physicochemical quality of the drugs was assessed according to the United States and European Pharmacopoeia, encompassing mass uniformity of the tablets, amount of active compound and dissolution profile. Both drugs were highly efficacious against A. lumbricoides (>97%), but showed poor efficacy against T. trichiura (~20%). For hookworms, Ovis was significantly (p < 0.05) more efficacious compared to Bendex (98.1% vs. 88.7%). Assessment of the physicochemical quality of the drugs revealed a significant difference in dissolution profile, with Bendex having a slower dissolution than Ovis. The study revealed that differences in efficacy between the two brands of albendazole (ABZ) tablets against hookworm are linked to the differences in the in-vitro drug release profile. Differences in uptake and metabolism of this benzimidazole drug among different helminth species may explain that this efficacy difference was only observed in hookworms and not in the two other species. The results of the present study underscore the importance of assessing the chemical and physicochemical quality of drugs before conducting efficacy assessment in any clinical trials to ensure appropriate therapeutic efficacy and to exclude poor drug quality as a factor of reduced drug efficacy other than anthelminthic resistance. Overall, this paper demonstrates that "all medicines are not created equal".

  3. 21 CFR 107.50 - Terms and conditions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... manufacturer shall maintain records of such quality control procedures sufficient to permit a public health... Food Safety and Applied Nutrition will review information submitted by infant formula manufacturers...

  4. Psychosocial functioning, quality of life and clinical correlates of comorbid alcohol and drug dependence syndromes in people with schizophrenia across Europe.

    PubMed

    Carrà, Giuseppe; Johnson, Sonia; Crocamo, Cristina; Angermeyer, Matthias C; Brugha, Traolach; Azorin, Jean-Michel; Toumi, Mondher; Bebbington, Paul E

    2016-05-30

    Little is known about the correlates of comorbid drug and alcohol dependence in people with schizophrenia outside the USA. We tested hypotheses that dependence on alcohol/drugs would be associated with more severe symptoms, and poorer psychosocial functioning and quality of life. The EuroSC Cohort study (N=1204), based in France, Germany and the UK, used semi-structured clinical interviews for diagnoses, and standardized tools to assess correlates. We used mixed models to compare outcomes between past-year comorbid dependence on alcohol/drugs, controlling for covariates and modelling both subject and country-level effects. Participants dependent on alcohol or drugs had fewer negative symptoms on PANSS than their non-dependent counterparts. However, those dependent on alcohol scored higher on PANSS general psychopathology than those who were not, or dependent only on drugs. People with schizophrenia dependent on drugs had poorer quality of life, more extrapyramidal side effects, and scored worse on Global Assessment of Functioning (GAF) than those without dependence. People with alcohol dependence reported more reasons for non-compliance with medication, and poorer functioning on GAF, though not on Global Assessment of Relational Functioning. In people with schizophrenia, comorbid dependence on alcohol or drugs is associated with impaired clinical and psychosocial adjustment, and poorer quality of life. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  5. 21 CFR 820.50 - Purchasing controls.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Purchasing controls. 820.50 Section 820.50 Food... DEVICES QUALITY SYSTEM REGULATION Purchasing Controls § 820.50 Purchasing controls. Each manufacturer... control to be exercised over the product, services, suppliers, contractors, and consultants, based on the...

  6. 21 CFR 226.58 - Laboratory controls.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Laboratory controls. 226.58 Section 226.58 Food...: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES Product Quality Control § 226.58 Laboratory controls. Laboratory controls shall include the establishment of adequate specifications and test...

  7. 21 CFR 820.50 - Purchasing controls.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Purchasing controls. 820.50 Section 820.50 Food... DEVICES QUALITY SYSTEM REGULATION Purchasing Controls § 820.50 Purchasing controls. Each manufacturer... control to be exercised over the product, services, suppliers, contractors, and consultants, based on the...

  8. 21 CFR 226.58 - Laboratory controls.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Laboratory controls. 226.58 Section 226.58 Food...: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES Product Quality Control § 226.58 Laboratory controls. Laboratory controls shall include the establishment of adequate specifications and test...

  9. 21 CFR 820.50 - Purchasing controls.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Purchasing controls. 820.50 Section 820.50 Food... DEVICES QUALITY SYSTEM REGULATION Purchasing Controls § 820.50 Purchasing controls. Each manufacturer... control to be exercised over the product, services, suppliers, contractors, and consultants, based on the...

  10. 21 CFR 820.50 - Purchasing controls.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Purchasing controls. 820.50 Section 820.50 Food... DEVICES QUALITY SYSTEM REGULATION Purchasing Controls § 820.50 Purchasing controls. Each manufacturer... control to be exercised over the product, services, suppliers, contractors, and consultants, based on the...

  11. 21 CFR 226.58 - Laboratory controls.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Laboratory controls. 226.58 Section 226.58 Food...: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR TYPE A MEDICATED ARTICLES Product Quality Control § 226.58 Laboratory controls. Laboratory controls shall include the establishment of adequate specifications and test...

  12. 21 CFR 820.50 - Purchasing controls.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Purchasing controls. 820.50 Section 820.50 Food... DEVICES QUALITY SYSTEM REGULATION Purchasing Controls § 820.50 Purchasing controls. Each manufacturer... control to be exercised over the product, services, suppliers, contractors, and consultants, based on the...

  13. Implementation research to improve quality of maternal and newborn health care, Malawi.

    PubMed

    Brenner, Stephan; Wilhelm, Danielle; Lohmann, Julia; Kambala, Christabel; Chinkhumba, Jobiba; Muula, Adamson S; De Allegri, Manuela

    2017-07-01

    To evaluate the impact of a performance-based financing scheme on maternal and neonatal health service quality in Malawi. We conducted a non-randomized controlled before and after study to evaluate the effects of district- and facility-level performance incentives for health workers and management teams. We assessed changes in the facilities' essential drug stocks, equipment maintenance and clinical obstetric care processes. Difference-in-difference regression models were used to analyse effects of the scheme on adherence to obstetric care treatment protocols and provision of essential drugs, supplies and equipment. We observed 33 health facilities, 23 intervention facilities and 10 control facilities and 401 pregnant women across four districts. The scheme improved the availability of both functional equipment and essential drug stocks in the intervention facilities. We observed positive effects in respect to drug procurement and clinical care activities at non-intervention facilities, likely in response to improved district management performance. Birth assistants' adherence to clinical protocols improved across all studied facilities as district health managers supervised and coached clinical staff more actively. Despite nation-wide stock-outs and extreme health worker shortages, facilities in the study districts managed to improve maternal and neonatal health service quality by overcoming bottlenecks related to supply procurement, equipment maintenance and clinical performance. To strengthen and reform health management structures, performance-based financing may be a promising approach to sustainable improvements in quality of health care.

  14. Drug pricing reform in China: analysis of piloted approaches and potential impact of the reform

    PubMed Central

    Chen, Yixi; Hu, Shanlian; Dong, Peng; Kornfeld, Åsa; Jaros, Patrycja; Yan, Jing; Ma, Fangfang; Toumi, Mondher

    2016-01-01

    Objectives In 2009, the Chinese government launched a national healthcare reform programme aiming to control healthcare expenditure and increase the quality of care. As part of this programme, a new drug pricing reform was initiated on 1 June 2015. The objective of this study was to describe the changing landscape of drug pricing policy in China and analyse the potential impact of the reform. Methods The authors conducted thorough research on the drug pricing reform using three Chinese databases (CNKI, Wanfang, and Weipu), Chinese health authority websites, relevant press releases, and pharmaceutical blogs and discussion forums. This research was complemented with qualitative research based on targeted interviews with key Chinese opinion leaders representing the authorities’ and prescribers’ perspectives. Results With the current reform, the government has attempted to replace its direct control over the prices of reimbursable drugs with indirect, incentive-driven influence. Although the exact implementation of the reform remains unclear at the moment, the changes introduced so far and the pilot project designs indicate that China is considering adaptation of some form of internal and external reference pricing policies, commonly used in the Organisation for Economic Co-operation and Development countries. Several challenges related to the potential new mechanism were identified: 1) the risk of hospital underfunding, if hospital funding reform is not prioritised; 2) the risk of promoting the use of cheap, low-quality drugs, if a reliable quality control system is not in place and discrepancy between the available drugs is present; 3) the risk of increasing disparity in access to care between poor and rich regions, in case of country-wide price convergence; and 4) the risk of industry underinvestment, resulting in reduced competition, issues with quality and sustainability of supply, and potentially negative social impact. Conclusions Foreign pricing policies cannot be transferred to China without prioritising historical, cultural, and economic contextualisation. Otherwise, the new policy may be counterproductive and affect the whole healthcare chain, as well as the health outcomes of Chinese patients. PMID:27123191

  15. 21 CFR 820.40 - Document controls.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Document controls. 820.40 Section 820.40 Food and... QUALITY SYSTEM REGULATION Document Controls § 820.40 Document controls. Each manufacturer shall establish and maintain procedures to control all documents that are required by this part. The procedures shall...

  16. 21 CFR 820.40 - Document controls.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Document controls. 820.40 Section 820.40 Food and... QUALITY SYSTEM REGULATION Document Controls § 820.40 Document controls. Each manufacturer shall establish and maintain procedures to control all documents that are required by this part. The procedures shall...

  17. 21 CFR 820.40 - Document controls.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Document controls. 820.40 Section 820.40 Food and... QUALITY SYSTEM REGULATION Document Controls § 820.40 Document controls. Each manufacturer shall establish and maintain procedures to control all documents that are required by this part. The procedures shall...

  18. 21 CFR 820.40 - Document controls.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Document controls. 820.40 Section 820.40 Food and... QUALITY SYSTEM REGULATION Document Controls § 820.40 Document controls. Each manufacturer shall establish and maintain procedures to control all documents that are required by this part. The procedures shall...

  19. 21 CFR 820.40 - Document controls.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Document controls. 820.40 Section 820.40 Food and... QUALITY SYSTEM REGULATION Document Controls § 820.40 Document controls. Each manufacturer shall establish and maintain procedures to control all documents that are required by this part. The procedures shall...

  20. Current good manufacturing practices, quality control procedures, quality factors, notification requirements, and records and reports, for infant formula. Final rule.

    PubMed

    2014-06-10

    The Food and Drug Administration (FDA or we) is issuing a final rule that adopts, with some modifications, the interim final rule (IFR) entitled "Current Good Manufacturing Practices, Quality Control Procedures, Quality Factors, Notification Requirements, and Records and Reports, for Infant Formula'' (February 10, 2014). This final rule affirms the IFR's changes to FDA's regulations and provides additional modifications and clarifications. The final rule also responds to certain comments submitted in response to the request for comments in the IFR.

  1. Psychosocial interventions for pregnant women in outpatient illicit drug treatment programs compared to other interventions.

    PubMed

    Terplan, Mishka; Ramanadhan, Shaalini; Locke, Abigail; Longinaker, Nyaradzo; Lui, Steve

    2015-04-02

    Illicit drug use in pregnancy is a complex social and public health problem. The consequences of drug use in pregnancy are high for both the woman and her child. Therefore, it is important to develop and evaluate effective treatments. There is evidence for the effectiveness of psychosocial interventions in drug treatment but it is unclear whether they are effective in pregnant women. This is an update of a Cochrane review originally published in 2007. To evaluate the effectiveness of psychosocial interventions in pregnant women enrolled in illicit drug treatment programmes on birth and neonatal outcomes, on attendance and retention in treatment, as well as on maternal and neonatal drug abstinence. In short, do psychosocial interventions translate into less illicit drug use, greater abstinence, better birth outcomes, or greater clinic attendance? We conducted the original literature search in May 2006 and performed the search update up to January 2015. For both review stages (original and update), we searched the Cochrane Drugs and Alcohol Group Trial's register (May 2006 and January 2015); the Cochrane Central Register of Trials (CENTRAL; the Cochrane Library 2015, Issue 1); PubMed (1996 to January 2015); EMBASE (1996 to January 2015); and CINAHL (1982 to January 2015). We included randomized controlled trials comparing any psychosocial intervention vs. a control intervention that could include pharmacological treatment, such as methadone maintenance, a different psychosocial intervention, counselling, prenatal care, STD counselling and testing, transportation, or childcare. We used standard methodological procedures expected by the Cochrane Collaboration. We performed analyses based on three comparisons: any psychosocial intervention vs. control, contingency management (CM) interventions vs. control, and motivational interviewing based (MIB) interventions vs. In total, we included 14 studies with 1298 participants: nine studies (704 participants) compared CM vs. control, and five studies (594 participants) compared MIB interventions vs. We did not find any studies that assessed other types of psychosocial interventions. For the most part, it was unclear if included studies adequately controlled for biases within their studies as such information was not often reported. We assessed risk of bias in the included studies relating to participant selection, allocation concealment, personnel and outcome assessor blinding, and attrition.The included trials rarely captured maternal and neonatal outcomes. For studies that did measure such outcomes, no difference was observed in pre-term birth rates (RR 0.71, 95% confidence interval (CI) 0.34 to 1.51; three trials, 264 participants, moderate quality evidence), maternal toxicity at delivery (RR 1.18, 95% CI 0.52 to 2.65; two trials, 217 participants, moderate quality evidence), or low birth weight (RR 0.72, 95% CI 0.36 to 1.43; one trial, 160 participants, moderate quality evidence). However, the results did show that neonates remained in hospital for fewer days after delivery in CM intervention groups (RR -1.27, 95% CI -2.52 to -0.03; two trials, 103 participants, moderate quality evidence). There were no differences observed at the end of studies in retention or abstinence (as assessed by positive drug test at the end of treatment) in any psychosocial intervention group compared to control (Retention: RR 0.99, 95% CI 0.93 to 1.06, nine trials, 743 participants, low quality evidence; and Abstinence: RR 1.14, 95% CI 0.75 to 1.73, three trials, 367 participants, low quality evidence). These results held for both CM and MIB combined. Overall, the quality of the evidence was low to moderate. The present evidence suggests that there is no difference in treatment outcomes to address drug use in pregnant women with use of psychosocial interventions, when taken in the presence of other comprehensive care options. However, few studies evaluated obstetrical or neonatal outcomes and rarely did so in a systematic way, making it difficult to assess the effect of psychosocial interventions on these clinically important outcomes. It is important to develop a better evidence base to evaluate psychosocial modalities of treatment in this important population.

  2. 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.

  3. Some aspects of doping and medication control in equine sports.

    PubMed

    Houghton, Ed; Maynard, Steve

    2010-01-01

    This chapter reviews drug and medication control in equestrian sports and addresses the rules of racing, the technological advances that have been made in drug detection and the importance of metabolism studies in the development of effective drug surveillance programmes. Typical approaches to screening and confirmatory analysis are discussed, as are the quality processes that underpin these procedures. The chapter also addresses four specific topics relevant to equestrian sports: substances controlled by threshold values, the approach adopted recently by European racing authorities to control some therapeutic substances, anabolic steroids in the horse and LC-MS analysis in drug testing in animal sports and metabolism studies. The purpose of discussing these specific topics is to emphasise the importance of research and development and collaboration to further global harmonisation and the development and support of international rules.

  4. A critical appraisal of probiotics (as drugs or food supplements) in gastrointestinal diseases.

    PubMed

    Passariello, Annalisa; Agricole, Pascal; Malfertheiner, Peter

    2014-06-01

    Probiotics may be registered as food supplements or drugs. This article summarizes differences in European regulations of probiotics registered as food supplements and drugs, as well as issues related to the quality of probiotic products. For registration as a drug, the European Medicines Agency demands extensive and detailed quality, efficacy and safety evidence; whereas compulsory analyses requested for food supplements consist only in a nutritional analysis. As a result, the quality of those probiotics registered as drugs, compared to food supplements, is in general controlled with higher standards. Despite these differences and whatever the status of the probiotic product, its efficacy and safety has to be documented in well conducted randomized controlled trials (RCTs). Furthermore, this paper reviews recent evidence on the use of probiotics for gastrointestinal diseases, evaluating all the existing information up to January 2014. In all eligible published studies in which use of probiotics for gastrointestinal diseases were investigated and reported, no language limitations were applied. Special focus is placed on RCTs (or their meta-analyses) showing positive results, so that the findings may be applicable to everyday clinical practice. Currently, the best documented clinical areas appear to be probiotics efficacy for the treatment of acute gastroenteritis in children and for the prevention of antibiotic-associated diarrhea both in children and in adults. In other gastrointestinal conditions, some promising observations are emerging, but no definitive conclusions can be reached at present.

  5. The impact of physician-level drug budgets on prescribing behavior.

    PubMed

    Fischer, Katharina Elisabeth; Koch, Taika; Kostev, Karel; Stargardt, Tom

    2018-03-01

    To contain pharmaceutical spending, drug budgets have been introduced across health systems. Apart from analyzing whether drug budgets fulfill their overall goal of reducing spending, changes in the cost and quality of prescribing and the enforcement mechanisms put in place need evaluation to assess the effectiveness of drug budgets at the physician level. In this study, we aim to analyze the cost and quality of prescribing conditional on the level of utilization of the drug budget and in view of varying levels of enforcement in cases of overspending. We observed drug budget utilization in a panel of 440 physicians in three federal states of Germany from 2005 to 2011. At the physician level, we retrospectively calculated drug budgets, the level of drug budget utilization, and differentiated by varying levels of enforcement where physicians overspent their budgets (i.e., more than 115/125% of the drug budget). Using lagged dependent-variable regression models, we analyzed whether the level of drug budget utilization in the previous year affected current prescribing in terms of various indicators to describe the cost and quality of prescribing. We controlled for patient and physician characteristics. The mean drug budget utilization is 92.3%. The level of drug budget utilization influences selected dimensions of cost and quality of prescribing (i.e., generic share (estimate 0.000215; p = 0.0246), concentration of generic brands (estimate 0.000585; p = 0.0056) and therapeutic substances (estimate -0.000060; p < 0.0001) and the share of potentially inappropriate medicines in the elderly (estimate 0.001; p < 0.0001)), whereas the level of enforcement does not. Physicians seem to gradually adjust their prescription patterns, especially in terms of generic substitution.

  6. Fixed-dose combinations of drugs versus single-drug formulations for treating pulmonary tuberculosis

    PubMed Central

    Gallardo, Carmen R; Rigau Comas, David; Valderrama Rodríguez, Angélica; Roqué i Figuls, Marta; Parker, Lucy Anne; Caylà, Joan; Bonfill Cosp, Xavier

    2016-01-01

    Background People who are newly diagnosed with pulmonary tuberculosis (TB) typically receive a standard first-line treatment regimen that consists of two months of isoniazid, rifampicin, pyrazinamide, and ethambutol followed by four months of isoniazid and rifampicin. Fixed-dose combinations (FDCs) of these drugs are widely recommended. Objectives To compare the efficacy, safety, and acceptability of anti-tuberculosis regimens given as fixed-dose combinations compared to single-drug formulations for treating people with newly diagnosed pulmonary tuberculosis. Search methods We searched the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL, published in the Cochrane Library, Issue 11 2015); MEDLINE (1966 to 20 November 2015); EMBASE (1980 to 20 November 2015); LILACS (1982 to 20 November 2015); the metaRegister of Controlled Trials; and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), without language restrictions, up to 20 November 2015. Selection criteria Randomized controlled trials that compared the use of FDCs with single-drug formulations in adults (aged 15 years or more) newly diagnosed with pulmonary TB. Data collection and analysis Two review authors independently assessed studies for inclusion, and assessed the risk of bias and extracted data from the included trials. We used risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with 95% confidence intervals (CIs). We attempted to assess the effect of treatment for time-to-event measures with hazard ratios and their 95% CIs. We used the Cochrane 'Risk of bias' assessment tool to determine the risk of bias in included trials. We used the fixed-effect model when there was little heterogeneity and the random-effects model with moderate heterogeneity. We used an I² statistic value of 75% or greater to denote significant heterogeneity, in which case we did not perform a meta-analysis. We assessed the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Main results We included 13 randomized controlled trials (RCTs) in the review, which enrolled 5824 participants. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. Overall there is little or no difference detected between FDCs and single-drug formulations for most outcomes reported. We did not detect a difference in treatment failure between FDCs compared with single-drug formulations (RR 1.28, 95% CI 0.82 to 2.00; 3606 participants, seven trials, moderate quality evidence). Relapse may be more frequent in people treated with FDCs compared to single-drug formulations, although the confidence interval (CI) includes no difference (RR 1.28, 95% CI 1.00 to 1.64; 3621 participants, 10 trials, low quality evidence). We did not detect any difference in death between fixed-dose and single-drug formulation groups (RR 0.96, 95% CI 0.67 to 1.39; 4800 participants, 11 trials, moderate quality evidence). When we compared FDCs with single-drug formulations we found little or no difference for sputum smear or culture conversion at the end of treatment (RR 0.99, 95% CI 0.96 to 1.02; 2319 participants, seven trials, high quality evidence), for serious adverse events (RR 1.45, 95% CI 0.90 to 2.33; 3388 participants, six trials, moderate quality evidence), and for adverse events that led to discontinuation of therapy (RR 0.96, 95% CI 0.56 to 1.66; 5530 participants, 13 trials, low quality evidence). We conducted a sensitivity analysis excluding studies at high risk of bias and this did not alter the review findings. Authors' conclusions Fixed-dose combinations and single-drug formulations probably have similar effects for treating people with newly diagnosed pulmonary TB. PLAIN LANGUAGE SUMMARY Fixed-dose combinations for treating pulmonary tuberculosis What are fixed-dose combinations and how might they improve care of people with tuberculosis Tuberculosis (TB) is an important health problem, especially in developing countries. The treatment for pulmonary TB in new patients includes four oral medicines taken for six months, sometimes as fixed-dose combinations (FDCs) that are combined in one tablet, or taken separately as single-drug formulations. The World Health Organization recommends prescribers use fixed-dose combinations to reduce the number of tablets that people take. On the supply side, this might reduce prescribing errors and improve drug supply efficiency; on the patient's side, FDCS simplify treatment and improve adherence. We conducted a review to assess the efficacy, safety, and acceptability of FDCs compared with single-drug formulations for treating people with newly diagnosed pulmonary TB. What the research says We searched for relevant trials up to 20 November 2015, and included 13 randomized controlled trials that enrolled 5824 people. Trials were published between 1987 and 2015 and included participants in treatment with newly diagnosed pulmonary TB in countries with high TB prevalence. Only two trials reported the HIV status of included participants. There is probably little or no difference in FDCs compared to single-drug formulations for treatment failure (moderate quality evidence); relapse may be more frequent (low quality evidence); and the number of deaths were similar (moderate quality evidence). There is little or no difference in sputum smear or culture conversion (high quality evidence), and no difference was shown for serious adverse events (moderate quality evidence) or adverse events that led to discontinuation of therapy (low quality evidence). Authors' conclusions We concluded that fixed-dose combinations have similar efficacy to single-drug formulations for treating people with newly diagnosed pulmonary TB. PMID:27186634

  7. Zhen gan xi feng decoction, a traditional chinese herbal formula, for the treatment of essential hypertension: a systematic review of randomized controlled trials.

    PubMed

    Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

    2013-01-01

    Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use.

  8. 42 CFR 423.162 - Quality improvement organization activities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Quality improvement organization activities. 423.162 Section 423.162 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control...

  9. [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.

  10. Benefits of a Pharmacology Antimalarial Reference Standard and Proficiency Testing Program Provided by the Worldwide Antimalarial Resistance Network (WWARN)

    PubMed Central

    Lourens, Chris; Lindegardh, Niklas; Barnes, Karen I.; Guerin, Philippe J.; Sibley, Carol H.; White, Nicholas J.

    2014-01-01

    Comprehensive assessment of antimalarial drug resistance should include measurements of antimalarial blood or plasma concentrations in clinical trials and in individual assessments of treatment failure so that true resistance can be differentiated from inadequate drug exposure. Pharmacometric modeling is necessary to assess pharmacokinetic-pharmacodynamic relationships in different populations to optimize dosing. To accomplish both effectively and to allow comparison of data from different laboratories, it is essential that drug concentration measurement is accurate. Proficiency testing (PT) of laboratory procedures is necessary for verification of assay results. Within the Worldwide Antimalarial Resistance Network (WWARN), the goal of the quality assurance/quality control (QA/QC) program is to facilitate and sustain high-quality antimalarial assays. The QA/QC program consists of an international PT program for pharmacology laboratories and a reference material (RM) program for the provision of antimalarial drug standards, metabolites, and internal standards for laboratory use. The RM program currently distributes accurately weighed quantities of antimalarial drug standards, metabolites, and internal standards to 44 pharmacology, in vitro, and drug quality testing laboratories. The pharmacology PT program has sent samples to eight laboratories in four rounds of testing. WWARN technical experts have provided advice for correcting identified problems to improve performance of subsequent analysis and ultimately improved the quality of data. Many participants have demonstrated substantial improvements over subsequent rounds of PT. The WWARN QA/QC program has improved the quality and value of antimalarial drug measurement in laboratories globally. It is a model that has potential to be applied to strengthening laboratories more widely and improving the therapeutics of other infectious diseases. PMID:24777099

  11. The relevance of polymeric synthetic membranes in topical formulation assessment and drug diffusion study.

    PubMed

    Ng, Shiow-Fern; Rouse, Jennifer J; Sanderson, Francis D; Eccleston, Gillian M

    2012-03-01

    Synthetic membranes are composed of thin sheets of polymeric macromolecules that can control the passage of components through them. Generally, synthetic membranes used in drug diffusion studies have one of two functions: skin simulation or quality control. Synthetic membranes for skin simulation, such as the silicone-based membranes polydimethylsiloxane and Carbosil, are generally hydrophobic and rate limiting, imitating the stratum corneum. In contrast, synthetic membranes for quality control, such as cellulose esters and polysulfone, are required to act as a support rather than a barrier. These synthetic membranes also often contain pores; hence, they are called porous membranes. The significance of Franz diffusion studies and synthetic membranes in quality control studies involves an understanding of the fundamentals of synthetic membranes. This article provides a general overview of synthetic membranes, including a brief background of the history and the common applications of synthetic membranes. This review then explores the types of synthetic membranes, the transport mechanisms across them, and their relevance in choosing a synthetic membrane in Franz diffusion cell studies for formulation assessment purposes.

  12. 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…

  13. 21 CFR 106.100 - Records.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 2 2014-04-01 2014-04-01 false Records. 106.100 Section 106.100 Food and Drugs... CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES (Eff. until 7-10-14) Records and Reports § 106.100 Records. (a) Every manufacturer of infant formula shall maintain the records specified in this regulation...

  14. 21 CFR 106.100 - Records.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 2 2012-04-01 2012-04-01 false Records. 106.100 Section 106.100 Food and Drugs... CONSUMPTION INFANT FORMULA QUALITY CONTROL PROCEDURES Records and Reports § 106.100 Records. (a) Every manufacturer of infant formula shall maintain the records specified in this regulation in order to permit the...

  15. 21 CFR 820.150 - Storage.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Storage. 820.150 Section 820.150 Food and Drugs... QUALITY SYSTEM REGULATION Handling, Storage, Distribution, and Installation § 820.150 Storage. (a) Each manufacturer shall establish and maintain procedures for the control of storage areas and stock rooms for...

  16. 21 CFR 820.150 - Storage.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Storage. 820.150 Section 820.150 Food and Drugs... QUALITY SYSTEM REGULATION Handling, Storage, Distribution, and Installation § 820.150 Storage. (a) Each manufacturer shall establish and maintain procedures for the control of storage areas and stock rooms for...

  17. 21 CFR 820.150 - Storage.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Storage. 820.150 Section 820.150 Food and Drugs... QUALITY SYSTEM REGULATION Handling, Storage, Distribution, and Installation § 820.150 Storage. (a) Each manufacturer shall establish and maintain procedures for the control of storage areas and stock rooms for...

  18. 21 CFR 820.150 - Storage.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Storage. 820.150 Section 820.150 Food and Drugs... QUALITY SYSTEM REGULATION Handling, Storage, Distribution, and Installation § 820.150 Storage. (a) Each manufacturer shall establish and maintain procedures for the control of storage areas and stock rooms for...

  19. 21 CFR 820.30 - Design controls.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Design controls. 820.30 Section 820.30 Food and... QUALITY SYSTEM REGULATION Design Controls § 820.30 Design controls. (a) General. (1) Each manufacturer of..., shall establish and maintain procedures to control the design of the device in order to ensure that...

  20. 21 CFR 820.30 - Design controls.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Design controls. 820.30 Section 820.30 Food and... QUALITY SYSTEM REGULATION Design Controls § 820.30 Design controls. (a) General. (1) Each manufacturer of..., shall establish and maintain procedures to control the design of the device in order to ensure that...

  1. 21 CFR 820.30 - Design controls.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Design controls. 820.30 Section 820.30 Food and... QUALITY SYSTEM REGULATION Design Controls § 820.30 Design controls. (a) General. (1) Each manufacturer of..., shall establish and maintain procedures to control the design of the device in order to ensure that...

  2. 21 CFR 820.30 - Design controls.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Design controls. 820.30 Section 820.30 Food and... QUALITY SYSTEM REGULATION Design Controls § 820.30 Design controls. (a) General. (1) Each manufacturer of..., shall establish and maintain procedures to control the design of the device in order to ensure that...

  3. 21 CFR 820.30 - Design controls.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Design controls. 820.30 Section 820.30 Food and... QUALITY SYSTEM REGULATION Design Controls § 820.30 Design controls. (a) General. (1) Each manufacturer of..., shall establish and maintain procedures to control the design of the device in order to ensure that...

  4. The impact of commonly prescribed drugs on male fertility.

    PubMed

    Hayashi, Tetsuo; Miyata, Akiomi; Yamada, Takumi

    2008-09-01

    To analyze the impact of commonly used drugs on male fertility, we assessed the clinical characteristics of patients with impaired semen quality while they were taking medication for chronic diseases and after switching therapies. Of 1768 infertile males, 201 patients were taking medications and had impaired semen quality without any seminal tract obstruction, spermatogenic abnormalities or hypogonadotropic hypogonadism. Of these 201 men, a total of 165 had no history of testicular diseases nor abnormalities in any examinations. Amongst them, H1 receptor antagonists were the most common medication taken, followed by antiepileptics and antibiotics. They were divided into two groups: an intervention group (73 patients), who could stop or switch their medications, and a control group (92 patients), who could not. In the intervention group, semen quality improvement rate and conception rate (93% and 85%, respectively) were much higher than those of the control group (12% and 10%, respectively). After switching therapies, the time interval before conception was 7.3 months, which was significantly shorter in asthenozoospermia than oligozoospermia. Our results confirm the potential fertility hazards of commonly used drugs and their reversibility. Moreover, after switching medication, drug-induced asthenozoospermia was cured more rapidly than oligozoospermia, suggesting that further delineation of such differences may help to elucidate mechanisms of spermatogenesis and might facilitate the development of non-hormonal male contraceptive agents.

  5. The complications of controlling agency time discretion: FDA review deadlines and postmarket drug safety.

    PubMed

    Carpenter, Daniel; Chattopadhyay, Jacqueline; Moffitt, Susan; Nall, Clayton

    2012-01-01

    Public agencies have discretion on the time domain, and politicians deploy numerous policy instruments to constrain it. Yet little is known about how administrative procedures that affect timing also affect the quality of agency decisions. We examine whether administrative deadlines shape decision timing and the observed quality of decisions. Using a unique and rich dataset of FDA drug approvals that allows us to examine decision timing and quality, we find that this administrative tool induces a piling of decisions before deadlines, and that these “just-before-deadline” approvals are linked with higher rates of postmarket safety problems (market withdrawals, severe safety warnings, safety alerts). Examination of data from FDA advisory committees suggests that the deadlines may impede quality by impairing late-stage deliberation and agency risk communication. Our results both support and challenge reigning theories about administrative procedures, suggesting they embody expected control-expertise trade-offs, but may also create unanticipated constituency losses.

  6. High school drug use predicts job-related outcomes at age 29.

    PubMed

    Ringel, Jeanne S; Ellickson, Phyllis L; Collins, Rebecca L

    2007-03-01

    The present study examines the relationship between hard drug use in high school and occupational and job quality outcomes measured at approximately age 29. We use two different methods aimed at ruling out the possibility of spurious correlations between high school drug use and occupational outcomes: (1) directly controlling for pre-high school characteristics that may affect both high school drug use and later occupational characteristics (e.g., educational orientation, early drug use and deviant behavior); and (2) matching high school users with a subset of nonusers that have very similar characteristics and then estimating the difference in labor market outcomes for these two groups (i.e., propensity score matching). Overall, the results suggest that adolescent drug use is linked with poorer occupational and job quality outcomes as much as 10 years after high school. Interestingly, which job-related outcomes are affected by early hard drug use varies by gender. Females who use hard drugs as adolescents end up in lower skill, lower status jobs while males who use hard drugs as adolescents are more likely to end up in jobs with fewer benefits (e.g., health, retirement).

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

    Green, D.W.; Heinrich, R.R.; Graczyk, D.G.

    The ACL activities covered IFR fuel reprocessing, corium-concrete interactions, environmental samples, wastes, WIPP support, Advanced Photon Source, H-Tc superconductors, EBWR vessel, soils, illegal drug detection, quality control, etc.

  8. Implementation research to improve quality of maternal and newborn health care, Malawi

    PubMed Central

    Wilhelm, Danielle; Lohmann, Julia; Kambala, Christabel; Chinkhumba, Jobiba; Muula, Adamson S; De Allegri, Manuela

    2017-01-01

    Abstract Objective To evaluate the impact of a performance-based financing scheme on maternal and neonatal health service quality in Malawi. Methods We conducted a non-randomized controlled before and after study to evaluate the effects of district- and facility-level performance incentives for health workers and management teams. We assessed changes in the facilities’ essential drug stocks, equipment maintenance and clinical obstetric care processes. Difference-in-difference regression models were used to analyse effects of the scheme on adherence to obstetric care treatment protocols and provision of essential drugs, supplies and equipment. Findings We observed 33 health facilities, 23 intervention facilities and 10 control facilities and 401 pregnant women across four districts. The scheme improved the availability of both functional equipment and essential drug stocks in the intervention facilities. We observed positive effects in respect to drug procurement and clinical care activities at non-intervention facilities, likely in response to improved district management performance. Birth assistants’ adherence to clinical protocols improved across all studied facilities as district health managers supervised and coached clinical staff more actively. Conclusion Despite nation-wide stock-outs and extreme health worker shortages, facilities in the study districts managed to improve maternal and neonatal health service quality by overcoming bottlenecks related to supply procurement, equipment maintenance and clinical performance. To strengthen and reform health management structures, performance-based financing may be a promising approach to sustainable improvements in quality of health care. PMID:28670014

  9. Pharmaceutical quality by design: product and process development, understanding, and control.

    PubMed

    Yu, Lawrence X

    2008-04-01

    The purpose of this paper is to discuss the pharmaceutical Quality by Design (QbD) and describe how it can be used to ensure pharmaceutical quality. The QbD was described and some of its elements identified. Process parameters and quality attributes were identified for each unit operation during manufacture of solid oral dosage forms. The use of QbD was contrasted with the evaluation of product quality by testing alone. The QbD is a systemic approach to pharmaceutical development. It means designing and developing formulations and manufacturing processes to ensure predefined product quality. Some of the QbD elements include: Defining target product quality profile; Designing product and manufacturing processes; Identifying critical quality attributes, process parameters, and sources of variability; Controlling manufacturing processes to produce consistent quality over time. Using QbD, pharmaceutical quality is assured by understanding and controlling formulation and manufacturing variables. Product testing confirms the product quality. Implementation of QbD will enable transformation of the chemistry, manufacturing, and controls (CMC) review of abbreviated new drug applications (ANDAs) into a science-based pharmaceutical quality assessment.

  10. Financial incentives linked to self-assessment of prescribing patterns: a new approach for quality improvement of drug prescribing in primary care.

    PubMed

    Wettermark, Björn; Pehrsson, Ake; Juhasz-Haverinen, Maria; Veg, Aniko; Edlert, Maria; Törnwall-Bergendahl, Gunilla; Almkvist, Henrik; Godman, Brian; Granath, Fredrik; Bergman, Ulf

    2009-01-01

    Financial incentives have been suggested to be effective in increasing the quality and efficiency of drug prescribing. Concern has been raised in relation to potential negative consequences on the quality of care. To describe and analyse the impact of an incentives model linking payment with adherence to drug and therapeutics committee (DTC) guidelines and self-reflection of prescribing pattern in a 'prescribing quality report'. The study was performed in the county of Stockholm, Sweden, with 139 (out of 154) primary healthcare centres (PHCs) participating in the project and 15 PHCs not participating. The study consisted of two parts: a quantitative observational study of prescribing patterns and a qualitative analysis of the submitted prescribing quality reports. All prescriptions issued from PHCs and dispensed at pharmacies during October to December 2005 and October to December 2006 were analysed, using adherence to the regional DTC guidelines as the main outcome measure. Adherence was assessed using the drug utilisation 90% methodology, i.e. focusing on drugs constituting 90% of the prescribed volume and the proportion of drugs included in the guidelines. The qualitative analysis focused on reports on the quality of drug prescribing submitted by each PHC in early 2007. The 139 PHCs participating in the programme accounted for 85% of all prescriptions issued in primary care during October to December 2006. Mean adherence to guidelines increased among participating practices by 3.3 percentage units (95% confidence interval (CI) 2.9-3.7%) to 83% (82.6-83.7%) during the year. The adherence among practices not participating increased by 3.1 percentage units (95% CI 1.7-4.4%) to 78.8% (95% CI 76.7-80.9%). The higher adherence achieved during the year corresponded to savings estimated at five times greater than the cost of running the programme including the financial incentives. In addition, many areas for improving prescribing were identified, such as limiting the prescribing of drugs with uncertain safety profiles and documentation as well as reporting adverse drug reactions. Although no causal effect can be attributed without a control group, we have shown the feasibility of a model linking payment to DTC adherence. This approach with its own quality assessment and goal setting offers an example to other regions and countries of how to increase the quality and efficiency of drug prescribing within limited resources.

  11. The quality of antimalarials available in Yemen

    PubMed Central

    Abdo-Rabbo, Ahmed; Bassili, Amal; Atta, Hoda

    2005-01-01

    Background Malaria has always been a major public health problem in Yemen. Several studies in developing countries have demonstrated ineffective and poor quality drugs including antimalarials. Therefore, quality assessment of antimalarial drugs is of crucial importance. This study aimed to assess the quality of antimalarials (chloroquine and sulfadoxine/pyrimethamine) available in Yemen and to determine whether the quality of these products was related to the level of the distribution chain at which the samples were collected or related to the manufacturers. Methods Four samples from each antimalarial product were collected from each of the various levels of the distribution chain. One sample was kept with the research team. Two were tested at Sana'a and Aden Drug Quality Control Laboratories. The fourth was sent to the Centre for Quality Assurance of Medicines in Potchefstroom, South Africa, for analysis. Quality indicators measured were the content of the active ingredient and dissolution rate (for tablets only) in comparison to standard specifications for these products in the relevant pharmacopoeia. Results The results identified several problems of sub-standard products within the drug distribution chain. They included high and low failures in ingredient content for chloroquine tablets and chloroquine syrup. There was some dissolution failure for chloroquine tablets, and high sulfadoxine/pyrimethamine tablets dissolution failures. Failures with the dissolution of the pyrimethamine were found at most of the collection points. No clear relationship neither between the quality products and the level of the distribution chain, nor between locally manufactured and imported products was observed. Conclusion There are sub-standard antimalarial products circulating within the drug distribution chains in the country, which will have serious implications on the reduced therapeutic effectiveness and on the development of drug resistance. This appears to be due to non-compliance with Good Manufacturing Practice guidelines by manufacturers in the production of the antimalarials. PMID:15987508

  12. E‐learning in order to improve drug prescription for hospitalized older patients: a cluster‐randomized controlled study

    PubMed Central

    Tettamanti, Mauro; Djade, Codjo Dgnefa; Pasina, Luca; Mannucci, Pier Mannuccio; Onder, Graziano; Gussoni, Gualberto; Manfellotto, Dario; Bonassi, Stefano; Salerno, Francesco; Nobili, Alessandro

    2016-01-01

    Aims The aim of the study was to evaluate the effect of an e‐learning educational program meant to foster the quality of drug prescription in hospitalized elderly patients. Methods Twenty geriatric and internal medicine wards were randomized to intervention (e‐learning educational program) or control (basic geriatric pharmacology notions). Logistic regression analysis was used in order to assess the effect of the intervention on the use of potentially inappropriate medication (PIM, primary outcome) at hospital discharge. Secondary outcomes were a reduced prevalence of at least one potential drug–drug interaction (DDI) and potentially severe DDI at discharge. Mortality rate and incidence of re‐hospitalizations were other secondary outcomes assessed at the 12‐month follow‐up. Results A total of 697 patients (347 in the intervention and 350 in the control arms) were enrolled. No difference in the prevalence of PIM at discharge was found between arms (OR 1.29 95%CI 0.87–1.91). We also found no decrease in the prevalence of DDI (OR 0.67 95%CI 0.34–1.28) and potentially severe DDI (OR 0.86 95%CI 0.63–1.15) at discharge, nor in mortality rates and incidence of re‐hospitalization at 12‐month follow‐up. Conclusions This e‐learning educational program had no clear effect on the quality of drug prescription and clinical outcomes in hospitalized elderly patients. Given the high prevalence of PIMs and potential DDIs recorded in the frame of this study, other approaches should be developed in order to improve the quality of drug prescription in this population. PMID:26922904

  13. 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.

  14. Application of a handheld NIR spectrometer in prediction of drug content in inkjet printed orodispersible formulations containing prednisolone and levothyroxine.

    PubMed

    Vakili, Hossein; Wickström, Henrika; Desai, Diti; Preis, Maren; Sandler, Niklas

    2017-05-30

    Quality control tools to assess the quality of printable orodispersible formulations are yet to be defined. Four different orodispersible dosage forms containing two poorly soluble drugs, levothyroxine and prednisolone, were produced on two different edible substrates by piezoelectric inkjet printing. Square shaped units of 4cm 2 were printed in different resolutions to achieve an escalating drug dose by highly accurate and uniform displacement of droplets in picoliter range from the printhead onto the substrates. In addition, the stability of drug inks in a course of 24h as well as the mechanical properties and disintegration behavior of the printed units were examined. A compact handheld near-infrared (NIR) spectral device in the range of 1550-1950nm was used for quantitative estimation of the drug amount in printed formulations. The spectral data was treated with mean centering, Savitzky-Golay filtering and a third derivative approach. Principal component analysis (PCA) and orthogonal partial least squares (OPLS) regression were applied to build predictive models for quality control of the printed dosage forms. The accurate tuning of the dose in each formulation was confirmed by UV spectrophotometry for prednisolone (0.43-1.95mg with R 2 =0.999) and high performance liquid chromatography for levothyroxine (0.15-0.86mg with R 2 =0.997). It was verified that the models were capable of clustering and predicting the drug dose in the formulations with both Q 2 and R 2 Y values between 0.94-0.99. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective.

    PubMed

    Feltelius, Nils; Gedeborg, Rolf; Holm, Lennart; Zethelius, Björn

    2017-06-01

    The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making. A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance. The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials. Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers.

  16. Utility of registries for post-marketing evaluation of medicines. A survey of Swedish health care quality registries from a regulatory perspective

    PubMed Central

    Feltelius, Nils; Gedeborg, Rolf; Holm, Lennart; Zethelius, Björn

    2017-01-01

    Aim The aim of this study was to describe content and procedures in some selected Swedish health care quality registries (QRs) of relevance to regulatory decision-making. Methods A workshop was organized with participation of seven Swedish QRs which subsequently answered a questionnaire regarding registry content on drug treatments and outcomes. Patient populations, coverage, data handling and quality control, as well as legal and ethical aspects are presented. Scientific publications from the QRs are used as a complementary measure of quality and scientific relevance. Results The registries under study collect clinical data of high relevance to regulatory and health technology agencies. Five out of seven registries provide information on the drug of interest. When applying external quality criteria, we found a high degree of fulfillment, although information on medication was not sufficient to answer all questions of regulatory interest. A notable strength is the option for linkage to the Prescribed Drug Registry and to information on education and socioeconomic status. Data on drugs used during hospitalization were also collected to some extent. Outcome measures collected resemble those used in relevant clinical trials. All registries collected patient-reported outcome measures. The number of publications from the registries was substantial, with studies of appropriate design, including randomized registry trials. Conclusions Quality registries may provide a valuable source of post-marketing data on drug effectiveness, safety, and cost-effectiveness. Closer collaboration between registries and regulators to improve quality and usefulness of registry data could benefit both regulatory utility and value for health care providers. PMID:28276780

  17. The usefulness of Quality of Life Childhood Epilepsy (QOLCE) questionnaire in evaluating the quality of life of children with epilepsy.

    PubMed

    Talarska, D

    2007-01-01

    Evaluation of quality of life has become a frequently used method in treatment effects supervision. Quality of Life Childhood Epilepsy (QOLCE) questionnaire, which is completed by patients' parents, has been prepared for children with epilepsy. It enables to determine the quality of life in children aged 4-18 years. The aim of the study was to show the usefulness of QOLCE questionnaire in evaluating the quality of life of children with epilepsy. 160 epileptic children, aged 8-18 years and their parents were examined in the Chair and Department of Developmental Neurology, K. Marcinkowski University of Medical Sciences in Poznań. QOLCE questionnaire was completed by parents and "Young people and epilepsy" questionnaire was designed for children. Reliability index of the complete questionnaire in own research and in the original amounted to 0.93 Cronbach alpha coefficient. Epileptic, drug-resistant children constituted 28% of the examined group. Parents of children with controlled seizures evaluated children's functioning in analyzed areas of quality of life higher. 1. QOLCE questionnaire is a suitable tool to evaluate the quality of children's and adolescents' life. 2. The most significant differences in functioning of epileptic, drug-resistant patients and those with controlled seizures were observed in areas of cognitive processes and social activity.

  18. 76 FR 37814 - Agency Information Collection Activities; Proposed Collection; Comment Request; New Animal Drugs...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-28

    ... laboratory studies with good laboratory practices, (4) name and address of each clinical investigator, (5... assumptions used; (3) ways to enhance the quality, utility, and clarity of the information to be collected... technology. New Animal Drugs for Investigational Uses--21 CFR Part 511 (OMB Control Number 0910-0117...

  19. A day in the life of a pharmacovigilance case processor.

    PubMed

    Bhangale, Ritesh; Vaity, Sayali; Kulkarni, Niranjan

    2017-01-01

    Pharmacovigilance (PV) has grown significantly in India in the last couple of decades. The etymological roots for the word "pharmacovigilance" are "Pharmakon" (Greek for drug) and "Vigilare" (Latin for to keep watch). It relies on information gathered from the collection of individual case safety reports and other pharmacoepidemiological data. The PV data processing cycle starts with data collection in computerized systems followed by complete data entry which includes adverse event coding, drug coding, causality and expectedness assessment, narrative writing, quality control, and report submissions followed by data storage and maintenance. A case processor plays an important role in conducting these various tasks. The case processor should also manage drug safety information, possess updated knowledge about global drug safety regulations, summarize clinical safety data, participate in meetings, write narratives with medical input from a physician, report serious adverse events to the regulatory authorities, participate in the training of operational staff on drug safety issues, quality control work of other staff in the department, and take on any other task as assigned by the manager or medical director within the capabilities of the drug safety associate. There can be challenges while handling all these tasks at a time, hence the associate will have to maintain a balance to overcome them and keep on updating their knowledge on drug safety regulations, which in turn, would help in increasing their learning curve.

  20. 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.

  1. [Feedforward control strategy and its application in quality improvement of ethanol precipitation process of danhong injection].

    PubMed

    Yan, Bin-Jun; Guo, Zheng-Tai; Qu, Hai-Bin; Zhao, Bu-Chang; Zhao, Tao

    2013-06-01

    In this work, a feedforward control strategy basing on the concept of quality by design was established for the manufacturing process of traditional Chinese medicine to reduce the impact of the quality variation of raw materials on drug. In the research, the ethanol precipitation process of Danhong injection was taken as an application case of the method established. Box-Behnken design of experiments was conducted. Mathematical models relating the attributes of the concentrate, the process parameters and the quality of the supernatants produced were established. Then an optimization model for calculating the best process parameters basing on the attributes of the concentrate was built. The quality of the supernatants produced by ethanol precipitation with optimized and non-optimized process parameters were compared. The results showed that using the feedforward control strategy for process parameters optimization can control the quality of the supernatants effectively. The feedforward control strategy proposed can enhance the batch-to-batch consistency of the supernatants produced by ethanol precipitation.

  2. PCMO L01-Setting Specifications for Biological Investigational Medicinal Products.

    PubMed

    Krause, Stephan O

    2015-01-01

    This paper provides overall guidance and best practices for the setting of specifications for clinical biological drug substances and drug products within the framework of ICH guidelines on pharmaceutical development [Q8(R2) and Q11], quality risk management (Q9), and quality systems (Q10). A review is provided of the current regulatory expectations for the specification setting process as part of a control strategy during product development, pointing to existing challenges for the investigational new drug/investigational medicinal product dossier (IND/IMPD) sponsor. A case study illustrates how the investigational medicinal product specification revision process can be managed within a flexible quality system, and how specifications can be set and justified for early and late development stages. This paper provides an overview for the setting of product specifications for investigational medicinal products used in clinical trials. A case study illustrates how product specifications of investigational medicinal products can be justified and managed within a modern product quality system. © PDA, Inc. 2015.

  3. 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.

  4. Growing Problem of Multidrug-Resistant Enteric Pathogens in Africa

    PubMed Central

    Aboderin, Oladiipo A.; Byarugaba, Denis K.; Ojo, Kayode K.; Opintan, Japheth A.

    2007-01-01

    Control of fecal–orally transmitted pathogens is inadequate in many developing countries, in particular, in sub-Saharan Africa. Acquired resistance to antimicrobial drugs is becoming more prevalent among Vibrio cholerae, Salmonella enteritidis, diarrheagenic Escherichia coli, and other pathogens in this region. The poor, who experience most of the infections caused by these organisms, bear the brunt of extended illness and exacerbated proportion of deaths brought about by resistance. Improved antimicrobial drug stewardship is an often cited, but inadequately implemented, intervention for resistance control. Resistance containment also requires improvements in infectious disease control, access to and quality assurance of antimicrobial agents, as well as diagnostic facilities. Structural improvements along these lines will also enhance disease prevention and control as well as rational antimicrobial drug use. Additionally, more research is needed to identify low-cost, high-impact interventions for resistance control. PMID:18217545

  5. Quality of antimalarial drugs and antibiotics in Papua New Guinea: a survey of the health facility supply chain.

    PubMed

    Hetzel, Manuel W; Page-Sharp, Madhu; Bala, Nancy; Pulford, Justin; Betuela, Inoni; Davis, Timothy M E; Lavu, Evelyn K

    2014-01-01

    Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG. Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC). Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3) contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4%) primaquine, 3/70 (4.3%) amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions. This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory mechanisms. Measures to stop the availability of poor-quality medicines should include limiting procurement to WHO prequalified products and implementing routine quality testing.

  6. Quality of Antimalarial Drugs and Antibiotics in Papua New Guinea: A Survey of the Health Facility Supply Chain

    PubMed Central

    Hetzel, Manuel W.; Page-Sharp, Madhu; Bala, Nancy; Pulford, Justin; Betuela, Inoni; Davis, Timothy M. E.; Lavu, Evelyn K.

    2014-01-01

    Background Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG. Methods and Findings Medicines were obtained from randomly sampled health facilities and selected warehouses and hospitals across PNG and analysed for API content using validated high performance liquid chromatography (HPLC). Of 360 tablet/capsule samples from 60 providers, 9.7% (95% CI 6.9, 13.3) contained less, and 0.6% more, API than pharmacopoeial reference ranges, including 29/37 (78.4%) primaquine, 3/70 (4.3%) amodiaquine, and one sample each of quinine, artemether, sulphadoxine-pyrimethamine and amoxicillin. According to the package label, 86.5% of poor-quality samples originated from India. Poor-quality medicines were found in 48.3% of providers at all levels of the supply chain. Drug quality was unrelated to storage conditions. Conclusions This study documents the presence of poor-quality medicines, particularly primaquine, throughout PNG. Primaquine is the only available transmission-blocking antimalarial, likely to become important to prevent the spread of artemisinin-resistant P. falciparum and eliminating P. vivax hypnozoites. The availability of poor-quality medicines reflects the lack of adequate quality control and regulatory mechanisms. Measures to stop the availability of poor-quality medicines should include limiting procurement to WHO prequalified products and implementing routine quality testing. PMID:24828338

  7. Safety, Tolerability and Efficacy of Drugs for Treating Behavioural Insomnia in Children with Attention-Deficit/Hyperactivity Disorder: A Systematic Review with Methodological Quality Assessment.

    PubMed

    Anand, Shweta; Tong, Henry; Besag, Frank M C; Chan, Esther W; Cortese, Samuele; Wong, Ian C K

    2017-06-01

    A large proportion of paediatric patients with attention-deficit/hyperactivity disorder (ADHD) have associated sleep problems which not only affect the child's wellbeing but also impact family functioning. Management of sleep problems is consequently an important aspect of overall ADHD management in paediatric patients. Although some drugs are being used off-label for the management of paediatric insomnia, there is scant clinical evidence supporting their use. Our aim was to identify and assess the quality of published studies reporting the safety, tolerability and efficacy of drugs used for treating behavioural insomnia in children with ADHD. After an initial screen to determine which drugs were most commonly used, we conducted a systematic review of English-language publications from searches of PubMed, EMBASE, PsycINFO and two trial register databases to February 2017, using keywords 'clonidine', 'melatonin', 'zolpidem', 'eszopiclone', 'L-theanine', 'guanfacine', 'ADHD', 'sleep disorder' and 'children'. For quality assessment of included studies, we used the CONSORT checklist for randomised control trials (RCTs) and the Downs and Black checklist for non-RCTs. Twelve studies were included. Two case series for clonidine, two RCTs and four observational studies for melatonin and one RCT each for zolpidem, eszopiclone, L-theanine and guanfacine. Of the 12 included studies, only one on eszopiclone scored excellent for quality. The quality of the rest of the studies varied from moderate to low. For clonidine, melatonin and L-theanine, improvements in sleep-onset latency and total sleep duration were reported; however, zolpidem, eszopiclone and guanfacine failed to show any improvement when compared with placebo. Clonidine, melatonin, L-theanine, eszopiclone and guanfacine were well tolerated with mild to moderate adverse events; zolpidem was associated with neuropsychiatric adverse effects. There is generally poor evidence for prescribing drugs for behavioural insomnia in children with ADHD. Further controlled studies are warranted.

  8. Zhen Gan Xi Feng Decoction, a Traditional Chinese Herbal Formula, for the Treatment of Essential Hypertension: A Systematic Review of Randomized Controlled Trials

    PubMed Central

    Xiong, Xingjiang; Yang, Xiaochen; Feng, Bo; Liu, Wei; Duan, Lian; Gao, Ao; Li, Haixia; Ma, Jizheng; Du, Xinliang; Li, Nan; Wang, Pengqian; Su, Kelei; Chu, Fuyong; Zhang, Guohao; Li, Xiaoke; Wang, Jie

    2013-01-01

    Objectives. To assess the clinical effectiveness and adverse effects of Zhen Gan Xi Feng Decoction (ZGXFD) for essential hypertension (EH). Methods. Five major electronic databases were searched up to August 2012 to retrieve any potential randomized controlled trials designed to evaluate the clinical effectiveness of ZGXFD for EH reported in any language, with main outcome measure as blood pressure (BP). Results. Six randomized trials were included. Methodological quality of the trials was evaluated as generally low. Four trials compared prescriptions based on ZGXFD with antihypertensive drugs. Meta-analysis showed that ZGXFD was more effective in BP control and TCM syndrome and symptom differentiation (TCM-SSD) scores than antihypertensive drugs. Two trials compared the combination of modified ZGXFD plus antihypertensive drugs with antihypertensive drugs. Meta-analysis showed that there is significant beneficial effect on TCM-SSD scores. However, no significant effect on BP was found. The safety of ZGXFD is still uncertain. Conclusions. ZGXFD appears to be effective in improving blood pressure and hypertension-related symptoms for EH. However, the evidence remains weak due to poor methodological quality of the included studies. More rigorous trials are warranted to support their clinical use. PMID:23573163

  9. The use of crack and other illicit drugs impacts oral health-related quality of life in Brazilians.

    PubMed

    Antoniazzi, R P; Zanatta, F B; Ardenghi, T M; Feldens, C A

    2018-04-01

    The aim of this study was to investigate the impact of the use of crack and other illicit drugs on oral health-related quality of life (OHRQoL) in young adults. This cross-sectional study evaluated 106 crack users at a public treatment center for drug addiction and 106 controls matched for gender, age, and use of tobacco. Clinical examinations were performed for dental caries and periodontal disease. The outcome was OHRQoL, which was determined using the Oral Health Impact Profile (OHIP-14). The association between OHRQoL and illicit drugs was modeled using conditional Poisson regression. Users of crack and other illicit drugs had a poorer OHRQoL than the controls (p < .001). Among the crack users, the odds ratio to yield high OHIP-14 was 3.40 (95% confidence interval, 1.91-6.08). Adjustment for sex, age, schooling, income, smoking, dental caries, and periodontal disease did not change such an estimate considerably. The functional limitation and psychological discomfort domains were associated with the use of illicit drugs. Users of crack and other illicit drugs exerted a negative impact on OHRQoL independently of socio-demographic characteristics and tobacco use, suggesting the need for special attention regarding the specific oral health needs of this population as well as drug prevention and treatment strategies. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  10. Effectiveness, safety and cost of drug substitution in hypertension

    PubMed Central

    Johnston, Atholl; Stafylas, Panagiotis; Stergiou, George S

    2010-01-01

    Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost-effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse-event profiles of available alternative drugs, differences in the ‘inactive’ components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended. PMID:20716230

  11. Effectiveness, safety and cost of drug substitution in hypertension.

    PubMed

    Johnston, Atholl; Stafylas, Panagiotis; Stergiou, George S

    2010-09-01

    Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost-effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse-event profiles of available alternative drugs, differences in the 'inactive' components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended.

  12. Real-time product attribute control to manufacture antibodies with defined N-linked glycan levels.

    PubMed

    Zupke, Craig; Brady, Lowell J; Slade, Peter G; Clark, Philip; Caspary, R Guy; Livingston, Brittney; Taylor, Lisa; Bigham, Kyle; Morris, Arvia E; Bailey, Robert W

    2015-01-01

    Pressures for cost-effective new therapies and an increased emphasis on emerging markets require technological advancements and a flexible future manufacturing network for the production of biologic medicines. The safety and efficacy of a product is crucial, and consistent product quality is an essential feature of any therapeutic manufacturing process. The active control of product quality in a typical biologic process is challenging because of measurement lags and nonlinearities present in the system. The current study uses nonlinear model predictive control to maintain a critical product quality attribute at a predetermined value during pilot scale manufacturing operations. This approach to product quality control ensures a more consistent product for patients, enables greater manufacturing efficiency, and eliminates the need for extensive process characterization by providing direct measures of critical product quality attributes for real time release of drug product. © 2015 American Institute of Chemical Engineers.

  13. Scientific and Regulatory Considerations in Solid Oral Modified Release Drug Product Development.

    PubMed

    Li, Min; Sander, Sanna; Duan, John; Rosencrance, Susan; Miksinski, Sarah Pope; Yu, Lawrence; Seo, Paul; Rege, Bhagwant

    2016-11-01

    This review presents scientific and regulatory considerations for the development of solid oral modified release (MR) drug products. It includes a rationale for patient-focused development based on Quality-by-Design (QbD) principles. Product and process understanding of MR products includes identification and risk-based evaluation of critical material attributes (CMAs), critical process parameters (CPPs), and their impact on critical quality attributes (CQAs) that affect the clinical performance. The use of various biopharmaceutics tools that link the CQAs to a predictable and reproducible clinical performance for patient benefit is emphasized. Product and process understanding lead to a more comprehensive control strategy that can maintain product quality through the shelf life and the lifecycle of the drug product. The overall goal is to develop MR products that consistently meet the clinical objectives while mitigating the risks to patients by reducing the probability and increasing the detectability of CQA failures.

  14. Recent Advancement and Technological Aspects of Pulsatile Drug Delivery System - A Laconic Review.

    PubMed

    Pandit, Vinay; Kumar, Ajay; Ashawat, Mahendra S; Verma, Chander P; Kumar, Pravin

    2017-01-01

    Pulsatile drug delivery system (PDDS) shows potential significance in the field of drug delivery to release the maximum amount of drug at a definite site and at specific time. PDDS are mainly time controlled delivery devices having a definite pause period for drug release, which is not affected by acidity, alkalinity, motility and enzymes present in the gastrointestinal tract. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. The review article, discuss the general concepts, marketed formulations and patents or any other recent advancement in pulsatile release technology. It also highlights on diseases requiring therapy by pulsatile release, various researches on herbal pulsatile formulations and quality control aspects of PDDS. Pulsatile medication possess the potential to deliver the drugs in the therapy of diseases where drug dose is essential during sleep, drugs having greater first pass metabolism and absorption at precise location in digestive tract. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Comparative study of quality and efficacy of originator's and generic ABZ for the mass treatment of soil-transmitted nematode infections in Nepal

    PubMed Central

    Albonico, Marco; Mathema P., Pragya; Montresor, Antonio; Khakurel, Balkrishna; Reggi, Valerio; Pandey, Sharada; Savioli, Lorenzo

    2017-01-01

    Quality and efficacy of two locally-manufactured generic albendazole (ABZ) products (Curex and Royal Drug) used for de-worming children in Nepal since 1999 were tested against the originator product (GSK). The study conducted disintegration and dissolution testing and a randomised controlled clinical trial comparing cure rates (CR) and egg reduction rates (ERR) for Ascaris lumbricoides, Trichuris trichiura and hookworm infections. Stool samples from 1277 children were examined before and 21 days after treatment. For A. lumbricoides GSK's (97.0%) and Royal Drug's (95.0 %) product provided significantly higher CR than Curex's (82.6%); however, all products provided ERR higher than 90%. For T. trichiura Curex's product showed significantly lower ERR (63.2%). For hookworm, GSK's product performed significantly better (CR 74.3%, ERR 87.1%) than Royal Drug's (CR 53.3%, ERR 80.8%) and Curex's (CR 50.7%, ERR 73.1%). Only GSK's product passed both disintegration and dissolution. Both generic products failed dissolution. Curex's product showed poor disintegration. Despite its lower efficacy the cheaper Curex's product achieved good results in controlling morbidity due to soil-transmitted helminth (STH) infections. This study shows that cost-effectiveness of drugs used in mass de-worming campaigns should not be inferred on the basis of one single quality testing parameter. PMID:17129592

  16. 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.

  17. 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.

  18. [Quality process control system of Chinese medicine preparation based on "holistic view"].

    PubMed

    Wang, Ya-Qi; Jiao, Jiao-Jiao; Wu, Zhen-Feng; Zheng, Qin; Yang, Ming

    2018-01-01

    "High quality, safety and effectiveness" are the primary principles for the pharmaceutical research and development process in China. The quality of products relies not only on the inspection method, but also on the design and development, process control and standardized management. The quality depends on the process control level. In this paper, the history and current development of quality control of traditional Chinese medicine (TCM) preparations are reviewed systematically. Based on the development model of international drug quality control and the misunderstanding of quality control of TCM preparations, the reasons for impacting the homogeneity of TCM preparations are analyzed and summarized. According to TCM characteristics, efforts were made to control the diversity of TCM, make "unstable" TCM into "stable" Chinese patent medicines, put forward the concepts of "holistic view" and "QbD (quality by design)", so as to create the "holistic, modular, data, standardized" model as the core of TCM preparation quality process control model. Scientific studies shall conform to the actual production of TCM preparations, and be conducive to supporting advanced equipment and technology upgrade, thoroughly applying the scientific research achievements in Chinese patent medicines, and promoting the cluster application and transformation application of TCM pharmaceutical technology, so as to improve the quality and effectiveness of the TCM industry and realize the green development. Copyright© by the Chinese Pharmaceutical Association.

  19. In vivo drug metabolite identification in preclinical ADME studies by means of UPLC/TWIMS/high resolution-QTOF MS(E) and control comparison: cost and benefit of vehicle-dosed control samples.

    PubMed

    Fiebig, Lukas; Laux, Ralf; Binder, Rudolf; Ebner, Thomas

    2016-10-01

    1. Liquid chromatography (LC)-high resolution mass spectrometry (HRMS) techniques proved to be well suited for the identification of predicted and unexpected drug metabolites in complex biological matrices. 2. To efficiently discriminate between drug-related and endogenous matrix compounds, however, sophisticated postacquisition data mining tools, such as control comparison techniques are needed. For preclinical absorption, distribution, metabolism and excretion (ADME) studies that usually lack a placebo-dosed control group, the question arises how high-quality control data can be yielded using only a minimum number of control animals. 3. In the present study, the combination of LC-traveling wave ion mobility separation (TWIMS)-HRMS(E) and multivariate data analysis was used to study the polymer patterns of the frequently used formulation constituents polyethylene glycol 400 and polysorbate 80 in rat plasma and urine after oral and intravenous administration, respectively. 4. Complex peak patterns of both constituents were identified underlining the general importance of a vehicle-dosed control group in ADME studies for control comparison. Furthermore, the detailed analysis of administration route, blood sampling time and gender influences on both vehicle peak pattern as well as endogenous matrix background revealed that high-quality control data is obtained when (i) control animals receive an intravenous dose of the vehicle, (ii) the blood sampling time point is the same for analyte and control sample and (iii) analyte and control samples of the same gender are compared.

  20. 42 CFR 423.156 - Consumer satisfaction surveys.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality... as of July of the prior year must contract with approved Medicare Consumer Assessment of Healthcare...

  1. The Prevalence and Determinants of Controlled Substance Discrepancies in a Level I Trauma Hospital

    PubMed Central

    Anyanwu, Chukwuma; Egwim, Oliver

    2016-01-01

    Background Healthcare institutions are often faced with challenges and accreditation requirements for improving treatment quality, reducing waste, and avoiding diversion of drugs, particularly controlled substances. Many automated systems have replaced manual systems but may be fraught with challenges, especially when multiple users are involved. Objective To describe the characteristics of controlled substance discrepancies observed in a Level I trauma hospital for Medicare. Methods Discrepancy data were captured for each user involved in a transaction for a controlled substance at the Level I trauma hospital (in Ben Taub Hospital, Houston, TX), and the information was stored in a computerized database repository. Data for the 1-year study period (from January 1 through December 31, 2013) were collected for Medicare beneficiaries, using an Excel 2013 spreadsheet, and were analyzed according to basic discrepancy characteristics and descriptive statistics. Results During the 12-month study period, 114,000 controlled substance discrepancies were found for 100,000 Medicare patients at this Level I trauma hospital. Vending activities accounted for the majority (52.6%) of these discrepancies. Discrepancies were most likely to occur on Wednesdays, and the medications involved most frequently were combination drugs of hydrocodone and acetaminophen. Conclusion Approximately 1 (1.14) discrepancy involving a controlled substance occurred for each Medicare patient treated at the study facility. Healthcare institutions need to improve their efforts to ensure high-quality care and prevent diversion of drugs. PMID:27606038

  2. Ion mobility spectrometry for the rapid analysis of over-the-counter drugs and beverages

    PubMed Central

    Fernández-Maestre, Roberto

    2009-01-01

    In the pharmaceutical industry, there are increasing requirements for analytical methods in quality assessment for the production of drugs. In this investigation, ion mobility spectrometry (IMS) was used for the rapid qualitative separation and identification of active ingredients in generic over-the-counter drugs and food additives in beverages. The active ingredients determined in drugs were acetaminophen, aspartame, bisacodyl, caffeine, dextromethorphan, diphenhydramine, famotidine, glucosamine, guaifenesin, loratadine, niacin, phenylephrine, pyridoxine, thiamin, and tetrahydrozoline. Aspartame and caffeine were determined in beverages. Fourteen over-the-counter drugs and beverages were analyzed. Analysis times below 10 s were obtained for IMS, and reduced mobilities were reported for the first time for 12 compounds. A quadrupole mass spectrometer coupled to a mobility spectrometer was used to assure a correct peak assignation. The combination of fast analysis, low cost, and inexpensive maintenance of IMS instruments makes IMS an attractive technique for the qualitative determination of the active ingredients in over-the-counter drugs and food additives in manufacture quality control and cleaning verification for the drug and food industries. PMID:20835390

  3. Development, validation and comparison of NIR and Raman methods for the identification and assay of poor-quality oral quinine drops.

    PubMed

    Mbinze, J K; Sacré, P-Y; Yemoa, A; Mavar Tayey Mbay, J; Habyalimana, V; Kalenda, N; Hubert, Ph; Marini, R D; Ziemons, E

    2015-01-01

    Poor quality antimalarial drugs are one of the public's major health problems in Africa. The depth of this problem may be explained in part by the lack of effective enforcement and the lack of efficient local drug analysis laboratories. To tackle part of this issue, two spectroscopic methods with the ability to detect and to quantify quinine dihydrochloride in children's oral drops formulations were developed and validated. Raman and near infrared (NIR) spectroscopy were selected for the drug analysis due to their low cost, non-destructive and rapid characteristics. Both of the methods developed were successfully validated using the total error approach in the range of 50-150% of the target concentration (20%W/V) within the 10% acceptance limits. Samples collected on the Congolese pharmaceutical market were analyzed by both techniques to detect potentially substandard drugs. After a comparison of the analytical performance of both methods, it has been decided to implement the method based on NIR spectroscopy to perform the routine analysis of quinine oral drop samples in the Quality Control Laboratory of Drugs at the University of Kinshasa (DRC). Copyright © 2015 Elsevier B.V. All rights reserved.

  4. [A strategy of constructing the technological system for quality control of Chinese medicine based on process control and management].

    PubMed

    Cheng, Yi-Yu; Qian, Zhong-Zhi; Zhang, Bo-Li

    2017-01-01

    The current situation, bottleneck problems and severe challenges in quality control technology of Chinese Medicine (CM) are briefly described. It is presented to change the phenomenon related to the post-test as the main means and contempt for process control in drug regulation, reverse the situation of neglecting the development of process control and management technology for pharmaceutical manufacture and reconstruct the technological system for quality control of CM products. The regulation and technology system based on process control and management for controlling CM quality should be established to solve weighty realistic problems of CM industry from the root causes, including backwardness of quality control technology, weakness of quality risk control measures, poor reputation of product quality and so on. By this way, the obstacles from poor controllability of CM product quality could be broken. Concentrating on those difficult problems and weak links in the technical field of CM quality control, it is proposed to build CMC (Chemistry, Manufacturing and Controls) regulation for CM products with Chinese characteristics and promote the regulation international recognition as soon as possible. The CMC technical framework, which is clinical efficacy-oriented, manufacturing manner-centered and process control-focused, was designed. To address the clinical characteristics of traditional Chinese medicine (TCM) and the production feature of CM manufacture, it is suggested to establish quality control engineering for CM manufacturing by integrating pharmaceutical analysis, TCM chemistry, TCM pharmacology, pharmaceutical engineering, control engineering, management engineering and other disciplines. Further, a theoretical model of quality control engineering for CM manufacturing and the methodology of digital pharmaceutical engineering are proposed. A technology pathway for promoting CM standard and realizing the strategic goal of CM internationalization is elaborated. Copyright© by the Chinese Pharmaceutical Association.

  5. Identification of quality markers of Yuanhu Zhitong tablets based on integrative pharmacology and data mining.

    PubMed

    Li, Ke; Li, Junfang; Su, Jin; Xiao, Xuefeng; Peng, Xiujuan; Liu, Feng; Li, Defeng; Zhang, Yi; Chong, Tao; Xu, Haiyu; Liu, Changxiao; Yang, Hongjun

    2018-03-07

    The quality evaluation of traditional Chinese medicine (TCM) formulations is needed to guarantee the safety and efficacy. In our laboratory, we established interaction rules between chemical quality control and biological activity evaluations to study Yuanhu Zhitong tablets (YZTs). Moreover, a quality marker (Q-marker) has recently been proposed as a new concept in the quality control of TCM. However, no appropriate methods are available for the identification of Q-markers from the complex TCM systems. We aimed to use an integrative pharmacological (IP) approach to further identify Q-markers from YZTs through the integration of multidisciplinary knowledge. In addition, data mining was used to determine the correlation between multiple constituents of this TCM and its bioactivity to improve quality control. The IP approach was used to identify the active constituents of YZTs and elucidate the molecular mechanisms by integrating chemical and biosynthetic analyses, drug metabolism, and network pharmacology. Data mining methods including grey relational analysis (GRA) and least squares support vector machine (LS-SVM) regression techniques, were used to establish the correlations among the constituents and efficacy, and dose efficacy in multiple dimensions. Seven constituents (tetrahydropalmatine, α-allocryptopine, protopine, corydaline, imperatorin, isoimperatorin, and byakangelicin) were identified as Q-markers of YZT using IP based on their high abundance, specific presence in the individual herbal constituents and the product, appropriate drug-like properties, and critical contribution to the bioactivity of the mixture of YZT constituents. Moreover, three Q-markers (protopine, α-allocryptopine, and corydaline) were highly correlated with the multiple bioactivities of the YZTs, as found using data mining. Finally, three constituents (tetrahydropalmatine, corydaline, and imperatorin) were chosen as minimum combinations that both distinguished the authentic components from false products and indicated the intensity of bioactivity to improve the quality control of YZTs. Tetrahydropalmatine, imperatorin, and corydaline could be used as minimum combinations to effectively control the quality of YZTs. Copyright © 2018. Published by Elsevier GmbH.

  6. 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.

  7. Pharmaceutical product development: A quality by design approach

    PubMed Central

    Pramod, Kannissery; Tahir, M. Abu; Charoo, Naseem A.; Ansari, Shahid H.; Ali, Javed

    2016-01-01

    The application of quality by design (QbD) in pharmaceutical product development is now a thrust area for the regulatory authorities and the pharmaceutical industry. International Conference on Harmonization and United States Food and Drug Administration (USFDA) emphasized the principles and applications of QbD in pharmaceutical development in their guidance for the industry. QbD attributes are addressed in question-based review, developed by USFDA for chemistry, manufacturing, and controls section of abbreviated new drug applications. QbD principles, when implemented, lead to a successful product development, subsequent prompt regulatory approval, reduce exhaustive validation burden, and significantly reduce post-approval changes. The key elements of QbD viz., target product quality profile, critical quality attributes, risk assessments, design space, control strategy, product lifecycle management, and continual improvement are discussed to understand the performance of dosage forms within design space. Design of experiments, risk assessment tools, and process analytical technology are also discussed for their role in QbD. This review underlines the importance of QbD in inculcating science-based approach in pharmaceutical product development. PMID:27606256

  8. Pharmaceutical product development: A quality by design approach.

    PubMed

    Pramod, Kannissery; Tahir, M Abu; Charoo, Naseem A; Ansari, Shahid H; Ali, Javed

    2016-01-01

    The application of quality by design (QbD) in pharmaceutical product development is now a thrust area for the regulatory authorities and the pharmaceutical industry. International Conference on Harmonization and United States Food and Drug Administration (USFDA) emphasized the principles and applications of QbD in pharmaceutical development in their guidance for the industry. QbD attributes are addressed in question-based review, developed by USFDA for chemistry, manufacturing, and controls section of abbreviated new drug applications. QbD principles, when implemented, lead to a successful product development, subsequent prompt regulatory approval, reduce exhaustive validation burden, and significantly reduce post-approval changes. The key elements of QbD viz., target product quality profile, critical quality attributes, risk assessments, design space, control strategy, product lifecycle management, and continual improvement are discussed to understand the performance of dosage forms within design space. Design of experiments, risk assessment tools, and process analytical technology are also discussed for their role in QbD. This review underlines the importance of QbD in inculcating science-based approach in pharmaceutical product development.

  9. Review of nuclear pharmacy practice in hospitals

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

    Kawada, T.K.; Tubis, M.; Ebenkamp, T.

    1982-02-01

    An operational profile for nuclear pharmacy practice is presented, and the technical and professional role of nuclear pharmacists is reviewed. Key aspects of nuclear pharmacy practice in hospitals discussed are the basic facilities and equipment for the preparation, quality control, and distribution of radioactive drug products. Standards for receiving, storing, and processing radioactive material are described. The elements of a radiopharmaceutical quality assurance program, including the working procedures, documentation systems, data analysis, and specific control tests, are presented. Details of dose preparation and administration and systems of inventory control for radioactive products are outlined.

  10. Occurrence of Multiple Sclerosis After Drug Exposure: Insights From Evidence Mapping.

    PubMed

    Antonazzo, Ippazio Cosimo; Raschi, Emanuel; Vignatelli, Luca; Baldin, Elisa; Riise, Trond; D'Alessandro, Roberto; De Ponti, Fabrizio; Poluzzi, Elisabetta

    2017-09-01

    The role of drugs in the occurrence of multiple sclerosis (MS) is perceived to be insufficiently investigated. The aim of this study was to map and assess the evidence on MS occurrence after drug exposure, in order to identify possible signals of causal association. A search strategy was performed in MEDLINE and Embase as of July 2016; references consistent with the aim of the study were analysed to extract relevant measures of causal association between drugs and MS. The Newcastle-Ottawa Scale and appropriate guidelines from the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) were used to assess the quality of included studies. After screening 832 articles, 58 were selected (of which 14 were found by checking the reference lists of reviews): 30 case reports and case series, 24 longitudinal studies and four randomized controlled trials. Seven longitudinal studies had good (at least 7 out of 9) quality scores, whereas case reports/case series presented several limitations. Half of included articles focused on immunomodulatory drugs (etanercept, infliximab and adalimumab), especially in case reports/series, suggesting an association with MS occurrence. Contraceptives and antibacterials were investigated in some population-based studies, without definite results. A heterogeneous pharmacological profile of identified classes emerged. Low strength of evidence and conflicting results highlighted the difficulties in addressing the possible contribution of drugs in MS occurrence. Methodological advances are needed, especially to control the confounding role of underlying disease for specific drug classes.

  11. Weighing the evidence: trends in managed care formulary decision making.

    PubMed

    de Lissovoy, Gregory

    2003-01-01

    Health plans, pharmacy benefit managers, and other organizations use drug formularies to promote quality care while controlling costs. However, restrictive formularies are often viewed as constraints on physician practice and potential barriers to optimal patient care. Reluctance to add new drugs to an established formulary is rational economic behavior. Innovative compounds may have unknown properties with uncertain outcomes and therefore may impose costs in the form of risk. Products that seemingly duplicate drugs already on formulary may increase transaction costs without additional benefit. In evaluating new products, formulary managers face the task of identifying, assembling, and synthesizing a wide range of complex information. Manufacturers, who may be in the best position to supply that information, have been severely restricted by U.S. Food and Drug Administration (FDA) regulations that limited marketing communications to findings from well-controlled clinical trials. The FDA Modernization Act of 1997 eased these restrictions somewhat by acknowledging that sophisticated purchasers such as organized health plans were capable of weighing the quality and impartiality of manufacturer-supplied evidence. The Academy of Managed Care Pharmacy (AMCP) created a standardized template that formularies can use to request comprehensive information about specific drugs from manufacturers. Widespread adoption of the AMCP format by health plans and manufacturers will greatly increase access to information about new drugs, speeding the process of formulary committee deliberation, and instilling greater confidence in the outcome of those decisions. Wider access to new drugs may result.

  12. GC-C-IRMS in routine doping control practice: 3 years of drug testing data, quality control and evolution of the method.

    PubMed

    Polet, Michael; Van Eenoo, Peter

    2015-06-01

    In order to detect the misuse of endogenous anabolic steroids, doping control laboratories require methods that allow differentiation between endogenous steroids and their synthetic copies. Gas chromatography combustion isotope ratio mass spectrometry (GC-C-IRMS) is capable of measuring the carbon isotope ratio of urinary steroids and this allows differentiation between both. GC-C-IRMS and its application to doping control has evolved a lot during the last decade and so have the World Anti-Doping Agency (WADA) technical documents that describe how GC-C-IRMS should be applied. Especially the WADA technical document of 2014 introduced a number of obligatory quality controls and a fixed methodology that should be used by all the doping control laboratories. This document imposed more uniform methods between the laboratories in order to decrease the interlaboratory standard deviation and acquire similar results for the analysis of the same urine samples. In this paper, 3 years of drug testing data of our GC-C-IRMS method in routine doping control practice is described, with an emphasis on the new WADA technical document and its implementation. Useful data for other doping control laboratories is presented focussing on general method setup, quality control and data collected from routine samples. The paper concentrates on how IRMS results shift or remain similar by switching to the 2014 WADA technical document and gives insight in a straightforward approach to calculate the measurement uncertainty.

  13. Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials.

    PubMed

    Walter, Martin A; Briel, Matthias; Christ-Crain, Mirjam; Bonnema, Steen J; Connell, John; Cooper, David S; Bucher, Heiner C; Müller-Brand, Jan; Müller, Beat

    2007-03-10

    To determine the effect of adjunctive antithyroid drugs on the risk of treatment failure, hypothyroidism, and adverse events after radioiodine treatment. Meta-analysis. Electronic databases (Cochrane central register of controlled trials, Medline, Embase) searched to August 2006 and contact with experts. Review methods Three reviewers independently assessed trial eligibility and quality. Pooled relative risks for treatment failure and hypothyroidism after radioiodine treatment with and without adjunctive antithyroid drugs were calculated with a random effects model. We identified 14 relevant randomised controlled trials with a total of 1306 participants. Adjunctive antithyroid medication was associated with an increased risk of treatment failure (relative risk 1.28, 95% confidence interval 1.07 to 1.52; P=0.006) and a reduced risk for hypothyroidism (0.68, 0.53 to 0.87; P=0.006) after radioiodine treatment. We found no difference in summary estimates for the different antithyroid drugs or for whether antithyroid drugs were given before or after radioiodine treatment. Antithyroid drugs potentially increase rates of failure and reduce rates of hypothyroidism if they are given in the week before or after radioiodine treatment, respectively.

  14. Importance of rate control or rate regulation for improving exercise capacity and quality of life in patients with permanent atrial fibrillation and normal left ventricular function: a randomised controlled study

    PubMed Central

    Levy, T; Walker, S; Mason, M; Spurrell, P; Rex, S; Brant, S; Paul, V

    2001-01-01

    OBJECTIVE—To determine the importance of rhythm regulation or rate control in patients with permanent atrial fibrillation (AF) and normal left ventricular function.
PATIENTS AND INTERVENTIONS—Thirty six patients with a mixed fast and slow ventricular response rate to their AF were randomised to either His bundle ablation (HBA) and VVIR pacemaker (HBA group) or VVI pacemaker and atrioventricular modifying drugs (Med group). Outcomes assessed at one, three, six, and 12 months included exercise duration and quality of life.
RESULTS—Exercise duration significantly improved from baseline in both groups. There was no difference in outcome between the groups (Med +40% v HBA +20%, p = NS). The heart rate profile on exercise was similarly slowed in both groups compared to baseline. Quality of life significantly improved in both treatment arms for the modified Karolinska questionnaire (KQ) (Med +50% v HBA +50%, p = NS) and the Nottingham health profile (NHP) (Med +40% v HBA +20%, p = NS). However, for the individual symptom scores of each questionnaire more were improved in the Med group (KQ-Med 6 improved v HBA 4, NHP-Med 3 v HBA 1). Left ventricular function was equally preserved by both treatments during follow up.
CONCLUSION—In these patients control of ventricular response rate with either HBA + VVIR pacemaker or atrioventricular modifying drugs + VVI pacemaker will lead to a significant improvement in exercise duration and quality of life. Rhythm regulation by HBA did not confer additional benefit, suggesting rate control alone is necessary for the successful symptomatic treatment of these patients in permanent AF.


Keywords: ablation; atrial fibrillation; pacemaker; atrioventricular modifying drugs PMID:11156667

  15. First-line drugs for hypertension.

    PubMed

    Wright, James M; Musini, Vijaya M; Gill, Rupam

    2018-04-18

    This is the first update of a review published in 2009. Sustained moderate to severe elevations in resting blood pressure leads to a critically important clinical question: What class of drug to use first-line? This review attempted to answer that question. To quantify the mortality and morbidity effects from different first-line antihypertensive drug classes: thiazides (low-dose and high-dose), beta-blockers, calcium channel blockers, ACE inhibitors, angiotensin II receptor blockers (ARB), and alpha-blockers, compared to placebo or no treatment.Secondary objectives: when different antihypertensive drug classes are used as the first-line drug, to quantify the blood pressure lowering effect and the rate of withdrawal due to adverse drug effects, compared to placebo or no treatment. The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to November 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work. Randomized trials (RCT) of at least one year duration, comparing one of six major drug classes with a placebo or no treatment, in adult patients with blood pressure over 140/90 mmHg at baseline. The majority (over 70%) of the patients in the treatment group were taking the drug class of interest after one year. We included trials with both hypertensive and normotensive patients in this review if the majority (over 70%) of patients had elevated blood pressure, or the trial separately reported outcome data on patients with elevated blood pressure. The outcomes assessed were mortality, stroke, coronary heart disease (CHD), total cardiovascular events (CVS), decrease in systolic and diastolic blood pressure, and withdrawals due to adverse drug effects. We used a fixed-effect model to to combine dichotomous outcomes across trials and calculate risk ratio (RR) with 95% confidence interval (CI). We presented blood pressure data as mean difference (MD) with 99% CI. The 2017 updated search failed to identify any new trials. The original review identified 24 trials with 28 active treatment arms, including 58,040 patients. We found no RCTs for ARBs or alpha-blockers. These results are mostly applicable to adult patients with moderate to severe primary hypertension. The mean age of participants was 56 years, and mean duration of follow-up was three to five years.High-quality evidence showed that first-line low-dose thiazides reduced mortality (11.0% with control versus 9.8% with treatment; RR 0.89, 95% CI 0.82 to 0.97); total CVS (12.9% with control versus 9.0% with treatment; RR 0.70, 95% CI 0.64 to 0.76), stroke (6.2% with control versus 4.2% with treatment; RR 0.68, 95% CI 0.60 to 0.77), and coronary heart disease (3.9% with control versus 2.8% with treatment; RR 0.72, 95% CI 0.61 to 0.84).Low- to moderate-quality evidence showed that first-line high-dose thiazides reduced stroke (1.9% with control versus 0.9% with treatment; RR 0.47, 95% CI 0.37 to 0.61) and total CVS (5.1% with control versus 3.7% with treatment; RR 0.72, 95% CI 0.63 to 0.82), but did not reduce mortality (3.1% with control versus 2.8% with treatment; RR 0.90, 95% CI 0.76 to 1.05), or coronary heart disease (2.7% with control versus 2.7% with treatment; RR 1.01, 95% CI 0.85 to 1.20).Low- to moderate-quality evidence showed that first-line beta-blockers did not reduce mortality (6.2% with control versus 6.0% with treatment; RR 0.96, 95% CI 0.86 to 1.07) or coronary heart disease (4.4% with control versus 3.9% with treatment; RR 0.90, 95% CI 0.78 to 1.03), but reduced stroke (3.4% with control versus 2.8% with treatment; RR 0.83, 95% CI 0.72 to 0.97) and total CVS (7.6% with control versus 6.8% with treatment; RR 0.89, 95% CI 0.81 to 0.98).Low- to moderate-quality evidence showed that first-line ACE inhibitors reduced mortality (13.6% with control versus 11.3% with treatment; RR 0.83, 95% CI 0.72 to 0.95), stroke (6.0% with control versus 3.9% with treatment; RR 0.65, 95% CI 0.52 to 0.82), coronary heart disease (13.5% with control versus 11.0% with treatment; RR 0.81, 95% CI 0.70 to 0.94), and total CVS (20.1% with control versus 15.3% with treatment; RR 0.76, 95% CI 0.67 to 0.85).Low-quality evidence showed that first-line calcium channel blockers reduced stroke (3.4% with control versus 1.9% with treatment; RR 0.58, 95% CI 0.41 to 0.84) and total CVS (8.0% with control versus 5.7% with treatment; RR 0.71, 95% CI 0.57 to 0.87), but not coronary heart disease (3.1% with control versus 2.4% with treatment; RR 0.77, 95% CI 0.55 to 1.09), or mortality (6.0% with control versus 5.1% with treatment; RR 0.86, 95% CI 0.68 to 1.09).There was low-quality evidence that withdrawals due to adverse effects were increased with first-line low-dose thiazides (5.0% with control versus 11.3% with treatment; RR 2.38, 95% CI 2.06 to 2.75), high-dose thiazides (2.2% with control versus 9.8% with treatment; RR 4.48, 95% CI 3.83 to 5.24), and beta-blockers (3.1% with control versus 14.4% with treatment; RR 4.59, 95% CI 4.11 to 5.13). No data for these outcomes were available for first-line ACE inhibitors or calcium channel blockers. The blood pressure data were not used to assess the effect of the different classes of drugs as the data were heterogeneous, and the number of drugs used in the trials differed. First-line low-dose thiazides reduced all morbidity and mortality outcomes in adult patients with moderate to severe primary hypertension. First-line ACE inhibitors and calcium channel blockers may be similarly effective, but the evidence was of lower quality. First-line high-dose thiazides and first-line beta-blockers were inferior to first-line low-dose thiazides.

  16. Hard gains through soft contracts: productive engagement of private providers in tuberculosis control.

    PubMed Central

    Lönnroth, Knut; Uplekar, Mukund; Blanc, Léopold

    2006-01-01

    Over the past decade, there has been a rapid increase in the number of initiatives involving "for-profit" private health care providers in national tuberculosis (TB) control efforts. We reviewed 15 such initiatives with respect to contractual arrangements, quality of care and success achieved in TB control. In seven initiatives, the National TB Programme (NTP) interacted directly with for-profit providers; while in the remaining eight, the NTP collaborated with for-profit providers through intermediary not-for-profit nongovernmental organizations. All but one of the initiatives used relational "drugs-for-performance contracts" to engage for-profit providers, i.e. drugs were provided free of charge by the NTP emphasizing that providers dispense them free of charge to patients and follow national guidelines for diagnosis and treatment. We found that 90% (range 61-96%) of new smear-positive pulmonary TB cases were successfully treated across all initiatives and TB case detection rates increased between 10% and 36%. We conclude that for-profit providers can be effectively involved in TB control through informal, but well defined drugs-for-performance contracts. The contracting party should be able to reach a common understanding concerning goals and role division with for-profit providers and monitor them for content and quality. Relational drugs-for-performance contracts minimize the need for handling the legal and financial aspects of classical contracting. We opine that further analysis is required to assess if such "soft" contracts are sufficient to scale up private for-profit provider involvement in TB control and other priority health interventions. PMID:17143461

  17. Quality assurance of chemical ingredient classification for the National Drug File - Reference Terminology.

    PubMed

    Zheng, Ling; Yumak, Hasan; Chen, Ling; Ochs, Christopher; Geller, James; Kapusnik-Uner, Joan; Perl, Yehoshua

    2017-09-01

    The National Drug File - Reference Terminology (NDF-RT) is a large and complex drug terminology consisting of several classification hierarchies on top of an extensive collection of drug concepts. These hierarchies provide important information about clinical drugs, e.g., their chemical ingredients, mechanisms of action, dosage form and physiological effects. Within NDF-RT such information is represented using tens of thousands of roles connecting drugs to classifications. In previous studies, we have introduced various kinds of Abstraction Networks to summarize the content and structure of terminologies in order to facilitate their visual comprehension, and support quality assurance of terminologies. However, these previous kinds of Abstraction Networks are not appropriate for summarizing the NDF-RT classification hierarchies, due to its unique structure. In this paper, we present the novel Ingredient Abstraction Network (IAbN) to summarize, visualize and support the audit of NDF-RT's Chemical Ingredients hierarchy and its associated drugs. A common theme in our quality assurance framework is to use characterizations of sets of concepts, revealed by the Abstraction Network structure, to capture concepts, the modeling of which is more complex than for other concepts. For the IAbN, we characterize drug ingredient concepts as more complex if they belong to IAbN groups with multiple parent groups. We show that such concepts have a statistically significantly higher rate of errors than a control sample and identify two especially common patterns of errors. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. WHO Expert Committee on Specifications for Pharmaceutical Preparations.

    PubMed

    2003-01-01

    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, the report discusses activities related to the development of The International Pharmacopoeia and basic tests for pharmaceutical substances and dosage forms, as well as quality control of reference materials, good manufacturing practices (GMP), stability studies, inspection, hazard analysis, procurement, storage and other aspects of quality assurance of pharmaceuticals, and regulatory issues. The report is complemented by a number of annexes, including recommendations on the risk of transmitting animal spongiform encephalopathy agents via medicinal products, guidelines on GMP for pharmaceutical products, a model certificate for GMP and guidance on a GMP inspection report. The final annexes provide guidance on the application of Hazard Analysis and Critical Control Point (HACCP) method to pharmaceuticals, good storage practices and a procedure for assessing acceptability of pharmaceutical products for purchase by United Nations agencies.

  19. Unified Software Solution for Efficient SPR Data Analysis in Drug Research

    PubMed Central

    Dahl, Göran; Steigele, Stephan; Hillertz, Per; Tigerström, Anna; Egnéus, Anders; Mehrle, Alexander; Ginkel, Martin; Edfeldt, Fredrik; Holdgate, Geoff; O’Connell, Nichole; Kappler, Bernd; Brodte, Annette; Rawlins, Philip B.; Davies, Gareth; Westberg, Eva-Lotta; Folmer, Rutger H. A.; Heyse, Stephan

    2016-01-01

    Surface plasmon resonance (SPR) is a powerful method for obtaining detailed molecular interaction parameters. Modern instrumentation with its increased throughput has enabled routine screening by SPR in hit-to-lead and lead optimization programs, and SPR has become a mainstream drug discovery technology. However, the processing and reporting of SPR data in drug discovery are typically performed manually, which is both time-consuming and tedious. Here, we present the workflow concept, design and experiences with a software module relying on a single, browser-based software platform for the processing, analysis, and reporting of SPR data. The efficiency of this concept lies in the immediate availability of end results: data are processed and analyzed upon loading the raw data file, allowing the user to immediately quality control the results. Once completed, the user can automatically report those results to data repositories for corporate access and quickly generate printed reports or documents. The software module has resulted in a very efficient and effective workflow through saved time and improved quality control. We discuss these benefits and show how this process defines a new benchmark in the drug discovery industry for the handling, interpretation, visualization, and sharing of SPR data. PMID:27789754

  20. Improving the quality of randomized controlled trials in Chinese herbal medicine, part II: control group design.

    PubMed

    Bian, Zhao-Xiang; Moher, David; Dagenais, Simon; Li, You-Ping; Liu, Liang; Wu, Tai-Xiang; Miao, Jiang-Xia

    2006-03-01

    To discuss the types of control groups in randomized controlled trials (RCTs) of Chinese herbal medicine (CHM), and to provide suggestions for improving the design of control group in future clinical studies in this therapeutic area. A search of the Cochrane Library was conducted in July 2005 to identify RCTs of CHM, and 66 RCTs with CHM for type 2 diabetes mellitus were obtained as the basis for further analysis. Of 66 RCTs with CHM for type 2 diabetes mellitus, 61 (92.4%) trials had both a treatment group and a control group. Twenty-seven (40.9%) RCTs compared CHM plus conventional drug vs conventional drug, 24 (36.4%) compared CHM vs conventional drug, 5 (7.6%) compared CHM vs placebo, 3 (4.5%) compared CHM plus conventional drug vs conventional drug plus placebo, 3 (4.5%) compared CHM plus conventional drug vs other CHM, 1 (1.5%) compared CHM vs no treatment, 1 (1.5%) compared CHM plus placebo vs conventional drug plus placebo, 1 (1.5%) compared CHM vs CHM plus conventional drug vs conventional drug vs placebo, and 1 (1.5%) compared CHM vs conventional drug vs CHM plus conventional drug. A variety of control groups were used in RCTs of CHM for type 2 diabetes mellitus, including placebo, active, and no treatment control groups. Justification for selecting particular types of control groups were not provided in the trials reviewed in this study. Different control groups may be appropriate according to the study objectives, and several factors should be considered prior to selecting control groups in future RCTs of CHM. (1) Investigators of CHM who design clinical trials should understand the rationale for selecting different types of control groups; (2) Control groups for RCTs should be selected according to study objectives; (3) Active control groups should select interventions for comparisons that have the strongest evidence of efficacy and prescribe them as recommended; (4) Placebo control groups should select a placebo that mimics the physical characteristics of test intervention as closely as possible and is completely inert; (5) No treatment control groups should only be used when withholding treatment is ethical and objectives outcomes will not be subject to bias due to absent blinding; (6) Crossover control groups may be appropriate in chronic and stable conditions.

  1. Substandard Antimalarials Available in Afghanistan: A Case for Assessing the Quality of Drugs in Resource Poor Settings

    PubMed Central

    Lalani, Mirza; Kaur, Harparkash; Mohammed, Nader; Mailk, Naiela; van Wyk, Albert; Jan, Sakhi; Kakar, Rishtya Meena; Mojadidi, Mohammed Khalid; Leslie, Toby

    2015-01-01

    Good-quality antimalarials are crucial for the effective treatment and control of malaria. A total of 7,740 individual and packaged tablets, ampoules, and syrups were obtained from 60 randomly selected public (N = 35) and private outlets (N = 25) in Afghanistan. Of these, 134 samples were screened using the Global Pharma Health Fund (GPHF) MiniLab® in Kabul with 33/126 (26%) samples failing the MiniLab® disintegration test. The quality of a subsample (N = 37) of cholorquine, quinine, and sulfadoxine/pyrimethamine tablets was assessed by in vitro dissolution testing following U.S. Pharmacopeia (USP) monographs at a bioanalytical laboratory in London, United Kingdom. Overall, 12/32 (32%) samples of sulfadoxine/pyrimethamine and quinine were found not to comply with the USP tolerance limits. Substandard antimalarials were available in Afghanistan demonstrating that continuous monitoring of drug quality is warranted. However, in Afghanistan as in many low-income countries, capacity to determine and monitor drug quality using methods such as dissolution testing needs to be established to empower national authorities to take appropriate action in setting up legislation and regulation. PMID:25897070

  2. Brief interventions for illicit drug use among peripartum women.

    PubMed

    Farr, Sherry L; Hutchings, Yalonda L; Ondersma, Steven J; Creanga, Andreea A

    2014-10-01

    We review the evidence and identify limitations of the current literature on the effectiveness of brief interventions (≤5 intervention sessions) on illicit drug use, treatment enrollment/retention, and pregnancy outcomes among pregnant and postpartum women; and consider this evidence in the context of the broader brief intervention literature. Among 4 published studies identified via systematic review and meeting a priori quality criteria, we found limited, yet promising evidence of the benefit of brief interventions to reduce illicit drug use among postpartum women. Two of the 4 randomized controlled trials tested similar computer-delivered single-session interventions; both demonstrate effects on postpartum drug use. Neither of the 2 randomized controlled trials that assessed treatment use found differences between intervention and control groups. Studies examining brief interventions for smoking and alcohol use among pregnant women, and for illicit drug use in the general adult population, have shown small but statistically significant results of the effectiveness of such interventions. Larger studies, those that examine the effect of assessment alone on illicit drug use, and those that use technology-delivered brief interventions are needed to assess the effectiveness of brief interventions for drug use in the peripartum period. Published by Elsevier Inc.

  3. Proteostasis in cardiac health and disease.

    PubMed

    Henning, Robert H; Brundel, Bianca J J M

    2017-11-01

    The incidence and prevalence of cardiac diseases, which are the main cause of death worldwide, are likely to increase because of population ageing. Prevailing theories about the mechanisms of ageing feature the gradual derailment of cellular protein homeostasis (proteostasis) and loss of protein quality control as central factors. In the heart, loss of protein patency, owing to flaws in genetically-determined design or because of environmentally-induced 'wear and tear', can overwhelm protein quality control, thereby triggering derailment of proteostasis and contributing to cardiac ageing. Failure of protein quality control involves impairment of chaperones, ubiquitin-proteosomal systems, autophagy, and loss of sarcomeric and cytoskeletal proteins, all of which relate to induction of cardiomyocyte senescence. Targeting protein quality control to maintain cardiac proteostasis offers a novel therapeutic strategy to promote cardiac health and combat cardiac disease. Currently marketed drugs are available to explore this concept in the clinical setting.

  4. Standardized methods and quality control limits for agar and broth microdilution susceptibility testing of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum.

    PubMed

    Waites, Ken B; Duffy, Lynn B; Bébéar, Cécile M; Matlow, Anne; Talkington, Deborah F; Kenny, George E; Totten, Patricia A; Bade, Donald J; Zheng, Xiaotian; Davidson, Maureen K; Shortridge, Virginia D; Watts, Jeffrey L; Brown, Steven D

    2012-11-01

    An international multilaboratory collaborative study was conducted to develop standard media and consensus methods for the performance and quality control of antimicrobial susceptibility testing of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum using broth microdilution and agar dilution techniques. A reference strain from the American Type Culture Collection was designated for each species, which was to be used for quality control purposes. Repeat testing of replicate samples of each reference strain by participating laboratories utilizing both methods and different lots of media enabled a 3- to 4-dilution MIC range to be established for drugs in several different classes, including tetracyclines, macrolides, ketolides, lincosamides, and fluoroquinolones. This represents the first multilaboratory collaboration to standardize susceptibility testing methods and to designate quality control parameters to ensure accurate and reliable assay results for mycoplasmas and ureaplasmas that infect humans.

  5. Current Status of Herbal Drug Standards in the Indian Pharmacopoeia.

    PubMed

    Prakash, Jai; Srivastava, Sushma; Ray, R S; Singh, Neha; Rajpali, Roshni; Singh, Gyanendra Nath

    2017-12-01

    The benefits of herbal drugs were well understood way back. They have been used for the promotion of health and medical purposes - in disease conditions. It is a conventional belief that herbal drugs have no side effects, are cheaper and locally available. Among Indian systems of medicines, herbs/herbal formulations are used to a larger extent. The quality control of the marketed herbs/herbal formulations is important for acquiring optimum therapeutic benefit as well as for expanding global outreach. Therefore, herbal drug standards are important. Reference standards, the Indian Pharmacopoeia Reference Substances especially the botanical reference substances and the phytochemical reference substances are required for comparison of quality of herbal drugs. The Indian Pharmacopoeia Commission has initiated the process of providing Indian Pharmacopoeia Reference Substances to the stakeholders. Therefore, this article provides an overview of the history and the status of herbal drug standards in the current and forthcoming issues of Indian Pharmacopoeia. In Indian Pharmacopeia, efforts have been made for the harmonization of standards with international counterparts wherever possible. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  6. Patient-centered Outcomes with Concomitant Use of Proton Pump Inhibitors and Other Drugs.

    PubMed

    Shamliyan, Tatyana A; Middleton, Maria; Borst, Clarissa

    2017-02-01

    We performed a systematic review of patient-centered outcomes after the concomitant use of proton pump inhibitors (PPIs) and other drugs. We searched 4 databases in July 2016 to find studies that reported mortality and morbidity after the concomitant use of PPIs and other drugs. We conducted direct meta-analyses using a random-effects model and graded the quality of evidence according to the Grading of Recommendations Assessment, Development and Evaluation working group approach. We included data from 17 systematic reviews and meta-analyses, 16 randomized controlled trials, and 16 observational studies that examined the concomitant use of PPIs with medications from 10 drug classes. Low-quality evidence suggests that the use of PPIs is associated with greater morbidity when administered with antiplatelet drugs, bisphosphonates, antibiotics, anticoagulants, metformin, mycophenolate mofetil, or nelfinavir. Concomitant PPIs reduce drug-induced gastrointestinal bleeding and are associated with greater docetaxel and cisplatin response rates in patients with metastatic breast cancer. For demonstrated statistically significant relative risks and benefits from concomitant PPIs, the magnitudes of the effects are small, with <100 attributable events per 1000 patients treated, and the effects are inconsistent among specific drugs. Among individual PPIs, the concomitant use of pantoprazole or esomeprazole, but not omeprazole or lansoprazole, is associated with an increased risk for all-cause mortality, nonfatal myocardial infarction, or stroke. Clopidogrel is associated with a greater risk for myocardial infarction compared with prasugrel. Conflicting results between randomized controlled trials and observational studies and high risk for bias in the body of evidence lessened our confidence in the results. Available evidence suggests a greater risk for adverse patient outcomes after the concomitant use of PPIs and medications from 9 drug classes and warns against inappropriate drug combinations. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  7. Quality of drug information on the World Wide Web and strategies to improve pages with poor information quality. An intervention study on pages about sildenafil.

    PubMed

    Martin-Facklam, Meret; Kostrzewa, Michael; Martin, Peter; Haefeli, Walter E

    2004-01-01

    The generally poor quality of health information on the world wide web (WWW) has caused preventable adverse outcomes. Quality management of information on the internet is therefore critical given its widespread use. In order to develop strategies for the safe use of drugs, we scored general and content quality of pages about sildenafil and performed an intervention to improve their quality. The internet was searched with Yahoo and AltaVista for pages about sildenafil and 303 pages were included. For assessment of content quality a score based on accuracy and completeness of essential drug information was assigned. For assessment of general quality, four criteria were evaluated and their association with high content quality was determined by multivariate logistic regression analysis. The pages were randomly allocated to either control or intervention group. Evaluation took place before, as well as 7 and 22 weeks after an intervention which consisted of two letters with individualized feedback information on the respective page which were sent electronically to the address mentioned on the page. Providing references to scientific publications or prescribing information was significantly associated with high content quality (odds ratio: 8.2, 95% CI 3.2, 20.5). The intervention had no influence on general or content quality. To prevent adverse outcomes caused by misinformation on the WWW individualized feedback to the address mentioned on the page was ineffective. It is currently probably the most straight-forward approach to inform lay persons about indicators of high information quality, i.e. the provision of references.

  8. Risk of endometrial cancer in women treated with ovary-stimulating drugs for subfertility.

    PubMed

    Skalkidou, Alkistis; Sergentanis, Theodoros N; Gialamas, Spyros P; Georgakis, Marios K; Psaltopoulou, Theodora; Trivella, Marialena; Siristatidis, Charalampos S; Evangelou, Evangelos; Petridou, Eleni

    2017-03-25

    Medical treatment for subfertility principally involves the use of ovary-stimulating agents, including selective oestrogen receptor modulators (SERMs), such as clomiphene citrate, gonadotropins, gonadotropin-releasing hormone (GnRH) agonists and antagonists, as well as human chorionic gonadotropin. Ovary-stimulating drugs may act directly or indirectly upon the endometrium (lining of the womb). Nulliparity and some causes of subfertility are recognized as risk factors for endometrial cancer. To evaluate the association between the use of ovary-stimulating drugs for the treatment of subfertility and the risk of endometrial cancer. A search was performed in CENTRAL, MEDLINE (Ovid) and Embase (Ovid) databases up to July 2016, using a predefined search algorithm. A search in OpenGrey, ProQuest, ClinicalTrials.gov, ZETOC and reports of major conferences was also performed. We did not impose language and publication status restrictions. Cohort and case-control studies reporting on the association between endometrial cancer and exposure to ovary-stimulating drugs for subfertility in adult women were deemed eligible. Study characteristics and findings were extracted by review authors independently working in pairs. Inconsistency between studies was quantified by estimating I 2 . Random-effects (RE) models were used to calculate pooled effect estimates. Separate analyses were performed, comparing treated subfertile women versus general population and/or unexposed subfertile women, to address the superimposition of subfertility as an independent risk factor for endometrial cancer. Nineteen studies were eligible for inclusion (1,937,880 participants). Overall, the quality of evidence was very low, due to serious risk of bias and indirectness (non-randomised studies (NRS), which was reflected on the GRADE assessment.Six eligible studies, including subfertile women, without a general population control group, found that exposure to any ovary-stimulating drug was not associated with an increased risk of endometrial cancer (RR 0.96, 95% CI 0.67 to 1.37; 156,774 participants; very low quality evidence). Fifteen eligible studies, using a general population as the control group, found an increased risk after exposure to any ovary-stimulating drug (RR 1.75, 95% CI 1.18 to 2.61; 1,762,829 participants; very low quality evidence).Five eligible studies, confined to subfertile women (92,849 participants), reported on exposure to clomiphene citrate; the pooled studies indicated a positive association ( RR 1.32; 95% CI 1.01 to 1.71; 88,618 participants; very low quality evidence), although only at high dosage (RR 1.69, 95% CI 1.07 to 2.68; two studies; 12,073 participants) and at a high number of cycles (RR 1.69, 95% CI 1.16 to 2.47; three studies; 13,757 participants). Four studies found an increased risk of endometrial cancer in subfertile women who required clomiphene citrate compared to a general population control group (RR 1.87, 95% CI 1.00 to 3.48; four studies, 19,614 participants; very low quality evidence). These data do not tell us whether the association is due to the underlying conditions requiring clomiphene or the treatment itself.Using unexposed subfertile women as controls, exposure to gonadotropins was associated with an increased risk of endometrial cancer (RR 1.55, 95% CI 1.03 to 2.34; four studies; 17,769 participants; very low quality evidence). The respective analysis of two studies (1595 participants) versus the general population found no difference in risk (RR 2.12, 95% CI 0.79 to 5.64: very low quality evidence).Exposure to a combination of clomiphene citrate and gonadotropins, compared to unexposed subfertile women, produced no difference in risk of endometrial cancer (RR 1.18, 95% CI 0.57 to 2.44; two studies; 6345 participants; very low quality evidence). However, when compared to the general population, an increased risk was found , suggesting that the key factor might be subfertility, rather than treatment (RR 2.99, 95% CI 1.53 to 5.86; three studies; 7789 participants; very low quality evidence). The synthesis of the currently available evidence does not allow us to draw robust conclusions, due to the very low quality of evidence. It seems that exposure to clomiphene citrate as an ovary-stimulating drug in subfertile women is associated with increased risk of endometrial cancer, especially at doses greater than 2000 mg and high (more than 7) number of cycles. This may largely be due to underlying risk factors in women who need treatment with clomiphene citrate, such as polycystic ovary syndrome, rather than exposure to the drug itself. The evidence regarding exposure to gonadotropins was inconclusive.

  9. Effects of interactive patient smartphone support app on drug adherence and lifestyle changes in myocardial infarction patients: A randomized study.

    PubMed

    Johnston, Nina; Bodegard, Johan; Jerström, Susanna; Åkesson, Johanna; Brorsson, Hilja; Alfredsson, Joakim; Albertsson, Per A; Karlsson, Jan-Erik; Varenhorst, Christoph

    2016-08-01

    Patients with myocardial infarction (MI) seldom reach recommended targets for secondary prevention. This study evaluated a smartphone application ("app") aimed at improving treatment adherence and cardiovascular lifestyle in MI patients. Multicenter, randomized trial. A total of 174 ticagrelor-treated MI patients were randomized to either an interactive patient support tool (active group) or a simplified tool (control group) in addition to usual post-MI care. Primary end point was a composite nonadherence score measuring patient-registered ticagrelor adherence, defined as a combination of adherence failure events (2 missed doses registered in 7-day cycles) and treatment gaps (4 consecutive missed doses). Secondary end points included change in cardiovascular risk factors, quality of life (European Quality of Life-5 Dimensions), and patient device satisfaction (System Usability Scale). Patient mean age was 58 years, 81% were men, and 21% were current smokers. At 6 months, greater patient-registered drug adherence was achieved in the active vs the control group (nonadherence score: 16.6 vs 22.8 [P = .025]). Numerically, the active group was associated with higher degree of smoking cessation, increased physical activity, and change in quality of life; however, this did not reach statistical significance. Patient satisfaction was significantly higher in the active vs the control group (system usability score: 87.3 vs 78.1 [P = .001]). In MI patients, use of an interactive patient support tool improved patient self-reported drug adherence and may be associated with a trend toward improved cardiovascular lifestyle changes and quality of life. Use of a disease-specific interactive patient support tool may be an appreciated, simple, and promising complement to standard secondary prevention. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. 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.

  11. Management of impulse control disorders in Parkinson's disease: Controversies and future approaches.

    PubMed

    Samuel, Michael; Rodriguez-Oroz, Maria; Antonini, Angelo; Brotchie, Jonathan M; Ray Chaudhuri, Kallol; Brown, Richard G; Galpern, Wendy R; Nirenberg, Melissa J; Okun, Michael S; Lang, Anthony E

    2015-02-01

    Impulse control disorders in Parkinson's disease are a group of impulsive behaviors most often associated with dopaminergic treatment. Presently, there is a lack of high quality evidence available to guide their management. This manuscript reviews current management strategies, before concentrating on the concept of dopamine agonist withdrawal syndrome and its implications for the management of impulse control disorders. Further, we focus on controversies, including the role of more recently available anti-parkinsonian drugs, and potential future approaches involving routes of drug delivery, nonpharmacological treatments (such as cognitive behavioral therapy and deep brain stimulation), and other as yet experimental strategies. © 2015 International Parkinson and Movement Disorder Society.

  12. Impulse Control Disorders in Parkinson’s Disease:Management, Controversies, and Potential Approaches

    PubMed Central

    Samuel, M; Rodriguez-Oroz, M; Antonini, A; Brotchie, JM; Ray Chaudhuri, K; Brown, RG; Galpern, WR; Nirenberg, MJ; Okun, MS; Lang, AE

    2016-01-01

    Impulse control disorders in Parkinson’s disease are a group of impulsive behaviors most often associated with dopaminergic treatment. Presently, there is a lack of high quality evidence available to guide their management. This manuscript reviews current management strategies, before concentrating on the concept of dopamine agonist withdrawal syndrome and its implications for the management of impulse control disorders. Further, we focus on controversies including the role of more recently available anti-parkinsonian drugs, and potential future approaches involving routes of drug delivery, non-pharmacological treatments (such as cognitive behaviour therapy and deep brain stimulation), and other as yet experimental strategies. PMID:25607799

  13. Association of industry funding with the outcome and quality of randomized controlled trials of drug therapy for rheumatoid arthritis.

    PubMed

    Khan, Nasim A; Lombeida, Juan I; Singh, Manisha; Spencer, Horace J; Torralba, Karina D

    2012-07-01

    To assess the association of industry funding with the characteristics, outcome, and reported quality of randomized controlled trials (RCTs) of drug therapy for rheumatoid arthritis (RA). The Medline and Cochrane Central Register of Controlled Trials databases were searched to identify original RA drug therapy RCTs published in 2002-2003 and 2006-2007. Two reviewers independently assessed each RCT for the funding source, characteristics, outcome (positive [statistically significant result favoring experimental drug for the primary outcome] or not positive), and reporting of methodologic measures whose inadequate performance may have biased the assessment of treatment effect. RCTs that were registered at ClinicalTrials.gov and completed during the study years were assessed for publication bias. Of the 103 eligible RCTs identified, 58 (56.3%) were funded by industry, 19 (18.4%) were funded by nonprofit sources, 6 (5.8%) had mixed funding, and funding for 20 (19.4%) was not specified. Industry-funded RCTs had significantly more study centers and subjects, while nonprofit agency-funded RCTs had longer duration and were more likely to study different treatment strategies. Outcome could be assessed for 86 (83.5%) of the 103 RCTs studied. The funding source was not associated with a higher likelihood of positive outcomes favoring the sponsored experimental drug (75.5% of industry-funded RCTs had a positive outcome, compared with 68.8% of non-industry-funded RCTs, 40% of RCTs with mixed funding, and 81.2% of RCTs for which funding was not specified). Industry-funded RCTs showed a trend toward a higher likelihood of nonpublication (P=0.093). Industry-funded RCTs were more frequently associated with double-blinding, an adequate description of participant flow, and performance of an intent-to-treat analysis. Industry funding was not associated with a higher likelihood of positive outcomes of published RCTs of drug therapy for RA, and industry-funded RCTs performed significantly better than non-industry-funded RCTs in terms of reporting the use of some key methodologic quality measures. Copyright © 2012 by the American College of Rheumatology.

  14. Effect of interventions to reduce potentially inappropriate use of drugs in nursing homes: a systematic review of randomised controlled trials

    PubMed Central

    2011-01-01

    Background Studies have shown that residents in nursing homes often are exposed to inappropriate medication. Particular concern has been raised about the consumption of psychoactive drugs, which are commonly prescribed for nursing home residents suffering from dementia. This review is an update of a Norwegian systematic review commissioned by the Norwegian Directorate of Health. The purpose of the review was to identify and summarise the effect of interventions aimed at reducing potentially inappropriate use or prescribing of drugs in nursing homes. Methods We searched for systematic reviews and randomised controlled trials in the Cochrane Library, MEDLINE, EMBASE, ISI Web of Knowledge, DARE and HTA, with the last update in April 2010. Two of the authors independently screened titles and abstracts for inclusion or exclusion. Data on interventions, participants, comparison intervention, and outcomes were extracted from the included studies. Risk of bias and quality of evidence were assessed using the Cochrane Risk of Bias Table and GRADE, respectively. Outcomes assessed were use of or prescribing of drugs (primary) and the health-related outcomes falls, physical limitation, hospitalisation and mortality (secondary). Results Due to heterogeneity in interventions and outcomes, we employed a narrative approach. Twenty randomised controlled trials were included from 1631 evaluated references. Ten studies tested different kinds of educational interventions while seven studies tested medication reviews by pharmacists. Only one study was found for each of the interventions geriatric care teams, early psychiatric intervening or activities for the residents combined with education of health care personnel. Several reviews were identified, but these either concerned elderly in general or did not satisfy all the requirements for systematic reviews. Conclusions Interventions using educational outreach, on-site education given alone or as part of an intervention package and pharmacist medication review may under certain circumstances reduce inappropriate drug use, but the evidence is of low quality. Due to poor quality of the evidence, no conclusions may be drawn about the effect of the other three interventions on drug use, or of either intervention on health-related outcomes. PMID:21496345

  15. Dropwise additive manufacturing of pharmaceutical products for melt-based dosage forms.

    PubMed

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

    2015-05-01

    The US Food and Drug Administration introduced the quality by design approach and process analytical technology guidance to encourage innovation and efficiency in pharmaceutical development, manufacturing, and quality assurance. As part of this renewed emphasis on the improvement of manufacturing, the pharmaceutical industry has begun to develop more efficient production processes with more intensive use of online measurement and sensing, real-time quality control, and process control tools. Here, we present dropwise additive manufacturing of pharmaceutical products (DAMPP) as an alternative to conventional pharmaceutical manufacturing methods. This mini-manufacturing process for the production of pharmaceuticals utilizes drop on demand printing technology for automated and controlled deposition of melt-based formulations onto edible substrates. The advantages of drop-on-demand technology, including reproducible production of small droplets, adjustable drop sizing, high placement accuracy, and flexible use of different formulations, enable production of individualized dosing even for low-dose and high-potency drugs. In this work, DAMPP is used to produce solid oral dosage forms from hot melts of an active pharmaceutical ingredient and a polymer. The dosage forms are analyzed to show the reproducibility of dosing and the dissolution behavior of different formulations. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  16. Improving depression and enhancing resilience in family dementia caregivers: a pilot randomized placebo-controlled trial of escitalopram.

    PubMed

    Lavretsky, Helen; Siddarth, Prabha; Irwin, Michael R

    2010-02-01

    This study examined the potential of an antidepressant drug, escitalopram, to improve depression, resilience to stress, and quality of life in family dementia caregivers in a randomized placebo-controlled double-blinded trial. Forty family caregivers (43-91 years of age, 25 children and 15 spouses; 26 women) who were taking care of their relatives with Alzheimer disease were randomized to receive either escitalopram 10 mg/day or placebo for 12 weeks. Severity of depression, resilience, burden, distress, quality of life, and severity of care-recipient's cognitive and behavioral disturbances were assessed at baseline and over the course of the study. The Hamilton Depression Rating Scale scores at baseline ranged between 10 and 28. The groups were stratified by the diagnosis of major and minor depression. Most outcomes favored escitalopram over placebo. The severity of depression improved, and the remission rate was greater with the drug compared with placebo. Measures of anxiety, resilience, burden, and distress improved on escitalopram compared with placebo. Among caregivers, this small randomized controlled trial found that escitalopram use resulted in improvement in depression, resilience, burden and distress, and quality of life. Our results need to be confirmed in a larger sample.

  17. Implementation of a reference standard and proficiency testing programme by the World Wide Antimalarial Resistance Network (WWARN)

    PubMed Central

    2010-01-01

    Background The Worldwide Antimalarial Resistance Network (WWARN) is a global collaboration to support the objective that anyone affected by malaria receives effective and safe drug treatment. The Pharmacology module aims to inform optimal anti-malarial drug selection. There is an urgent need to define the drug exposure - effect relationship for most anti-malarial drugs. Few anti-malarials have had their therapeutic blood concentration levels defined. One of the main challenges in assessing safety and efficacy data in relation to drug concentrations is the comparability of data generated from different laboratories. To explain differences in anti-malarial pharmacokinetics in studies with different measurement laboratories it is necessary to confirm the accuracy of the assay methods. This requires the establishment of an external quality assurance process to assure results that can be compared. This paper describes this process. Methods The pharmacology module of WWARN has established a quality assurance/quality control (QA/QC) programme consisting of two separate components: 1. A proficiency testing programme where blank human plasma spiked with certified reference material (CRM) in different concentrations is sent out to participating bioanalytical laboratories. 2. A certified reference standard programme where accurately weighed amounts of certified anti-malarial reference standards, metabolites, and internal standards are sent to participating bioanalytical and in vitro laboratories. Conclusion The proficiency testing programme is designed as a cooperative effort to help participating laboratories assess their ability to carry out drug analysis, resolve any potential problem areas and to improve their results - and, in so doing, to improve the quality of anti-malarial pharmacokinetic data published and shared with WWARN. By utilizing the same source of standards for all laboratories, it is possible to minimize bias arising from poor quality reference standards. By providing anti-malarial drug standards from a central point, it is possible to lower the cost of these standards. PMID:21184684

  18. Control of Antimicrobial Resistance Requires an Ethical Approach

    PubMed Central

    Parsonage, Ben; Hagglund, Philip K.; Keogh, Lloyd; Wheelhouse, Nick; Brown, Richard E.; Dancer, Stephanie J.

    2017-01-01

    Ethical behavior encompasses actions that benefit both self and society. This means that tackling antimicrobial resistance (AMR) becomes an ethical obligation, because the prospect of declining anti-infectives affects everyone. Without preventive action, loss of drugs that have saved lives over the past century, will condemn ourselves, people we know, and people we don’t know, to unacceptable risk of untreatable infection. Policies aimed at extending antimicrobial life should be considered within an ethical framework, in order to balance the choice, range, and quality of drugs against stewardship activities. Conserving availability and effectiveness for future use should not compromise today’s patients. Practices such as antimicrobial prophylaxis for healthy people ‘at risk’ should receive full debate. There are additional ethical considerations for AMR involving veterinary care, agriculture, and relevant bio-industries. Restrictions for farmers potentially threaten the quality and quantity of food production with economic consequences. Antibiotics for companion animals do not necessarily spare those used for humans. While low-income countries cannot afford much-needed drugs, pharmaceutical companies are reluctant to develop novel agents for short-term return only. Public demand encourages over-the-counter, internet, black market, and counterfeit drugs, all of which compromise international control. Prescribers themselves require educational support to balance therapeutic choice against collateral damage to both body and environment. Predicted mortality due to AMR provides justification for international co-operation, commitment and investment to support surveillance and stewardship along with development of novel antimicrobial drugs. Ethical arguments for, and against, control of antimicrobial resistance strategies are presented and discussed in this review. PMID:29163414

  19. What explains the association between neighborhood-level income inequality and the risk of fatal overdose in New York City?

    PubMed

    Nandi, Arijit; Galea, Sandro; Ahern, Jennifer; Bucciarelli, Angela; Vlahov, David; Tardiff, Kenneth

    2006-08-01

    Accidental drug overdose is a substantial cause of mortality for drug users. Using a multilevel case-control study we previously have shown that neighborhood-level income inequality may be an important determinant of overdose death independent of individual-level factors. Here we hypothesized that the level of environmental disorder, the level of police activity, and the quality of the built environment in a neighborhood mediate this association. Data from the New York City (NYC) Mayor's Management Report, the NYC Police Department, and the NYC Housing and Vacancy Survey were used to define constructs for the level of environmental disorder, the level of police activity and the quality of the built environment, respectively. In multivariable models the odds of death due to drug overdose in neighborhoods in the top decile of income inequality compared to the most equitable neighborhoods decreased from 1.63 to 1.12 when adjusting for the three potential mediators. Path analyses show that the association between income inequality and the rate of drug overdose mortality was primarily explained by an indirect effect through the level of environmental disorder and the quality of the built environment in a neighborhood. Implications of these findings for the reduction of drug overdose mortality associated with the distribution of income are discussed.

  20. Company observational post-marketing studies: drug risk assessment and drug research in special populations--a study-based analysis.

    PubMed

    Hasford, J; Lamprecht, T

    1998-01-01

    Company observational post-marketing studies (COPS) claim to provide essential data about drug risks and effectiveness in special populations not admitted to pre-approval clinical trials. Since COPS are often mainly regarded as a marketing activity, this study-based analysis tries to evaluate the scientific contributions of COPS. Thirty-five COPS were identified by hand-searching through medical journals, writing to pharmaceutical manufacturers and using MEDLINE. Fourteen COPS evaluated cardiovascular drugs, 9 evaluated NSAIDs and 12 evaluated various other indications. Thirty-five COPS listed effectiveness, 31 listed safety and 8 listed patient compliance as principal objectives. Not a single COPS included a control group. Seventeen of 21 evaluable COPS mentioned extensive exclusion criteria similar to those in clinical trials. Median observation time was 8 weeks, too short for chronic diseases and for adverse drug reactions with longer latency periods. One new adverse event was regarded. Global assessments of the outcomes by physicians dominated and were not based on objective clinical findings. None of the studies specified any details concerning the standardisation of observations or quality-control procedures. The current COPS scheme does not contribute significantly to our knowledge of drug safety and the effects in special populations. Despite serious criticism over the past 20 years, the poor quality of COPS compared with dramatic improvements of pre-approval trials - implies a need for detailed guidelines for non-experimental phase IV research, similar to the Good Clinical Practice-Guideline of the European Community.

  1. FDA 2011 process validation guidance: lifecycle compliance model.

    PubMed

    Campbell, Cliff

    2014-01-01

    This article has been written as a contribution to the industry's efforts in migrating from a document-driven to a data-driven compliance mindset. A combination of target product profile, control engineering, and general sum principle techniques is presented as the basis of a simple but scalable lifecycle compliance model in support of modernized process validation. Unit operations and significant variables occupy pole position within the model, documentation requirements being treated as a derivative or consequence of the modeling process. The quality system is repositioned as a subordinate of system quality, this being defined as the integral of related "system qualities". The article represents a structured interpretation of the U.S. Food and Drug Administration's 2011 Guidance for Industry on Process Validation and is based on the author's educational background and his manufacturing/consulting experience in the validation field. The U.S. Food and Drug Administration's Guidance for Industry on Process Validation (2011) provides a wide-ranging and rigorous outline of compliant drug manufacturing requirements relative to its 20(th) century predecessor (1987). Its declared focus is patient safety, and it identifies three inter-related (and obvious) stages of the compliance lifecycle. Firstly, processes must be designed, both from a technical and quality perspective. Secondly, processes must be qualified, providing evidence that the manufacturing facility is fully "roadworthy" and fit for its intended purpose. Thirdly, processes must be verified, meaning that commercial batches must be monitored to ensure that processes remain in a state of control throughout their lifetime.

  2. Analysis of Gap in Service Quality in Drug Addiction Treatment Centers of Kerman, Iran, Using SERVQUAL Model.

    PubMed

    Naqavi, Mohammad Reza; Refaiee, Raheleh; Baneshi, Mohammad Reza; Nakhaee, Nouzar

    2014-01-01

    Treatment of drug addicts is one of the main strategies of drug control in Iran. Client satisfaction strongly influences the success of any treatment program. This study aimed to explore the difference between customer expectations and perceptions in drug addiction treatment centers of Kerman, Iran, using SERVQUAL model. Using a cross-sectional design 260 clients referring to drug addiction treatment centers of Kerman, were enrolled in 2012. From among 84 clinics, 20 centers were selected randomly. Based on the number of clients registered in each center, a random sample proportional to the size was selected and 290 subjects were invited for interviews. A well validated 22-item questionnaire, which measured the 5 dimensions of service quality (reliability, assurance, tangibility, empathy, and responsiveness), was completed by participants. Each item measured 2 aspects of service quality; expectations and perceptions. Mean ± SD (Standard deviation) age of the subjects was 37.7 ± 9.4. Most of them were male (87.7%). Less than half of them had an educational level lower than diploma. The total score of clients` expectations was higher than their perceptions (P < 0.001). Considering the 5 dimensions of the SERVQUAL model, only 1 dimension (i.e., assurance) showed no difference between perceptions and expectations of the participants (P = 0.134). There was a gap between the clients' expectations and what they actually perceived in the clinics. Thus, more attention should be devoted to the clients' views regarding service quality in addiction treatment clinics.

  3. Development of the Quality Assurance/Quality Control Procedures for a Neutron Interrogation System

    NASA Astrophysics Data System (ADS)

    Obhođaš, Jasmina; Sudac, Davorin; Valković, Vladivoj

    2016-06-01

    In order to perform Quality Assurance/Quality Control (QA/QC) procedures for a system dedicated to the neutron interrogation of objects for the presence of threat materials one needs to perform measurements of reference materials (RM) i.e. simulants having the same (or similar) atomic ratios as real materials. It is well known that explosives, drugs, and various other benign materials, contain chemical elements such as hydrogen, oxygen, carbon and nitrogen in distinctly different quantities. For example, a high carbon-to-oxygen ratio (C/O) is characteristic of drugs. Explosives can be differentiated by measurement of both (C/O) and nitrogen-to-oxygen (N/O) ratios. The C/N ratio of the chemical warfare agents, coupled with the measurement of elements such as fluorine and phosphorus, clearly differentiate them from the conventional explosives. Here we present the RM preparation, calibration procedure and correlations attained between theoretical values and experimentally obtained results in laboratory conditions for C/O and N/C ratios of prepared hexogen (RDX), TNT, DLM2, TATP, cocaine, heroin, yperite, tetranitromethane, peroxide methylethylketone, nitromethane and ethyleneglycol dinitrate simulants. We have shown that analyses of the gamma ray spectra by using simple unfolding model developed for this purpose gave a nice agreement with the chemical formula of created simulants, thus the calibration quality was successfully tested.

  4. Modern European monographs for quality control of Chinese herbs.

    PubMed

    Bauer, Rudolf; Franz, Gerhard

    2010-12-01

    The actual concern about the safety and efficacy of herbal drugs originating from traditional Chinese medicine (TCM) is based on observations that these medicinal plants may have a high risk potential due to insufficient definitions, problems with identity, purity and falsifications. No uniform legal status for these groups of herbal drugs currently exists in the European Union. For quality control, monographs for TCM herbs can mainly be found in the Pharmacopoeia of the Peoples Republic of China. Based on these facts the Commission of the European Pharmacopoeia decided in 2005 to establish TCM-herbal drug monographs for the most important medicinal plants imported from Far East. These new monographs had to be established and evaluated on the basis of existing monographs in the Chinese Pharmacopoeia (ChP), English edition 2005. Due to important differences in the overall features of EP and ChP, a simple adapt/adopt procedure was not feasible. Therefore, specialist groups were mandated with a corresponding working programme. Some results and actual problems related to this working programme will be presented and discussed. © Georg Thieme Verlag KG Stuttgart · New York.

  5. The impact of medicinal drugs on traffic safety: a systematic review of epidemiological studies.

    PubMed

    Orriols, Ludivine; Salmi, Louis-Rachid; Philip, Pierre; Moore, Nicholas; Delorme, Bernard; Castot, Anne; Lagarde, Emmanuel

    2009-08-01

    To evaluate the quality of epidemiological research into effects of medicinal drugs on traffic safety and the current knowledge in this area. The bibliographic search was done in Medline electronic database using the keywords: ((accident* or crash*) and traffic and drug*) leading to 1141 references. Additional references were retrieved from the Safetylit website and the reference lists of selected studies. Original articles published in English or French, between 1 April 1979 and 31 July 2008, were considered for inclusion. We excluded descriptive studies, studies limited to alcohol or illicit drug involvement and investigations of injuries other than from traffic crashes. Studies based on laboratory tests, driving simulators or on-the-road driving tests were also excluded. Eligible studies had to evaluate the causal relationship between the use of medicinal drugs and the risk of traffic crashes. Study quality was assessed by two independent experts, according to a grid adapted from the strengthening the reporting of observational studies in epidemiology (STROBE) statement. Twenty two studies of variable methodological quality were included. Definition of drug exposure varied across studies and depended on the data sources. Potential confounding due to the interaction between the effects of the medicinal drug and disease-related symptoms was often not controlled. The risk of motor-vehicle crashes related to benzodiazepines has been amply studied and demonstrated. Results for other medicinal drugs remain controversial. There is a need for large studies, investigating the role of individual substances in the risk of road traffic crashes. Copyright 2009 John Wiley & Sons, Ltd.

  6. Pharmacovigilance practice and risk control of Traditional Chinese Medicine drugs in China: current status and future perspective.

    PubMed

    Zhang, Li; Yan, Jingbo; Liu, Xinmin; Ye, Zuguang; Yang, Xiaohui; Meyboom, Ronald; Chan, Kelvin; Shaw, Debbie; Duez, Pierre

    2012-04-10

    Traditional Chinese Medicine (TCM), including Traditional Chinese Medicine drugs (TCM drugs), has been playing a very important role in health protection and disease control for thousands of years in China. Relying on natural products, mainly of herbal origin, used either as raw materials for decoction, as prepared herbal medicines or as formulated traditional medicines, TCM is still widely accepted by Chinese people, especially for chronic diseases treatment. This extensive use warrants safety measures and so TCM drug safety monitoring and risk management are becoming increasingly important tasks for the Chinese State Food and Drug Administration (SFDA). The Adverse Drug Reaction (ADR) monitoring system in China was established both for western and TCM drugs in 1989 as a voluntary reporting system with a National Center collecting and compiling reports. Serious or multi-case reports on individual TCM drug or formulated products are detailed in the Chinese ADR Information Bulletin to inform the public and Drug Administrative authorities for risk management. About 10-15% of the ADR reports received by the National Center are related to TCM drugs and mainly pertaining to the formulated products. In certain cases, the suspension of a particular TCM preparation is decided by SFDA China. The model of safety monitoring and risk management of TCM drugs is still under exploration. Indeed, the characteristics and risk factors associated with these drugs require both proper understanding and control of the risk by strengthening standardization of clinical applications, basic science research, quality control in manufacturing, exploration of the actives monitoring methodology and enhancement of international communication and cooperation. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  7. Economic and policy analysis of university-based drug "detailing".

    PubMed

    Soumerai, S B; Avorn, J

    1986-04-01

    The cost-effectiveness of quality assurance programs is often poorly documented, especially for innovative approaches. The authors analyzed the economic effects of an experimental educational outreach program designed to reduce inappropriate drug prescribing, based on a four-state randomized controlled trial (N = 435 physicians). Primary care physicians randomized into the face-to-face group were offered two individualized educational sessions with clinical pharmacists, lasting an average of 18 minutes each, concerning optimal use of three drug groups that are often used inappropriately. After the program, expenditures for target drugs prescribed by these physicians to Medicaid patients decreased by 13%, compared with controls (P = 0.002); this effect was stable over three quarters. Implementation of this program for 10,000 physicians would lead to projected drug savings (to Medicaid only) of $2,050,000, compared with resource costs of $940,000. Net savings remain high, even after adjustment for use of substitution medications. Although there was a ninefold difference in average preintervention prescribing levels between the highest and lowest thirds of the sample, all groups reduced target drug expenditures at the same rate. Targeting of higher-volume prescribers would thus further raise the observed benefit-to-cost ratio from approximately 1.8 to at least 3.0. Net benefits would also increase further if non-Medicaid savings were added, or if the analysis included quality-of-care considerations. Although print materials alone may be marginally cost-effective, print plus face-to-face approaches offer greater net benefits. The authors conclude that a program of brief, face-to-face "detailing" visits conducted by academic rather than commercial sources can be a highly cost-effective method for improving drug therapy decisions. Such an approach makes possible the enhancement of physicians' clinical expertise without relying on restriction of drug choices.

  8. Effects of antithyroid drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled trials

    PubMed Central

    Briel, Matthias; Christ-Crain, Mirjam; Bonnema, Steen J; Connell, John; Cooper, David S; Bucher, Heiner C; Müller-Brand, Jan; Müller, Beat

    2007-01-01

    Objective To determine the effect of adjunctive antithyroid drugs on the risk of treatment failure, hypothyroidism, and adverse events after radioiodine treatment. Design Meta-analysis. Data sources Electronic databases (Cochrane central register of controlled trials, Medline, Embase) searched to August 2006 and contact with experts. Review methods Three reviewers independently assessed trial eligibility and quality. Pooled relative risks for treatment failure and hypothyroidism after radioiodine treatment with and without adjunctive antithyroid drugs were calculated with a random effects model. Results We identified 14 relevant randomised controlled trials with a total of 1306 participants. Adjunctive antithyroid medication was associated with an increased risk of treatment failure (relative risk 1.28, 95% confidence interval 1.07 to 1.52; P=0.006) and a reduced risk for hypothyroidism (0.68, 0.53 to 0.87; P=0.006) after radioiodine treatment. We found no difference in summary estimates for the different antithyroid drugs or for whether antithyroid drugs were given before or after radioiodine treatment. Conclusions Antithyroid drugs potentially increase rates of failure and reduce rates of hypothyroidism if they are given in the week before or after radioiodine treatment, respectively. PMID:17309884

  9. Oromucosal multilayer films for tailor-made, controlled drug delivery.

    PubMed

    Lindert, Sandra; Breitkreutz, Jörg

    2017-11-01

    The oral mucosa has recently become increasingly important as an alternative administration route for tailor-made, controlled drug delivery. Oromucosal multilayer films, assigned to the monograph oromucosal preparations in the Ph.Eur. may be a promising dosage form to overcome the requirements related to this drug delivery site. Areas covered: We provide an overview of multilayer films as drug delivery tools, and discuss manufacturing processes and characterization methods. We focus on the suitability of characterization methods for particular requirements of multilayer films. A classification was performed covering indication areas and APIs incorporated in multilayer film systems for oromucosal use in order to provide a summary of data published in this field. Expert opinion: The shift in drug development to high molecular weight drugs will influence the field of pharmaceutical development and delivery technologies. For a high number of indication areas, such as hormonal disorders, cardiovascular diseases or local treatment of infections, the flexible layer design of oromucosal multilayer films provides a promising option for tailor-made, controlled delivery of APIs to or through defined surfaces in the oral cavity. However, there is a lack of discriminating or standardized testing methods to assess the quality of multilayer films in a reliable way.

  10. Drug utilization and medication costs at the end of life.

    PubMed

    Pont, Lisa; Jansen, Kristian; Schaufel, Margrete Aase; Haugen, Dagny Faksvåg; Ruths, Sabine

    2016-01-01

    In the end stages of life, drug treatment goals shift to symptom control and quality of life and as such changes in drug utilization are expected. The aim of this paper is to review the extent to which costs are considered in drug utilization research at the end of life, with a particular focus on the outcome measures being used. This systematic review identified seven studies across varied settings studies reporting both drug utilization and medication cost outcome measures. The main factors identified that impacted medication use and cost were the time period considered and the provision of specialist palliative care services. Combining drug utilization and medication cost outcomes is critical for the allocation of healthcare resources and the development of a sound health policy.

  11. Microfinance investments in quality at private clinics in Uganda: a case-control study.

    PubMed

    Seiber, Eric E; Robinson, Amara L

    2007-10-18

    Small private-sector health care providers can play an important role in meeting the developing country health care needs, but a lack of credit can prove major constraint to small-provider expansion. This study examines the potential of small, microfinance loans to strengthen the private health sector and improve access to quality preventive and curative health services in Uganda. This study estimates logistic regressions using 2,387 client exit interviews to assess the impact of microfinance loans on perceived quality and the viability and sustainability of small, private clinics. The study finds perceived quality improved with loan recipients' clients being more likely to choose clinics on the basis of drug availability, fair charges, cleanliness, and confidentiality. In addition, the assessment found evidence of increased client flows, but the changes produced mixed results for sustainability with respondents being only half as likely to "always" visit a particular clinic. The results indicate that the microfinance program improved perceived quality at loan recipient clinics, especially as reliable drug outlets.

  12. Cognitive function in ecstasy naive abstinent drug dependants and MDMA users.

    PubMed

    Potter, Adam; Downey, Luke; Stough, Con

    2013-03-01

    'Hidden' symptoms, or subtle cognitive deficits and long-term changes in mood, have been linked to the recreational use of 3, 4-methylenedioxymethamphetamine/MDMA, and are notionally present in non-heavy polydrug users. This study assessed the cognitive functioning and mood profiles of clinically diagnosed drug dependents who had never consumed MDMA, recreational drug users that had previously consumed MDMA, with both groups having not consumed illicit drugs for 6-months, and a control group with limited illicit drug use and no MDMA usage in their past. Cognitive functioning was assessed using the Cognitive Drug Research computerised cognitive assessment system and participants completed the Profile of Mood States and Beck Depression Inventory to assess their current mood and depression. Participants in the clinically diagnosed drug dependent group scored significantly worse on the 'Quality of Working Memory' cognitive factor score than both the MDMA and control group (F (2, 33) = 5.75, p = 0.007). The control and clinical groups also differed on depression scores (U [16] = 13.00, p = 0.016) and Tension/Anxiety scores (U [16] = 16.00, p = 0.034), with the clinical group scoring significantly higher in both cases. The MDMA group did not differ from the control group on the measures of cognition or mood. These results suggest that despite a 6-month prolonged abstinence the cognitive deficits ostensibly caused by 'heavy' usage or the dependence on or abuse of illicit drugs are not reversed by abstinence.

  13. The potential of magneto-electric nanocarriers for drug delivery

    PubMed Central

    Kaushik, Ajeet; Jayant, Rahul Dev; Sagar, Vidya; Nair, Madhavan

    2015-01-01

    Introduction The development and design of personalized nanomedicine for better health quality is receiving great attention. In order to deliver and release a therapeutic concentration at the target site, novel nanocarriers (NCs) were designed, for example, magneto-electric (ME) which possess ideal properties of high drug loading, site-specificity and precise on-demand controlled drug delivery. Areas covered This review explores the potential of ME-NCs for on-demand and site-specific drug delivery and release for personalized therapeutics. The main features including effect of magnetism, improvement in drug loading, drug transport across blood-brain barriers and on-demand controlled release are also discussed. The future directions and possible impacts on upcoming nanomedicine are highlighted. Expert opinion Numerous reports suggest that there is an urgent need to explore novel NC formulations for safe and targeted drug delivery and release at specific disease sites. The challenges of formulation lie in the development of NCs that improve biocompatibility and surface modifications for optimum drug loading/preservation/transmigration and tailoring of electrical–magnetic properties for on-demand drug release. Thus, the development of novel NCs is anticipated to overcome the problems of targeted delivery of therapeutic agents with desired precision that may lead to better patient compliance. PMID:24986772

  14. The potential of magneto-electric nanocarriers for drug delivery.

    PubMed

    Kaushik, Ajeet; Jayant, Rahul Dev; Sagar, Vidya; Nair, Madhavan

    2014-10-01

    The development and design of personalized nanomedicine for better health quality is receiving great attention. In order to deliver and release a therapeutic concentration at the target site, novel nanocarriers (NCs) were designed, for example, magneto-electric (ME) which possess ideal properties of high drug loading, site-specificity and precise on-demand controlled drug delivery. This review explores the potential of ME-NCs for on-demand and site-specific drug delivery and release for personalized therapeutics. The main features including effect of magnetism, improvement in drug loading, drug transport across blood-brain barriers and on-demand controlled release are also discussed. The future directions and possible impacts on upcoming nanomedicine are highlighted. Numerous reports suggest that there is an urgent need to explore novel NC formulations for safe and targeted drug delivery and release at specific disease sites. The challenges of formulation lie in the development of NCs that improve biocompatibility and surface modifications for optimum drug loading/preservation/transmigration and tailoring of electrical-magnetic properties for on-demand drug release. Thus, the development of novel NCs is anticipated to overcome the problems of targeted delivery of therapeutic agents with desired precision that may lead to better patient compliance.

  15. Quality control and in vitro antioxidant potential of Coriandrum sativum Linn.

    PubMed Central

    Singh, Mhaveer; Tamboli, E. T.; Kamal, Y. T.; Ahmad, Wasim; Ansari, S. H.; Ahmad, Sayeed

    2015-01-01

    Background: Coriandrum sativum Linn., commonly known as coriander, is a well-known spice and drug in India. It has various health-related benefits and used in various Unani formulations. In this present study, quality assessment of coriander fruits was carried out by studying anatomical characters, physicochemical tests, and chemoprofiling using high performance thin layer chromatography (HPTLC) and gas chromatography-mass spectroscopy (GC-MS) along with in vitro antioxidant potential. Materials and Methods: Standardization was carried out as per the pharmacopeial guidelines. Estimation of heavy metals, pesticides, and aflatoxins was carried out to ascertain the presence of any contaminant in the sample. Chemoprofiling was achieved by thin layer chromatography (TLC) by optimizing the mobile phase for different extracts. The most of the pharmacological activities of coriander are based on volatile oil constituents. Hence, GC-MS profiling was also carried out using hexane-soluble fraction of hydro-alcoholic extract. The total phenolic contents and in vitro antioxidant efficacy were determined using previously established methods. Results: The quality control and anatomical studies were very valuable for the identification whereas good antioxidant potential was observed when compared to ascorbic acid. The drug was found free of contaminant when analyzed for pesticides and aflatoxins whereas heavy metals were found under reported limits. Conclusion: The work embodied in this present research can be utilized for the identification and the quality control of the coriander fruit. PMID:26681883

  16. Measuring effectiveness of drugs in observational databanks: promises and perils

    PubMed Central

    Krishnan, Eswar; Fries, James F

    2004-01-01

    Observational databanks have inherent strengths and shortcomings. As in randomized controlled trials, poor design of these databanks can either exaggerate or reduce estimates of drug effectiveness and can limit generalizability. This commentary highlights selected aspects of study design, data collection and statistical analysis that can help overcome many of these inadequacies. An international metaRegister and a formal mechanism for standardizing and sharing drug data could help improve the utility of databanks. Medical journals have a vital role in enforcing a quality checklist that improves reporting. PMID:15059263

  17. [Contemporary opinions on classification, pathogenesis and treatment of drug-resistant epilepsy].

    PubMed

    Jóźwiak, Sergiusz

    2007-01-01

    Epilepsy is one of the most frequent neurological disorders, both in children and adult persons. About 0.5-1% of general population suffer from epilepsy, which means that about 50 million people in the world are affected. First years of life and very late adulthood are periods in human's life particularly predisposing to epilepsy. Repetitive epileptic seizures may cause many life-threatening situations and significantly lower patient's quality of life. To the most serious complications belong status epilepticus and sudden unexpected deaths due to epilepsy (SUDEP). Absences from work or school caused by seizures, difficulties in social life, frequent injuries and necessity of polytherapy are also important for patients. All these factors result in low self-esteem and poor quality of life. The main aim of the treatment was control of epileptic seizures. However, despite of new antiepileptic drugs developed almost every year, in one third of all patients with epilepsy seizures remain out of control. Those patients are regarded to have "drug-resistant epilepsy". Despite of significant scale of the problem, there is no one definition of the phenomenon. In the presented review the authors outline current definitions, recent opinions on pathogenesis and risk factors, and provide practical rules of pharmacotherapy of epilepsy, which should help to restrict drug-resistancy.

  18. Quality of drug information on the World Wide Web and strategies to improve pages with poor information quality. An intervention study on pages about sildenafil

    PubMed Central

    Martin-Facklam, Meret; Kostrzewa, Michael; Martin, Peter; Haefeli, Walter E

    2004-01-01

    Aims The generally poor quality of health information on the world wide web (WWW) has caused preventable adverse outcomes. Quality management of information on the internet is therefore critical given its widespread use. In order to develop strategies for the safe use of drugs, we scored general and content quality of pages about sildenafil and performed an intervention to improve their quality. Methods The internet was searched with Yahoo and AltaVista for pages about sildenafil and 303 pages were included. For assessment of content quality a score based on accuracy and completeness of essential drug information was assigned. For assessment of general quality, four criteria were evaluated and their association with high content quality was determined by multivariate logistic regression analysis. The pages were randomly allocated to either control or intervention group. Evaluation took place before, as well as 7 and 22 weeks after an intervention which consisted of two letters with individualized feedback information on the respective page which were sent electronically to the address mentioned on the page. Results Providing references to scientific publications or prescribing information was significantly associated with high content quality (odds ratio: 8.2, 95% CI 3.2, 20.5). The intervention had no influence on general or content quality. Conclusions To prevent adverse outcomes caused by misinformation on the WWW individualized feedback to the address mentioned on the page was ineffective. It is currently probably the most straight-forward approach to inform lay persons about indicators of high information quality, i.e. the provision of references. PMID:14678344

  19. The International Interlaboratory Quality Control Program for Measurement of Antiretroviral Drugs in Plasma: a global proficiency testing program.

    PubMed

    Burger, David; Teulen, Marga; Eerland, Jaco; Harteveld, Anneke; Aarnoutse, Rob; Touw, Daan

    2011-04-01

    The International Interlaboratory Quality Control Program for Measurement of Antiretroviral Drugs in Plasma was initiated in 1999 by Radboud University Nijmegen Medical Center, The Netherlands, and continued later on in collaboration with the Dutch Association for Quality Assessment in Therapeutic Drug Monitoring and Clinical Toxicology (www.kkgt.nl). The aim of this analysis was to evaluate the first 10 years of the Program and to determine variables associated with reporting of less accurate results. Two rounds are organized annually in which blind samples are shipped to participants containing a low, medium, or high concentration of each antiretroviral drug. Any reported result that deviates more than 20% from the spiked concentration is defined as inaccurate. By the end of 2009, the number of laboratories participating in the Program had increased to 56; 44 (79%) are located in Europe. A total of 12,798 test results was available for analysis, of which 2104 (16.4%) were reported as inaccurate. Performance was best for samples containing nevirapine (mean of inadequate scores per round: 11.1%) and lopinavir (11.9%) and worst for indinavir (18.7%), atazanavir (18.9%), saquinavir (19.6%), and nelfinavir (21.3%). High and medium concentrations were less frequently reported as inaccurate than low concentrations: 13.5%, 13.0%, and 22.4%, respectively. Although the overall performance of the laboratories varied per year, a trend was visible for improvement over time with 19.9% of the results being inaccurate in 2002 (n = 20 laboratories) to 15.7% in 2009 (n = 56 laboratories). The Program provides a proficiency testing program in which laboratories are alerted to potential analytical errors while performing therapeutic drug monitoring in HIV-infected patients. Laboratories should put more effort in adequately analyzing concentrations of antiretroviral drugs with low minimum effective concentrations.

  20. Rating the raters: assessing the quality of Hamilton rating scale for depression clinical interviews in two industry-sponsored clinical drug trials.

    PubMed

    Engelhardt, Nina; Feiger, Alan D; Cogger, Kenneth O; Sikich, Dawn; DeBrota, David J; Lipsitz, Joshua D; Kobak, Kenneth A; Evans, Kenneth R; Potter, William Z

    2006-02-01

    The quality of clinical interviews conducted in industry-sponsored clinical drug trials is an important but frequently overlooked variable that may influence the outcome of a study. We evaluated the quality of Hamilton Rating Scale for Depression (HAM-D) clinical interviews performed at baseline in 2 similar multicenter, randomized, placebo-controlled depression trials sponsored by 2 pharmaceutical companies. A total of 104 audiotaped HAM-D clinical interviews were evaluated by a blinded expert reviewer for interview quality using the Rater Applied Performance Scale (RAPS). The RAPS assesses adherence to a structured interview guide, clarification of and follow-up to patient responses, neutrality, rapport, and adequacy of information obtained. HAM-D interviews were brief and cursory and the quality of interviews was below what would be expected in a clinical drug trial. Thirty-nine percent of the interviews were conducted in 10 minutes or less, and most interviews were rated fair or unsatisfactory on most RAPS dimensions. Results from our small sample illustrate that the clinical interview skills of raters who administered the HAM-D were below what many would consider acceptable. Evaluation and training of clinical interview skills should be considered as part of a rater training program.

  1. A Method of Retrospective Computerized System Validation for Drug Manufacturing Software Considering Modifications

    NASA Astrophysics Data System (ADS)

    Takahashi, Masakazu; Fukue, Yoshinori

    This paper proposes a Retrospective Computerized System Validation (RCSV) method for Drug Manufacturing Software (DMSW) that relates to drug production considering software modification. Because DMSW that is used for quality management and facility control affects big impact to quality of drugs, regulatory agency required proofs of adequacy for DMSW's functions and performance based on developed documents and test results. Especially, the work that explains adequacy for previously developed DMSW based on existing documents and operational records is called RCSV. When modifying RCSV conducted DMSW, it was difficult to secure consistency between developed documents and test results for modified DMSW parts and existing documents and operational records for non-modified DMSW parts. This made conducting RCSV difficult. In this paper, we proposed (a) definition of documents architecture, (b) definition of descriptive items and levels in the documents, (c) management of design information using database, (d) exhaustive testing, and (e) integrated RCSV procedure. As a result, we could conduct adequate RCSV securing consistency.

  2. Quality control of the paracetamol drug by chemometrics and imaging spectroscopy in the near infrared region

    NASA Astrophysics Data System (ADS)

    Baptistao, Mariana; Rocha, Werickson Fortunato de Carvalho; Poppi, Ronei Jesus

    2011-09-01

    In this work, it was used imaging spectroscopy and chemometric tools for the development and analysis of paracetamol and excipients in pharmaceutical formulations. It was also built concentration maps to study the distribution of the drug in the tablets surface. Multivariate models based on PLS regression were developed for paracetamol and excipients concentrations prediction. For the construction of the models it was used 31 samples in the tablet form containing the active principle in a concentration range of 30.0-90.0% (w/w) and errors below to 5% were obtained for validation samples. Finally, the study of the distribution in the drug was performed through the distribution maps of concentration of active principle and excipients. The analysis of maps showed the complementarity between the active principle and excipients in the tablets. The region with a high concentration of a constituent must have, necessarily, absence or low concentration of the other one. Thus, an alternative method for the paracetamol drug quality monitoring is presented.

  3. Ensuring the Quality of Stem Cell-Derived In Vitro Models for Toxicity Testing.

    PubMed

    Stacey, Glyn N; Coecke, Sandra; Price, Anna-Bal; Healy, Lyn; Jennings, Paul; Wilmes, Anja; Pinset, Christian; Ingelman-Sundberg, Magnus; Louisse, Jochem; Haupt, Simone; Kidd, Darren; Robitski, Andrea; Jahnke, Heinz-Georg; Lemaitre, Gilles; Myatt, Glenn

    Quality control of cell cultures used in new in vitro toxicology assays is crucial to the provision of reliable, reproducible and accurate toxicity data on new drugs or constituents of new consumer products. This chapter explores the key scientific and ethical criteria that must be addressed at the earliest stages of developing toxicology assays based on human pluripotent stem cell (hPSC) lines. It also identifies key considerations for such assays to be acceptable for regulatory, laboratory safety and commercial purposes. Also addressed is the development of hPSC-based assays for the tissue and cell types of greatest interest in drug toxicology. The chapter draws on a range of expert opinion within the European Commission/Cosmetics Europe-funded alternative testing cluster SEURAT-1 and consensus from international groups delivering this guidance such as the International Stem Cell Banking Initiative. Accordingly, the chapter summarizes the most up-date best practices in the use and quality control of human Pluripotent Stem Cell lines in the development of in vitro toxicity assays from leading experts in the field.

  4. Long-Term Seizure, Quality of Life, Depression, and Verbal Memory Outcomes in a Controlled Mesial Temporal Lobe Epilepsy Surgical Series Using Portuguese-Validated Instruments.

    PubMed

    Dias, Luis Augusto; Angelis, Geisa de; Teixeira, Wagner Afonso; Casulari, Luiz Augusto

    2017-08-01

    We aimed to evaluate long-term surgical outcomes in patients treated for mesial temporal lobe epilepsy compared with a similar group of patients who underwent a preoperative evaluation. Patient interviews were conducted by an independent neuropsychologist and included a sociodemographic questionnaire and validated versions of the Beck Depression Inventory-II, Adverse Events Profile, Quality of Life in Epilepsy-31, and Rey Auditory Verbal Learning Test. Seventy-one patients who underwent surgery and 20 who underwent mesial temporal lobe epilepsy preoperative evaluations were interviewed. After an 81-month mean postoperative follow-up, 44% of the surgical patients achieved complete seizure relief according to the Engel classification and 68% according to the International League Against Epilepsy classification. The surgical group had a significantly lower prevalence of depression (P = 0.002) and drug-related adverse effects (P = 0.002). Improvement on unemployment (P = 0.02) was achieved but not on driving or education. Delayed verbal memory recall was impaired in 76% of the surgical and 65% of the control cases (P = 0.32). Regarding the Quality of Life in Epilepsy-31, the operated patients scored higher in their total score (mean, 75.44 vs. mean, 60.08; P < 0.001) and in all but the cognitive functioning domain irrespective of the follow-up length. Seizure control, Beck Depression Score, and Adverse Events Profile severity explained 73% of the variance in the surgical group quality of life. Our study found that, although surgical treatment was effective, its impact on social indicators was modest. Moreover, the self-reported quality of life relied not only on seizure control but also on depressive symptoms and antiepileptic drug burden. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  5. Independent Evaluation of Middle School-Based Drug Prevention Curricula: A Systematic Review.

    PubMed

    Flynn, Anna B; Falco, Mathea; Hocini, Sophia

    2015-11-01

    Lack of robust program evaluation has hindered the effectiveness of school-based drug abuse prevention curricula overall. Independently evaluated randomized controlled trials (RCTs) of universal, middle school-based drug abuse prevention curricula are the most useful indicators of whether such programs are effective or ineffective. To conduct a systematic review identifying independently evaluated RCTs of universal, middle school-based drug abuse prevention curricula; extract data on study quality and substance use outcomes; and assess evidence of program effectiveness. PsycInfo, Educational Resources Information Center, Science Citation Index, Social Science Citation Index, Cumulative Index to Nursing and Allied Health Literature, MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched between January 1, 1984, and March 15, 2015. Search terms included variations of drug, alcohol, tobacco, and marijuana use, as well as school, prevention, and effectiveness. Studies included in the review were RCTs carried out by independent evaluators of universal school-based drug prevention curricula available for dissemination in the United States that reported alcohol, tobacco, marijuana, or other drug use outcomes. Two researchers extracted data on study quality and outcomes independently using a data extraction form and met to resolve disagreements. A total of 5071 publications were reviewed, with 13 articles meeting final inclusion criteria. Of the 13 articles, 6 RCTs of 4 distinct school-based curricula were identified for inclusion. Outcomes were reported for 42 single-drug measures in the independent RCTs, with just 3 presenting statistically significant (P < .05) differences between the intervention group and the control group. One program revealed statistically significant positive effects at final follow-up (Lions-Quest Skills for Adolescence). The results of our review demonstrate the dearth of independent research that appropriately evaluates the effectiveness of universal, middle school-based drug prevention curricula. Independent evaluations show little evidence of effectiveness for widely used programs. New methods may be necessary to approach school-based adolescent drug prevention.

  6. Antimalarial Drug: From its Development to Deface.

    PubMed

    Barik, Tapan Kumar

    2015-01-01

    Wiping out malaria is now the global concern as about three billion people are at risk of malaria infection globally. Despite of extensive research in the field of vaccine development for malaria, till now, no effective vaccine is available for use and hence only antimalarial drugs remain our best hope for both treatment and prevention of malaria. However, emergence and spread of drug resistance has been a major obstacle for the success of malaria elimination globally. This review will summarize the information related to antimalarial drugs, drug development strategies, drug delivery through nanoparticles, few current issues like adverse side effects of most antimalarial drugs, non availability of drugs in the market and use of fake/poor quality drugs that are hurdles to malaria control. As we don't have any other option in the present scenario, we have to take care of the existing tools and make them available to almost all malaria affected area.

  7. Competitive pricing within pharmaceutical classes: evidence on "follow-on" drugs in Germany 1993-2008.

    PubMed

    Mueller, Michael T; Frenzel, Alexander

    2015-01-01

    Competition from "follow-on" drugs has been a highly controversial issue. Manufacturers launching new molecules in existing drug classes have often been criticized for inflating health systems' expenses, but it has been argued that such drugs increase therapeutic options. Economic theory suggests that follow-on drugs induce price competition. We contribute to this discussion by addressing the topic of pricing at market entry and price development in the German market. We measure determinants of price strategies of follow-on drugs using regression analyses, considering all new molecules launched in the German market from 1993 to 2008. Prices of products are standardized on defined daily dosages controlling for sales volumes based on data from the IMS Health DPM database and for the therapeutic quality of a new product using ratings by Fricke/Klaus as a proxy for innovation. We identify prices correlating with therapeutic value at market entry. While the first two molecules engage in quality competition, price discounts below the market price can be observed from the third entrant on. Price discounts are even more distinct in development races with several drugs entering the market within 2 years and in classes with a low degree of therapeutic differentiation. Prices remain relatively constant over time. This study contributes to assessments of competition in pharmaceutical markets focusing on price strategies of new market entrants. After an initial phase of market building, further follow-on products induce price competition. Largely unchanged prices after 4 years may be interpreted as quality competition and can be attributed to prices in Germany being anchor points for international price referencing.

  8. [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.

  9. Rationale for Quality Assurance in Fecal Egg Monitoring of Soil-Transmitted Helminthiasis

    PubMed Central

    Hoekendijk, David J. L.; Hill, Philip C.; Sowerby, Stephen J.

    2016-01-01

    Substantial investment has been made into the once “neglected” tropical disease, soil-transmitted helminthiasis, and into control programs that operate within a framework of mapping baseline disease distribution, measuring the effectiveness of applied interventions, establishing when to cease drug administration, and for posttreatment evaluations. However, critical to each of these stages is the determination of helminth infection. The limitations of traditional microscope-based fecal egg diagnostics have not provided quality assurance in the monitoring of parasite disease and suboptimal treatment regimes provide for the potential development of parasite resistance to anthelmintic drugs. Improved diagnostic and surveillance tools are required to protect therapeutic effectiveness and to maintain funder confidence. Such tools may be on the horizon with emergent technologies that offer potential for enhanced visualization and quality-assured quantitation of helminth eggs. PMID:27352875

  10. Insight into the Development of Dissolution Media for BCS Class II Drugs: A Review from Quality Control and Prediction of In Vivo Performance Perspectives.

    PubMed

    Wu, Chunnuan; Liu, Yan; He, Zhonggui; Sun, Jin

    2016-01-01

    To assess in vivo behavior through in vitro method, the dissolution test is mostly used, both for quality control (QC) and for development purpose. In view of the fact that a dissolution test can hardly achieve two goals at the same time, the design of dissolution testing generally varies along with the development stage of drug products and therefore the selection of dissolution media may change with the goals of the dissolution test. To serve the QC purpose, a dissolution medium is designed to provide a sink condition; for development purpose, the dissolution medium is required to simulate the physiological conditions in the gastrointestinal tract as far as possible. In this review, we intended to provide an initial introduction to the various dissolution media applied for QC and formulation development purposes for poorly water soluble drugs. We focused on these methods like addition of cosolvents, surfactants and utilization of biphasic media, applied to provide sink conditions which are difficult to be achieved by simple aqueous buffers for lipophilic drugs, and introduced the development of physiologically relevant media for human and animals like dog and rat with respect to the choice of buffers, bile salts, lipids and so on. In addition, we further discussed the influence of biorelevant dissolution media on the modification of drug Biopharmaceutical Classification System (BCS) classification, especially for BCS class II drugs with low solubility and high permeability, the solubility of which is relatively sensitive to the presence of bile salts and lipids.

  11. Analyzing compound and project progress through multi-objective-based compound quality assessment.

    PubMed

    Nissink, J Willem M; Degorce, Sébastien

    2013-05-01

    Compound-quality scoring methods designed to evaluate multiple drug properties concurrently are useful to analyze and prioritize output from drug-design efforts. However, formalized multiparameter optimization approaches are not widely used in drug design. We rank molecules synthesized in drug-discovery projects using simple and aggregated desirability functions reflecting medicinal chemistry 'rules'. Our quality score deals transparently with missing data, a key requirement in drug-hunting projects where data availability is often limited. We further estimate confidence in the interpretation of such a compound-quality measure. Scores and associated confidences provide systematic insight in the quality of emerging chemical equity. Tracking quality of synthetic output over time yields valuable insight into the progress of drug-design teams, with potential applications in risk and resource management of a drug portfolio.

  12. Chinese Herbal Medicine for Acute Mountain Sickness: A Systematic Review of Randomized Controlled Trials

    PubMed Central

    Wang, Jie; Xiong, Xingjiang; Xing, Yanwei; Liu, Zhen; Jiang, Wenrui; Huang, Junyi; Feng, Bo

    2013-01-01

    Objectives. We aimed to assess the current clinical evidence of Chinese herbal medicine for AMS. Methods. Seven electronic databases were searched until January 2013. We included randomized clinical trials testing Chinese herbal medicine against placebo, no drugs, Western drugs, or a combination of routine treatment drugs against routine treatment drugs. Study selection, data extraction, quality assessment, and data analyses were conducted according to Cochrane standards. Results. Nine randomized trials were included. The methodological quality of the included trials was evaluated as low. Two trials compared prescriptions of Chinese formula used alone with Western drugs. A meta-analysis showed a beneficial effect in decreasing the score of AMS (MD: −2.23 [−3.98, −0.49], P = 0.01). Only one trial compared prescriptions of Chinese formula used alone with no drugs. A meta-analysis showed a significant beneficial effect in decreasing the score of AMS (MD: −6.00 [−6.45, −5.55], P < 0.00001). Four trials compared Chinese formula used alone with placebo. A meta-analysis also showed a significant beneficial effect in decreasing the score of AMS (MD: −1.10 [−1.64, −0.55], P < 0.0001). Two trials compared the combination of Chinese formula plus routine treatment drugs with routine treatment drugs. A meta-analysis showed a beneficial effect in decreasing the score of AMS (MD: −5.99 [−11.11, −0.86], P = 0.02). Conclusions. No firm conclusion on the effectiveness and safety of Chinese herbal medicine for AMS can be made. More rigorous high-quality trials are required to generate a high level of evidence and to confirm the results. PMID:24454510

  13. Analysis of Gap in Service Quality in Drug Addiction Treatment Centers of Kerman, Iran, Using SERVQUAL Model

    PubMed Central

    Naqavi, Mohammad Reza; Refaiee, Raheleh; Baneshi, Mohammad Reza; Nakhaee, Nouzar

    2014-01-01

    Background Treatment of drug addicts is one of the main strategies of drug control in Iran. Client satisfaction strongly influences the success of any treatment program. This study aimed to explore the difference between customer expectations and perceptions in drug addiction treatment centers of Kerman, Iran, using SERVQUAL model. Methods Using a cross-sectional design 260 clients referring to drug addiction treatment centers of Kerman, were enrolled in 2012. From among 84 clinics, 20 centers were selected randomly. Based on the number of clients registered in each center, a random sample proportional to the size was selected and 290 subjects were invited for interviews. A well validated 22-item questionnaire, which measured the 5 dimensions of service quality (reliability, assurance, tangibility, empathy, and responsiveness), was completed by participants. Each item measured 2 aspects of service quality; expectations and perceptions. Findings Mean ± SD (Standard deviation) age of the subjects was 37.7 ± 9.4. Most of them were male (87.7%). Less than half of them had an educational level lower than diploma. The total score of clients` expectations was higher than their perceptions (P < 0.001). Considering the 5 dimensions of the SERVQUAL model, only 1 dimension (i.e., assurance) showed no difference between perceptions and expectations of the participants (P = 0.134). Conclusion There was a gap between the clients’ expectations and what they actually perceived in the clinics. Thus, more attention should be devoted to the clients’ views regarding service quality in addiction treatment clinics. PMID:25984274

  14. [Good drug distribution practice and its implementation in drug distribution companies].

    PubMed

    Draksiene, Gailute

    2002-01-01

    Good Distribution Practice is based on the Directive of the Board of the European Community 92/25/EEC regarding the wholesale distribution of drugs for human consumption. It is stated in the Directive that the whole drug distribution channel is to be controlled from the point of drug production or import down to the supplies to the end user. In order to reach the goal, the drug distribution company must create the quality assurance system and facilitate its correct functioning. This aim requires development of the rules of the Good Distribution Practice. Those rules set the general requirements of the Good Distribution Practice for distribution companies that they must conduct. The article explains main requirements postulated in the rules of the Good Distribution Practice and implementation of the Good Distribution Practice requirements in drug distribution companies.

  15. Quality control in the diagnosis of Trichuris trichiura and Ascaris lumbricoides using the Kato-Katz technique: experience from three randomised controlled trials.

    PubMed

    Speich, Benjamin; Ali, Said M; Ame, Shaali M; Albonico, Marco; Utzinger, Jürg; Keiser, Jennifer

    2015-02-05

    An accurate diagnosis of soil-transmitted helminthiasis is important for individual patient management, for drug efficacy evaluation and for monitoring control programmes. The Kato-Katz technique is the most widely used method detecting soil-transmitted helminth eggs in faecal samples. However, detailed analyses of quality control, including false-positive and faecal egg count (FEC) estimates, have received little attention. Over a 3-year period, within the frame of a series of randomised controlled trials conducted in Pemba, United Republic of Tanzania, 10% of randomly selected Kato-Katz thick smears were re-read for Trichuris trichiura and Ascaris lumbricoides eggs. In case of discordant result (i.e. positive versus negative) the slides were re-examined a third time. A result was assumed to be false-positive or false-negative if the result from the initial reading did not agree with the quality control as well as the third reading. We also evaluated the general agreement in FECs between the first and second reading, according to internal and World Health Organization (WHO) guidelines. From the 1,445 Kato-Katz thick smears subjected to quality control, 1,181 (81.7%) were positive for T. trichiura and 290 (20.1%) were positive for A. lumbricoides. During quality control, very low rates of false-positive results were observed; 0.35% (n = 5) for T. trichiura and 0.28% (n = 4) for A. lumbricoides. False-negative readings of Kato-Katz thick smears were obtained in 28 (1.94%) and 6 (0.42%) instances for T. trichiura and A. lumbricoides, respectively. A high frequency of discordant results in FECs was observed (i.e. 10.0-23.9% for T. trichiura, and 9.0-11.4% for A. lumbricoides). Our analyses show that the rate of false-positive diagnoses of soil-transmitted helminths is low. As the probability of false-positive results increases after examination of multiple stool samples from a single individual, the potential influence of false-positive results on epidemiological studies and anthelminthic drug efficacy studies should be determined. Existing WHO guidelines for quality control might be overambitious and might have to be revised, specifically with regard to handling disagreements in FECs.

  16. Improving depression and enhancing resilience in family dementia caregivers: a pilot randomized placebo-controlled trial of escitalopram

    PubMed Central

    Lavretsky, H.; Siddarth, P.; Irwin, M. R.

    2009-01-01

    Background This study examined the potential of an antidepressant drug, escitalopram, to improve depression, resilience to stress, and quality of life in family dementia caregivers in a randomized placebo-controlled double-blind trial. Methods Forty family caregivers (43–91 years of age, 25 children and 15 spouses; 26 women) who were taking care of their relatives with Alzheimer’s disease were randomized to receive either escitalopram 10 mg/day or placebo for 12 weeks. Severity of depression, resilience, burden, distress, quality of life, and severity of care-recipient’s cognitive and behavioral disturbances were assessed at baseline and over the course of the study. The Hamilton Depression Rating Scale (HDRS) scores at baseline ranged between 10–28. The groups were stratified by the diagnosis of major and minor depression. Results Most outcomes favored escitalopram over placebo. The severity of depression improved and the remission rate was greater with the drug compared to placebo. Measures of anxiety, resilience, burden and distress improved on escitalopram compared to placebo. Discussion Among caregivers, this small randomized controlled trial found that escitalopram use resulted in improvement in depression, resilience, burden and distress, and quality of life. Our results need to be confirmed in a larger sample. PMID:20104071

  17. Combining ISO/IEC 17025:2005 and European Commission Decision 2002/657 audit requirements: a practical way forward.

    PubMed

    Kay, Jack F

    2012-08-01

    Laboratories involved in the analyses of veterinary drug residues are under increasing pressure to demonstrate that they produce meaningful and reliable data. Quality assurance and quality control systems are implemented in laboratories to provide evidence of this and these are subject to external assessment to ensure that they are effective. Audits to ISO/IEC 17025:2005, an internationally accepted standard, and subsequent accreditation provide laboratories and their customers with a degree of assurance that the laboratories are operating in control and the data they report can be relied on. However, national or regional authorities may place additional requirements on laboratories to ensure quality data are reported. For example, in the European Union, all official control laboratories involved in veterinary drug residue analyses must also meet the requirements of European Commission Decision 2002/657/EC which sets performance criteria for analytical methods used in this area and these are subject to additional audits by national or regional authorities. All audits place considerable time and resource demands on laboratories and this paper discusses the burden audits place on laboratories and describes a UK initiative to combine these audits to the benefit of both the regulatory authority and the laboratory. © 2012 John Wiley & Sons, Ltd.

  18. Mass drug administration for malaria

    PubMed Central

    Poirot, Eugenie; Skarbinski, Jacek; Sinclair, David; Kachur, S Patrick; Slutsker, Laurence; Hwang, Jimee

    2013-01-01

    Background Mass drug administration (MDA), defined as the empiric administration of a therapeutic antimalarial regimen to an entire population at the same time, has been a historic component of many malaria control and elimination programmes, but is not currently recommended. With renewed interest in MDA and its role in malaria elimination, this review aims to summarize the findings from existing research studies and program experiences of MDA strategies for reducing malaria burden and transmission. Objectives To assess the impact of antimalarial MDA on population asexual parasitaemia prevalence, parasitaemia incidence, gametocytaemia prevalence, anaemia prevalence, mortality and MDA-associated adverse events. Search methods We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE+, EMBASE, to February 2013. We also searched CABS Abstracts, LILACS, reference lists, and recent conference proceedings. Selection criteria Cluster-randomized trials and non-randomized controlled studies comparing therapeutic MDA versus placebo or no MDA, and uncontrolled before-and-after studies comparing post-MDA to baseline data were selected. Studies administering intermittent preventive treatment (IPT) to sub-populations (for example, pregnant women, children or infants) were excluded. Data collection and analysis Two authors independently reviewed studies for inclusion, extracted data and assessed risk of bias. Studies were stratified by study design and then subgrouped by endemicity, by co-administration of 8-aminoquinoline plus schizonticide drugs and by plasmodium species. The quality of evidence was assessed using the GRADE approach. Main results Two cluster-randomized trials, eight non-randomized controlled studies and 22 uncontrolled before-and-after studies are included in this review. Twenty-two studies (29 comparisons) compared MDA to placebo or no intervention of which two comparisons were conducted in areas of low endemicity (≤5%), 12 in areas of moderate endemicity (6-39%) and 15 in areas of high endemicity (≥ 40%). Ten studies evaluated MDA plus other vector control measures. The studies used a wide variety of MDA regimens incorporating different drugs, dosages, timings and numbers of MDA rounds. Many of the studies are now more than 30 years old. Areas of low endemicity (≤5%) Within the first month post-MDA, a single uncontrolled before-and-after study conducted in 1955 on a small Taiwanese island reported a much lower prevalence of parasitaemia following a single course of chloroquine compared to baseline (1 study, very low quality evidence). This lower parasite prevalence was still present after more than 12 months (one study, very low quality evidence). In addition, one cluster-randomized trial evaluating MDA in a low endemic setting reported zero episodes of parasitaemia at baseline, and throughout five months of follow-up in both the control and intervention arms (one study, very low quality evidence). Areas of moderate endemicity (6-39%) Within the first month post-MDA, the prevalence of parasitaemia was much lower in three non-randomized controlled studies from Kenya and India in the 1950s (RR 0.03, 95% CI 0.01 to 0.08, three studies, moderate quality evidence), and in three uncontrolled before-and-after studies conducted between 1954 and 1961 (RR 0.29, 95% CI 0.17 to 0.48, three studies,low quality evidence). The longest follow-up in these settings was four to six months. At this time point, the prevalence of parasitaemia remained substantially lower than controls in the two non-randomized controlled studies (RR 0.18, 95% CI 0.10 to 0.33, two studies, low quality evidence). In contrast, the two uncontrolled before-and-after studies found mixed results: one found no difference and one found a substantially higher prevalence compared to baseline (not pooled, two studies, very low quality evidence). Areas of high endemicity (≥40%) Within the first month post-MDA, the single cluster-randomized trial from the Gambia in 1999 found no significant difference in parasite prevalence (one study, low quality evidence). However, prevalence was much lower during the MDA programmes in three non-randomized controlled studies conducted in the 1960s and 1970s (RR 0.17, 95% CI 0.11 to 0.27, three studies, moderate quality evidence), and within one month of MDA in four uncontrolled before-and-after studies (RR 0.37, 95% CI 0.28 to 0.49, four studies,low quality evidence). Four trials reported changes in prevalence beyond three months. In the Gambia, the single cluster-randomized trial found no difference at five months (one trial, moderate quality evidence). The three uncontrolled before-and-after studies had mixed findings with large studies from Palestine and Cambodia showing sustained reductions at four months and 12 months, respectively, and a small study from Malaysia showing no difference after four to six months of follow-up (three studies,low quality evidence). 8-aminoquinolines We found no studies directly comparing MDA regimens that included 8-aminoquinolines with regimens that did not. In a crude subgroup analysis with a limited number of studies, we were unable to detect any evidence of additional benefit of primaquine in moderate- and high-transmission settings. Plasmodium species In studies that reported species-specific outcomes, the same interventions resulted in a larger impact on Plasmodium falciparum compared to P. vivax. Authors' conclusions MDA appears to reduce substantially the initial risk of malaria parasitaemia. However, few studies showed sustained impact beyond six months post-MDA, and those that did were conducted on small islands or in highland settings. To assess whether there is an impact of MDA on malaria transmission in the longer term requires more quasi experimental studies with the intention of elimination, especially in low- and moderate-transmission settings. These studies need to address any long-term outcomes, any potential barriers for community uptake, and contribution to the development of drug resistance. PLAIN LANGUAGE SUMMARY Administration of antimalarial drugs to whole populations Malaria is the most important mosquito-borne disease caused by a parasite, accounting for an estimated 660,000 deaths annually. Fortunately, malaria is both preventable and treatable. Several malaria control tools currently exist, and new and innovative approaches are continually under development. The administration of drugs against malaria to whole populations, termed mass drug administration (MDA), was a component of many malaria elimination programmes in the 1950s, and is once again attracting interest as a malaria elimination tool. As a consequence, it is important to review the currently available literature in order to assess the potential for this strategy to reduce malaria burden and transmission, and to identify gaps in our understanding. This review assessed the impact of MDA on several malaria-specific outcome measures. Thirty-two studies were included in this review, from sites in Asia, Africa, Europe and the Americas. The review found that although MDA can reduce the initial risk of malaria-specific outcomes, these reductions are often not sustained. However, a few studies conducted on small islands or in highland areas did show sustained impact more than six months after MDA. Adverse events were inadequately addressed in most studies. Notable severe drug reactions, including haemolysis, haemoglobinuria, severe anaemia and death, were reported with 8-aminoquinoline plus schizonticide drug co-administration, while severe skin reactions were reported with sulphadoxine-pyrimethamine plus artesunate plus primaquine. Assessing the true impact of MDA programmes can be a challenge due to the heterogeneity of the study methods employed. Nonetheless, this review can help guide future antimalarial MDA interventions and their evaluation. PMID:24318836

  19. Association between drug insurance cost sharing strategies and outcomes in patients with chronic diseases: a systematic review.

    PubMed

    Mann, Bikaramjit S; Barnieh, Lianne; Tang, Karen; Campbell, David J T; Clement, Fiona; Hemmelgarn, Brenda; Tonelli, Marcello; Lorenzetti, Diane; Manns, Braden J

    2014-01-01

    Prescription drugs are used in people with hypertension, diabetes, and cardiovascular disease to manage their illness. Patient cost sharing strategies such as copayments and deductibles are often employed to lower expenditures for prescription drug insurance plans, but the impact on health outcomes in these patients is unclear. To determine the association between drug insurance and patient cost sharing strategies on medication adherence, clinical and economic outcomes in those with chronic diseases (defined herein as diabetes, hypertension, hypercholesterolemia, coronary artery disease, and cerebrovascular disease). Studies were included if they examined various cost sharing strategies including copayments, coinsurance, fixed copayments, deductibles and maximum out-of-pocket expenditures. Value-based insurance design and reference based pricing studies were excluded. Two reviewers independently identified original intervention studies (randomized controlled trials, interrupted time series, and controlled before-after designs). MEDLINE, EMBASE, Cochrane Library, CINAHL, and relevant reference lists were searched until March 2013. Two reviewers independently assessed studies for inclusion, quality, and extracted data. Eleven studies, assessing the impact of seven policy changes, were included: 2 separate reports of one randomized controlled trial, 4 interrupted time series, and 5 controlled before-after studies. Outcomes included medication adherence, clinical events (myocardial infarction, stroke, death), quality of life, healthcare utilization, or cost. The heterogeneity among the studies precluded meta-analysis. Few studies reported the impact of cost sharing strategies on mortality, clinical and economic outcomes. The association between patient copayments and medication adherence varied across studies, ranging from no difference to significantly lower adherence, depending on the amount of the copayment. Lowering cost sharing in patients with chronic diseases may improve adherence, but the impact on clinical and economic outcomes is uncertain.

  20. Lamotrigine add-on for drug-resistant partial epilepsy.

    PubMed

    Ramaratnam, S; Marson, A G; Baker, G A

    2001-01-01

    Epilepsy is a common neurological disorder, affecting almost 0.5 to 1% of the population. Nearly 30% of patients with epilepsy are refractory to currently available drugs. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. To examine the effects of lamotrigine on seizures, side effects, cognition and quality of life, when used as an add-on treatment for patients with drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 2, 2001), MEDLINE (January 1966 to April 2001) and reference lists of articles. We also contacted the manufacturers of lamotrigine (Glaxo-Wellcome). Randomized placebo controlled trials, of patients with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomization was used. The studies may be double, single or unblinded. For crossover studies, the first treatment period was treated as a parallel trial. Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), side effects, effects on cognition, and quality of life. We found three parallel add-on studies and eight cross-over studies, which included 1243 patients (199 children and 1044 adults). The overall Peto's Odds Ratio (OR) and 95% confidence intervals (CIs) across all studies for 50% or greater reduction in seizure frequency was 2.71 (1.87, 3.91) indicating that lamotrigine is significantly more effective than placebo in reducing seizure frequency. The overall OR (95%CI) for treatment withdrawal (for any reason) is 1.12 (0.78, 1.61). The 99% CIs for ataxia, dizziness, nausea, and diplopia do not include unity, indicating that they are significantly associated with lamotrigine. The limited data available precludes any conclusions about effects on cognition and quality of life, though there may be minor benefits in affect balance (happiness) and mastery. Lamotrigine add-on therapy is effective in reducing the seizure frequency, in patients with drug-resistant partial epilepsy. Further trials are needed to assess the long term effects of lamotrigine, and to compare it with other add-on drugs.

  1. Lamotrigine add-on for drug-resistant partial epilepsy.

    PubMed

    Ramaratnam, S; Marson, A G; Baker, G A

    2000-01-01

    Epilepsy is a common neurological disorder, affecting almost 0.5 to 1% of the population. Nearly 30% of patients with epilepsy are refractory to currently available drugs. Lamotrigine is one of the newer antiepileptic drugs and is the topic of this review. To examine the effects of lamotrigine on seizures, side effects, cognition and quality of life, when used as an add-on treatment for patients with drug-resistant partial epilepsy. We searched the Cochrane Epilepsy Group trials register, the Cochrane Controlled Trials Register (Cochrane Library Issue 1, 2000), MEDLINE (January 1966 to December 1999) and reference lists of articles. We also contacted the manufacturers of lamotrigine (Glaxo-Wellcome). Randomized placebo controlled trials, of patients with drug-resistant partial epilepsy of any age, in which an adequate method of concealment of randomization was used. The studies may be double, single or unblinded. For crossover studies, the first treatment period was treated as a parallel trial. Two reviewers independently assessed the trials for inclusion and extracted data. Primary analyses were by intention to treat. Outcomes included 50% or greater reduction in seizure frequency, treatment withdrawal (any reason), side effects, effects on cognition, and quality of life. We found three parallel add-on studies and eight cross-over studies, which included 1243 patients (199 children and 1044 adults). The overall Peto's Odds Ratio (OR) and 95% confidence intervals (CIs) across all studies for 50% or greater reduction in seizure frequency was 2.71 (1.87, 3.91) indicating that lamotrigine is significantly more effective than placebo in reducing seizure frequency. The overall OR (95%CI) for treatment withdrawal (for any reason) is 1.12 (0.78, 1. 61). The 99% CIs for ataxia, dizziness, nausea, and diplopia do not include unity, indicating that they are significantly associated with lamotrigine. The limited data available preclude any conclusions about effects on cognition and quality of life, though there may be minor benefits in affect balance (happiness) and mastery. Lamotrigine add-on therapy is effective in reducing the seizure frequency, in patients with drug-resistant partial epilepsy. Further trials are needed to assess the long term effects of lamotrigine, and to compare it with other add-on drugs.

  2. Controlled local drug delivery strategies from chitosan hydrogels for wound healing.

    PubMed

    Elviri, Lisa; Bianchera, Annalisa; Bergonzi, Carlo; Bettini, Ruggero

    2017-07-01

    The main target of tissue engineering is the preparation and application of adequate materials for the design and production of scaffolds, that possess properties promoting cell adhesion, proliferation and differentiation. The use of natural polysaccharides, such as chitosan, to prepare hydrogels for wound healing and controlled drug delivery is a research topic of wide and increasing interest. Areas covered: This review presents the latest results and challenges in the preparation of chitosan and chitosan-based scaffold/hydrogel for wound healing applications. A detailed overview of their behavior in terms of controlled drug delivery, divided by drug categories, and efficacy was provided and critically discussed. Expert opinion: The need to establish and exploit the advantages of natural biomaterials in combination with active compounds is playing a pivotal role in the regenerative medicine fields. The challenges posed by the many variables affecting tissue repair and regeneration need to be standardized and adhere to recognized guidelines to improve the quality of evidence in the wound healing process. Currently, different methodologies are followed to prepare innovative scaffold formulations and structures. Innovative technologies such as 3D printing or bio-electrospray are promising to create chitosan-based scaffolds with finely controlled structures with customizable shape porosity and thickness. Chitosan scaffolds could be designed in combination with a variety of polysaccharides or active compounds with selected and reproducible spacial distribution, providing active wound dressing with highly tunable controlled drug delivery.

  3. Quality standards of the European Pharmacopoeia.

    PubMed

    Bouin, Anne-Sophie; Wierer, Michael

    2014-12-02

    The European Pharmacopoeia (Ph. Eur.) provides a legal and scientific reference for the quality control of medicines. It is legally binding in the 38 signatory parties of the Convention on the elaboration of a European Pharmacopoeia (37 member states and the European Union). The requirements for a specific herbal drug are prescribed in the corresponding individual monograph and the relevant general monographs. Criteria for pesticides and heavy metals for example are defined in the general monograph on Herbal drugs. The Ph. Eur. also provides general methods including methods for determination of aflatoxins B1 and ochratoxin A. Screening methods for aristolochic acids are applied for herbal drugs that may be subject to adulteration or substitution with plant material containing aristolochic acids. The Ph. Eur. collaborate in many areas with the European Medicines Agency (EMA) to ensure close collaboration as regards the respective work programmes and approach. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. A qualitative systematic review of head-to-head randomized controlled trials of oral analgesics in neuropathic pain

    PubMed Central

    Watson, C Peter N; Gilron, Ian; Sawynok, Jana

    2010-01-01

    BACKGROUND: Neuropathic pain (NP) encompasses many difficult-to-treat disorders. There are few head-to-head, comparative, randomized controlled trials (RCTs) of drugs for NP in different analgesic categories, or of different drugs within a category, despite many placebo-controlled RCTs for individual agents. Well-designed head-to-head comparative trials are an effective way to determine the relative efficacy and safety of a new drug. OBJECTIVE: To perform a systematic review of head-to-head RCTs of oral analgesics in NP. METHODS: A systematic review of RCTs involving NP patients was performed, of which head-to-head comparative trials were selected. Reference lists from published systematic reviews were searched. These studies were rated according to the Jadad scale for quality. RESULTS AND CONCLUSIONS: Twenty-seven such trials were identified. Seventeen were comparisons of different analgesics, and 10 were of different drugs within an analgesic class. Important information was obtained about the relative efficacy and safety of drugs in different categories and within a category. Some significant differences between active treatments were reported. Trial inadequacies were identified. More and improved head-to-head RCTs are needed to inform clinical choices. PMID:20577657

  5. International drug price comparisons: quality assessment.

    PubMed

    Machado, Márcio; O'Brodovich, Ryan; Krahn, Murray; Einarson, Thomas R

    2011-01-01

    To quantitatively summarize results (i.e., prices and affordability) reported from international drug price comparison studies and assess their methodological quality. A systematic search of the most relevant databases-Medline, Embase, International Pharmaceutical Abstracts (IPA), and Scopus, from their inception to May 2009-was conducted to identify original research comparing international drug prices. International drug price information was extracted and recorded from accepted papers. Affordability was reported as drug prices adjusted for income. Study quality was assessed using six criteria: use of similar countries, use of a representative sample of drugs, selection of specific types of prices, identification of drug packaging, different weights on price indices, and the type of currency conversion used. Of the 1 828 studies identified, 21 were included. Only one study adequately addressed all quality issues. A large variation in study quality was observed due to the many methods used to conduct the drug price comparisons, such as different indices, economic parameters, price types, basket of drugs, and more. Thus, the quality of published studies was considered poor. Results varied across studies, but generally, higher income countries had higher drug prices. However, after adjusting drug prices for affordability, higher income countries had more affordable prices than lower income countries. Differences between drug prices and affordability in different countries were found. Low income countries reported less affordability of drugs, leaving room for potential problems with drug access, and consequently, a negative impact on health. The quality of the literature on this topic needs improvement.

  6. 42 CFR 423.150 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Scope. 423.150 Section 423.150 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality Improvement Requirements...

  7. 42 CFR 423.168 - Accreditation organizations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Accreditation organizations. 423.168 Section 423.168 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality...

  8. Nano-sized crystalline drug production by milling technology.

    PubMed

    Moribe, Kunikazu; Ueda, Keisuke; Limwikrant, Waree; Higashi, Kenjirou; Yamamoto, Keiji

    2013-01-01

    Nano-formulation of poorly water-soluble drugs has been developed to enhance drug dissolution. In this review, we introduce nano-milling technology described in recently published papers. Factors affecting the size of drug crystals are compared based on the preparation methods and drug and excipient types. A top-down approach using the comminution process is a method conventionally used to prepare crystalline drug nanoparticles. Wet milling using media is well studied and several wet-milled drug formulations are now on the market. Several trials on drug nanosuspension preparation using different apparatuses, materials, and conditions have been reported. Wet milling using a high-pressure homogenizer is another alternative to preparing production-scale drug nanosuspensions. Dry milling is a simple method of preparing a solid-state drug nano-formulation. The effect of size on the dissolution of a drug from nanoparticles is an area of fundamental research, but it is sometimes incorrectly evaluated. Here, we discuss evaluation procedures and the associated problems. Lastly, the importance of quality control, process optimization, and physicochemical characterization are briefly discussed.

  9. Quality assurance in nuclear medicine facilities; availability of final recommendations--FDA. Notice.

    PubMed

    1985-05-13

    The Food and Drug Administration (FDA) is announcing the availability of final recommendations prepared by its Center for Devices and Radiological Health (CDRH) on quality assurance programs in nuclear medicine facilities. The final recommendations include the agency's rationale for the recommendations as well as references that can be used as well as references that can be used as guides in conducting quality control monitoring. These final recommendations are available as a technical report in CDRH's radiation recommendations series. They are intended to encourage and promote the development of voluntary quality assurance programs in nuclear medicine facilities.

  10. Proceedings of the drug testing laboratory managers symposium, 28 January--1 February 1974. Final report

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

    Noe, E.R.; Romanchick, W.A.; Ainsworth, C.A. III

    1975-06-01

    This report deals with broad concepts of managing mass screening programs for drugs of abuse; e.g., morphine, barbiturate, amphetamine, cocaine, and methaqualone. The interactions of the screening process and of the rehabilitation program were covered. Psychotherapy and group therapy are both utilized in rehabilitation programs. The semiautomated radioimmunoassay (RIA) screening procedures are both sensitive and specific at nanogram quantities. Future evaluations of a wafer disk transferral system and of a latex test for morphine are presented. The unique quality control system employed by military drug abuse testing laboratories is discussed. (Author) (GRA)

  11. Accelerated in-vitro release testing methods for extended-release parenteral dosage forms.

    PubMed

    Shen, Jie; Burgess, Diane J

    2012-07-01

    This review highlights current methods and strategies for accelerated in-vitro drug release testing of extended-release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in-situ depot-forming systems and implants. Extended-release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, 'real-time' in-vitro release tests for these dosage forms are often run over a long time period. Accelerated in-vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in-vitro release methods using United States Pharmacopeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended-release parenteral dosage forms, along with the accelerated in-vitro release testing methods currently employed are discussed. Accelerated in-vitro release testing methods with good discriminatory ability are critical for quality control of extended-release parenteral products. Methods that can be used in the development of in-vitro-in-vivo correlation (IVIVC) are desirable; however, for complex parenteral products this may not always be achievable. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  12. Accelerated in vitro release testing methods for extended release parenteral dosage forms

    PubMed Central

    Shen, Jie; Burgess, Diane J.

    2012-01-01

    Objectives This review highlights current methods and strategies for accelerated in vitro drug release testing of extended release parenteral dosage forms such as polymeric microparticulate systems, lipid microparticulate systems, in situ depot-forming systems, and implants. Key findings Extended release parenteral dosage forms are typically designed to maintain the effective drug concentration over periods of weeks, months or even years. Consequently, “real-time” in vitro release tests for these dosage forms are often run over a long time period. Accelerated in vitro release methods can provide rapid evaluation and therefore are desirable for quality control purposes. To this end, different accelerated in vitro release methods using United States Pharmacopoeia (USP) apparatus have been developed. Different mechanisms of accelerating drug release from extended release parenteral dosage forms, along with the accelerated in vitro release testing methods currently employed are discussed. Conclusions Accelerated in vitro release testing methods with good discriminatory ability are critical for quality control of extended release parenteral products. Methods that can be used in the development of in vitro-in vivo correlation (IVIVC) are desirable, however for complex parenteral products this may not always be achievable. PMID:22686344

  13. The NARCONON drug education curriculum for high school students: a non-randomized, controlled prevention trial.

    PubMed

    Lennox, Richard D; Cecchini, Marie A

    2008-03-19

    An estimated 13 million youths aged 12 to 17 become involved with alcohol, tobacco and other drugs annually. The number of 12- to 17-year olds abusing controlled prescription drugs increased an alarming 212 percent between 1992 and 2003. For many youths, substance abuse precedes academic and health problems including lower grades, higher truancy, drop out decisions, delayed or damaged physical, cognitive, and emotional development, or a variety of other costly consequences. For thirty years the Narconon program has worked with schools and community groups providing single educational modules aimed at supplementing existing classroom-based prevention activities. In 2004, Narconon International developed a multi-module, universal prevention curriculum for high school ages based on drug abuse etiology, program quality management data, prevention theory and best practices. We review the curriculum and its rationale and test its ability to change drug use behavior, perceptions of risk/benefits, and general knowledge. After informed parental consent, approximately 1000 Oklahoma and Hawai'i high school students completed a modified Center for Substance Abuse Prevention (CSAP) Participant Outcome Measures for Discretionary Programs survey at three testing points: baseline, one month later, and six month follow-up. Schools assigned to experimental conditions scheduled the Narconon curriculum between the baseline and one-month follow-up test; schools in control conditions received drug education after the six-month follow-up. Student responses were analyzed controlling for baseline differences using analysis of covariance. At six month follow-up, youths who received the Narconon drug education curriculum showed reduced drug use compared with controls across all drug categories tested. The strongest effects were seen in all tobacco products and cigarette frequency followed by marijuana. There were also significant reductions measured for alcohol and amphetamines. The program also produced changes in knowledge, attitudes and perception of risk. The eight-module Narconon curriculum has thorough grounding in substance abuse etiology and prevention theory. Incorporating several historically successful prevention strategies this curriculum reduced drug use among youths.

  14. Efficient use of retention time for the analysis of 302 drugs in equine plasma by liquid chromatography-MS/MS with scheduled multiple reaction monitoring and instant library searching for doping control.

    PubMed

    Liu, Ying; Uboh, Cornelius E; Soma, Lawrence R; Li, Xiaoqing; Guan, Fuyu; You, Youwen; Chen, Jin-Wen

    2011-09-01

    Multiple drug target analysis (MDTA) used in doping control is more efficient than single drug target analysis (SDTA). The number of drugs with the potential for abuse is so extensive that full coverage is not possible with SDTA. To address this problem, a liquid chromatography tandem mass spectrometric method was developed for simultaneous analysis of 302 drugs using a scheduled multiple reaction monitoring (s-MRM) algorithm. With a known retention time of an analyte, the s-MRM algorithm monitors each MRM transition only around its expected retention time. Analytes were recovered from plasma by liquid-liquid extraction. Information-dependent acquisition (IDA) functionality was used to combine s-MRM with enhanced product ion (EPI) scans within the same chromatographic analysis. An EPI spectrum library was also generated for rapid identification of analytes. Analysis time for the 302 drugs was 7 min. Scheduled MRM improved the quality of the chromatograms, signal response, reproducibility, and enhanced signal-to-noise ratio (S/N), resulting in more data points. Reduction in total cycle time from 2.4 s in conventional MRM (c-MRM) to 1 s in s-MRM allowed completion of the EPI scan at the same time. The speed for screening and identification of multiple drugs in equine plasma for doping control analysis was greatly improved by this method.

  15. Perceptions of parental bonding in freebase cocaine users versus non-illicit drug users

    PubMed Central

    Pettenon, Márcia; Kessler, Felix Henrique Paim; Guimarães, Luciano S. P.; Pedroso, Rosemeri Siqueira; Hauck, Simone; Pechansky, Flavio

    2014-01-01

    Background & objectives: Evidence has suggested that parenting styles have peculiar characteristics in families with drug-related issues. This study was undertaken to investigate the perception of crack (smoke cocaine) users and non-users about parental bonding quality regarding care and control in Brazil. Methods: A total of 198 hospitalized crack users and 104 users of any non-illicit drug were assessed using the Parental Bonding Instrument (PBI), the sixth version of the Addiction Severity Index (ASI) and Mini International Neuropsychiatric Interview (MINI). Results: Adjusted logistic regression analysis showed that crack users were more likely (ORadj = 9.68; 95% CI: 2.82, 33.20) to perceive neglectful mothers, as well as more likely (ORadj = 4.71, 95% CI: 2.17, 10.22) to perceive controlling and affectionless fathers in comparison with non-illicit drug users who were more likely to perceive optimal parenting. Interpretation & conclusions: Our findings indicate that the perception of neglectful mothers and affectionless controlling fathers may be associated with the tendency of the children to be less resilient when facing stressful events, leading them to a greater risk to use crack. PMID:25109717

  16. A good chew or good riddance--how to move forward in the regulation of khat consumption.

    PubMed

    Klein, Axel; Metaal, Pien

    2010-12-01

    To review the status of khat, the most recent plant based psychoactive substance to reach a global market, and consider policy making processes in general and the framework of drug control in particular. Desk review of literature on khat and wider drug policy processes. The risk assessment and classification of psychoactive drugs is a contested arena where political, economic and moral agendas collide, leaving countries that have banned khat, with significant social costs. To best manage the risks arising from the increasing availability of khat it is therefore suggested to draft a regulatory framework with clear objectives and guiding principles. Given that medical risks of khat use are modest, the objective of the regulatory framework should be the protection of consumers and community. This is best achieved by establishing processes for the quality control of khat imports, and by regulating access and availability. It should therefore not be considered as a drug to be controlled but as a licit substance that needs to be regulated. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  17. Physical therapy with drug treatment in Bell palsy: a focused review.

    PubMed

    Ferreira, Margarida; Marques, Elisa E; Duarte, José A; Santos, Paula C

    2015-04-01

    The physical therapy (PT) associated with standard drug treatment (SDT) in Bell palsy has never been investigated. Randomized controlled trials or quasirandomized controlled trials have compared facial PT (except treatments such as acupuncture and osteopathic) combined with SDT against a control group with SDT alone. Participants included those older than 15 yrs with a clinical diagnosis of Bell palsy, and the primary outcome measure was motor function recovery by the House-Brackmann scale. The methodologic quality of each study was also independently assessed by two reviewers using the PEDro scale. Four studies met the inclusion criteria. Three trials indicate that PT in association with SDT supports higher motor function recovery than SDT alone between 15 days and 1 yr of follow-up. On the other hand, one trial showed that electrical stimulation added to conventional PT with SDT did not influence treatment outcomes. The present review suggests that the current practice of Bell palsy treatment by PT associated with SDT seems to have a positive effect on grade and time recovery compared with SDT alone. However, there is very little quality evidence from randomized controlled trials, and such evidence is insufficient to decide whether combined treatment is beneficial in the management of Bell palsy.

  18. Improved statistical signal detection in pharmacovigilance by combining multiple strength-of-evidence aspects in vigiRank.

    PubMed

    Caster, Ola; Juhlin, Kristina; Watson, Sarah; Norén, G Niklas

    2014-08-01

    Detection of unknown risks with marketed medicines is key to securing the optimal care of individual patients and to reducing the societal burden from adverse drug reactions. Large collections of individual case reports remain the primary source of information and require effective analytics to guide clinical assessors towards likely drug safety signals. Disproportionality analysis is based solely on aggregate numbers of reports and naively disregards report quality and content. However, these latter features are the very fundament of the ensuing clinical assessment. Our objective was to develop and evaluate a data-driven screening algorithm for emerging drug safety signals that accounts for report quality and content. vigiRank is a predictive model for emerging safety signals, here implemented with shrinkage logistic regression to identify predictive variables and estimate their respective contributions. The variables considered for inclusion capture different aspects of strength of evidence, including quality and clinical content of individual reports, as well as trends in time and geographic spread. A reference set of 264 positive controls (historical safety signals from 2003 to 2007) and 5,280 negative controls (pairs of drugs and adverse events not listed in the Summary of Product Characteristics of that drug in 2012) was used for model fitting and evaluation; the latter used fivefold cross-validation to protect against over-fitting. All analyses were performed on a reconstructed version of VigiBase(®) as of 31 December 2004, at around which time most safety signals in our reference set were emerging. The following aspects of strength of evidence were selected for inclusion into vigiRank: the numbers of informative and recent reports, respectively; disproportional reporting; the number of reports with free-text descriptions of the case; and the geographic spread of reporting. vigiRank offered a statistically significant improvement in area under the receiver operating characteristics curve (AUC) over screening based on the Information Component (IC) and raw numbers of reports, respectively (0.775 vs. 0.736 and 0.707, cross-validated). Accounting for multiple aspects of strength of evidence has clear conceptual and empirical advantages over disproportionality analysis. vigiRank is a first-of-its-kind predictive model to factor in report quality and content in first-pass screening to better meet tomorrow's post-marketing drug safety surveillance needs.

  19. The quality control theory of aging.

    PubMed

    Ladiges, Warren

    2014-01-01

    The quality control (QC) theory of aging is based on the concept that aging is the result of a reduction in QC of cellular systems designed to maintain lifelong homeostasis. Four QC systems associated with aging are 1) inadequate protein processing in a distressed endoplasmic reticulum (ER); 2) histone deacetylase (HDAC) processing of genomic histones and gene silencing; 3) suppressed AMPK nutrient sensing with inefficient energy utilization and excessive fat accumulation; and 4) beta-adrenergic receptor (BAR) signaling and environmental and emotional stress. Reprogramming these systems to maintain efficiency and prevent aging would be a rational strategy for increased lifespan and improved health. The QC theory can be tested with a pharmacological approach using three well-known and safe, FDA-approved drugs: 1) phenyl butyric acid, a chemical chaperone that enhances ER function and is also an HDAC inhibitor, 2) metformin, which activates AMPK and is used to treat type 2 diabetes, and 3) propranolol, a beta blocker which inhibits BAR signaling and is used to treat hypertension and anxiety. A critical aspect of the QC theory, then, is that aging is associated with multiple cellular systems that can be targeted with drug combinations more effectively than with single drugs. But more importantly, these drug combinations will effectively prevent, delay, or reverse chronic diseases of aging that impose such a tremendous health burden on our society.

  20. Microfinance investments in quality at private clinics in Uganda: a case-control study

    PubMed Central

    Seiber, Eric E; Robinson, Amara L

    2007-01-01

    Background Small private-sector health care providers can play an important role in meeting the developing country health care needs, but a lack of credit can prove major constraint to small-provider expansion. This study examines the potential of small, microfinance loans to strengthen the private health sector and improve access to quality preventive and curative health services in Uganda. Methods This study estimates logistic regressions using 2,387 client exit interviews to assess the impact of microfinance loans on perceived quality and the viability and sustainability of small, private clinics. Results The study finds perceived quality improved with loan recipients' clients being more likely to choose clinics on the basis of drug availability, fair charges, cleanliness, and confidentiality. In addition, the assessment found evidence of increased client flows, but the changes produced mixed results for sustainability with respondents being only half as likely to "always" visit a particular clinic. Conclusion The results indicate that the microfinance program improved perceived quality at loan recipient clinics, especially as reliable drug outlets. PMID:17945024

  1. Pharmacological interventions for prevention or treatment of postoperative pain in people undergoing laparoscopic cholecystectomy.

    PubMed

    Gurusamy, Kurinchi Selvan; Vaughan, Jessica; Toon, Clare D; Davidson, Brian R

    2014-03-28

    While laparoscopic cholecystectomy is generally considered less painful than open surgery, pain is one of the important reasons for delayed discharge after day-surgery and overnight stay following laparoscopic cholecystectomy. The safety and effectiveness of different pharmacological interventions such as non-steroidal anti-inflammatory drugs, opioids, and anticonvulsant analgesics in people undergoing laparoscopic cholecystectomy is unknown. To assess the benefits and harms of different analgesics in people undergoing laparoscopic cholecystectomy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, and the World Health Organization International Clinical Trials Registry Platform portal (WHO ICTRP) to March 2013 to identify randomised clinical trials of relevance to this review. We considered only randomised clinical trials (irrespective of language, blinding, or publication status) comparing different pharmacological interventions with no intervention or inactive controls for outcomes related to benefit in this review. We considered comparative non-randomised studies with regards to treatment-related harms. We also considered trials that compared one class of drug with another class of drug for this review. Two review authors collected the data independently. We analysed the data with both fixed-effect and random-effects models using Review Manager 5 analysis. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI). We included 25 trials with 2505 participants randomised to the different pharmacological agents and inactive controls. All the trials were at unclear risk of bias. Most trials included only low anaesthetic risk people undergoing elective laparoscopic cholecystectomy. Participants were allowed to take additional analgesics as required in 24 of the trials. The pharmacological interventions in all the included trials were aimed at preventing pain after laparoscopic cholecystectomy. There were considerable differences in the pharmacological agents used and the methods of administration. The estimated effects of the intervention on the proportion of participants who were discharged as day-surgery, the length of hospital stay, or the time taken to return to work were imprecise in all the comparisons in which these outcomes were reported (very low quality evidence). There was no mortality in any of the groups in the two trials that reported mortality (183 participants, very low quality evidence). Differences in serious morbidity outcomes between the groups were imprecise across all the comparisons (very low quality evidence). None of the trials reported patient quality of life or time taken to return to normal activity. The pain at 4 to 8 hours was generally reduced by about 1 to 2 cm on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence). The pain at 9 to 24 hours was generally reduced by about 0.5 cm (a modest reduction) on the visual analogue scale of 1 to 10 cm in the comparisons involving the different pharmacological agents and inactive controls (low or very low quality evidence). There is evidence of very low quality that different pharmacological agents including non-steroidal anti-inflammatory drugs, opioid analgesics, and anticonvulsant analgesics reduce pain scores in people at low anaesthetic risk undergoing elective laparoscopic cholecystectomy. However, the decision to use these drugs has to weigh the clinically small reduction in pain against uncertain evidence of serious adverse events associated with many of these agents. Further randomised clinical trials of low risk of systematic and random errors are necessary. Such trials should include important clinical outcomes such as quality of life and time to return to work in their assessment.

  2. 42 CFR 423.156 - Consumer satisfaction surveys.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Consumer satisfaction surveys. 423.156 Section 423.156 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality...

  3. 21 CFR 820.250 - Statistical techniques.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Statistical techniques. 820.250 Section 820.250...) MEDICAL DEVICES QUALITY SYSTEM REGULATION Statistical Techniques § 820.250 Statistical techniques. (a... statistical techniques required for establishing, controlling, and verifying the acceptability of process...

  4. 7 CFR 981.442 - Quality control.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., pieces of kernels, meal accumulated in manufacturing, or other material, to crushers, feed manufacturers... contamination in accordance with the provisions of this section. (1) Treatment process. Treatment processes... Salmonella bacteria in almonds, pursuant to a letter of determination issued by the Food and Drug...

  5. 21 CFR 820.250 - Statistical techniques.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Statistical techniques. 820.250 Section 820.250...) MEDICAL DEVICES QUALITY SYSTEM REGULATION Statistical Techniques § 820.250 Statistical techniques. (a... statistical techniques required for establishing, controlling, and verifying the acceptability of process...

  6. Rationale for Quality Assurance in Fecal Egg Monitoring of Soil-Transmitted Helminthiasis.

    PubMed

    Hoekendijk, David J L; Hill, Philip C; Sowerby, Stephen J

    2016-09-07

    Substantial investment has been made into the once "neglected" tropical disease, soil-transmitted helminthiasis, and into control programs that operate within a framework of mapping baseline disease distribution, measuring the effectiveness of applied interventions, establishing when to cease drug administration, and for posttreatment evaluations. However, critical to each of these stages is the determination of helminth infection. The limitations of traditional microscope-based fecal egg diagnostics have not provided quality assurance in the monitoring of parasite disease and suboptimal treatment regimes provide for the potential development of parasite resistance to anthelmintic drugs. Improved diagnostic and surveillance tools are required to protect therapeutic effectiveness and to maintain funder confidence. Such tools may be on the horizon with emergent technologies that offer potential for enhanced visualization and quality-assured quantitation of helminth eggs. © The American Society of Tropical Medicine and Hygiene.

  7. The contribution of the French Muskoka Fund to improving access to essential medicines and priority health products for mothers and children.

    PubMed

    Macé, C; Nikiema, J-B

    2016-11-01

    One objective of the French Muskoka Fund since 2011 has been to improve the availability of quality healthcare services for mothers and children and thus to contribute to the continued presence of essential drugs and affordable quality health products and to their rational use by healthcare personnel. This project thus contributed to reinforcing the work of the national regulatory authorities, guarantor of the quality of the products supplied to the populations, but also to strengthening the coordination of supplies at the country level. It also enabled the provision of support for the implementation of drug price controls and helped to strengthen the ability of healthcare staff to optimize their use of the products available to them. This work should be continued in these countries as they meet the agenda of the Sustainable Development Goals, which require the establishment of universal healthcare coverage.

  8. Quality control of anti-tuberculosis FDC formulations in the global market: part II-accelerated stability studies.

    PubMed

    Ashokraj, Y; Kohli, G; Kaul, C L; Panchagnula, R

    2005-11-01

    To determine the quality and performance of rifampicin (RMP) containing fixed-dose combination (FDC) formulations of anti-tuberculosis drugs sourced from the international market with respect to physical, chemical and dissolution properties after storage at accelerated stability conditions (40 degrees C/75% relative humidity) and to identify appropriate storage specifications. Formulations across different companies and combinations were subjected to 6-month accelerated stability testing in packaging conditions recommended by the manufacturer. Various pharmacopeial and nonpharmacopeial tests for tablets were performed for 3- and 6-month samples. All the formulations were found to be stable, where extent of dissolution was within +/- 10% of that of the initial value, and all formulations passed the pharmacopeial limits for assay and content uniformity of 90-110% and +/- 15% of average drug content, respectively. Good quality RMP-containing FDCs that remain stable after 6-month accelerated stability testing are available in the marketplace.

  9. 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.

  10. Quantitative impurity analysis of monoclonal antibody size heterogeneity by CE-LIF: example of development and validation through a quality-by-design framework.

    PubMed

    Michels, David A; Parker, Monica; Salas-Solano, Oscar

    2012-03-01

    This paper describes the framework of quality by design applied to the development, optimization and validation of a sensitive capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) assay for monitoring impurities that potentially impact drug efficacy or patient safety produced in the manufacture of therapeutic MAb products. Drug substance or drug product samples are derivatized with fluorogenic 3-(2-furoyl)quinoline-2-carboxaldehyde and nucleophilic cyanide before separation by CE-SDS coupled to LIF detection. Three design-of-experiments enabled critical labeling parameters to meet method requirements for detecting minor impurities while building precision and robustness into the assay during development. The screening design predicted optimal conditions to control labeling artifacts while two full factorial designs demonstrated method robustness through control of temperature and cyanide parameters within the normal operating range. Subsequent validation according to the guidelines of the International Committee of Harmonization showed the CE-SDS/LIF assay was specific, accurate, and precise (RSD ≤ 0.8%) for relative peak distribution and linear (R > 0.997) between the range of 0.5-1.5 mg/mL with LOD and LOQ of 10 ng/mL and 35 ng/mL, respectively. Validation confirmed the system suitability criteria used as a level of control to ensure reliable method performance. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Evaluation of the potential use of hybrid LC-MS/MS for active drug quantification applying the 'free analyte QC concept'.

    PubMed

    Jordan, Gregor; Onami, Ichio; Heinrich, Julia; Staack, Roland F

    2017-11-01

    Assessment of active drug exposure of biologics may be crucial for drug development. Typically, ligand-binding assay methods are used to provide free/active drug concentrations. To what extent hybrid LC-MS/MS procedures enable correct 'active' drug quantification is currently under consideration. Experimental & results: The relevance of appropriate extraction condition was evaluated by a hybrid target capture immuno-affinity LC-MS/MS method using total and free/active quality controls (QCs). The rapid extraction (10 min) provided correct results, whereas overnight incubation resulted in significant overestimation of the free/active drug (monclonal antibody) concentration. Conventional total QCs were inappropriate to determine optimal method conditions in contrast to free/active QCs. The 'free/active analyte QC concept' enables development of appropriate extraction conditions for correct active drug quantification by hybrid LC-MS/MS.

  12. Continuous production of fenofibrate solid lipid nanoparticles by hot-melt extrusion technology: a systematic study based on a quality by design approach.

    PubMed

    Patil, Hemlata; Feng, Xin; Ye, Xingyou; Majumdar, Soumyajit; Repka, Michael A

    2015-01-01

    This contribution describes a continuous process for the production of solid lipid nanoparticles (SLN) as drug-carrier systems via hot-melt extrusion (HME). Presently, HME technology has not been used for the manufacturing of SLN. Generally, SLN are prepared as a batch process, which is time consuming and may result in variability of end-product quality attributes. In this study, using Quality by Design (QbD) principles, we were able to achieve continuous production of SLN by combining two processes: HME technology for melt-emulsification and high-pressure homogenization (HPH) for size reduction. Fenofibrate (FBT), a poorly water-soluble model drug, was incorporated into SLN using HME-HPH methods. The developed novel platform demonstrated better process control and size reduction compared to the conventional process of hot homogenization (batch process). Varying the process parameters enabled the production of SLN below 200 nm. The dissolution profile of the FBT SLN prepared by the novel HME-HPH method was faster than that of the crude FBT and a micronized marketed FBT formulation. At the end of a 5-h in vitro dissolution study, a SLN formulation released 92-93% of drug, whereas drug release was approximately 65 and 45% for the marketed micronized formulation and crude drug, respectively. Also, pharmacokinetic study results demonstrated a statistical increase in Cmax, Tmax, and AUC0-24 h in the rate of drug absorption from SLN formulations as compared to the crude drug and marketed micronized formulation. In summary, the present study demonstrated the potential use of hot-melt extrusion technology for continuous and large-scale production of SLN.

  13. Policies and perceptions on generic drugs: The case of Greece.

    PubMed

    Xanthopoulou, Sofia-Sotiria; Katsaliaki, Korina

    2018-01-01

    The increase in the consumption of generic drugs to reduce pharmaceutical expenditure is a challenge for many countries, especially during the economic crisis. The purpose of the present study is to review the Greek market of generic drugs and the decisions that shape it, to determine the factors that affect Greek patients' and doctors' attitudes about generic substitution and present a set of measures for all stakeholders based on the findings of the secondary and primary analysis. The study includes (a) an analysis of international and national reports and legislation on drugs policies and (b) a questionnaire survey of 242 hospital patients and 85 doctors regarding their perceptions on generics. A small increase in the volume of generics is recorded, yet not followed by sales value, over the recent years that the measures for promoting generics prescription took effect. Distrust from both patients and doctors was observed toward generics' effectiveness and toward the appropriateness of the regulatory authorities' quality controls. The study presents a structured set of viable measures, applicable to many countries, for promoting generic drug consumption that can lead to economic efficiency without degrading the health care quality.

  14. Modified Chaihu Shugan Powder for Functional Dyspepsia: Meta-Analysis for Randomized Controlled Trial

    PubMed Central

    Yang, Nan; Jiang, Xuehua; Hu, Zhiqiang; Wang, Ling; Song, Minxian

    2013-01-01

    Context. Modified Chaihu Shugan powder (MCSP) is a popular traditional Chinese herbal formula for functional dyspepsia, which is revised from Chaihu Shugan San and recorded in a medical classic works of China. However, its role and effect in treating functional dyspepsia have not been well established. Objective. To assess the effect and safety of modified Chaihu Shugan powder for functional dyspepsia. Methods. We searched the published and unpublished studies up to August 2012. Only RCTs of modified Chaihu Shugan powder with or without prokinetic drugs versus prokinetic drugs in the patients diagnosed with functional dyspepsia were included. Results. Twenty-two clinical trials involving 1998 participants were included. There were evidences that modified Chaihu Shugan powder (RR = 1.20, 95%, CI 1.14 to 1.27) and modified Chaihu Shugan powder plus prokinetic drugs (RR = 1.18, 95%, CI 1.11 to 1.25) were significantly better treatment options than prokinetic drugs alone in improving symptoms. No serious adverse events were described in the included trials. Conclusions. This meta-analysis showed that modified Chaihu Shugan powder alone or in combination with prokinetic drugs might be more effective than prokinetic drugs alone. However, with poor methodological quality, all the included trials were at high risk of bias. Further large-scale high-quality trials are required for assessment. PMID:23762161

  15. Defining a reference set to support methodological research in drug safety.

    PubMed

    Ryan, Patrick B; Schuemie, Martijn J; Welebob, Emily; Duke, Jon; Valentine, Sarah; Hartzema, Abraham G

    2013-10-01

    Methodological research to evaluate the performance of methods requires a benchmark to serve as a referent comparison. In drug safety, the performance of analyses of spontaneous adverse event reporting databases and observational healthcare data, such as administrative claims and electronic health records, has been limited by the lack of such standards. To establish a reference set of test cases that contain both positive and negative controls, which can serve the basis for methodological research in evaluating methods performance in identifying drug safety issues. Systematic literature review and natural language processing of structured product labeling was performed to identify evidence to support the classification of drugs as either positive controls or negative controls for four outcomes: acute liver injury, acute kidney injury, acute myocardial infarction, and upper gastrointestinal bleeding. Three-hundred and ninety-nine test cases comprised of 165 positive controls and 234 negative controls were identified across the four outcomes. The majority of positive controls for acute kidney injury and upper gastrointestinal bleeding were supported by randomized clinical trial evidence, while the majority of positive controls for acute liver injury and acute myocardial infarction were only supported based on published case reports. Literature estimates for the positive controls shows substantial variability that limits the ability to establish a reference set with known effect sizes. A reference set of test cases can be established to facilitate methodological research in drug safety. Creating a sufficient sample of drug-outcome pairs with binary classification of having no effect (negative controls) or having an increased effect (positive controls) is possible and can enable estimation of predictive accuracy through discrimination. Since the magnitude of the positive effects cannot be reliably obtained and the quality of evidence may vary across outcomes, assumptions are required to use the test cases in real data for purposes of measuring bias, mean squared error, or coverage probability.

  16. Impact of normalization methods on high-throughput screening data with high hit rates and drug testing with dose-response data.

    PubMed

    Mpindi, John-Patrick; Swapnil, Potdar; Dmitrii, Bychkov; Jani, Saarela; Saeed, Khalid; Wennerberg, Krister; Aittokallio, Tero; Östling, Päivi; Kallioniemi, Olli

    2015-12-01

    Most data analysis tools for high-throughput screening (HTS) seek to uncover interesting hits for further analysis. They typically assume a low hit rate per plate. Hit rates can be dramatically higher in secondary screening, RNAi screening and in drug sensitivity testing using biologically active drugs. In particular, drug sensitivity testing on primary cells is often based on dose-response experiments, which pose a more stringent requirement for data quality and for intra- and inter-plate variation. Here, we compared common plate normalization and noise-reduction methods, including the B-score and the Loess a local polynomial fit method under high hit-rate scenarios of drug sensitivity testing. We generated simulated 384-well plate HTS datasets, each with 71 plates having a range of 20 (5%) to 160 (42%) hits per plate, with controls placed either at the edge of the plates or in a scattered configuration. We identified 20% (77/384) as the critical hit-rate after which the normalizations started to perform poorly. Results from real drug testing experiments supported this estimation. In particular, the B-score resulted in incorrect normalization of high hit-rate plates, leading to poor data quality, which could be attributed to its dependency on the median polish algorithm. We conclude that a combination of a scattered layout of controls per plate and normalization using a polynomial least squares fit method, such as Loess helps to reduce column, row and edge effects in HTS experiments with high hit-rates and is optimal for generating accurate dose-response curves. john.mpindi@helsinki.fi. Supplementary information: R code and Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press.

  17. Novel approach for a PTX/VEGF dual drug delivery system in cardiovascular applications-an innovative bulk and surface drug immobilization.

    PubMed

    Wulf, Katharina; Teske, Michael; Matschegewski, Claudia; Arbeiter, Daniela; Bajer, Dalibor; Eickner, Thomas; Schmitz, Klaus-Peter; Grabow, Niels

    2018-06-01

    The successive incorporation of several drugs into the polymeric bulk of implants mostly results in loss of considerable quantity of one drug, and/or the loss in quality of the coating and also in changes of drug release time points. A dual drug delivery system (DDDS) based on poly-L-lactide (PLLA) copolymers combining the effective inhibition of smooth muscle cell proliferation while simultaneously promoting re-endothelialization was successfully developed. To overcome possible antagonistic drug interactions and the limitation of the polymeric bulk material as release system for dual drugs, a novel concept which combines the bulk and surface drug immobilization for a DDDS was investigated. The advantage of this DDDS is that the bulk incorporation of fluorescein diacetate (FDAc) (model drug for paclitaxel (PTX)) via spray coating enhanced the subsequent cleavable surface coupling of vascular endothelial growth factor (VEGF) via the crosslinker bissulfosuccinimidyl suberate (BS 3 ). In the presence of the embedded FDAc, the VEGF loading and release are about twice times higher than in absence. Furthermore, the DDDS combines the diffusion drug delivery (FDAc or PTX) and the chemical controlled drug release, VEGF via hydrolysable ester bonds, without loss in quantity and quality of the drug release curves. Additionally, the performed in vitro biocompatibility study showed the bimodal influences of PTX and VEGF on human endothelial EA.hy926 cells. In conclusion, it was possible to show the feasibility to develop a novel DDDS which has a high potential for the medical application due to the possible easy and short modification of a polymer-based PTX delivery system.

  18. Improving drug-therapy decisions through educational outreach. A randomized controlled trial of academically based "detailing".

    PubMed

    Avorn, J; Soumerai, S B

    1983-06-16

    Improving precision and economy in the prescribing of drugs is a goal whose importance has increased with the proliferation of new and potent agents and with growing economic pressures to contain health-care costs. We implemented an office-based physician education program to reduce the excessive use of three drug groups: cerebral and peripheral vasodilators, an oral cephalosporin, and propoxyphene. A four-state sample of 435 prescribers of these drugs was identified through Medicaid records and randomly assigned to one of three groups. Physicians who were offered personal educational visits by clinical pharmacists along with a series of mailed "unadvertisements" reduced their prescribing of the target drugs by 14 per cent as compared with controls (P = 0.0001). A comparable reduction in the number of dollars reimbursed for these drugs was also seen between the two groups, resulting in substantial cost savings. No such change was seen in physicians who received mailed print materials only. The effect persisted for at least nine months after the start of the intervention, and no significant increase in the use of expensive substitute drugs was found. Academically based "detailing" may represent a useful and cost-effective way to improve the quality of drug-therapy decisions and reduce unnecessary expenditures.

  19. Attentional Bias for Non-drug Reward is Magnified in Addiction

    PubMed Central

    Anderson, Brian A.; Faulkner, Monica L.; Rilee, Jessica J.; Yantis, Steven; Marvel, Cherie L.

    2014-01-01

    Attentional biases for drug-related stimuli play a prominent role in addiction, predicting treatment outcome. Attentional biases also develop for stimuli that have been paired with non-drug reward in adults without a history of addiction, the magnitude of which is predicted by visual working memory capacity and impulsiveness. We tested the hypothesis that addiction is associated with an increased attentional bias for non-drug (monetary) reward relative to that of healthy controls, and that this bias is related to working memory impairments and increased impulsiveness. Seventeen patients receiving methadone maintenance treatment for opioid dependence and seventeen healthy controls participated. Impulsiveness was measured using the Barratt Impulsiveness Scale (BIS-11), visual working memory capacity was measured as the ability to recognize briefly presented color stimuli, and attentional bias was measured as the magnitude of response time slowing caused by irrelevant but previously reward-associated distractors in a visual search task. The results showed that attention was biased toward the distractors across all participants, replicating previous findings. Importantly, this bias was significantly greater in the patients than in the controls and was negatively correlated with visual working memory capacity. Patients were also significantly more impulsive than controls as a group. Our findings demonstrate that patients in treatment for addiction experience greater difficulty ignoring stimuli associated with non-drug reward. This non-specific reward-related bias could mediate the distracting quality of drug-related stimuli previously observed in addiction. PMID:24128148

  20. Causes and consequences of anti-infective drug stock-outs.

    PubMed

    Luans, C; Cardiet, I; Rogé, P; Baslé, B; Le Corre, P; Revest, M; Michelet, C; Tattevin, P

    2014-10-01

    Anti-infective drugs stock-outs are increasingly frequent, and this is unlikely to change. There are numerous causes for this, mostly related to parameters difficult to control: i) 60 to 80% of raw material or components are produced outside of Europe (compared to 20% 30 years ago), with subsequent loss of independence for their procurement; ii) the economic crisis drives the pharmaceutical companies to stop producing drugs of limited profitability (even among important drugs); iii) the enforcement of regulatory requirements and quality control procedures result in an increasing number of drugs being blocked during production. The therapeutic class most affected by drug stock-outs is that of anti-infective drugs, especially injectable ones, and many therapeutic dead ends have recently occurred. We provide an update on this issue, and suggest 2 major actions for improvement: i) to implement a group dedicated to anticipating drug stock-outs within the anti-infective committee in each health care center, with the objectives of organizing and coordinating the response whenever a drug stock-out is deemed at risk (i.e., contingency plans, substitution, communication to prescribers); ii) a national reflection lead by scientific societies, in collaboration with government agencies, upstream of the most problematic drug stock-outs, to elaborate and disseminate consensus guidelines for the management of these stock-outs. Copyright © 2014. Published by Elsevier SAS.

  1. 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.

  2. The nine-year sustained cost-containment impact of swiss pilot physicians-pharmacists quality circles.

    PubMed

    Niquille, Anne; Ruggli, Martine; Buchmann, Michel; Jordan, Dominique; Bugnon, Olivier

    2010-04-01

    Six pioneer physicians-pharmacists quality circles (PPQCs) located in the Swiss canton of Fribourg (administratively corresponding to a state in the US) were under the responsibility of 6 trained community pharmacists moderating the prescribing process of 24 general practitioners (GPs). PPQCs are based on a multifaceted collaborative process mediated by community pharmacists for improving compliance with clinical guidelines within GPs' prescribing practices. To assess, over a 9-year period (1999-2007), the cost-containment impact of the PPQCs. The key elements of PPQCs are a structured continuous quality improvement and education process; local networking; feedback of comparative and detailed data regarding costs, drug choice, and frequency of prescribed drugs; and structured independent literature review for interdisciplinary continuing education. The data are issued from the community pharmacy invoices to the health insurance companies. The study analyzed the cost-containment impact of the PPQCs in comparison with GPs working in similar conditions of care without particular collaboration with pharmacists, the percentage of generic prescriptions for specific cardiovascular drug classes, and the percentage of drug costs or units prescribed for specific cardiovascular drugs. For the 9-year period, there was a 42% decrease in the drug costs in the PPQC group as compared to the control group, representing a $225,000 (USD) savings per GP only in 2007. These results are explained by better compliance with clinical and pharmacovigilance guidelines, larger distribution of generic drugs, a more balanced attitude toward marketing strategies, and interdisciplinary continuing education on the rational use of drugs. The PPQC work process has yielded sustainable results, such as significant cost savings, higher penetration of generics and reflection on patient safety, and the place of "new" drugs in therapy. The PPQCs may also constitute a solid basis for implementing more comprehensive collaborative programs, such as medication reviews, adherence-enhancing interventions, or disease management approaches.

  3. Effects of atypical antipsychotic drugs on QT interval in patients with mental disorders

    PubMed Central

    Aronow, Wilbert S.

    2018-01-01

    Background Drug-induced QT prolongation is associated with higher risk of cardiac arrhythmias and cardiovascular mortality. We investigated the effects of atypical antipsychotic drugs on QT interval in children and adults with mental disorders. Methods We conducted random-effects direct frequentist meta-analyses of aggregate data from randomized controlled trials (RCT) and appraised the quality of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Our search in PubMed, EMBASE, the Cochrane Library, clinicaltrials.gov, and PharmaPendium up to October 2017 identified studies that examined aripiprazole, quetiapine, risperidone, olanzapine, ziprasidone and brexpiprazole. Results Low quality evidence suggests that aripiprazole (four meta-analyses and twelve RCTs), brexpiprazole (one systematic review and four RCTs) or olanzapine (five meta-analyses and twenty RCTs) do not increase QT interval. Low quality evidence suggests that ziprasidone (five meta-analyses and 11 RCTs) increases QT interval and the rates of QT prolongation while risperidone (four meta-analyses, 70 RCTs) and quetiapine (two meta-analyses and seven RCTs) are associated with QT prolongation and greater odds of torsades de pointes ventricular tachycardia especially in cases of drug overdose. Conclusions The main conclusion of our study is that in people with mental disorders and under treatment with atypical antipsychotic drugs, in order to avoid QT prolongation and reduce the risk of ventricular tachycardia clinicians may recommend aripiprazole, brexpiprazole or olanzapine in licensed doses. Long-term comparative safety needs to be established. PMID:29862236

  4. 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.

  5. Industry guidelines, laws and regulations ignored: quality of drug advertising in medical journals.

    PubMed

    Lankinen, Kari S; Levola, Tero; Marttinen, Kati; Puumalainen, Inka; Helin-Salmivaara, Arja

    2004-11-01

    To document the quality of evidence base for marketing claims in prescription drug advertisements, to facilitate identification of potential targets for quality improvement. A sample of 1036 advertisements from four major Finnish medical journals published in 2002. Marketing claims were classified in four groups: unambiguous clinical outcome, vague clinical outcome, emotive or immeasurable outcome and non-clinical outcome. Medline references were traced and classified according to the level of evidence available. The statistical variables used in the advertisements were also documented. The sample included 245 distinct advertisements with 883 marketing claims, 1-10 claims per advertisement. Three hundred thirty seven (38%) of the claims were referenced. Each claim could be supported by one reference or more, so the number of references analysed totalled 381, 1-9 references per advertisement. Nine percent of the claims implied unambiguous clinical outcomes, 68% included vague or emotive statements. Twenty one percent of the references were irrelevant to the claim. There was a fair amount of non-scientific and scientific support for the 73 unambiguous claims, but not a single claim was supported by strong scientific evidence. Vague, emotive and non-clinical claims were significantly more often supported by non-Medline or irrelevant references than unambiguous claims. Statistical parameters were stated only 34 times. Referenced marketing claims may appear more scientific, but the use of references does not guarantee the quality of the claims. For the benefit of all stakeholders, both the regulatory control and industry's self-control of drug marketing should adopt more active monitoring roles, and apply sanctions when appropriate. Concerted efforts by several stakeholders might be more effective. Copyright 2004 John Wiley & Sons, Ltd.

  6. 21 CFR 225.65 - Equipment cleanout procedures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR MEDICATED FEEDS Product Quality Control § 225.65 Equipment cleanout procedures. (a) Adequate cleanout procedures for all equipment used in the manufacture... sequential production of feeds. (2) If flushing is utilized, the flush material shall be properly identified...

  7. 42 CFR 423.160 - Standards for electronic prescribing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Standards for electronic prescribing. 423.160 Section 423.160 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICARE PROGRAM VOLUNTARY MEDICARE PRESCRIPTION DRUG BENEFIT Cost Control and Quality...

  8. 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...

  9. The US regulatory and pharmacopeia response to the global heparin contamination crisis.

    PubMed

    Szajek, Anita Y; Chess, Edward; Johansen, Kristian; Gratzl, Gyöngyi; Gray, Elaine; Keire, David; Linhardt, Robert J; Liu, Jian; Morris, Tina; Mulloy, Barbara; Nasr, Moheb; Shriver, Zachary; Torralba, Pearle; Viskov, Christian; Williams, Roger; Woodcock, Janet; Workman, Wesley; Al-Hakim, Ali

    2016-06-09

    The contamination of the widely used lifesaving anticoagulant drug heparin in 2007 has drawn renewed attention to the challenges that are associated with the characterization, quality control and standardization of complex biological medicines from natural sources. Heparin is a linear, highly sulfated polysaccharide consisting of alternating glucosamine and uronic acid monosaccharide residues. Heparin has been used successfully as an injectable antithrombotic medicine since the 1930s, and its isolation from animal sources (primarily porcine intestine) as well as its manufacturing processes have not changed substantially since its introduction. The 2007 heparin contamination crisis resulted in several deaths in the United States and hundreds of adverse reactions worldwide, revealing the vulnerability of a complex global supply chain to sophisticated adulteration. This Perspective discusses how the US Food and Drug Administration (FDA), the United States Pharmacopeial Convention (USP) and international stakeholders collaborated to redefine quality expectations for heparin, thus making an important natural product better controlled and less susceptible to economically motivated adulteration.

  10. Effect of Perioperative Pregabalin on Postoperative Quality of Recovery in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting (OPCABG): A Prospective, Randomized, Double-Blind Trial.

    PubMed

    Borde, Deepak Prakash; Futane, Savani Sameer; Asegaonkar, Balaji; Apsingekar, Pramod; Khade, Sujeet; Khodve, Bapu; Puranik, Manish; George, Antony; Joshi, Shreedhar

    2017-08-01

    Use of pregabalin is increasing in cardiac surgical patients. However, studies using comprehensive scoring systems are lacking on the drug's impact on postoperative recovery. The authors tested the hypothesis that perioperative oral pregabalin improves the postoperative quality of recovery as assessed using the Quality of Recovery (QoR-40) questionnaire in patients undergoing off-pump coronary artery bypass grafting (OPCABG). This was a randomized, double-blind, placebo-controlled study. Tertiary-care hospital. Patients undergoing OPCABG. Patients were assigned randomly to the following 2 groups: the pregabalin group (those who received pregabalin, 150 mg capsule orally, 1 hour before surgery and 2 days postoperatively [75 mg twice a day] starting after extubation; n = 37); and the control group (those who received 2 similar-looking multivitamin capsules at similar times; n = 34). The QoR-40 scores were noted preoperatively and 24 hours after extubation. Both groups were comparable in terms of preoperative patient characteristics and baseline QoR-40 scores. Global scores were significantly improved in the pregabalin group compared with the control group in the postoperative period (177±9 v 170±9; p = 0.002). QoR-40 values in the dimensions of emotional state (p = 0.005), physical comfort (p = 0.04), and pain (p = 0.02) were improved in the pregabalin group. Perioperative pregabalin improved postoperative quality of recovery as assessed using the QoR-40 questionnaire in patients undergoing OPCABG. Perioperative pregabalin offered advantages beyond better pain control, such as improved physical comfort and better emotional state; therefore, the drug's use in the perioperative period is recommended. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Parkinson's disease management strategies.

    PubMed

    Rajput, Alex; Rajput, Ali H

    2006-01-01

    Parkinson's disease (PD) treatment strategies should consider each patient individually. Drug therapy is the mainstay of treatment. An average 62-year-old male first diagnosed with PD will likely live for 20 years and treatment should be geared for long-term control of symptoms and quality of life. Of the currently available drugs, none are neurotoxic to the human substantia nigra and none are neuroprotective. As PD is a progressive disorder, all drugs have adverse effects and reduced efficacy with time. PD patients need regular follow-ups to make necessary medication adjustments. There is no perfect treatment. The authors have discussed their treatment methods and the reasoning behind it. Depending on the patient's age, the predominant symptoms and quality of life, treatment is individualized. In an average patient the least potent drugs, such as anticholinergics or amantadine, are administered first adding a dopamine agonist later on. Levodopa (LD) remains the most useful drug for PD and is reserved for later stages of disease. The objective is to keep the patient at Hoehn and Yahr Stage 2.0 or lower level of disability (bilateral findings with preserved postural reflexes) during off-stage and to avoid adverse effects. There is no long-term difference between standard preparations and control release formulations of LD/carbidopa or LD/benserazide. In older subjects, the first choice is LD. In patients who cannot be managed medically, surgical treatment is an option in selected patients (nondemented, <70 years old, previous good LD response). The surgical treatment of choice is currently subthalamic nucleus deep-brain stimulation. Physiotherapy, occupational therapy and speech therapy are valuable in advanced PD cases.

  12. Comparative mass spectrometry & nuclear magnetic resonance metabolomic approaches for nutraceuticals quality control analysis: a brief review.

    PubMed

    Farag, Mohamed A

    2014-01-01

    The number of botanical dietary supplements in the market has recently increased primarily due to increased health awareness. Standardization and quality control of the constituents of these plant extracts is an important topic, particularly when such ingredients are used long term as dietary supplements, or in cases where higher doses are marketed as drugs. The development of fast, comprehensive, and effective untargeted analytical methods for plant extracts is of high interest. Nuclear magnetic resonance spectroscopy and mass spectrometry are the most informative tools, each of which enables high-throughput and global analysis of hundreds of metabolites in a single step. Although only one of the two techniques is utilized in the majority of plant metabolomics applications, there is a growing interest in combining the data from both platforms to effectively unravel the complexity of plant samples. The application of combined MS and NMR in the quality control of nutraceuticals forms the major part of this review. Finally I will look at the future developments and perspectives of these two technologies for the quality control of herbal materials.

  13. Quantitative Method for Analysis of Hydrocodone, Hydromorphone and Norhydrocodone in Human Plasma by Liquid Chromatography-tandem Mass Spectrometry

    DTIC Science & Technology

    2013-03-01

    ratio ranges obtained for the six standards. Twelve samples were analyzed to demonstrate the efficiency of the extraction procedure. Drug and internal...frozen (−70 ◦C). Refrigerated samples were tested after 2 months of storage ; frozen samples were tested for up to 1 year from stor- age date. The...freeze–thaw stability was evaluated by analyzing three subject samples with known drug concentrations and two quality control samples at concentrations

  14. Food and Drug Administration regulation and evaluation of vaccines.

    PubMed

    Marshall, Valerie; Baylor, Norman W

    2011-05-01

    The vaccine-approval process in the United States is regulated by the Center for Biologics Evaluation and Research of the US Food and Drug Administration. Throughout the life cycle of development, from preclinical studies to after licensure, vaccines are subject to rigorous testing and oversight. Manufacturers must adhere to good manufacturing practices and control procedures to ensure the quality of vaccines. As mandated by Title 21 of the Code of Regulations, licensed vaccines must meet stringent criteria for safety, efficacy, and potency.

  15. 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.

  16. A Structural Model of the Retail Market for Illicit Drugs.

    PubMed

    Galenianos, Manolis; Gavazza, Alessandro

    2017-03-01

    We estimate a model of illicit drugs markets using data on purchases of crack cocaine. Buyers are searching for high-quality drugs, but they determine drugs' quality (i.e., their purity) only after consuming them. Hence, sellers can rip off first-time buyers or can offer higher-quality drugs to induce buyers to purchase from them again. In equilibrium, a distribution of qualities persists. The estimated model implies that if drugs were legalized, in which case purity could be regulated and hence observable, the average purity of drugs would increase by approximately 20 percent and the dispersion would decrease by approximately 80 percent. Moreover, increasing penalties may raise the purity and affordability of the drugs traded by increasing sellers’ relative profitability of targeting loyal buyers versus first-time buyers.

  17. Planning schistosomiasis control: investigation of alternative sampling strategies for Schistosoma mansoni to target mass drug administration of praziquantel in East Africa.

    PubMed

    Sturrock, Hugh J W; Gething, Pete W; Ashton, Ruth A; Kolaczinski, Jan H; Kabatereine, Narcis B; Brooker, Simon

    2011-09-01

    In schistosomiasis control, there is a need to geographically target treatment to populations at high risk of morbidity. This paper evaluates alternative sampling strategies for surveys of Schistosoma mansoni to target mass drug administration in Kenya and Ethiopia. Two main designs are considered: lot quality assurance sampling (LQAS) of children from all schools; and a geostatistical design that samples a subset of schools and uses semi-variogram analysis and spatial interpolation to predict prevalence in the remaining unsurveyed schools. Computerized simulations are used to investigate the performance of sampling strategies in correctly classifying schools according to treatment needs and their cost-effectiveness in identifying high prevalence schools. LQAS performs better than geostatistical sampling in correctly classifying schools, but at a cost with a higher cost per high prevalence school correctly classified. It is suggested that the optimal surveying strategy for S. mansoni needs to take into account the goals of the control programme and the financial and drug resources available.

  18. Quality variations in black musli (curculigo orchioides gaertn.).

    PubMed

    Mathew, P P Joy Samuel; Savithri, K E; Skaria, Baby P; Kurien, Kochurani

    2004-07-01

    Black musli (Curculigo orchioides Gaertn.) one of the ayurvedic dasapushpa and a rejuvenating and aphrodisiac drug. Is on the verge of extinction and needs to be conserved and cultivated. Large variations are also observed in the quality of the crude drug available in the market. Study on the quality of C. orchioides in natural habitat, under cultivation and in trade in south India showed that there was considerable variation with biotypes and habitats. Drugs collected form the natural habitat was superior in quality to that produced by cultivation. Among the market samples collected from the various Zones of kerala, those from the High Ranges were superior in most of the quality parameters, which indicated its superiority for high quality drug formulation. Among the southern states, Tamil Nadu samples ranked next to High Range samples in this respect. There exists large variability in the market samples and there is felt-need for proper standardization of the crude drug for ensuring quality in the drug formulations.

  19. Quality risk management of top spray fluidized bed process for antihypertensive drug formulation with control strategy engendered by Box-behnken experimental design space.

    PubMed

    Mukharya, Amit; Patel, Paresh U; Shenoy, Dinesh; Chaudhary, Shivang

    2013-01-01

    Lacidipine (LCDP) is a very low soluble and highly biovariable calcium channel blocker used in the treatment of hypertension. To increase its apparent solubility and to reduce its biovariability, solid dispersion fluid bed processing technology was explored, as it produces highly dispersible granules with a characteristic porous structure that enhances dispersibility, wettability, blend uniformity (by dissolving and spraying a solution of actives), flow ability and compressibility of granules for tableting and reducing variability by uniform drug-binder solution distribution on carrier molecules. Main object of this quality risk management (QRM) study is to provide a sophisticated "robust and rugged" Fluidized Bed Process (FBP) for the preparation of LCDP tablets with desired quality (stability) and performance (dissolution) by quality by design (QbD) concept. THIS STUDY IS PRINCIPALLY FOCUSING ON THOROUGH MECHANISTIC UNDERSTANDING OF THE FBP BY WHICH IT IS DEVELOPED AND SCALED UP WITH A KNOWLEDGE OF THE CRITICAL RISKS INVOLVED IN MANUFACTURING PROCESS ANALYZED BY RISK ASSESSMENT TOOLS LIKE: Qualitative Initial Risk-based Matrix Analysis (IRMA) and Quantitative Failure Mode Effective Analysis (FMEA) to identify and rank parameters with potential to have an impact on In Process/Finished Product Critical Quality Attributes (IP/FP CQAs). These Critical Process Parameters (CPPs) were further refined by DoE and MVDA to develop design space with Real Time Release Testing (RTRT) that leads to implementation of a control strategy to achieve consistent finished product quality at lab scale itself to prevent possible product failure at larger manufacturing scale.

  20. Quality risk management of top spray fluidized bed process for antihypertensive drug formulation with control strategy engendered by Box-behnken experimental design space

    PubMed Central

    Mukharya, Amit; Patel, Paresh U; Shenoy, Dinesh; Chaudhary, Shivang

    2013-01-01

    Introduction: Lacidipine (LCDP) is a very low soluble and highly biovariable calcium channel blocker used in the treatment of hypertension. To increase its apparent solubility and to reduce its biovariability, solid dispersion fluid bed processing technology was explored, as it produces highly dispersible granules with a characteristic porous structure that enhances dispersibility, wettability, blend uniformity (by dissolving and spraying a solution of actives), flow ability and compressibility of granules for tableting and reducing variability by uniform drug-binder solution distribution on carrier molecules. Materials and Methods: Main object of this quality risk management (QRM) study is to provide a sophisticated “robust and rugged” Fluidized Bed Process (FBP) for the preparation of LCDP tablets with desired quality (stability) and performance (dissolution) by quality by design (QbD) concept. Results and Conclusion: This study is principally focusing on thorough mechanistic understanding of the FBP by which it is developed and scaled up with a knowledge of the critical risks involved in manufacturing process analyzed by risk assessment tools like: Qualitative Initial Risk-based Matrix Analysis (IRMA) and Quantitative Failure Mode Effective Analysis (FMEA) to identify and rank parameters with potential to have an impact on In Process/Finished Product Critical Quality Attributes (IP/FP CQAs). These Critical Process Parameters (CPPs) were further refined by DoE and MVDA to develop design space with Real Time Release Testing (RTRT) that leads to implementation of a control strategy to achieve consistent finished product quality at lab scale itself to prevent possible product failure at larger manufacturing scale. PMID:23799202

  1. Advancing Evidence in Preterm Neonatal Medicine

    ERIC Educational Resources Information Center

    Donahue, Pamela K.; Robinson, Karen A.

    2010-01-01

    Few interventions and treatments for premature infants have undergone the rigors of a randomized controlled trial (RCT), the cornerstone of evidence-based healthcare. Multiple barriers in establishing a quality evidence base for the care of preterm infants are examined including the systematic exclusion of children from drug trials, vulnerability…

  2. Ethnically diverse pluripotent stem cells for drug development.

    PubMed

    Fakunle, Eyitayo S; Loring, Jeanne F

    2012-12-01

    Genetic variation is an identified factor underlying drug efficacy and toxicity, and adverse drug reactions, such as liver toxicity, are the primary reasons for post-marketing drug failure. Genetic predisposition to toxicity might be detected early in the drug development pipeline by introducing cell-based assays that reflect the genetic and ethnic variation of the expected treatment population. One challenge for this approach is obtaining a collection of suitable cell lines derived from ethnically diverse populations. Induced pluripotent stem cells (iPSCs) seem ideal for this purpose. They can be obtained from any individual, can be differentiated into multiple relevant cell types, and their self-renewal capability makes it possible to generate large quantities of quality-controlled cell types. Here, we discuss the benefits and challenges of using iPSCs to introduce genetic diversity into the drug development process. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. [Food, health claims and drugs. Conclusions - recommendations. The National Academy of Pharmacy].

    PubMed

    Bourlioux, P

    2008-01-01

    Even if the activity of health claim foods is not relevant to the activity of drugs, we are just at the frontier of two fields which needs the greatest attention. Since foods and drugs are present in the same domain of prevention, the French Academy of Pharmacy draws attention on the necessary relevant and scientifically proven demonstration of the health claims using the same quality standard than those used for drugs (good clinical practises, methodologies correspondent to the current requirement, etc.). It is why the Academy wishes to express five recommendations fearing that the risks of confusion and abuse prevail on the possibilities of information and control. Make sure that foods are not mistaken with drugs; largely spread the lists of authorised claims; introduce the new notion of "nutrivigilance"; make sure that the only authorised health claims use advertising; reject the terms "alicaments" and "nutraceuticals" which are confusing with drugs.

  4. 76 FR 25358 - 2011 Parenteral Drug Association/Food and Drug Administration Glass Quality Conference; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-04

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2011-N-0002] 2011 Parenteral Drug Association/Food and Drug Administration Glass Quality Conference; Public Conference AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public conference. SUMMARY: The Food...

  5. National post-market surveillance assessment of veterinary medicines in Korea during the past decade.

    PubMed

    Kang, JeongWoo; Park, Hae-Chul; Jang, Yang Ho; Hossain, Md Akil; Jeong, Kyunghun; Jeong, Mi Young; Yun, Seon-Jong; Park, Sung-Won; Kim, Dae Gyun; Lee, Kwang-Jick

    2017-05-22

    Veterinary medicines have been widely used for the prevention and treatment of diseases, growth promotion, and to promote feeding efficacy in livestock. As the veterinary medicine industry has steadily grown, it is crucial to set up a baseline for the quality of medicine as well as the insufficiency or excessiveness of the active ingredients in drug products to ensure the compliance, safety and efficacy of these medicines. Thus, the 10 years data of post-marketing quality control study was summarized to determine the rate and extent of non-compliance of these medicines and to establish baseline data for future quality control measures of veterinary medicine. In this study, 1650 drugs for veterinary use were collected per year from each city and province in Korea and analysed for the quantity of active ingredients according to the "national post-market surveillance (NPMS) system" over the past decade. The NPMS assessment was performed using liquid and gas chromatography, titration, UV/Vis spectrophotometry, and bioassays. A total of 358 cases were deemed noncompliant, with the average noncompliance rate for all medicine types being 2.0%. The average noncompliance rates for antibiotics, biologics and other chemical drugs except antibiotics (OCD) were 1.1%, 1.2%, and 3.0%, respectively. The first leading cause for noncompliant products was insufficient quantity of major ingredients (283 cases), and the second leading cause was the existence of excess amount of active ingredients (60 cases). Tylosin, spiramycin, ampicillin, tetracyclines and penicillins were most frequently found to be noncompliant among antibiotics. Among the OCD, the noncompliance was found commonly in vitamin A. The overall trend presented gradually decreasing violation rates, suggesting that the quality of veterinary medicines has improved. Consistent application of the NPMS assessment and the establishment of the Korea Veterinary Good Manufacturing Practice (KVGMP) will help to maintain the good quality of medicine.

  6. 'Heads held high': an exploratory study of legal highs in pre-legislation Ireland.

    PubMed

    Van Hout, Marie Claire; Brennan, Rebekah

    2011-01-01

    The research aimed to present a unique 'snapshot' of legal psychoactive drug use prior to legislative control in Ireland, in relation to the types of products used; sourcings; consumptive practices and particular social settings for use; gauging of dosage; licit and illicit drug transitions, individualisation of drug decision-making and experiences; and future intentions regarding drug switching post legislation. Semi-structured in depth interviews (n = 32) were conducted with adults aged 18-33 years who had used legal highs in the 6 months prior to fieldwork. The findings indicate some support for 'differentiated' displacement consumptive patterns between illegal and legal drugs, with user pathways grounded in 'legal high' availability; perceived user effect, safety, legality, quality and price. Mephedrone emerged as most popular drug of choice. Internet sales, stockpiling and diversion of previously 'legal highs' onto the illegal street drug market remain of concern, against a background of emerging new designer drugs in Ireland.

  7. [Significance of re-evaluation and development of Chinese herbal drugs].

    PubMed

    Gao, Yue; Ma, Zengchun; Zhang, Boli

    2012-01-01

    The research of new herbal drugs involves in new herbal drugs development and renew the old drugs. It is necessary to research new herbal drugs based on the theory of traditional Chinese medicine (TCM). The current development of famous TCM focuses on the manufacture process, quality control standards, material basis and clinical research. But system management of security evaluation is deficient, the relevant system for the safety assessment TCM has not been established. The causes of security problems, security risks, target organ of toxicity, weak link of safety evaluation, and ideas of safety evaluation are discussed in this paper. The toxicology research of chinese herbal drugs is necessary based on standard of good laboratory practices (GLP), the characteristic of Chinese herbal drugs is necessary to be fully integrated into safety evaluation. The safety of new drug research is necessary to be integrated throughout the entire process. Famous Chinese medicine safety research must be paid more attention in the future.

  8. Palliative pharmacological sedation for terminally ill adults.

    PubMed

    Beller, Elaine M; van Driel, Mieke L; McGregor, Leanne; Truong, Shani; Mitchell, Geoffrey

    2015-01-02

    Terminally ill people experience a variety of symptoms in the last hours and days of life, including delirium, agitation, anxiety, terminal restlessness, dyspnoea, pain, vomiting, and psychological and physical distress. In the terminal phase of life, these symptoms may become refractory, and unable to be controlled by supportive and palliative therapies specifically targeted to these symptoms. Palliative sedation therapy is one potential solution to providing relief from these refractory symptoms. Sedation in terminally ill people is intended to provide relief from refractory symptoms that are not controlled by other methods. Sedative drugs such as benzodiazepines are titrated to achieve the desired level of sedation; the level of sedation can be easily maintained and the effect is reversible. To assess the evidence for the benefit of palliative pharmacological sedation on quality of life, survival, and specific refractory symptoms in terminally ill adults during their last few days of life. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 11), MEDLINE (1946 to November 2014), and EMBASE (1974 to December 2014), using search terms representing the sedative drug names and classes, disease stage, and study designs. We included randomised controlled trials (RCTs), quasi-RCTs, non-RCTs, and observational studies (e.g. before-and-after, interrupted-time-series) with quantitative outcomes. We excluded studies with only qualitative outcomes or that had no comparison (i.e. no control group or no within-group comparison) (e.g. single arm case series). Two review authors independently screened titles and abstracts of citations, and full text of potentially eligible studies. Two review authors independently carried out data extraction using standard data extraction forms. A third review author acted as arbiter for both stages. We carried out no meta-analyses due to insufficient data for pooling on any outcome; therefore, we reported outcomes narratively. The searches resulted in 14 included studies, involving 4167 adults, of whom 1137 received palliative sedation. More than 95% of people had cancer. No studies were randomised or quasi-randomised. All were consecutive case series, with only three having prospective data collection. Risk of bias was high, due to lack of randomisation. No studies measured quality of life or participant well-being, which was the primary outcome of the review. Five studies measured symptom control, using four different methods, so pooling was not possible. The results demonstrated that despite sedation, delirium and dyspnoea were still troublesome symptoms in these people in the last few days of life. Control of other symptoms appeared to be similar in sedated and non-sedated people. Only one study measured unintended adverse effects of sedative drugs and found no major events; however, four of 70 participants appeared to have drug-induced delirium. The study noticed no respiratory suppression. Thirteen of the 14 studies measured survival time from admission or referral to death, and all demonstrated no statistically significant difference between sedated and non-sedated groups. There was insufficient evidence about the efficacy of palliative sedation in terms of a person's quality of life or symptom control. There was evidence that palliative sedation did not hasten death, which has been a concern of physicians and families in prescribing this treatment. However, this evidence comes from low quality studies, so should be interpreted with caution. Further studies that specifically measure the efficacy and quality of life in sedated people, compared with non-sedated people, and quantify adverse effects are required.

  9. Recovery effect of pre-germinated brown rice on the alteration of sperm quality, testicular structure and androgen receptor expression in rat model of depression.

    PubMed

    Roboon, J; Nudmamud-Thanoi, S; Thanoi, S

    2017-02-01

    Depression and antidepressant drugs induce adverse effects in male reproduction. Therefore, it is important to investigate alternative treatment for depression without adverse effects on the male reproductive system. The aim of this study was to determine the effect of pre-germinated brown rice (PGBR) on sperm quality, testicular structure and androgen receptor (AR) expression in rat model of depression. Male Sprague Dawley rats were divided into five groups including control (distilled water only), depression induced by forced swimming test (FST), FST + fluoxetine (antidepressant drug), FST + GABA (gamma-aminobutyric acid) (standard) and FST + PGBR. When compared with the control, sperm motility showed a significant decrease in FST + fluoxetine group. Sperm morphology also decreased significantly in depression and FST + fluoxetine groups. The morphological changes of seminiferous tubules showed significant increases in depression and FST + fluoxetine groups, while AR expression showed significant decreases in depression, FST + fluoxetine and FST + GABA groups. Interestingly, there were no significant differences in all sperm quality parameters, testicular structure and AR expression in FST + PGBR group. These findings reflect the recovery effects of PGBR treatment on sperm quality, morphological changes of seminiferous tubules and AR expression in stress-induced rats. Therefore, PGBR may potentially develop for the treatment for depression without adverse effect on male reproduction. © 2016 Blackwell Verlag GmbH.

  10. Good clinical practice regulatory inspections: Lessons for Indian investigator sites

    PubMed Central

    Marwah, R.; Van de Voorde, K.; Parchman, J.

    2010-01-01

    Regulatory inspections are important to evaluate the integrity of the data submitted to health authorities (HAs), protect patient safety, and assess adequacy of site/sponsor quality systems to achieve the same. Inspections generally occur after submission of data for marketing approval of an investigational drug. In recent years, there has been a significant increase in number of inspections by different HAs, including in India. The assessors/inspectors generally do a thorough review of site data before inspections. All aspects of ICH-GCP, site infrastructure, and quality control systems are assessed during the inspection. Findings are discussed during the close out meeting and a detailed inspection report issued afterward, which has to be responded to within 15–30 days with effective Corrective and Preventive Action Plan (CAPA). Protocol noncompliance, inadequate/inaccurate records, inadequate drug accountability, informed consent issues, and adverse event reporting were some of the most common findings observed during recent Food and Drug Administration (FDA) inspections. Drug development is being increasingly globalized and an increased number of patients enrolled in studies submitted as part of applications come from all over the world including India. Because of the steep increase in research activity in the country, inexperienced sites, and more stakeholders, increased efforts will be required to ensure continuous quality and compliance. HAs have also made clear that enforcement will be increased and be swift, aggressive, and effective. PMID:21350732

  11. [Analysis of population survey for determining the factors associated with the control diabetes mellitus in Mexico].

    PubMed

    Hernández-Romieu, Alfonso Claudio; Elnecavé-Olaiz, Alejandro; Huerta-Uribe, Nidia; Reynoso-Noverón, Nancy

    2011-01-01

    Determine the influence of nutritional counseling, exercise, access to social healthcare and drugs, and the quality of medical care on the control of diabetics. The information and blood samples were obtained in 2005. Glycemic control was defined as good if HbA1c was ≤7.0%, poor from 7.01%-9.50% and very poor if HbA1c >9.5%. Binary logistic regression models were used to determine the association of these factors with HbA1c>9.5%. Thirty percent of the patients with a medical diagnosis of diabetes had adequate metabolic control. Nutritional guidance was associated with an increase in the degree of control. A majority of diabetics have poor or very poor glycemic control. Strengthening the quality of and access to medical care for these patients is urgently needed.

  12. Quality of Life in Atrial Fibrillation: Measurement Tools and Impact of Interventions

    PubMed Central

    REYNOLDS, MATTHEW R.; ELLIS, ETHAN; ZIMETBAUM, PETER

    2008-01-01

    QoL in AF. Quality of life (QoL) is of central importance in atrial fibrillation as both a treatment goal and an endpoint in the evaluation of new therapies. QoL appears to be impaired in the majority of patients with AF. A number of interventions for AF have been shown to improve QoL, including pharmacologic and nonpharmacologic rate control, antiarrhythmic drugs, and nonpharmacologic rhythm control strategies. This paper will review the rationale, design, strengths, and limitations of the questionnaires most commonly used to assess QoL in AF studies, and present QoL outcomes from major studies of AF interventions. PMID:18266667

  13. Factoring quality laboratory diagnosis into the malaria control agenda for sub-Saharan Africa.

    PubMed

    Aidoo, Michael

    2013-09-01

    Recent progress in malaria control in sub-Saharan Africa has been achieved primarily through provision of insecticide-treated nets, indoor residual spraying, and antimalarial drugs. Although these interventions are important, proper case identification and accurate measurement of their impact depend on quality diagnostic testing. Current availability of diagnostic testing for malaria in sub-Saharan Africa is inadequate to support disease management, prevention programs, and surveillance needs. Challenges faced include a dearth of skilled workforce, inadequate health systems infrastructure, and lack of political will. A coordinated approach to providing pre-service clinical and laboratory training together with systems that support a scale-up of laboratory services could provide means not only for effective malaria case management but also, management of non-malaria febrile illnesses, disease surveillance, and accurate control program evaluation. A synthesis of the challenges faced in ensuring quality malaria testing and how to include this information in the malaria control and elimination agenda are presented.

  14. Financial conflicts of interest and their association with outcome and quality of fibromyalgia drug therapy randomized controlled trials.

    PubMed

    Pang, Winnie K; Yeter, Karen C; Torralba, Karina D; Spencer, Horace J; Khan, Nasim A

    2015-07-01

    To evaluate the association of financial conflicts of interest (FCOI) with the characteristics, outcome and reported methodological quality of fibromyalgia drug therapy randomized controlled trials (FM-RCTs). A cross-sectional study of original, parallel-group, drug therapy FM-RCTs published between 1997 and 2011 from Medline and Cochrane Central Register of Controlled Trials was conducted. Two reviewers independently assessed each RCT for funding source, authors' FCOI(s), study characteristics, reporting of methodological measures important for internal validity and outcome (positive [statistically significant result favoring experimental drug for the primary outcome] or non-positive). Forty-seven RCTs were eligible with funding source as: 26 (55.3%) industry; eight (17%) non-profit source(s); five (10.6%) mixed; and eight (17%) unspecified. Industry-funded RCTs were more likely to be multicenter and enroll greater number of patients. Reporting of key methodological measures was suboptimal; however, industry and non-profit funded RCTs did not differ in their reporting. Thirty (63.8%) RCTs had ≥ one author who disclosed an FCOI (receipt of research grant [21, 44.7%], industry sponsor employee [20, 42.6%], receipt of consultancy fee/honorarium [16, 34%] and stock ownership [11, 23.4%]). Although industry funding and certain authors' FCOIs (employment and receipt of consultancy fee/honorarium) were univariately associated with positive outcome, such association was not observed after adjusting for study sample size. The majority of FM-RCTs were industry-sponsored, and had at least one author with an FCOI. Reporting of key methodological measures was suboptimal. After adjusting for study sample size, no association of industry funding or author's FCOI with study outcome was seen. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  15. Quality by Design (QbD) Approach for Development of Co-Processed Excipient Pellets (MOMLETS) By Extrusion-Spheronization Technique.

    PubMed

    Patel, Hetal; Patel, Kishan; Tiwari, Sanjay; Pandey, Sonia; Shah, Shailesh; Gohel, Mukesh

    2016-01-01

    Microcrystalline cellulose (MCC) is an excellent excipient for the production of pellets by extrusion spheronization. However, it causes slow release rate of poorly water soluble drugs from pellets. Co-processed excipient prepared by spray drying (US4744987; US5686107; WO2003051338) and coprecipitation technique (WO9517831) are patented. The objective of present study was to develop co-processed MCC pellets (MOMLETS) by extrusion-spheronization technique using the principle of Quality by Design (QbD). Co-processed excipient core pellets (MOMLETS) were developed by extrusion spheronization technique using Quality by Design (QbD) approach. BCS class II drug (telmisartan) was layered onto it in a fluidized bed processor. Quality Target Product Profile (QTPP) and Critical Quality Attributes (CQA) for pellets were identified. Risk assessment was reported using Ishikawa diagram. Plackett Burman design was used to check the effect of seven independent variables; superdisintegrant, extruder speed, ethanol: water, spheronizer speed, extruder screen, pore former and MCC: lactose; on percentage drug release at 30 min. Pareto chart and normal probability plot was constructed to identify the significant factors. Box-Behnken design (BBD) using three most significant factors (Extruder screen size, type of superdisintegrant and type of pore former) was used as an optimization design. The control space was identified in which desired quality of the pellets can be obtained. Co-processed excipient core pellets (MOMLETS) were successfully developed by QbD approach. Versatility, Industrial scalability and simplicity are the main features of the proposed research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Quality by Design approach for studying the impact of formulation and process variables on product quality of oral disintegrating films.

    PubMed

    Mazumder, Sonal; Pavurala, Naresh; Manda, Prashanth; Xu, Xiaoming; Cruz, Celia N; Krishnaiah, Yellela S R

    2017-07-15

    The present investigation was carried out to understand the impact of formulation and process variables on the quality of oral disintegrating films (ODF) using Quality by Design (QbD) approach. Lamotrigine (LMT) was used as a model drug. Formulation variable was plasticizer to film former ratio and process variables were drying temperature, air flow rate in the drying chamber, drying time and wet coat thickness of the film. A Definitive Screening Design of Experiments (DoE) was used to identify and classify the critical formulation and process variables impacting critical quality attributes (CQA). A total of 14 laboratory-scale DoE formulations were prepared and evaluated for mechanical properties (%elongation at break, yield stress, Young's modulus, folding endurance) and other CQA (dry thickness, disintegration time, dissolution rate, moisture content, moisture uptake, drug assay and drug content uniformity). The main factors affecting mechanical properties were plasticizer to film former ratio and drying temperature. Dissolution rate was found to be sensitive to air flow rate during drying and plasticizer to film former ratio. Data were analyzed for elucidating interactions between different variables, rank ordering the critical materials attributes (CMA) and critical process parameters (CPP), and for providing a predictive model for the process. Results suggested that plasticizer to film former ratio and process controls on drying are critical to manufacture LMT ODF with the desired CQA. Published by Elsevier B.V.

  17. Implementation of "Quality by Design (QbD)" Approach for the Development of 5-Fluorouracil Loaded Thermosensitive Hydrogel.

    PubMed

    Dalwadi, Chintan; Patel, Gayatri

    2016-01-01

    The purpose of this study was to investigate Quality by Design (QbD) principle for the preparation of hydrogel products to prove both practicability and utility of executing QbD concept to hydrogel based controlled release systems. Product and process understanding will help in decreasing the variability of critical material and process parameters, which give quality product output and reduce the risk. This study includes the identification of the Quality Target Product Profiles (QTPPs) and Critical Quality Attributes (CQAs) from literature or preliminary studies. To identify and control the variability in process and material attributes, two tools of QbD was utilized, Quality Risk Management (QRM) and Experimental Design. Further, it helps to identify the effect of these attributes on CQAs. Potential risk factors were identified from fishbone diagram and screened by risk assessment and optimized by 3-level 2- factor experimental design with center points in triplicate, to analyze the precision of the target process. This optimized formulation was further characterized by gelling time, gelling temperature, rheological parameters, in-vitro biodegradation and in-vitro drug release. Design space was created using experimental design tool that gives the control space and working within this controlled space reduces all the failure modes below the risk level. In conclusion, QbD approach with QRM tool provides potent and effectual pyramid to enhance the quality into the hydrogel.

  18. Intrathecal Drug Delivery and Spinal Cord Stimulation for the Treatment of Cancer Pain.

    PubMed

    Xing, Fangfang; Yong, R Jason; Kaye, Alan David; Urman, Richard D

    2018-02-05

    The purpose of the present investigation is to summarize the body and quality of evidence including the most recent studies in support of intrathecal drug delivery systems and spinal cord stimulation for the treatment of cancer-related pain. In the past 3 years, a number of prospective studies have been published supporting intrathecal drug delivery systems for cancer pain. Additional investigation with adjuvants to morphine-based analgesia including dexmedetomidine and ziconotide support drug-induced benefits of patient-controlled intrathecal analgesia. A study has also been recently published regarding cost-savings for intrathecal drug delivery system compared to pharmacologic management, but an analysis in the Ontario, Canada healthcare system projects additional financial costs. Finally, the Polyanalgesic Consensus Committee has updated its recommendations regarding clinical guidelines for intrathecal drug delivery systems to include new information on dosing, trialing, safety, and systemic opioid reduction. There is still a paucity of clinical evidence for spinal cord stimulation in the treatment of cancer pain. There are new intrathecal drugs under investigation including various conopeptides and AYX1. Large, prospective, modern, randomized controlled studies are still needed to support the use of both intrathecal drug delivery systems as well as spinal cord stimulation for cancer pain populations. There are multiple prospective and small randomized controlled studies that highlight a potential promising future for these interventional modalities. Related to the challenge and urgency of cancer pain, the pain practitioner community is moving toward a multimodal approach that includes discussions regarding the role of intrathecal therapies and spinal cord stimulation to the individualized treatment of patients.

  19. Tobacco, Alcohol, and Drug Use of People With Mood and Anxiety Disorders: Differential Impact of Family and Friends.

    PubMed

    Nam, Eunji; Fukui, Sadaaki

    2017-01-01

    Substance use among people with mood and anxiety disorders is highly prevalent. The literature suggests that substance use among people with mood and anxiety disorders is linked to social relational factors, yet it has rarely been the case that studies explicitly examine the differential impact of family and friends. This study investigated the association among family relationships, friendships, and substance use among people with mood and anxiety disorders. Using the National Survey of American Life, structural equation modeling tested the unique effects of family relationships and friendships on tobacco, alcohol, and drug use (n = 1,076). The quality of family relationships was assessed using 12 items on the frequency of contact with family, received help from family, closeness in feeling toward family, and emotional support from family. The quality of friendships was assessed using four items on the frequency of contact with friends, received and given help, and closeness in feeling toward friends. Substance use was measured using self-reported use of tobacco, alcohol, and drugs. Findings indicated that family relationships (β = -.101, p = .031) and friendships (β = .142, p = .004) were associated with drug use among people with mood and anxiety disorders, controlling for gender, age, race, education level, employment status, income, and family substance use history. Yet, family relationships and friendships were not significantly associated with tobacco and alcohol use. People with mood and anxiety disorders who had better family relationships were less likely to use drugs, while those who had better friendships were more likely to use drugs. Practitioners should be attentive to the differential impact of family and friends when working with people with mood and anxiety disorders to reduce the risk of drug use. Family interventions promoting and maintaining quality relationships with family will be helpful. However, friendships may facilitate drug use of people with mood and anxiety disorders. Practitioners should be cognizant of the potential risks of friendship networks for people with mood and anxiety disorders.

  20. An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems.

    PubMed

    Jug, Mario; Hafner, Anita; Lovrić, Jasmina; Kregar, Maja Lusina; Pepić, Ivan; Vanić, Željka; Cetina-Čižmek, Biserka; Filipović-Grčić, Jelena

    2018-01-05

    In vitro dissolution/release tests are an important tool in the drug product development phase as well as in its quality control and the regulatory approval process. Mucosal drug delivery systems are aimed to provide both local and systemic drug action via mucosal surfaces of the body and exhibit significant differences in formulation design, as well as in their physicochemical and release characteristics. Therefore it is not possible to devise a single test system which would be suitable for release testing of such complex dosage forms. This article is aimed to provide a comprehensive review of both compendial and noncompendial methods used for in vitro dissolution/release testing of novel mucosal drug delivery systems aimed for ocular, nasal, oromucosal, vaginal and rectal administration. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Statistical process control methods allow the analysis and improvement of anesthesia care.

    PubMed

    Fasting, Sigurd; Gisvold, Sven E

    2003-10-01

    Quality aspects of the anesthetic process are reflected in the rate of intraoperative adverse events. The purpose of this report is to illustrate how the quality of the anesthesia process can be analyzed using statistical process control methods, and exemplify how this analysis can be used for quality improvement. We prospectively recorded anesthesia-related data from all anesthetics for five years. The data included intraoperative adverse events, which were graded into four levels, according to severity. We selected four adverse events, representing important quality and safety aspects, for statistical process control analysis. These were: inadequate regional anesthesia, difficult emergence from general anesthesia, intubation difficulties and drug errors. We analyzed the underlying process using 'p-charts' for statistical process control. In 65,170 anesthetics we recorded adverse events in 18.3%; mostly of lesser severity. Control charts were used to define statistically the predictable normal variation in problem rate, and then used as a basis for analysis of the selected problems with the following results: Inadequate plexus anesthesia: stable process, but unacceptably high failure rate; Difficult emergence: unstable process, because of quality improvement efforts; Intubation difficulties: stable process, rate acceptable; Medication errors: methodology not suited because of low rate of errors. By applying statistical process control methods to the analysis of adverse events, we have exemplified how this allows us to determine if a process is stable, whether an intervention is required, and if quality improvement efforts have the desired effect.

  2. Drugs for relief of pain in patients with sciatica: systematic review and meta-analysis

    PubMed Central

    Maher, Chris G; Ferreira, Manuela L; Ferreira, Paulo H; Hancock, Mark; Oliveira, Vinicius C; McLachlan, Andrew J; Koes, Bart

    2012-01-01

    Objective To investigate the efficacy and tolerability of analgesic and adjuvant pain drugs typically administered in primary care for the management of patients with sciatica. Design Systematic review. Data source International Pharmaceutical Abstracts, PsycINFO, Medline, Embase, Cochrane Central Register of Clinical Trials (CENTRAL), CINAHL, and LILACS. Study selection Randomised controlled trials assessing the efficacy and tolerability of drugs versus placebo or other treatment for sciatica. Data extraction Two independent reviewers extracted data and assessed methodological quality using the PEDro scale. Pain and disability outcomes were converted to a common 0 to 100 scale. Data were pooled with a random effects model, and the GRADE approach was used in summary conclusions. Results Twenty three published reports met the inclusion criteria. The evidence to judge the efficacy of non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antidepressants, anticonvulsants, muscle relaxants, and opioid analgesics ranged from moderate to low quality. Most of the pooled estimates did not favour the active treatment over placebo. The pooled results of two trials of corticosteroids (mean difference in overall and leg pain −12.2, 95% confidence interval −20.9 to −3.4) and a single trial of the anticonvulsant gabapentin for chronic sciatica (mean difference in overall pain relief −26.6, −38.3 to −14.9) showed some benefits but only in the short term. The median rate of adverse events was 17% (interquartile range 10-30%) for the active drugs and 11% (3-23%) for placebo. Trial limitations included failure to use validated outcome measures, lack of long term follow-up, and small sample size. Conclusions As the existing evidence from clinical trials is of low quality, the efficacy and tolerability of drugs commonly prescribed for the management of sciatica in primary care is unclear. PMID:22331277

  3. Nonpharmacological treatment of epilepsy

    PubMed Central

    Saxena, V. S.; Nadkarni, V. V.

    2011-01-01

    Nonpharmacological treatment of epilepsy includes surgery, vagal nerve stimulation, ketogenic diet, and other alternative/complementary therapies, e.g., yoga, Ayurveda, electroencephalography (EEG) biofeedback technique, aerobic exercise, music therapy, transcranial magnetic stimulation, acupuncture, and herbal remedies (traditional Chinese medicine). Alternative therapies, despite the term, should not be considered as an alternative to antiepileptic medication; they complement accepted drug treatment. Alternative therapies like yoga, through techniques that relax the body and mind, reduce stress, improve seizure control, and also improve quality of life. Ketogenic diet is a safe and effective treatment for intractable epilepsies; it has been recommended since 1921. The diet induces ketosis, which may control seizures. The most successful treatment of epilepsy is with modern antiepileptic drugs, which can achieve control of seizures in 70–80% cases. Patients opt for alternative therapies because they may be dissatisfied with antiepileptic drugs due to their unpleasant side effects, the long duration of treatment, failure to achieve control of seizures, cultural beliefs and, in the case of women, because they wish to get pregnant Surgical treatment may lead to physical and psychological sequelae and is an option only for a minority of patients. This article presents supportive evidence from randomized controlled trials done to assess the benefit of non-pharmacological treatment. PMID:22028523

  4. 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.

  5. Chinese proprietary herbal medicine listed in 'China national essential drug list' for common cold: a systematic literature review.

    PubMed

    Chen, Wei; Lewith, George; Wang, Li-qiong; Ren, Jun; Xiong, Wen-jing; Lu, Fang; Liu, Jian-ping

    2014-01-01

    Chinese proprietary herbal medicines (CPHMs) have long history in China for the treatment of common cold, and lots of them have been listed in the 'China national essential drug list' by the Chinese Ministry of Health. The aim of this review is to provide a well-round clinical evidence assessment on the potential benefits and harms of CPHMs for common cold based on a systematic literature search to justify their clinical use and recommendation. We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites from their inception to 31 March 2013 for clinical studies of CPHMs listed in the 'China national essential drug list' for common cold. There was no restriction on study design. A total of 33 CPHMs were listed in 'China national essential drug list 2012' for the treatment of common cold but only 7 had supportive clinical evidences. A total of 6 randomised controlled trials (RCTs) and 7 case series (CSs) were included; no other study design was identified. All studies were conducted in China and published in Chinese between 1995 and 2012. All included studies had poor study design and methodological quality, and were graded as very low quality. The use of CPHMs for common cold is not supported by robust evidence. Further rigorous well designed placebo-controlled, randomized trials are needed to substantiate the clinical claims made for CPHMs.

  6. Review of drug treatment of oral submucous fibrosis.

    PubMed

    Chole, Revant H; Gondivkar, Shailesh M; Gadbail, Amol R; Balsaraf, Swati; Chaudhary, Sudesh; Dhore, Snehal V; Ghonmode, Sumeet; Balwani, Satish; Mankar, Mugdha; Tiwari, Manish; Parikh, Rima V

    2012-05-01

    This study undertook a review of the literature on drug treatment of oral submucous fibrosis. An electronic search was carried out for articles published between January 1960 to November 2011. Studies with high level of evidence were included. The levels of evidence of the articles were classified after the guidelines of the Oxford Centre for Evidence-Based Medicine. The main outcome measures used were improvement in oral ulceration, burning sensation, blanching and trismus. Only 13 publications showed a high level of evidence (3 randomized controlled trials and 10 clinical trials/controlled clinical trials), with a total of 1157 patients. Drugs like steroids, hyaluronidase, human placenta extracts, chymotrypsin and collagenase, pentoxifylline, nylidrin hydrochloride, iron and multivitamin supplements including lycopene, have been used. Only systemic agents were associated with few adverse effects like gastritis, gastric irritation and peripheral flushing with pentoxifylline, and flushingly warm skin with nylidrin hydrochloride; all other side-effects were mild and mainly local. Few studies with high levels of evidence were found. The drug treatment that is currently available for oral submucous fibrosis is clearly inadequate. There is a need for high-quality randomized controlled trials with carefully selected and standardized outcome measures. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. 21 CFR 212.20 - What activities must I perform to ensure drug quality?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false What activities must I perform to ensure drug quality? 212.20 Section 212.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR POSITRON EMISSION TOMOGRAPHY...

  8. 21 CFR 212.20 - What activities must I perform to ensure drug quality?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false What activities must I perform to ensure drug quality? 212.20 Section 212.20 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR POSITRON EMISSION TOMOGRAPHY...

  9. Nonsteroidal Anti-inflammatory Drugs for Sciatica: An Updated Cochrane Review.

    PubMed

    Rasmussen-Barr, Eva; Held, Ulrike; Grooten, Wilhelmus J A; Roelofs, Pepijn D D M; Koes, Bart W; van Tulder, Maurits W; Wertli, Maria M

    2017-04-15

    Systematic review and meta-analysis. To determine the efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) on pain reduction, overall improvement, and reported adverse effects in people with sciatica. NSAIDs are one of the most frequently prescribed drugs for sciatica. We updated a 2008 Cochrane Review through June 2015. Randomized controlled trials that compared NSAIDs with placebo, with other NSAIDs, or with other medication were included. Outcomes included pain using mean difference (MD, 95% confidence intervals [95% CI]). For global improvement and adverse effects risk ratios (RR, 95% CI) were used. We assessed level of evidence using the Grades of Recommendation, Assessment, Development and Evaluation approach. Ten trials were included (N = 1651). Nine out of 10 trials were assessed at high risk of bias. For pain reduction (visual analog scale, 0 to 100) NSAIDs were no more effective than placebo (MD -4.56, 95% CI -11.11 to 1.99, quality of evidence: very low). For global improvement NSAIDs were more effective than placebo (RR 1.14 [95% CI 1.03 to 1.27], low quality of evidence). One trial reported the effect of NSAIDs on disability with very low-quality evidence that NSAIDs are no more effective than placebo. There was low-quality evidence that the risk for adverse effects is higher for NSAID than placebo (RR 1.40, 95% CI 1.02 to 1.93). Our findings show very low-quality evidence that the efficacy of NSAIDs for pain reduction is comparable with that of placebo, low-quality evidence that NSAIDs is better than placebo for global improvement and low-quality evidence for higher risk of adverse effects using NSAIDs compared with placebo. The findings must be interpreted with caution, due to small study samples, inconsistent results, and a high risk of bias in the included trials. 1.

  10. A nurse-delivered advice intervention can reduce chronic non-steroidal anti-inflammatory drug use in general practice: a randomized controlled trial.

    PubMed

    Jones, A C; Coulson, L; Muir, K; Tolley, K; Lophatananon, A; Everitt, L; Pringle, M; Doherty, M

    2002-01-01

    To find out whether a nurse-delivered educational package can reduce chronic oral non-steroidal anti-inflammatory drug (NSAID) usage in general practice. A prospective randomized controlled trial with assessment of economic cost/benefits was carried out in five general practices in Nottinghamshire with computerized prescribing systems, representing a mix of rural/urban and fundholding/non-fundholding practices. Patients suffering from non-malignant, non-inflammatory musculoskeletal pain received repeat prescriptions for oral NSAIDs. Two hundred and twenty-two patients were randomized to a control group (simple advice regarding NSAID use) or an intervention group (asked to withdraw their NSAIDs and employ appropriate alternative drug and non-drug therapies). All advice was supported by patient literature and delivered by a nurse practitioner trained in musculoskeletal assessment. The primary outcome measure was change in NSAID use 6 months after the intervention. Secondary outcome measures were changes in health and quality of life (SF-36 and EQ-5D questionnaires) and drug, health service and patient costs. An extra 28% of patients in the intervention group either stopped taking oral NSAIDs or reduced dosage by > or =50% at 6 months compared with controls. There was no detrimental effect on health and well-being. Oral NSAID prescription costs were significantly lowered in the intervention group but not in the control group. A non-significant increase in total drug prescription costs occurred in both groups. Nurse-based intervention can reduce chronic NSAID usage and costs in primary care and would be cost-effective if maintained in the long term. This intervention package would be readily applicable in primary care.

  11. Safinamide for the treatment of Parkinson's disease.

    PubMed

    deSouza, Ruth Mary; Schapira, Anthony

    2017-06-01

    The major unmet needs in the medical treatment of Parkinson disease (PD) are reduction of motor side effects from dopaminergic drugs, management of non-motor symptoms and disease modification. Areas covered: Motor fluctuations and OFF periods are a significant determinant of quality of life in PD and reducing their duration and severity can significantly improve motor function. This aim may be partly facilitated by the development of effective adjunctive drugs for dopamine replacement. Safinamide (Xadago), which is a first generation anticonvulsant, has pharmacological properties which are of interest in the context of neurodegenerative diseases, leading to research into its potential as an adjunct to levodopa in PD. Expert opinion: Although its mechanism has not been fully defined, safinamide provides enhanced symptom control of motor function in advanced PD and improves quality of life.

  12. 78 FR 79465 - International Drug Scheduling; Convention on Psychotropic Substances; Single Convention on...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ... Essential Medicines and Health Products (EMP): http://www.who.int/medicines/areas/quality_safety/ECDD/en... medicine: --Please mention other, if any, medical use not included in the approved indications (off label...: (Controlled substances act/ Medicines law/Poisons acts/Consumer protection acts/Generic legislation/Analogue...

  13. 76 FR 31342 - Agency Information Collection Activities; Proposed Collection; Comment Request; Current Good...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-31

    ... product requirements are set forth. Section 211.173--Animals used in testing components, in-process... drug is adulterated if the methods used in, or the facilities or controls used for, its manufacture... can be used for evaluating, at least annually, the quality [[Page 31343

  14. 21 CFR 820.75 - Process validation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Process validation. 820.75 Section 820.75 Food and... QUALITY SYSTEM REGULATION Production and Process Controls § 820.75 Process validation. (a) Where the... validated with a high degree of assurance and approved according to established procedures. The validation...

  15. 21 CFR 820.75 - Process validation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Process validation. 820.75 Section 820.75 Food and... QUALITY SYSTEM REGULATION Production and Process Controls § 820.75 Process validation. (a) Where the... validated with a high degree of assurance and approved according to established procedures. The validation...

  16. 21 CFR 820.75 - Process validation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Process validation. 820.75 Section 820.75 Food and... QUALITY SYSTEM REGULATION Production and Process Controls § 820.75 Process validation. (a) Where the... validated with a high degree of assurance and approved according to established procedures. The validation...

  17. 21 CFR 820.75 - Process validation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Process validation. 820.75 Section 820.75 Food and... QUALITY SYSTEM REGULATION Production and Process Controls § 820.75 Process validation. (a) Where the... validated with a high degree of assurance and approved according to established procedures. The validation...

  18. 21 CFR 820.75 - Process validation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Process validation. 820.75 Section 820.75 Food and... QUALITY SYSTEM REGULATION Production and Process Controls § 820.75 Process validation. (a) Where the... validated with a high degree of assurance and approved according to established procedures. The validation...

  19. 21 CFR 820.130 - Device packaging.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Device packaging. 820.130 Section 820.130 Food and... QUALITY SYSTEM REGULATION Labeling and Packaging Control § 820.130 Device packaging. Each manufacturer shall ensure that device packaging and shipping containers are designed and constructed to protect the...

  20. 76 FR 15986 - Food and Drug Administration/Xavier University Global Medical Device Conference

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-22

    ... Small Business ( http://www.XavierMedCon.com . FDA has verified the Web site address, but is not.... Combination Products Panel. Update on Quality System Regulations. Warning Letter and Enforcement Action Trends... Trends for Sponsor-Monitors and CRO's. Supplier Controls. Advertising, and Promotion and Labeling Pre...

  1. QbD-Oriented Development and Characterization of Effervescent Floating-Bioadhesive Tablets of Cefuroxime Axetil.

    PubMed

    Bansal, Sanjay; Beg, Sarwar; Garg, Babita; Asthana, Abhay; Asthana, Gyati S; Singh, Bhupinder

    2016-10-01

    The objective of the present studies was systematic development of floating-bioadhesive gastroretentive tablets of cefuroxime axetil employing rational blend of hydrophilic polymers for attaining controlled release drug delivery. As per the QbD-based approach, the patient-centric target product profile and quality attributes of tablet were earmarked, and preliminary studies were conducted for screening the suitability of type of polymers, polymer ratio, granulation technique, and granulation time for formulation of tablets. A face-centered cubic design (FCCD) was employed for optimization of the critical material attributes, i.e., concentration of release controlling polymers, PEO 303 and HPMC K100 LV CR, and evaluating in vitro buoyancy, drug release, and ex vivo mucoadhesion strength. The optimized formulation was embarked upon through numerical optimization, which yield excellent floatation characteristic with drug release control (i.e., T 60% > 6 h) and bioadhesion strength. Drug-excipient compatibility studies through FTIR and P-XRD revealed the absence of any interaction between the drug and polymers. In vivo evaluation of the gastroretentive characteristics through X-ray imaging and in vivo pharmacokinetic studies in rabbits revealed significant extension in the rate of drug absorption (i.e., T max, K a, and MRT) from the optimized tablet formulation as compared to the marketed formulation. Successful establishment of various levels of in vitro/in vivo correlations (IVIVC) substantiated high degree of prognostic ability of in vitro dissolution conditions in predicting the in vivo performance. In a nutshell, the studies demonstrate successful development of the once-a-day gastroretentive formulations of cefuroxime axetil with controlled drug release profile and improved compliance.

  2. Docetaxel-carboxymethylcellulose nanoparticles display enhanced anti-tumor activity in murine models of castration-resistant prostate cancer.

    PubMed

    Hoang, Bryan; Ernsting, Mark J; Murakami, Mami; Undzys, Elijus; Li, Shyh-Dar

    2014-08-25

    Docetaxel (DTX) remains the only effective drug for prolonging survival and improving quality of life of metastatic castration resistant prostate cancer (mCRPC) patients. Despite some clinical successes with DTX-based therapies, advent of cumulative toxicity and development of drug resistance limit its long-term clinical application. The integration of nanotechnology for drug delivery can be exploited to overcome the major intrinsic limitations of DTX therapy for mCRPC. We evaluated whether reformulation of DTX by facile conjugation to carboxymethylcellulose nanoparticles (Cellax) can improve the efficacy and safety of the drug in s.c. and bone metastatic models of CRPC. A single dose of the nanoparticles completely regressed s.c. PC3 tumor xenografts in mice. In addition, Cellax elicited fewer side effects compared to native DTX. Importantly, Cellax did not increase the expression of drug resistance molecules in androgen-independent PC3 prostate cancer cells in comparison with DTX. Lastly, in a bone metastatic model of CRPC, Cellax treatment afforded a 2- to 3-fold improvement in survival and enhancements in quality-of-life of the animals over DTX and saline controls. These results demonstrate the potential of Cellax in improving the treatment of mCRPC. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Review of adverse reactions to injections of Chinese materia medica.

    PubMed

    Bian, Zhaoxiang; Shang, Hongcai; Cheng, Chungwah; Wu, Taixiang; Li, Youping; Zhang, Boli

    2010-05-01

    Using Chinese Materia Medica (CM) as injections is an innovation that is proving effective in extensive clinical use in Mainland China. However, recent reports have focused on adverse reactions, ignoring the considerable successes of these preparations. In order to achieve balance in the media and in the minds of the public, we suggest the first step is to clarify the concepts of and differences between adverse drug reactions (ADR) and adverse events (AE) for all concerned-the public, medical practitioners, government officials, and lawmakers. Second, the State Food and Drug Administration should raise the requirements for Chinese Materia Medica Injection (CMI) registration and license approval and emphasize the importance of evidence-based CMI development and evidence-based CMI license approval. Thirdly, drug companies and institutions should reinforce basic research about the quality control of herbs and CMI-drug interactions. Fourth, the Government should clarify the legal responsibilities for CMI approval agencies, CMI developers, medical doctors, and patients. Fifth, the medical association and Government should enhance training for health care professionals concerning the usage of CMIs. And finally sixth, State Food and Drug Administration should monitor the content and quality of the directions for use of CMI. © 2010 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

  4. Pharmacokinetic considerations and recommendations in palliative care, with focus on morphine, midazolam and haloperidol.

    PubMed

    Franken, L G; de Winter, B C M; van Esch, H J; van Zuylen, L; Baar, F P M; Tibboel, D; Mathôt, R A A; van Gelder, T; Koch, B C P

    2016-06-01

    A variety of medications are used for symptom control in palliative care, such as morphine, midazolam and haloperidol. The pharmacokinetics of these drugs may be altered in these patients as a result of physiological changes that occur at the end stage of life. This review gives an overview of how the pharmacokinetics in terminally ill patients may differ from the average population and discusses the effect of terminal illness on each of the four pharmacokinetic processes absorption, distribution, metabolism, and elimination. Specific considerations are also given for three commonly prescribed drugs in palliative care: morphine, midazolam and haloperidol). The pharmacokinetics of drugs in terminally ill patients can be complex and limited evidence exists on guided drug use in this population. To improve the quality of life of these patients, more knowledge and more pharmacokinetic/pharmacodynamics studies in terminally ill patients are needed to develop individualised dosing guidelines. Until then knowledge of pharmacokinetics and the physiological changes that occur in the final days of life can provide a base for dosing adjustments that will improve the quality of life of terminally ill patients. As the interaction of drugs with the physiology of dying is complex, pharmacological treatment is probably best assessed in a multi-disciplinary setting and the advice of a pharmacist, or clinical pharmacologist, is highly recommended.

  5. Assessing the Quality of Economic Evaluations of FDA Novel Drug Approvals: A Systematic Review.

    PubMed

    Woersching, Alex L; Borrego, Matthew E; Raisch, Dennis W

    2016-12-01

    To systematically review and assess the quality of the novel drugs' economic evaluation literature in print during the drugs' early commercial availability following US regulatory approval. MEDLINE and the United Kingdom National Health Service Economic Evaluation Database were searched from 1946 through December 2011 for economic evaluations of the 50 novel drugs approved by the FDA in 2008 and 2009. The inclusion criteria were English-language, peer-reviewed, original economic evaluations (cost-utility, cost-effectiveness, cost-minimization, and cost-benefit analyses). We extracted and analyzed data from 36 articles considering 19 of the 50 drugs. Two reviewers assessed each publication's quality using the Quality of Health Economic Studies (QHES) instrument and summarized study quality on a 100-point scale. Study quality had a mean of 70.0 ± 16.2 QHES points. The only study characteristics associated with QHES score (with P < 0.05) were having used modeling or advanced statistics, 75.1 versus 61.9 without; using quality-adjusted life years as an outcome, 75.9 versus 64.7 without; and cost-utility versus cost-minimization analysis, 75.9 versus 58.7. Studies most often satisfied quality aspects about stating study design choices and least often satisfied aspects about justifying design choices. The reviewed literature considered a minority of the 2008-2009 novel drugs and had mixed study quality. Cost-effectiveness stakeholders might benefit from efforts to improve the quality and quantity of literature examining novel drugs. Editors and reviewers may support quality improvement by stringently imposing economic evaluation guidelines about justifying study design choices. © The Author(s) 2016.

  6. Drug interactions between non-rifamycin antibiotics and hormonal contraception: a systematic review.

    PubMed

    Simmons, Katharine B; Haddad, Lisa B; Nanda, Kavita; Curtis, Kathryn M

    2018-01-01

    The purpose of this study was to determine whether interactions between non-rifamycin antibiotics and hormonal contraceptives result in decreased effectiveness or increased toxicity of either therapy. We searched MEDLINE, Embase, clinicaltrials.gov, and Cochrane libraries from database inception through June 2016. We included trials, cohort, case-control, and pharmacokinetic studies in any language that addressed pregnancy rates, pharmacodynamics, or pharmacokinetic outcomes when any hormonal contraceptive and non-rifamycin antibiotic were administered together vs apart. Of 7291 original records that were identified, 29 met criteria for inclusion. Two authors independently assessed study quality and risk of bias using the United States Preventive Services Task Force evidence grading system. Findings were tabulated by drug class. Study quality ranged from good to poor and addressed only oral contraceptive pills, emergency contraception pills, and the combined vaginal ring. Two studies demonstrated no difference in pregnancy rates in women who used oral contraceptives with and without non-rifamycin antibiotics. No differences in ovulation suppression or breakthrough bleeding were observed in any study that combined hormonal contraceptives with any antibiotic. No significant decreases in any progestin pharmacokinetic parameter occurred during co-administration with any antibiotic. Ethinyl estradiol area under the curve decreased when administered with dirithromycin, but no other drug. Evidence from clinical and pharmacokinetic outcomes studies does not support the existence of drug interactions between hormonal contraception and non-rifamycin antibiotics. Data are limited by low quantity and quality for some drug classes. Most women can expect no reduction in hormonal contraceptive effect with the concurrent use of non-rifamycin antibiotics. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. The impact of pharmaceutical innovation on premature cancer mortality in Switzerland, 1995-2012.

    PubMed

    Lichtenberg, Frank R

    2016-09-01

    The premature cancer mortality rate has been declining in Switzerland, but there has been considerable variation in the rate of decline across cancer sites (e.g., breast or digestive organs). I analyze the effect that pharmaceutical innovation had on premature cancer mortality in Switzerland during the period 1995-2012 by investigating whether the cancer sites that experienced more pharmaceutical innovation had larger declines in premature mortality, controlling for the number of people diagnosed and mean age at diagnosis. Premature cancer mortality before ages 75 and 65 is significantly inversely related to the cumulative number of drugs registered 5, 10, and 15 years earlier. The number of drugs registered during 1980-1997 explains 63 % of the variation across cancer sites in the 1995-2012 log change in the premature (before age 75) mortality rate. Controlling for the cumulative number of drugs, the cumulative number of chemical subgroups does not have a statistically significant effect on premature mortality. This suggests that drugs (chemical substances) within the same class (chemical subgroup) are not "therapeutically equivalent". Over 17,000 life-years before age 75 were gained in 2012 due to drugs registered during 1990-2007. The number of life-years before age 75 gained in 2012 from drugs registered during two earlier periods (1985-2002 and 1980-1997) were more than twice as great. Since mean utilization of new drugs is much lower than mean utilization of older drugs, more recent drug registrations may have a smaller effect on premature mortality than earlier drug registrations even if the average quality of newer drugs is higher. Estimates of the cost per life-year gained before ages 75 and 65 in 2012 from drugs registered during 1990-2007 are $21,228 and $28,673, respectively. These figures are below even the lowest estimates from the value-of-life literature of the value of a quality-adjusted life-year. The estimates indicate that the cost per life-year before age 75 gained from drugs registered during earlier periods (1985-2002 and 1980-1997) were considerably lower: $5299 and $3218, respectively. The largest reductions in premature mortality occur at least a decade after drugs are registered, when their utilization increases significantly. This suggests that if Switzerland is to obtain substantial additional reductions in premature cancer mortality in the future (a decade or more from now) at a modest cost, pharmaceutical innovation (registration of new drugs) is needed today.

  8. A novel cell line generated using the CRISPR/Cas9 technology as universal quality control material for KRAS G12V mutation testing.

    PubMed

    Jia, Shiyu; Zhang, Rui; Lin, Guigao; Peng, Rongxue; Gao, Peng; Han, Yanxi; Fu, Yu; Ding, Jiansheng; Wu, Qisheng; Zhang, Kuo; Xie, Jiehong; Li, Jinming

    2018-06-01

    KRAS mutations are the key indicator for EGFR monoclonal antibody-targeted therapy and acquired drug resistance, and their accurate detection is critical to the clinical decision-making of colorectal cancer. However, no proper quality control material is available for the current detection methods, particularly next-generation sequencing (NGS). The ideal quality control material for NGS needs to provide both the tumor mutation gene and the matched background genomic DNA, which is uncataloged in public databases, to accurately distinguish germline polymorphisms and somatic mutations. We developed a novel KRAS G12V mutant cell line using the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technique to make up for the deficiencies in existing quality control material and further validated the feasibility of the cell line as quality control material by amplification refractory mutation system (ARMS), Sanger sequencing, digital PCR (dPCR), and NGS. We verified that the edited cell line specifically had the G12V mutation, and the validation results presented a high consistency among the four methods of detection. The three cell lines screened contained the G12V mutation and the mutation allele fractions of G12V-1, G12V-2, and G12V-3 were 52.01%, 82.06%, and 17.29%, respectively. The novel KRAS G12V cell line generated using the CRISPR/Cas9 gene editing system is suitable as a quality control material for all current detection methods and provides a new direction in the development of quality control material. © 2018 Wiley Periodicals, Inc.

  9. Preventing Unnecessary Costs of Drug-Induced Hypoglycemia in Older Adults with Type 2 Diabetes in the United States and Canada.

    PubMed

    Boulin, Mathieu; Diaby, Vakaramoko; Tannenbaum, Cara

    2016-01-01

    The costs of drug-induced hypoglycemia are a critical but often neglected component of value-based arguments to reduce tight glycemic control in older adults with type 2 diabetes. An economic (decision-tree) analysis compared rates, costs, quality-adjusted life-years, and incremental costs per quality-adjusted life-year gained associated with mild, moderate and severe hypoglycemic events for 6 glucose-lowering medication classes in type 2 diabetic adults aged 65-79 versus those 80 years and older. The national U.S. (Center for Medicare Services) and Canadian public health payer perspectives were adopted. Incidence rates of drug-induced hypoglycemia were the highest for basal insulin and sulfonylureas: 8.64 and 4.32 events per person-year in 65-79 year olds, and 12.06 and 6.03 events per person-year for 80 years and older. In both the U.S. and Canada, metformin dominated sulfonylureas, basal insulin and glucagon-like peptide1 receptor agonists. Relative to sulfonylureas, thiazolidinediones had the lowest incremental cost-effectiveness ratios in the U.S. and dominated sulfonylureas in Canada for adults 80 years and older. Relative to sulfonylureas, dipeptidyl peptidase4 inhibitors were cost-effective for adults 80 years and older in both countries, and for 65-79 year olds in Canada. Annual costs of hypoglycemia for older adults attaining very tight glycemic control with the use of insulin or sulfonylureas were estimated at U.S.$509,214,473 in the U.S. and CAN$65,497,849 in Canada. Optimizing drug therapy for older type 2 diabetic adults through the avoidance of drug-induced hypoglycemia will dramatically improve patient health while also generating millions of dollars by saving unnecessary medical costs.

  10. The application of quantitative methods for identifying and exploring the presence of bias in systematic reviews: PDE-5 inhibitors for erectile dysfunction.

    PubMed

    Bekkering, G E; Abou-Setta, A M; Kleijnen, J

    2008-01-01

    A systematic review of PDE-5 inhibitors for erectile dysfunction was performed to evaluate the utility of quantitative methods for identifying and exploring the influence of bias and study quality on pooled outcomes from meta-analyses. We included 123 randomized controlled trials (RCTs). Methodological quality was poorly reported. All three drugs appeared highly effective. Indirect adjusted analyses showed no differences between the three drugs. Funnel plots and statistical tests showed no evidence of small-study effects for sildenafil whereas there was evidence of such bias for tadalafil and vardenafil. Adjustment for missing studies using trim and fill techniques did not alter the pooled estimates substantially. The exclusion of previous sildenafil nonresponders was associated with larger treatment effects for tadalafil. This investigation was hampered by poor reporting of methodological quality, a low number of studies, heterogeneity and large effect sizes. Despite such limitations, a comprehensive assessment of biases should be a routine in systematic reviews.

  11. Development In Drug Targeting And Delivery In Cervical Cancer.

    PubMed

    Aggarwal, Urvashi; Goyal, Amit Kumar; Rath, Goutam

    2017-10-09

    Cervical cancer is the second most common cancer in women. Standard treatment options available for cervical cancer including chemotherapy, surgery and radiation therapy associated with their own side effects and toxicities. Tumor-targeted delivery of anticancer drugs is perhaps one of the most appropriate strategies to achieve optimal outcomes from treatment and improve quality of life. Recently nanocarriers based drug delivery systems owing to their unique properties have been extensively investigated for anticancer drug delivery. In addition to that addressing the anatomical significance of cervical cancer, various local drug delivery strategies for the cancer treatment are introduced like: gels, nanoparticles, polymeric films, rods and wafers, lipid based nanocarrier. Localized drug delivery systems allows passive drug targeting results in high drug concentration at the target site. Further they can be tailor made to achieve both sustained and controlled release behavior, substantially improving therapeutic outcomes and minimizing side effects. This review summarizes the meaningful advances in drug delivery strategies to treat cervical cancer. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  12. Assessment of ART centres in India: client perspectives.

    PubMed

    Sogarwal, Ruchi; Bachani, Damodar

    2009-05-01

    Drug adherence and quality of antiretroviral therapy (ART) services are the keys for the successful ART programme. Hence, an attempt has been made to assess ART centres in India from client perspectives that are receiving services from the centres. Data were gathered through exit interviews with 1366 clients from 27 ART centres that were selected on the basis of drug adherence and client load. Analyses revealed that more than 80 per cent of the clients reported overall satisfaction with the services availed from the centre and 60 per cent reported that the quality of life has improved to a great extent after getting ART. Most of the clients strongly demanded to open ART centre in each district for better access as that will increase drug adherence and eventually control the HIV progression. It has been found that as many as 14% of respondents, ever been on ART, reported non-adherence and 70% of them cited distance and economic factors as the reasons for non-adherence. Study concludes that while majority of the clients were satisfied with ART services, shortage of staff, high level of non-drug adherence, long distances and poor referring system are the weak areas requiring attention.

  13. Quality evaluation and pattern recognition analyses of marker compounds from five medicinal drugs of Rutaceae family by HPLC/PDA.

    PubMed

    Zhao, Bing Tian; Kim, Eun Jung; Son, Kun Ho; Son, Jong Keun; Min, Byung Sun; Woo, Mi Hee

    2015-08-01

    To establish a standard of quality control and to identify different origins for the Rutaceae family [Citri Unshiu Peel (CU), Citri Unshiu Immature Peel (CI), Ponciri Immature Fructus (PI), Aurantii Immature Fructus (AI), and Aurantii Fructus (AU)], 13 standards including rutin (1), narirutin (2), naringin (3), hesperidin (4), neohesperidin (5), neoponcirin (6), poncirin (7), naringenin (8), isosinensetin (9), sinensetin (10), nobiletin (11), heptamethoxyflavone (12), and tangeretin (13) were determined by high performance liquid chromatography (HPLC)/photo-diode array (PDA) analysis. A YMC ODS C18 (250 × 4.6 mm, 5 µm) column was used and the ratio of mobile phases of water (A) and acetonitrile (B) delivered to the column for gradient elution was applied. This method was fully validated with respect to linearity, accuracy, precision, stability, and robustness. The HPLC/PDA method was applied successfully to quantify 13 major compounds in the extracts of CU, CI, PI, AI, and AU. The pattern recognition analysis combined with LC chromatographic data was performed by repeated analysis of 27 reference samples in the above five Rutaceae oriental medicinal drugs. The established HPLC method was rapid and reliable for quantitative analysis and quality control of multiple components in five Rutaceae species with different origins.

  14. National indicators for quality of drug therapy in older persons: the Swedish experience from the first 10 years.

    PubMed

    Fastbom, Johan; Johnell, Kristina

    2015-03-01

    Inappropriate drug use is an important health problem in elderly persons. Beginning with the Beers' criteria in the early 1990s, explicit criteria have been extensively used to measure and improve quality of drug use in older people. This article describes the Swedish indicators for quality of drug therapy in the elderly, introduced in 2004 and updated in 2010. These indicators were designed to be applied to people aged 75 years and over, regardless of residence and other characteristics. The indicators are divided into drug specific, covering choice, indication and dosage of drugs, polypharmacy, drug-drug interactions (DDIs), drug use in decreased renal function and in some symptoms; and diagnosis specific, covering the rational, irrational and hazardous drug use in common disorders in elderly people. During the 10 years since introduction, the Swedish indicators have several applications. They form the basis for recommendations for drug therapy in older people, are implemented in prescribing supports and drug utilisation reviews, are used in national benchmarking of the quality of Swedish healthcare and have contributed to initiatives from pensioner organisations. The indicators have also been used in several pharmacoepidemiological studies. Since 2005, there have been signs of improvement of the quality of drug prescribing to elderly persons in Sweden. For example, the prescribing of drugs that should be avoided in older persons decreased by 36 % between 2006 and 2012 in persons aged 80 years and older. Similarly, drug combinations that may cause DDIs decreased by 26 % and antipsychotics by 41 %. The indicators have likely contributed to this.

  15. Drug-vitamin D interactions: A systematic review of the literature

    PubMed Central

    Oppeneer, Sarah J.; Kelly, Julia A.; Hamilton-Reeves, Jill M.

    2017-01-01

    Extensive media coverage of the potential health benefits of vitamin D supplementation has translated into substantial increases in supplement sales over recent years. Yet, the potential for drug-vitamin D interactions is rarely considered. This systematic review of the literature was conducted to evaluate the extent to which drugs affect vitamin D status or supplementation alters drug effectiveness or toxicity in humans. Electronic databases were used to identify eligible peer-reviewed studies published through September 1, 2010. Study characteristics and findings were abstracted, and quality was assessed for each study. A total of 109 unique reports met the inclusion criteria. The majority of eligible studies were classified as Class C (non-randomized trials, case-control studies, or time series) or D (cross-sectional, trend, case report/series, or before-and-after studies). Only two Class C and three Class D studies were of positive quality. Insufficient evidence was available to determine whether lipase inhibitors, antimicrobial agents, antiepileptic drugs, highly active antiretroviral agents or H2 receptor antagonists alter serum 25(OH)D concentrations. Atorvastatin appears to increase 25(OH)D concentrations, while concurrent vitamin D supplementation decreases concentrations of atorvastatin. Use of thiazide diuretics in combination with calcium and vitamin D supplements may cause hypercalcemia in the elderly, or those with compromised renal function or hyperparathyroidism. Larger studies with stronger study designs are needed to clarify potential drug-vitamin D interactions, especially for drugs metabolized by cytochrome P450 3A4 (CYP3A4). Health care providers should be aware of the potential for drug-vitamin D interactions. PMID:23307906

  16. Spectrophotometric Method for the Determination of Two Coformulated Drugs with Highly Different Concentrations. Application on Vildagliptin and Metformin Hydrochloride

    NASA Astrophysics Data System (ADS)

    Zaazaa, H. E.; Elzanfaly, E. S.; Soudi, A. T.; Salem, M. Y.

    2016-03-01

    A new smart simple validated spectrophotometric method was developed for the determination of two drugs one of which is in a very low concentration compared to the other. The method is based on spiking and dilution then simple mathematical manipulation of the absorbance spectra. This method was applied for the determination of a binary mixture of vildagliptin and metformin hydrochloride in the ratio 50:850 in laboratory prepared mixtures containing both drugs in this ratio and in pharmaceutical dosage form with good recoveries. The developed method was validated according to ICH guidelines and can be used for routine quality control testing.

  17. Formulary decisions and health economics.

    PubMed

    Glazer, W M

    1998-01-01

    Because of increasing concerns about health care costs, physicians must consider the cost-effectiveness of a treatment strategy, as well as its efficacy and safety. The question of whether the greater expense of a newer drug is justified over the cost of a generic drug deserves a comprehensive evaluation. The determination of effectiveness and tolerability of the newer antipsychotics should be expanded to include quality-of-life issues, reintegration of the patient into the community, resource utilization, and medical costs. There are clear indications that patients who take atypical antipsychotics utilize fewer medical resources than patients who take typical antipsychotics; however, the positive outcomes of the newer drugs must be translated into cost benefits if formularies are to be intelligently controlled.

  18. The procedure of new drug application and the philosophy of critical rationalism or the limits of quality assurance with good clinical practice.

    PubMed

    Högel, J; Gaus, W

    1999-12-01

    K.R. Popper's philosophy of critical rationalism is concerned with the detection and removal of error. Fundamental contradictions exist between Popper's theory of knowledge and the present-day practice of the clinical investigation of new drugs. Currently, the public authorities concerned with the licensing of drugs pass judgment on trials, which are closely linked by the one-sponsor problem: the assertions made by the sponsor are not independently confirmed. This lack leads to excessive documentation and to costly monitoring and auditing, which are intended to ensure the credibility of results. In Popper's view, confirmatory trials, independent of the sponsor and supervised by the regulatory bodies, would be a better way to achieve reliable knowledge. The consequence would, among other things, be a reorganization of phase III of the clinical investigation of new drugs by dividing it into independent parts, one under the control of the sponsor and one under the control of the public authority. The implementation of this suggestion would lead to a more scientific manner of dealing with new drugs and to savings in terms of unproductive measures during the application process.

  19. Effect of drug reminder packaging on medication adherence: a systematic review revealing research gaps

    PubMed Central

    2014-01-01

    Background This was a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Evidence mapping was used to reveal the effect of drug reminder packaging on medication adherence, to identify research gaps and to make suggestions for future research. Methods PubMed, Embase, CINAHL and PsycINFO were searched with an end date of September 2013 using the Medical Subject Headings (MeSH) term ‘medication adherence’ and 20 different search terms for ‘drug reminder packaging’, limited to the English and German languages. Additional references were identified through cross-referencing. All prospective controlled trials with an intervention using drug reminder packaging for patients taking at least one medication without the assistance of a health-care professional were included in the evidence mapping of the effect of drug reminder packaging on adherence and outcomes according to the Economic, Clinical and Humanistic Outcomes (ECHO) model. Results A total of 30 studies met the inclusion criteria: 10 randomized controlled trials, 19 controlled clinical trials and 1 cohort study. Drug reminder packaging had a significant effect on at least one adherence parameter in 17 studies (57%). The methodological quality was strong in five studies. Two studies provided complete information. Clear research gaps emerged. Conclusions Overall, the studies showed a positive effect of drug reminder packaging on adherence and clinical outcomes. However, poor reporting and important gaps like missing humanistic and economic outcomes and neglected safety issues limit the drawing of firm conclusions. Suggestions are made for future research. PMID:24661495

  20. Comparative Application of PLS and PCR Methods to Simultaneous Quantitative Estimation and Simultaneous Dissolution Test of Zidovudine - Lamivudine Tablets.

    PubMed

    Üstündağ, Özgür; Dinç, Erdal; Özdemir, Nurten; Tilkan, M Günseli

    2015-01-01

    In the development strategies of new drug products and generic drug products, the simultaneous in-vitro dissolution behavior of oral dosage formulations is the most important indication for the quantitative estimation of efficiency and biopharmaceutical characteristics of drug substances. This is to force the related field's scientists to improve very powerful analytical methods to get more reliable, precise and accurate results in the quantitative analysis and dissolution testing of drug formulations. In this context, two new chemometric tools, partial least squares (PLS) and principal component regression (PCR) were improved for the simultaneous quantitative estimation and dissolution testing of zidovudine (ZID) and lamivudine (LAM) in a tablet dosage form. The results obtained in this study strongly encourage us to use them for the quality control, the routine analysis and the dissolution test of the marketing tablets containing ZID and LAM drugs.

  1. Quality evaluation of Yin Chen Hao Tang extract based on fingerprint chromatogram and simultaneous determination of five bioactive constituents.

    PubMed

    Wang, Xijun; Lv, Haitao; Sun, Hui; Jiang, Xingang; Wu, Zeming; Sun, Wenjun; Wang, Ping; Liu, Lian; Bi, Kaishun

    2008-01-01

    A completely validated method based on HPLC coupled with photodiode array detector (HPLC-UV) was described for evaluating and controlling quality of Yin Chen Hao Tang extract (YCHTE). First, HPLC-UV fingerprint chromatogram of YCHTE was established for preliminarily elucidating amount and chromatographic trajectory of chemical constituents in YCHTE. Second, for the first time, five mainly bioactive constituents in YCHTE were simultaneously determined based on fingerprint chromatogram for furthermore controlling the quality of YCHTE quantitatively. The developed method was applied to analyze 12 batches of YCHTE samples which consisted of herbal drugs from different places of production, showed acceptable linearity, intraday (RSD <5%), interday precision (RSD <4.80%), and accuracy (RSD <2.80%). As a result, fingerprint chromatogram determined 15 representative general fingerprint peaks, and the fingerprint chromatogram resemblances are all better than 0.9996. The contents of five analytes in different batches of YCHTE samples do not indicate significant difference. So, it is concluded that the developed HPLC-UV method is a more fully validated and complete method for evaluating and controlling the quality of YCHTE.

  2. Tramadol (opioid) abuse is associated with a dose- and time-dependent poor sperm quality and hyperprolactinaemia in young men.

    PubMed

    Farag, A G A; Basha, M A; Amin, S A; Elnaidany, N F; Elhelbawy, N G; Mostafa, M M T; Khodier, S A; Ibrahem, R A; Mahfouz, R Z

    2018-05-21

    Tramadol, one of the most commonly abused drugs in Middle East, impacts spermatogenesis and disturbs reproductive hormones in animal studies. We aimed to investigate tramadol impact on sperm quality and on levels of testosterone, prolactin and gonadotropins, in tramadol abusers (n = 30) to age-matched control (n = 30). Abusers had significantly low percentages of sperm motility, normal forms and vitality compared with control (95% CI -40.7 to -19.3, -13.5 to -9.3 and -31.9 to -9.7 respectively). Hypoandrogenism (95% CI -4.5 to -2.8), hyperprolactinaemia (CI (95%) 4.9 to 9.4) and hypergonadotropinaemia (95% CI 2.9 to 7.2 for FSH and 2.0 to 7.8 for LH) were observed in tramadol abusers vs controls. Smokers (26 of 30), concurrently abusing other drugs (11 of 30) and asymptomatic leucocytospermic (15 of 30) patients subgroups significantly abused tramadol beyond 3 years (p = .02, <.001, = .03 respectively) and in excess >450 mg/day (p = .02, = .01, = .005 respectively). Progressive motility (a + b%) was significantly low in young men <25 years old (p = .03) subgroup. Tramadol abuse is associated with poor sperm quality, hyperprolactinaemia and hypergonadotropic hypogonadism. We recommend semen analysis for tramadol long-intakes, question sperm donors and follow-up studies to prevent and reverse tramadol-induced testicular damage. © 2018 Blackwell Verlag GmbH.

  3. Acupuncture for the prevention of episodic migraine.

    PubMed

    Linde, Klaus; Allais, Gianni; Brinkhaus, Benno; Fei, Yutong; Mehring, Michael; Vertosick, Emily A; Vickers, Andrew; White, Adrian R

    2016-06-28

    Acupuncture is often used for migraine prevention but its effectiveness is still controversial. We present an update of our Cochrane review from 2009. To investigate whether acupuncture is a) more effective than no prophylactic treatment/routine care only; b) more effective than sham (placebo) acupuncture; and c) as effective as prophylactic treatment with drugs in reducing headache frequency in adults with episodic migraine. We searched the Cochrane Central Register of Controlled Trials (CENTRAL: 2016, issue 1); MEDLINE (via Ovid, 2008 to January 2016); Ovid EMBASE (2008 to January 2016); and Ovid AMED (1985 to January 2016). We checked PubMed for recent publications to April 2016. We searched the World Health Organization (WHO) Clinical Trials Registry Platform to February 2016 for ongoing and unpublished trials. We included randomized trials at least eight weeks in duration that compared an acupuncture intervention with a no-acupuncture control (no prophylactic treatment or routine care only), a sham-acupuncture intervention, or prophylactic drug in participants with episodic migraine. Two reviewers checked eligibility; extracted information on participants, interventions, methods and results, and assessed risk of bias and quality of the acupuncture intervention. The primary outcome was migraine frequency (preferably migraine days, attacks or headache days if migraine days not measured/reported) after treatment and at follow-up. The secondary outcome was response (at least 50% frequency reduction). Safety outcomes were number of participants dropping out due to adverse effects and number of participants reporting at least one adverse effect. We calculated pooled effect size estimates using a fixed-effect model. We assessed the evidence using GRADE and created 'Summary of findings' tables. Twenty-two trials including 4985 participants in total (median 71, range 30 to 1715) met our updated selection criteria. We excluded five previously included trials from this update because they included people who had had migraine for less than 12 months, and included five new trials. Five trials had a no-acupuncture control group (either treatment of attacks only or non-regulated routine care), 15 a sham-acupuncture control group, and five a comparator group receiving prophylactic drug treatment. In comparisons with no-acupuncture control groups and groups receiving prophylactic drug treatment, there was risk of performance and detection bias as blinding was not possible. Overall the quality of the evidence was moderate. Comparison with no acupunctureAcupuncture was associated with a moderate reduction of headache frequency over no acupuncture after treatment (four trials, 2199 participants; standardised mean difference (SMD) -0.56; 95% CI -0.65 to -0.48); findings were statistically heterogeneous (I² = 57%; moderate quality evidence). After treatment headache frequency at least halved in 41% of participants receiving acupuncture and 17% receiving no acupuncture (pooled risk ratio (RR) 2.40; 95% CI 2.08 to 2.76; 4 studies, 2519 participants) with a corresponding number needed to treat for an additional beneficial outcome (NNTB) of 4 (95% CI 3 to 6); there was no indication of statistical heterogeneity (I² = 7%; moderate quality evidence). The only trial with post-treatment follow-up found a small but significant benefit 12 months after randomisation (RR 2.16; 95% CI 1.35 to 3.45; NNT 7; 95% 4 to 25; 377 participants, low quality evidence). Comparison with sham acupunctureBoth after treatment (12 trials, 1646 participants) and at follow-up (10 trials, 1534 participants), acupuncture was associated with a small but statistically significant frequency reduction over sham (moderate quality evidence). The SMD was -0.18 (95% CI -0.28 to -0.08; I² = 47%) after treatment and -0.19 (95% CI -0.30 to -0.09; I² = 59%) at follow-up. After treatment headache frequency at least halved in 50% of participants receiving true acupuncture and 41% receiving sham acupuncture (pooled RR 1.23, 95% CI 1.11 to 1.36; I² = 48%; 14 trials, 1825 participants) and at follow-up in 53% and 42%, respectively (pooled RR 1.25, 95% CI 1.13 to 1.39; I² = 61%; 11 trials, 1683 participants; moderate quality evidence). The corresponding NNTBs are 11 (95% CI 7.00 to 20.00) and 10 (95% CI 6.00 to 18.00), respectively. The number of participants dropping out due to adverse effects (odds ratio (OR) 2.84; 95% CI 0.43 to 18.71; 7 trials, 931 participants; low quality evidence) and the number of participants reporting adverse effects (OR 1.15; 95% CI 0.85 to 1.56; 4 trials, 1414 participants; moderate quality evidence) did not differ significantly between acupuncture and sham groups. Comparison with prophylactic drug treatmentAcupuncture reduced migraine frequency significantly more than drug prophylaxis after treatment ( SMD -0.25; 95% CI -0.39 to -0.10; 3 trials, 739 participants), but the significance was not maintained at follow-up (SMD -0.13; 95% CI -0.28 to 0.01; 3 trials, 744 participants; moderate quality evidence). After three months headache frequency at least halved in 57% of participants receiving acupuncture and 46% receiving prophylactic drugs (pooled RR 1.24; 95% CI 1.08 to 1.44) and after six months in 59% and 54%, respectively (pooled RR 1.11; 95% CI 0.97 to 1.26; moderate quality evidence). Findings were consistent among trials with I² being 0% in all analyses. Trial participants receiving acupuncture were less likely to drop out due to adverse effects (OR 0.27; 95% CI 0.08 to 0.86; 4 trials, 451 participants) and to report adverse effects (OR 0.25; 95% CI 0.10 to 0.62; 5 trials 931 participants) than participants receiving prophylactic drugs (moderate quality evidence). The available evidence suggests that adding acupuncture to symptomatic treatment of attacks reduces the frequency of headaches. Contrary to the previous findings, the updated evidence also suggests that there is an effect over sham, but this effect is small. The available trials also suggest that acupuncture may be at least similarly effective as treatment with prophylactic drugs. Acupuncture can be considered a treatment option for patients willing to undergo this treatment. As for other migraine treatments, long-term studies, more than one year in duration, are lacking.

  4. Substandard anti-malarial drugs in Burkina Faso

    PubMed Central

    Tipke, Maike; Diallo, Salou; Coulibaly, Boubacar; Störzinger, Dominic; Hoppe-Tichy, Torsten; Sie, Ali; Müller, Olaf

    2008-01-01

    Background There is concern about an increasing infiltration of markets by substandard and fake medications against life-threatening diseases in developing countries. This is particularly worrying with regard to the increasing resistance development of Plasmodium falciparum against affordable anti-malarial medications, which has led to a change to more expensive drugs in most endemic countries. Methods A representative sample of modern anti-malarial medications from licensed (public and private pharmacies, community health workers) and illicit (market and street vendors, shops) sources has been collected in the Nouna Health District in north-western Burkina Faso in 2006. All drugs were tested for their quality with the standard procedures of the German Pharma Health Fund-Minilab. Detected low standard drugs were re-tested with European Pharmacopoeia 2.9.1 standards for disintegration and ultraviolet-visible spectroscopy at the laboratory of the Heidelberg University for confirmation. Results Overall, 86 anti-malarial drug samples were collected, of which 77 samples have been included in the final analysis. The sample consisted of 39/77 (50%) chloroquine, 10/77 (13%) pyrimethamine-sulphadoxine, 9/77 (12%) quinine, 6/77 (8%) amodiaquine, 9/77 (12%) artesunate, and 4/77 (5%) artemether-lumefantrine. 32/77 (42%) drug samples were found to be of poor quality, of which 28 samples failed the visual inspection, nine samples had substandard concentrations of the active ingredient, four samples showed poor disintegration, and one sample contained non of the stated active ingredient. The licensed and the illicit market contributed 5/47 (10.6%) and 27/30 (90.0%) samples of substandard drugs respectively. Conclusion These findings provide further evidence for the wide-spread existence of substandard anti-malarial medications in Africa and call for strengthening of the regulatory and quality control capacity of affected countries, particularly in view of the now wider available and substantially more costly artemisinin-based combination therapies. PMID:18505584

  5. Twenty-Four-Hour Ambulatory Blood Pressure Monitoring in Hypertension

    PubMed Central

    2012-01-01

    Executive Summary Objective The objective of this health technology assessment was to determine the clinical effectiveness and cost-effectiveness of 24-hour ambulatory blood pressure monitoring (ABPM) for hypertension. Clinical Need: Condition and Target Population Hypertension occurs when either systolic blood pressure, the pressure in the artery when the heart contracts, or diastolic blood pressure, the pressure in the artery when the heart relaxes between beats, are consistently high. Blood pressure (BP) that is consistently more than 140/90 mmHg (systolic/diastolic) is considered high. A lower threshold, greater than 130/80 mmHg (systolic/diastolic), is set for individuals with diabetes or chronic kidney disease. In 2006 and 2007, the age-standardized incidence rate of diagnosed hypertension in Canada was 25.8 per 1,000 (450,000 individuals were newly diagnosed). During the same time period, 22.7% of adult Canadians were living with diagnosed hypertension. A smaller proportion of Canadians are unaware they have hypertension; therefore, the estimated number of Canadians affected by this disease may be higher. Diagnosis and management of hypertension are important, since elevated BP levels are related to the risk of cardiovascular disease, including stroke. In Canada in 2003, the costs to the health care system related to the diagnosis, treatment, and management of hypertension were over $2.3 billion (Cdn). Technology The 24-hour ABPM device consists of a standard inflatable cuff attached to a small computer weighing about 500 grams, which is worn over the shoulder or on a belt. The technology is noninvasive and fully automated. The device takes BP measurements every 15 to 30 minutes over a 24-to 28-hour time period, thus providing extended, continuous BP recordings even during a patient’s normal daily activities. Information on the multiple BP measurements can be downloaded to a computer. The main detection methods used by the device are auscultation and oscillometry. The device avoids some of the pitfalls of conventional office or clinic blood pressure monitoring (CBPM) using a cuff and mercury sphygmomanometer such as observer bias (the phenomenon of measurement error when the observer overemphasizes expected results) and white coat hypertension (the phenomenon of elevated BP when measured in the office or clinic but normal BP when measured outside of the medical setting). Research Questions Is there a difference in patient outcome and treatment protocol using 24-hour ABPM versus CBPM for uncomplicated hypertension? Is there a difference between the 2 technologies when white coat hypertension is taken into account? What is the cost-effectiveness and budget impact of 24-hour ABPM versus CBPM for uncomplicated hypertension? Research Methods Literature Search Search Strategy A literature search was performed on August 4, 2011 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 1997 to August 4, 2011. Abstracts were reviewed by a single reviewer. For those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low, or very low according to GRADE methodology. Inclusion Criteria English language articles; published between January 1, 1997 and August 4, 2011; adults aged 18 years of age or older; journal articles reporting on the effectiveness, cost-effectiveness, or safety for the comparison of interest; clearly described study design and methods; health technology assessments, systematic reviews, meta-analyses, or randomized controlled trials. Exclusion Criteria non-English papers; animal or in vitro studies; case reports, case series, or case-case studies; studies comparing different antihypertensive therapies and evaluating their antihypertensive effects using 24-hour ABPM; studies on home or self-monitoring of BP, and studies on automated office BP measurement; studies in high-risk subgroups (e.g. diabetes, pregnancy, kidney disease). Outcomes of Interest Patient Outcomes mortality: all cardiovascular events (e.g., myocardial infarction [MI], stroke); non-fatal: all cardiovascular events (e.g., MI, stroke); combined fatal and non-fatal: all cardiovascular events (e.g., MI, stroke); all non-cardiovascular events; control of BP (e.g. systolic and/or diastolic target level). Drug-Related Outcomes percentage of patients who show a reduction in, or stop, drug treatment; percentage of patients who begin multi-drug treatment; drug therapy use (e.g. number, intensity of drug use); drug-related adverse events. Quality of Evidence The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. As stated by the GRADE Working Group, the following definitions of quality were used in grading the quality of the evidence: High Further research is very unlikely to change confidence in the estimate of effect. Moderate Further research is likely to have an important impact on confidence in the estimate of effect and may change the estimate. Low Further research is very likely to have an important impact on confidence in the estimate of effect and is likely to change the estimate. Very Low Any estimate of effect is very uncertain. Summary of Findings Short-Term Follow-Up Studies (Length of Follow-Up of ≤ 1 Year) Based on very low quality of evidence, there is no difference between technologies for non-fatal cardiovascular events. Based on moderate quality of evidence, ABPM resulted in improved BP control among patients with sustained hypertension compared to CBPM. Based on low quality of evidence, ABPM resulted in hypertensive patients being more likely to stop antihypertensive therapy and less likely to proceed to multi-drug therapy compared to CBPM. Based on low quality of evidence, there is a beneficial effect of ABPM on the intensity of antihypertensive drug use compared to CBPM. Based on moderate quality of evidence, there is no difference between technologies in the number of antihypertensive drugs used. Based on low to very low quality of evidence, there is no difference between technologies in the risk for a drug-related adverse event or noncardiovascular event. Long-Term Follow-Up Study (Mean Length of Follow-Up of 5 Years) Based on moderate quality of evidence, there is a beneficial effect of ABPM on total combined cardiovascular events compared to CBPM. Based on low quality of evidence, there is a lack of a beneficial effect of ABPM on nonfatal cardiovascular events compared to CBPM; however, the lack of a beneficial effect is based on a borderline result. Based on low quality of evidence, there is no beneficial effect of ABPM on fatal cardiovascular events compared to CBPM. Based on low quality of evidence, there is no difference between technologies for the number of patients who began multi-drug therapy. Based on low quality of evidence, there is a beneficial effect of CBPM on control of BP compared to ABPM. This result is in the opposite direction than expected. Based on moderate quality of evidence, there is no difference between technologies in the risk for a drug-related adverse event. PMID:23074425

  6. Psychosocial interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users.

    PubMed

    Klimas, Jan; Tobin, Helen; Field, Catherine-Anne; O'Gorman, Clodagh S M; Glynn, Liam G; Keenan, Eamon; Saunders, Jean; Bury, Gerard; Dunne, Colum; Cullen, Walter

    2014-12-03

    Problem alcohol use is common among illicit drug users and is associated with adverse health outcomes. It is also an important factor contributing to a poor prognosis among drug users with hepatitis C virus (HCV) as it impacts on progression to hepatic cirrhosis or opiate overdose in opioid users. To assess the effects of psychosocial interventions for problem alcohol use in illicit drug users (principally problem drug users of opiates and stimulants). We searched the Cochrane Drugs and Alcohol Group trials register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 11, June 2014), MEDLINE (1966 to June 2014); EMBASE (1974 to June 2014); CINAHL (1982 to June 2014); PsycINFO (1872 to June 2014) and the reference lists of eligible articles. We also searched: 1) conference proceedings (online archives only) of the Society for the Study of Addiction, International Harm Reduction Association, International Conference on Alcohol Harm Reduction and American Association for the Treatment of Opioid Dependence; 2) online registers of clinical trials: Current Controlled Trials, Clinical Trials.org, Center Watch and the World Health Organization International Clinical Trials Registry Platform. Randomised controlled trials comparing psychosocial interventions with another therapy (other psychosocial treatment, including non-pharmacological therapies, or placebo) in adult (over the age of 18 years) illicit drug users with concurrent problem alcohol use. We used the standard methodological procedures expected by The Cochrane Collaboration. Four studies, involving 594 participants, were included. Half of the trials were rated as having a high or unclear risk of bias. The studies considered six different psychosocial interventions grouped into four comparisons: (1) cognitive-behavioural coping skills training versus 12-step facilitation (one study; 41 participants), (2) brief intervention versus treatment as usual (one study; 110 participants), (3) group or individual motivational interviewing (MI) versus hepatitis health promotion (one study; 256 participants) and (4) brief motivational intervention (BMI) versus assessment-only (one study; 187 participants). Differences between studies precluded any data pooling. Findings are described for each trial individually.Comparison 1: low-quality evidence; no significant difference for any of the outcomes considered Alcohol abstinence as maximum number of weeks of consecutive alcohol abstinence during treatment: mean difference (MD) 0.40 (95% confidence interval (CI) -1.14 to 1.94); illicit drug abstinence as maximum number of weeks of consecutive abstinence from cocaine during treatment: MD 0.80 (95% CI -0.70 to 2.30); alcohol abstinence as number achieving three or more weeks of consecutive alcohol abstinence during treatment: risk ratio (RR) 1.96 (95% CI 0.43 to 8.94); illicit drug abstinence as number achieving three or more weeks of consecutive abstinence from cocaine during treatment: RR 1.10 (95% CI 0.42 to 2.88); alcohol abstinence during follow-up year: RR 2.38 (95% CI 0.10 to 55.06); illicit drug abstinence as abstinence from cocaine during follow-up year: RR 0.39 (95% CI 0.04 to 3.98), moderate-quality evidence.Comparison 2: low-quality evidence, no significant difference for all the outcomes considered Alcohol use as AUDIT scores at three months: MD 0.80 (95% -1.80 to 3.40); alcohol use as AUDIT scores at nine months: MD 2.30 (95% CI -0.58 to 5.18); alcohol use as number of drinks per week at three months: MD 0.70 (95% CI -3.85 to 5.25); alcohol use as number of drinks per week at nine months: MD -0.30 (95% CI -4.79 to 4.19); alcohol use as decreased alcohol use at three months: RR 1.13 (95% CI 0.67 to 1.93); alcohol use as decreased alcohol use at nine months: RR 1.34 (95% CI 0.69 to 2.58), moderate-quality evidence.Comparison 3 (group and individual MI), low-quality evidence: no significant difference for all outcomes Group MI: number of standard drinks consumed per day over the past month: MD -0.40 (95% CI -2.03 to 1.23); frequency of drug use: MD 0.00 (95% CI -0.03 to 0.03); composite drug score (frequency*severity for all drugs taken): MD 0.00 (95% CI -0.42 to 0.42); greater than 50% reduction in number of standard drinks consumed per day over the last 30 days: RR 1.10 (95% CI 0.82 to 1.48); abstinence from alcohol over the last 30 days: RR 0.88 (95% CI 0.49 to 1.58).Individual MI: number of standard drinks consumed per day over the past month: MD -0.10 (95% CI -1.89 to 1.69); frequency of drug use (as measured using the Addiction Severity Index (ASI drug): MD 0.00 (95% CI -0.03 to 0.03); composite drug score (frequency*severity for all drugs taken): MD -0.10 (95% CI -0.46 to 0.26); greater than 50% reduction in number of standard drinks consumed per day over the last 30 days: RR 0.92 (95% CI 0.68 to 1.26); abstinence from alcohol over the last 30 days: RR 0.97 (95% CI 0.56 to 1.67).Comparison 4: more people reduced alcohol use (by seven or more days in the past month at 6 months) in the BMI group than in the control group (RR 1.67; 95% CI 1.08 to 2.60), moderate-quality evidence. No significant difference was reported for all other outcomes: number of days in the past 30 days with alcohol use at one month: MD -0.30 (95% CI -3.38 to 2.78); number of days in the past month with alcohol use at six months: MD -1.50 (95% CI -4.56 to 1.56); 25% reduction of drinking days in the past month: RR 1.23 (95% CI 0.96 to 1.57); 50% reduction of drinking days in the past month: RR 1.27 (95% CI 0.96 to 1.68); 75% reduction of drinking days in the past month: RR 1.21 (95% CI 0.84 to 1.75); one or more drinking days' reduction in the past month: RR 1.12 (95% CI 0.91 to 1.38). There is low-quality evidence to suggest that there is no difference in effectiveness between different types of interventions to reduce alcohol consumption in concurrent problem alcohol and illicit drug users and that brief interventions are not superior to assessment-only or to treatment as usual. No firm conclusions can be made because of the paucity of the data and the low quality of the retrieved studies.

  7. [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.

  8. Controlled-release, pegylation, liposomal formulations: new mechanisms in the delivery of injectable drugs.

    PubMed

    Reddy, K R

    2000-01-01

    To review recent developments in novel injectable drug delivery mechanisms and outline the advantages and disadvantages of each. A MEDLINE (1995-January 2000) search using the terms polyethylene glycol, liposomes, polymers, polylactic acid, and controlled release was conducted. Additional references were identified by scanning bibliographies. All articles were considered for inclusion. Abstracts were included only if they were judged to add critical information not otherwise available in the medical literature. A number of systems that alter the delivery of injectable drugs have been developed in attempts to improve pharmacodynamic and pharmacokinetic properties of therapeutic agents. New drug delivery systems can be produced either through a change in formulation (e.g., continuous-release products, liposomes) or an addition to the drug molecule (e.g., pegylation). Potential advantages of new delivery mechanisms include an increased or prolonged duration of pharmacologic activity, a decrease in adverse effects, and increased patient compliance and quality of life. Injectable continuous-release systems deliver drugs in a controlled, predetermined fashion and are particularly appropriate when it is important to avoid large fluctuations in plasma drug concentrations. Encapsulating a drug within a liposome can produce a prolonged half-life and a shift of distribution toward tissues with increased capillary permeability (e.g., tumors, infected tissue). Pegylation provides a method for modification of therapeutic proteins to minimize many of the limitations (e.g., poor stability, short half-life, immunogenicity) associated with these agents. Pegylation of therapeutic proteins is an established process with new applications. However, not all pegylated proteins are alike, and each requires optimization on a protein-by-protein basis to derive maximum clinical benefit. The language required to describe each pegylated therapeutic protein must be more precise to accurately distinguish each protein's differential pharmacologic properties.

  9. Cost-Effectiveness of Evaluating the New Technologies.

    ERIC Educational Resources Information Center

    Kastner, Theodore A.

    1997-01-01

    This commentary on a study comparing use of the brand name drug Depakene with generic valproic acid to control seizures in people with mental retardation focuses on issues of cost-effectiveness. It notes existing guidelines for pharmacoeconomic evaluation and suggests a possible model to include a threshold price (per quality-adjusted life year)…

  10. The quality of arterial hypertension treatment in cardiology service in Kosovo--a single center study.

    PubMed

    Bajraktari, Gani; Sylejmani, Xhevahire; Thaçi, Kimete; Elezi, Shpend; Ndrepepa, Gjin

    2009-04-01

    The epidemiological data have shown that the goal blood pressure (BP) control is achieved in only a small percentage of the hypertensive patients. The aim of this study was to assess the quality of the management of arterial hypertension (AH) in patients hospitalized in Service of Cardiology, University Clinical Centre of Kosovo, in Prishtina, and to determine the predictors of uncontrolled AH. This retrospective study included 938 consecutive hypertensive patients (63.1+/- 11.3 years, 55.1% females), admitted to our institution between January 2003 and June 2006. Systolic and diastolic blood pressure, blood analyses, drug prescription and echocardiographic findings were analyzed in all study patients. Multiple regression analysis was used to identify the independent associates of poor BP control. Overall, 83%f of patients were discharged on angiotensin-converting enzyme inhibitors (A), 71% - on beta-blockers (B), 26% - on calcium channel blockers (C) and 60% - on diuretics (D). The most frequent drug combination used was ABD (30.5%), followed by AB (18%) and AD (8%). The goal systolic and diastolic BP was achieved in 50% of patients. Multivariate analysis identified diabetes, (OR=0.479, 95% confidence interval [CI] 0.339-0.677, <0.001), creatinine level (OR=0.997, 95% CI 0.996-0.999, p=0.001], and ABCD combination therapy (OR=0.445, 95% CI 0.253-0.774, p=0.046)], as independent correlates of in-hospital poor BP control. Half of hypertensive patients hospitalized in the Service of Cardiology had achieved the goal blood pressure. The diabetes, level of creatinine and a combination of 4 antihypertensive drugs were independent predictors of poor hypertension control.

  11. Selection of chemical markers for the quality control of medicinal plants of the genus Cecropia.

    PubMed

    Rivera-Mondragón, Andrés; Ortíz, Orlando O; Bijttebier, Sebastiaan; Vlietinck, Arnold; Apers, Sandra; Pieters, Luc; Caballero-George, Catherina

    2017-12-01

    Several Cecropia (Cecropiaceae) species are traditionally used in Latin America for the treatment of a variety of diseases including diabetes, arterial hypertension, asthma, bronchitis, anxiety, and inflammation. At present, a number of commercial products based on these plants have been introduced into the market with very little information on methods for guaranteeing their quality and safety. This work proposes potential chemical markers for the quality control of the raw materials of Cecropia obtusifolia Bertol., Cecropia peltata L., Cecropia glaziovii Snethl., Cecropia pachystachya Trécul, and Cecropia hololeuca Miq. The Herbal Chemical Marker Ranking System (Herb MaRS) developed by the National Institute of Complementary Medicine (NICM) at the University of Western Sydney was used for selecting chemical markers for the quality control of selected medicinal species of Cecropia. This review covers the period from 1982 to 2016. Chlorogenic acid, flavonoidal glycosides (orientin, isoorientin, vitexin, isovitexin, and rutin), catechin, epicatechin, procyanidins (B2, B5, and C1), steroids (β-sitosterol), and triterpenoids (α-amyrin, pomolic, tormentic and ursolic acids) were selected as chemical markers for the quality control of the leaves. It is necessary to establish comprehensive standards for guaranteeing quality, safety and efficacy of herbal drugs. The selection of adequate chemical markers for quality control purposes requires a good knowledge about the chemical composition of medicinal plants and their associated biological properties. To the best of our knowledge this review article is the first to address the identification and quantitative determination of the chemical markers for the genus Cecropia.

  12. Raw materials in the manufacture of biotechnology products: regulatory considerations.

    PubMed

    Cordoba-Rodriguez, Ruth

    2010-01-01

    The Food and Drug Administration's Pharmaceutical cGMPs for the 21st Century initiative emphasizes science and risk-based approaches in the manufacture of drugs. These approaches are reflected in the International Conference on Harmonization (ICH) guidances ICH Q8, Q9, and Q10 and encourage a comprehensive assessment of the manufacture of a biologic, including all aspects of manufacture that have the potential to affect the finished drug product. Appropriate assessment and management of raw materials are an important part of this initiative. Ideally, a raw materials program should strive to assess and minimize the risk to product quality. With this in mind, risk-assessment concepts and control strategies will be discussed and illustrated by examples, with an emphasis on the impact of raw materials on cell substrates. Finally, the life cycle of the raw material will be considered, including its potential to affect the drug product life cycle. In this framework, the supply chain and the vendor-manufacturer relationship will be explored as important parts of an adequate raw materials control strategy.

  13. The role side effects play in the choice of antiepileptic therapy in brain tumor-related epilepsy: a comparative study on traditional antiepileptic drugs versus oxcarbazepine

    PubMed Central

    Maschio, Marta; Dinapoli, Loredana; Vidiri, Antonello; Pace, Andrea; Fabi, Alessandra; Pompili, Alfredo; Carapella, Maria Carmine; Jandolo, Bruno

    2009-01-01

    Background Seizure control doesn't represent the only challenging goal in patients with brain tumor-related epilepsy. Side effects have often taken precedence for patients' quality of life. Methods We performed an observational retrospective study on patients with brain tumor-related epilepsy: 35 who had assumed oxcarbazepine monotherapy and 35 patients who had undergone treatment with traditional antiepileptic drugs. Primary variable of efficacy was the mean seizure frequency per month and safety variables were the drop-out for side effects and total incidence of side effects. We applied the Propensity Score technique to minimize selection bias. Results Our results showed a similar efficacy of oxcarbazepine and traditional antiepileptic drugs over time, but the difference in safety and tolerability between the two groups was significant: traditional AEDs caused more side effects, both serious and non serious. Conclusion This study highlights the importance of taking into consideration not only seizure control but also the appearance of side effects when choosing antiepileptic drugs in this patients population. PMID:19419544

  14. Disease Activity Score on 28 Joints and Polypharmacy Are Independent Predictors for Health-Related Quality of Life Evaluated by INCAVISA in Patients With Rheumatoid Arthritis.

    PubMed

    González-Gamboa, Linda Mariana; Barocio-Ramírez, Ana Karen; Rocha-Muñoz, Alberto Daniel; de Santos-Ávila, Fabiola; Meda-Lara, Rosa M; González-López, Laura; Gámez-Nava, Jorge Iván; Gómez-Bañuelos, Eduardo; Chavarria-Avila, Efrain; Durán-Barragán, Sergio; Navarro-Hernández, Rosa Elena; Pizano-Martínez, Oscar Enrique; Nuñez-Atahualpa, Lourdes; Vázquez-Del Mercado, Mónica

    2016-12-01

    The aim of this study was to investigate the main factors associated to a diminished health-related quality of life (HRQoL) evaluated by INCAVISA (Health-Related Quality of Life Inventory for Latin American Patients) in patients with rheumatoid arthritis (RA). Female, 18 years or older, RA (American College of Rheumatology 1987 criteria and American College of Rheumatology/European League against Rheumatism 2010 criteria) patients who attended the outpatient rheumatology department of the Hospital Civil "Dr. Juan I. Menchaca," Guadalajara, Mexico, matched with healthy controls were included. Patients with any known comorbidities or treatment with antidepressive drugs were excluded. Trained physicians performed the RA clinical evaluation and INCAVISA. All data were analyzed using SPSS 21.0 software (SPSS Inc, Chicago, IL); P < 0.05 was considered statistically significant. Patients with polypharmacy (≥3 drugs) had a lower HRQoL by INCAVISA. The number of drugs, total comorbidities, and DAS-28 (Disease Activity Score on 28 Joints) were negatively correlated with total INCAVISA. In multivariate analysis, DAS-28 and polypharmacy were independent predictors for a negative perception of HRQoL evaluated by INCAVISA in RA patients. Disease activity and disability secondary to RA have a negative impact in the HRQoL. Other factors such as the number of drugs prescribed to these patients have been shown to be important for the negative perception of their HRQoL evaluated by INCAVISA.

  15. Probiotic use in at-risk populations.

    PubMed

    Sanders, Mary Ellen; Merenstein, Daniel J; Ouwehand, Arthur C; Reid, Gregor; Salminen, Seppo; Cabana, Michael D; Paraskevakos, George; Leyer, Gregory

    To inform health care providers about quality standards for manufacture of probiotic products being recommended for at-risk patient populations. Probiotics are used in a variety of clinical settings, sometimes in at-risk populations for therapeutic endpoints. Although probiotics might not be approved as drugs, they are sometimes used for the prevention or treatment of disease. In the United States, and many regions of the world, probiotic products are marketed as dietary supplements (not drugs) and are therefore subject to different manufacturing and quality control standards than approved drugs are. Health care providers need to be assured that probiotic products used in at-risk populations are safe for this use. Pharmacists should require certificates of analysis, which document quality standards, from manufacturers of products stocked in hospital formularies or other pharmacies dispensing to at-risk people. Although responsible manufacturers use stringent quality standards on their processes and finished products, using a third party to verify compliance with manufacturing and accuracy of product labeling adds assurance to end users that the product is of high quality. It is in patients' best interest to use probiotics in the prevention and treatment of conditions when the evidence is convincing. To protect high-risk patients, probiotic products should meet stringent microbiological standards. Product testing results should be available for review before recommending probiotic products to at-risk individuals. For products used in at-risk populations, manufacturers should provide this information or participate in a third-party verification program that certifies compliance. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  16. Data quality in drug discovery: the role of analytical performance in ligand binding assays

    NASA Astrophysics Data System (ADS)

    Wätzig, Hermann; Oltmann-Norden, Imke; Steinicke, Franziska; Alhazmi, Hassan A.; Nachbar, Markus; El-Hady, Deia Abd; Albishri, Hassan M.; Baumann, Knut; Exner, Thomas; Böckler, Frank M.; El Deeb, Sami

    2015-09-01

    Despite its importance and all the considerable efforts made, the progress in drug discovery is limited. One main reason for this is the partly questionable data quality. Models relating biological activity and structures and in silico predictions rely on precisely and accurately measured binding data. However, these data vary so strongly, such that only variations by orders of magnitude are considered as unreliable. This can certainly be improved considering the high analytical performance in pharmaceutical quality control. Thus the principles, properties and performances of biochemical and cell-based assays are revisited and evaluated. In the part of biochemical assays immunoassays, fluorescence assays, surface plasmon resonance, isothermal calorimetry, nuclear magnetic resonance and affinity capillary electrophoresis are discussed in details, in addition radiation-based ligand binding assays, mass spectrometry, atomic force microscopy and microscale thermophoresis are briefly evaluated. In addition, general sources of error, such as solvent, dilution, sample pretreatment and the quality of reagents and reference materials are discussed. Biochemical assays can be optimized to provide good accuracy and precision (e.g. percental relative standard deviation <10 %). Cell-based assays are often considered superior related to the biological significance, however, typically they cannot still be considered as really quantitative, in particular when results are compared over longer periods of time or between laboratories. A very careful choice of assays is therefore recommended. Strategies to further optimize assays are outlined, considering the evaluation and the decrease of the relevant error sources. Analytical performance and data quality are still advancing and will further advance the progress in drug development.

  17. Use of refractometry and colorimetry as field methods to rapidly assess antimalarial drug quality.

    PubMed

    Green, Michael D; Nettey, Henry; Villalva Rojas, Ofelia; Pamanivong, Chansapha; Khounsaknalath, Lamphet; Grande Ortiz, Miguel; Newton, Paul N; Fernández, Facundo M; Vongsack, Latsamy; Manolin, Ot

    2007-01-04

    The proliferation of counterfeit and poor-quality drugs is a major public health problem; especially in developing countries lacking adequate resources to effectively monitor their prevalence. Simple and affordable field methods provide a practical means of rapidly monitoring drug quality in circumstances where more advanced techniques are not available. Therefore, we have evaluated refractometry, colorimetry and a technique combining both processes as simple and accurate field assays to rapidly test the quality of the commonly available antimalarial drugs; artesunate, chloroquine, quinine, and sulfadoxine. Method bias, sensitivity, specificity and accuracy relative to high-performance liquid chromatographic (HPLC) analysis of drugs collected in the Lao PDR were assessed for each technique. The HPLC method for each drug was evaluated in terms of assay variability and accuracy. The accuracy of the combined method ranged from 0.96 to 1.00 for artesunate tablets, chloroquine injectables, quinine capsules, and sulfadoxine tablets while the accuracy was 0.78 for enterically coated chloroquine tablets. These techniques provide a generally accurate, yet simple and affordable means to assess drug quality in resource-poor settings.

  18. Rational quality assessment procedure for less-investigated herbal medicines: Case of a Congolese antimalarial drug with an analytical report.

    PubMed

    Tshitenge, Dieudonné Tshitenge; Ioset, Karine Ndjoko; Lami, José Nzunzu; Ndelo-di-Phanzu, Josaphat; Mufusama, Jean-Pierre Koy Sita; Bringmann, Gerhard

    2016-04-01

    Herbal medicines are the most globally used type of medical drugs. Their high cultural acceptability is due to the experienced safety and efficiency over centuries of use. Many of them are still phytochemically less-investigated, and are used without standardization or quality control. Choosing SIROP KILMA, an authorized Congolese antimalarial phytomedicine, as a model case, our study describes an interdisciplinary approach for a rational quality assessment of herbal drugs in general. It combines an authentication step of the herbal remedy prior to any fingerprinting, the isolation of the major constituents, the development and validation of an HPLC-DAD analytical method with internal markers, and the application of the method to several batches of the herbal medicine (here KILMA) thus permitting the establishment of a quantitative fingerprint. From the constitutive plants of KILMA, acteoside, isoacteoside, stachannin A, and pectolinarigenin-7-O-glucoside were isolated, and acteoside was used as the prime marker for the validation of an analytical method. This study contributes to the efforts of the WHO for the establishment of standards enabling the analytical evaluation of herbal materials. Moreover, the paper describes the first phytochemical and analytical report on a marketed Congolese phytomedicine. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Process audits versus product quality monitoring of bulk milk.

    PubMed

    Velthuis, A G J; van Asseldonk, M A P M

    2011-01-01

    Assessment of milk quality is based on bulk milk testing and farm certification on process quality audits. It is unknown to what extent dairy farm audits improve milk quality. A statistical analysis was conducted to quantify possible associations between bulk milk testing and dairy farm audits. The analysis comprised 64.373 audit outcomes on 26,953 dairy farms, which were merged with all conducted laboratory tests of bulk milk samples 12 mo before the audit. Each farm audit record included 271 binary checklist items and 52 attention point variables (given to farmers if serious deviations were observed), both indicating possible deviations from the desired farm situation. Test results included somatic cell count (SCC), total bacterial count (TBC), antimicrobial drug residues (ADR), level of butyric acid spores (BAB), freezing point depression (FPD), level of free fatty acid (FFA), and milk sediment (SED). Results show that numerous audit variables were related to bulk milk test results, although the goodness of fit of the models was generally low. Cow hygiene, clean cubicles, hygiene of milking parlor, and utility room were positively correlated with superior product quality, mainly with respect to SCC, TBC, BAB, FPD, FFA, and SED. Animal health or veterinary drugs management (i.e., drug treatment recording, marking of treated animals, and storage of veterinary drugs) related to SCC, FPD, FFA, and SED. The availability of drinking water was related to TBC, BAB, FFA, and SED, whereas maintenance of the milking equipment was related mainly to SCC, FPD, and FFA. In summary, bulk milk quality and farm audit outcomes are, to some degree, associated: if dairy farms are assessed negatively on specific audit aspects, the bulk milk quality is more likely to be inferior. However, the proportion of the total variance in milk test results explained by audits ranged between 4 and 13% (depending on the specific bulk milk test), showing that auditing dairy farms provides additional information but has a limited association with the outcome of a product quality control program. This study suggests that farm audits could be streamlined to include only relevant checklist items and that bulk milk quality monitoring could be used as a basis of selecting farms for more or less frequent audits. Copyright © 2011 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. Quality of phenobarbital solid-dosage forms in the urban community of Nouakchott (Mauritania).

    PubMed

    Laroche, Marie-Laure; Traore, Hamidou; Merle, Louis; Gaulier, Jean-Michel; Viana, Marylene; Preux, Pierre-Marie

    2005-08-01

    Epilepsy is a major public-health problem in Africa. The quality of available drugs is a limiting factor for an adequate management. The aim of this study was to describe the proportion of poor-quality phenobarbital (PB) solid-dosage forms and evaluate the factors associated with its quality in Nouakchott (Mauritania). A cross-sectional study was carried out within pharmacies, hospitals, and on the parallel market in March 2003. PB samples were bought by a native person and then assayed by a liquid chromatography method. A package was considered to be of good quality if the active-substance average content was between 85 and 115% of the stated content printed on the packet. Forty-five pharmaceutical stores were visited, enabling us to collect 146 samples of PB. Three brand names were available in Nouakchott. They originated from France, Morocco, Senegal, and Egypt. Results: A prevalence of 13.7%[95% confidence interval (CI), 8.8-20.0] of poor-quality PB was found. All samples from Morocco were underdosed. The generic active content was satisfactory, but saccharose, an excipient with a potential side effects, was identified. Two factors associated with the good quality of PB have been put forward: tablets manufactured in France and loose packaging as generics conditioned in such a way were of good quality. This study shows that the quality of antiepileptic drugs in Africa is still worrying. The setting up of medicine quality control in Mauritania is legitimate. Considering the good quality of generic PB and its lower cost, this type of medicine should be promoted in this region.

  1. 21 CFR 820.5 - Quality system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Quality system. 820.5 Section 820.5 Food and Drugs... QUALITY SYSTEM REGULATION General Provisions § 820.5 Quality system. Each manufacturer shall establish and maintain a quality system that is appropriate for the specific medical device(s) designed or manufactured...

  2. 21 CFR 820.5 - Quality system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Quality system. 820.5 Section 820.5 Food and Drugs... QUALITY SYSTEM REGULATION General Provisions § 820.5 Quality system. Each manufacturer shall establish and maintain a quality system that is appropriate for the specific medical device(s) designed or manufactured...

  3. 21 CFR 820.5 - Quality system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Quality system. 820.5 Section 820.5 Food and Drugs... QUALITY SYSTEM REGULATION General Provisions § 820.5 Quality system. Each manufacturer shall establish and maintain a quality system that is appropriate for the specific medical device(s) designed or manufactured...

  4. Enzymatically cross-linked injectable alginate-g-pyrrole hydrogels for neovascularization.

    PubMed

    Devolder, Ross; Antoniadou, Eleni; Kong, Hyunjoon

    2013-11-28

    Microparticles capable of releasing protein drugs are often incorporated into injectable hydrogels to minimize their displacement at an implantation site, reduce initial drug burst, and further control drug release rates over a broader range. However, there is still a need to develop methods for releasing drug molecules over extended periods of time, in order to sustain the bioactivity of drug molecules at an implantation site. In this study, we hypothesized that a hydrogel formed through the cross-linking of pyrrole units linked to a hydrophilic polymer would release protein drugs in a more sustained manner, because of an enhanced association between cross-linked pyrrole groups and the drug molecules. To examine this hypothesis, we prepared hydrogels of alginate substituted with pyrrole groups, alginate-g-pyrrole, through a horse-radish peroxidase (HRP)-activated cross-linking of the pyrrole groups. The hydrogels were encapsulated with poly(lactic-co-glycolic acid) (PLGA) microparticles loaded with vascular endothelial growth factor (VEGF). The resulting hydrogel system released VEGF in a more sustained manner than Ca(2+) alginate or Ca(2+) alginate-g-pyrrole gel systems. Finally, implantations of the VEGF-releasing HRP-activated alginate-g-pyrrole hydrogel system on chicken chorioallantoic membranes resulted in the formation of blood vessels in higher densities and with larger diameters, compared to other control conditions. Overall, the drug releasing system developed in this study will be broadly useful for regulating release rates of a wide array of protein drugs, and further enhance the quality of protein drug-based therapies. © 2013 Elsevier B.V. All rights reserved.

  5. Development and evaluation of accelerated drug release testing methods for a matrix-type intravaginal ring.

    PubMed

    Externbrink, Anna; Eggenreich, Karin; Eder, Simone; Mohr, Stefan; Nickisch, Klaus; Klein, Sandra

    2017-01-01

    Accelerated drug release testing is a valuable quality control tool for long-acting non-oral extended release formulations. Currently, several intravaginal ring candidates designed for the long-term delivery of steroids or anti-infective drugs are being in the developing pipeline. The present article addresses the demand for accelerated drug release methods for these formulations. We describe the development and evaluation of accelerated release methods for a steroid releasing matrix-type intravaginal ring. The drug release properties of the formulation were evaluated under real-time and accelerated test conditions. Under real-time test conditions drug release from the intravaginal ring was strongly affected by the steroid solubility in the release medium. Under sufficient sink conditions that were provided in release media containing surfactants drug release was Fickian diffusion driven. Both temperature and hydro-organic dissolution media were successfully employed to accelerate drug release from the formulation. Drug release could be further increased by combining the temperature effect with the application of a hydro-organic release medium. The formulation continued to exhibit a diffusion controlled release kinetic under the investigated accelerated conditions. Moreover, the accelerated methods were able to differentiate between different prototypes of the intravaginal ring that exhibited different release profiles under real-time test conditions. Overall, the results of the present study indicate that both temperature and hydro-organic release media are valid parameters for accelerating drug release from the intravaginal ring. Variation of either a single or both parameters yielded release profiles that correlated well with real-time release. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. [Research advances in secondary development of Chinese patent medicines based on quality by design concept].

    PubMed

    Gong, Xing-Chu; Chen, Teng; Qu, Hai-Bin

    2017-03-01

    Quality by design (QbD) concept is an advanced pharmaceutical quality control concept. The application of QbD concept in the research and development of pharmaceutical processes of traditional Chinese medicines (TCM) mainly contains five parts, including the definition of critical processes and their evaluation criteria, the determination of critical process parameters and critical material attributes, the establishment of quantitative models, the development of design space, as well as the application and continuous improvement of control strategy. In this work, recent research advances in QbD concept implementation methods in the secondary development of Chinese patent medicines were reviewed, and five promising fields of the implementation of QbD concept were pointed out, including the research and development of TCM new drugs and Chinese medicine granules for formulation, modeling of pharmaceutical processes, development of control strategy based on industrial big data, strengthening the research of process amplification rules, and the development of new pharmaceutical equipment.. Copyright© by the Chinese Pharmaceutical Association.

  7. Chinese Proprietary Herbal Medicine Listed in ‘China National Essential Drug List’ for Common Cold: A Systematic Literature Review

    PubMed Central

    Chen, Wei; Lewith, George; Wang, Li-qiong; Ren, Jun; Xiong, Wen-jing; Lu, Fang; Liu, Jian-ping

    2014-01-01

    Objective Chinese proprietary herbal medicines (CPHMs) have long history in China for the treatment of common cold, and lots of them have been listed in the ‘China national essential drug list’ by the Chinese Ministry of Health. The aim of this review is to provide a well-round clinical evidence assessment on the potential benefits and harms of CPHMs for common cold based on a systematic literature search to justify their clinical use and recommendation. Methods We searched CENTRAL, MEDLINE, EMBASE, SinoMed, CNKI, VIP, China Important Conference Papers Database, China Dissertation Database, and online clinical trial registry websites from their inception to 31 March 2013 for clinical studies of CPHMs listed in the ‘China national essential drug list’ for common cold. There was no restriction on study design. Results A total of 33 CPHMs were listed in ‘China national essential drug list 2012’ for the treatment of common cold but only 7 had supportive clinical evidences. A total of 6 randomised controlled trials (RCTs) and 7 case series (CSs) were included; no other study design was identified. All studies were conducted in China and published in Chinese between 1995 and 2012. All included studies had poor study design and methodological quality, and were graded as very low quality. Conclusions The use of CPHMs for common cold is not supported by robust evidence. Further rigorous well designed placebo-controlled, randomized trials are needed to substantiate the clinical claims made for CPHMs. PMID:25329481

  8. Drug pricing and control of health expenditures: a comparison between a proportional decision rule and a cost-per-QALY rule.

    PubMed

    Gandjour, Afschin

    2015-01-01

    In Germany, the Institute for Quality and Efficiency in Health Care (IQWiG) makes recommendations for reimbursement prices of drugs on the basis of a proportional relationship between costs and health benefits. This paper analyzed the potential of IQWiG's decision rule to control health expenditures and used a cost-per-quality-adjusted life year (QALY) rule as a comparison. A literature search was conducted, and a theoretical model of health expenditure growth was built. The literature search shows that the median incremental cost-effectiveness ratio of German cost-effectiveness analyses was €7650 per QALY gained, thus yielding a much lower threshold cost-effectiveness ratio for IQWiG's rule than an absolute rule at €30 000 per QALY. The theoretical model shows that IQWiG's rule is able to contain the long-term growth of health expenditures under the conservative assumption that future health increases at a constant absolute rate and that the threshold incremental cost-effectiveness ratio increases at a smaller rate than health expenditures. In contrast, an absolute rule offers the potential for manufacturers to raise drug prices in response to the threshold, thus resulting in an initial spike in expenditures. Results suggest that IQWiG's proportional rule will lead to lower drug prices and a slower growth of health expenditures than an absolute cost-effectiveness threshold at €30 000 per QALY. This finding is surprising as IQWiG's rule-in contrast to a cost-per-QALY rule-does not start from a fixed budget. Copyright © 2014 John Wiley & Sons, Ltd.

  9. 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

  10. The genome of Onchocerca volvulus, agent of river blindness

    PubMed Central

    Cotton, James A.; Bennuru, Sasisekhar; Grote, Alexandra; Harsha, Bhavana; Tracey, Alan; Beech, Robin; Doyle, Stephen R.; Dunn, Matthew; Dunning Hotopp, Julie C.; Holroyd, Nancy; Kikuchi, Taisei; Lambert, Olivia; Mhashilkar, Amruta; Mutowo, Prudence; Nursimulu, Nirvana; Ribeiro, Jose M. C.; Rogers, Matthew B.; Stanley, Eleanor; Swapna, Lakshmipuram S.; Tsai, Isheng J.; Unnasch, Thomas R.; Voronin, Denis; Parkinson, John; Nutman, Thomas B.; Ghedin, Elodie; Berriman, Matthew; Lustigman, Sara

    2017-01-01

    Human onchocerciasis is a serious neglected tropical disease caused by the filarial nematode Onchocerca volvulus that can lead to blindness and chronic disability. Control of the disease relies largely on mass administration of a single drug, and the development of new drugs and vaccines depends on a better knowledge of parasite biology. Here, we describe the chromosomes of O. volvulus and its Wolbachia endosymbiont. We provide the highest-quality sequence assembly for any parasitic nematode to date, giving a glimpse into the evolution of filarial parasite chromosomes and proteomes. This resource was used to investigate gene families with key functions that could be potentially exploited as targets for future drugs. Using metabolic reconstruction of the nematode and its endosymbiont, we identified enzymes that are likely to be essential for O. volvulus viability. In addition, we have generated a list of proteins that could be targeted by Federal-Drug-Agency-approved but repurposed drugs, providing starting points for anti-onchocerciasis drug development. PMID:27869790

  11. Otic drug delivery systems: formulation principles and recent developments.

    PubMed

    Liu, Xu; Li, Mingshuang; Smyth, Hugh; Zhang, Feng

    2018-04-25

    Disorders of the ear severely impact the quality of life of millions of people, but the treatment of these disorders is an ongoing, but often overlooked challenge particularly in terms of formulation design and product development. The prevalence of ear disorders has spurred significant efforts to develop new therapeutic agents, but perhaps less innovation has been applied to new drug delivery systems to improve the efficacy of ear disease treatments. This review provides a brief overview of physiology, major diseases, and current therapies used via the otic route of administration. The primary focuses are on the various administration routes and their formulation principles. The article also presents recent advances in otic drug deliveries as well as potential limitations. Otic drug delivery technology will likely evolve in the next decade and more efficient or specific treatments for ear disease will arise from the development of less invasive drug delivery methods, safe and highly controlled drug delivery systems, and biotechnology targeting therapies.

  12. Is the quality of brief motivational interventions for drug use in primary care associated with subsequent drug use?

    PubMed

    Palfai, Tibor P; Cheng, Debbie M; Bernstein, Judith A; Palmisano, Joseph; Lloyd-Travaglini, Christine A; Goodness, Tracie; Saitz, Richard

    2016-05-01

    Although a number of brief intervention approaches for drug use are based on motivational interviewing (MI), relatively little is known about whether the quality of motivational interviewing skills is associated with intervention outcomes. The current study examined whether indices of motivational interviewing skill were associated with subsequent drug use outcomes following two different MI-based brief interventions delivered in primary care; a 15 min Brief Negotiated Interview (BNI) and a 45 min adaptation of motivational interviewing (MOTIV). Audio recordings from 351 participants in a randomized controlled trial for drug use in primary care were coded using the Motivational Interviewing Treatment Integrity Scale, (MITI Version 3.1.1). Separate negative binomial regression analyses, stratified by intervention condition, were used to examine the associations between six MITI skill variables and the number of days that the participant used his/her main drug 6 weeks after study entry. Only one of the MITI variables (% reflections to questions) was significantly associated with the frequency of drug use in the MOTIV condition and this was opposite to the hypothesized direction (global p=0.01, adjusted IRR 1.50, 95%CI: 1.03-2.20 for middle vs. lowest tertile [higher skill, more drug use]. None were significantly associated with drug use in the BNI condition. Secondary analyses similarly failed to find consistent predictors of better drug outcomes. Overall, this study provides little evidence to suggest that the level of MI intervention skills are linked with better drug use outcomes among people who use drugs and receive brief interventions in primary care. Findings should be considered in light of the fact that data from the study are from negative trial of SBI and was limited to primary care patients. Future work should consider alternative ways of examining these process variables (i.e., comparing thresholds of proficient versus non-proficient skills) or considering alternative methods of coding intervention skills. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. 78 FR 31943 - Draft Guidance for Industry on Contract Manufacturing Arrangements for Drugs: Quality Agreements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-28

    ... documenting the responsibilities of all parties involved in drug manufacturing, testing, or other support... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-D-0558] Draft Guidance for Industry on Contract Manufacturing Arrangements for Drugs: Quality Agreements...

  14. Novel catalytic micromotor of porous zeolitic imidazolate framework-67 for precise drug delivery.

    PubMed

    Wang, Linlin; Zhu, Hongli; Shi, Ying; Ge, You; Feng, Xiaomiao; Liu, Ruiqing; Li, Yi; Ma, Yanwen; Wang, Lianhui

    2018-06-07

    Micromotors hold promise as drug carriers for targeted drug delivery owing to the characteristics of self-propulsion and directional navigation. However, several defects still exist, including high cost, short movement life, low drug loading and slow release rate. Herein, a novel catalytic micromotor based on porous zeolitic imidazolate framework-67 (ZIF-67) synthesized by a greatly simplified wet chemical method assisted with ultrasonication is described as an efficient anticancer drug carrier. These porous micromotors display effective autonomous motion in hydrogen peroxide and long durable movement life of up to 90 min. Moreover, the multifunctional micromotor ZIF-67/Fe3O4/DOX exhibits excellent performance in precise drug delivery under external magnetic field with high drug loading capacity of fluorescent anticancer drug DOX up to 682 μg mg-1 owing to its porous nature, high surface area and rapid drug release based on dual stimulus of catalytic reaction and solvent effects. Therefore, these porous ZIF-67-based catalytic micromotors combine the domains of metal-organic frameworks (MOFs) and micomotors, thus developing potential resources for micromotors and holding great potential as label-free and precisely controlled high-quality candidates of drug delivery systems for biomedical applications.

  15. A potentiometric titration method for the crystallization of drug-like organic molecules.

    PubMed

    Du-Cuny, Lei; Huwyler, Jörg; Fischer, Holger; Kansy, Manfred

    2007-09-05

    It is generally accepted, that crystalline solids representing a low energy polymorph should be selected for development of oral dosage forms. As a consequence, efficient and robust procedures are needed at an early stage during drug discovery to prepare crystals from drug-like organic molecules. In contrast to the use of supersaturated solutions, we present a potentiometric crystallization procedure where saturated solutions are prepared in a controlled manner by pH-titration. Crystallization is carried out under defined conditions using the sample concentration and experimental pK(a) values as input parameters. Crystals of high quality were obtained for 11 drugs selected to demonstrate the efficiency and applicability of the new method. Technical improvements are suggested to overcome practical limitations and to enhance the possibility of obtaining crystals from molecules in their uncharged form.

  16. Forensic toxicology.

    PubMed

    Drummer, Olaf H

    2010-01-01

    Forensic toxicology has developed as a forensic science in recent years and is now widely used to assist in death investigations, in civil and criminal matters involving drug use, in drugs of abuse testing in correctional settings and custodial medicine, in road and workplace safety, in matters involving environmental pollution, as well as in sports doping. Drugs most commonly targeted include amphetamines, benzodiazepines, cannabis, cocaine and the opiates, but can be any other illicit substance or almost any over-the-counter or prescribed drug, as well as poisons available to the community. The discipline requires high level skills in analytical techniques with a solid knowledge of pharmacology and pharmacokinetics. Modern techniques rely heavily on immunoassay screening analyses and mass spectrometry (MS) for confirmatory analyses using either high-performance liquid chromatography or gas chromatography as the separation technique. Tandem MS has become more and more popular compared to single-stage MS. It is essential that analytical systems are fully validated and fit for the purpose and the assay batches are monitored with quality controls. External proficiency programs monitor both the assay and the personnel performing the work. For a laboratory to perform optimally, it is vital that the circumstances and context of the case are known and the laboratory understands the limitations of the analytical systems used, including drug stability. Drugs and poisons can change concentration postmortem due to poor or unequal quality of blood and other specimens, anaerobic metabolism and redistribution. The latter provides the largest handicap in the interpretation of postmortem results.

  17. Stability of Tetrahydrocannabinol and Cannabidiol in Prepared Quality Control Medible Brownies.

    PubMed

    Wolf, Carl E; Poklis, Justin L; Poklis, Alphonse

    2017-03-01

    The legalization of marijuana in the USA for both medicinal and recreational use has increased in the past few years. Currently, 24 states have legalized marijuana for medicinal use. The US Drug Enforcement Administration has classified marijuana as a Schedule I substance. The US Food and Drug Administration does not regulate formulations or packages of marijuana that are currently marketed in states that have legalized marijuana. Marijuana edibles or "medibles" are typically packages of candies and baked goods consumed for medicinal as well as recreational marijuana use. They contain major psychoactive drug in marijuana, delta-9-tetrahydrocannabinol (THC) and/or cannabidiol (CBD), which has reputed medical properties. Presented is a method for the preparation and application of THC and CBD containing brownies used as quality control (QC) material for the analysis of marijuana or cannabinoid baked medibles. The performance parameters of the assay including possible matrix effects and cannabinoid stability in the brownie QC over time are presented. It was determined that the process used to prepare and bake the brownie control material did not degrade the THC or CBD. The brownie matrix was found not to interfere with the analysis of a THC or a CBD. Ten commercially available brownie matrixes were evaluated for potential interferences; none of them were found to interfere with the analysis of THC or CBD. The laboratory baked medible QC material was found to be stable at room temperature for at least 3 months. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Risk of road accident associated with the use of drugs: a systematic review and meta-analysis of evidence from epidemiological studies.

    PubMed

    Elvik, Rune

    2013-11-01

    This paper is a corrigendum to a previously published paper where errors were detected. The errors have been corrected in this paper. The paper is otherwise identical to the previously published paper. A systematic review and meta-analysis of studies that have assessed the risk of accident associated with the use of drugs when driving is presented. The meta-analysis included 66 studies containing a total of 264 estimates of the effects on accident risk of using illicit or prescribed drugs when driving. Summary estimates of the odds ratio of accident involvement are presented for amphetamines, analgesics, anti-asthmatics, anti-depressives, anti-histamines, benzodiazepines, cannabis, cocaine, opiates, penicillin and zopiclone (a sleeping pill). For most of the drugs, small or moderate increases in accident risk associated with the use of the drugs were found. Information about whether the drugs were actually used while driving and about the doses used was often imprecise. Most studies that have evaluated the presence of a dose-response relationship between the dose of drugs taken and the effects on accident risk confirm the existence of a dose-response relationship. Use of drugs while driving tends to have a larger effect on the risk of fatal and serious injury accidents than on the risk of less serious accidents (usually property-damage-only accidents). The quality of the studies that have assessed risk varied greatly. There was a tendency for the estimated effects of drug use on accident risk to be smaller in well-controlled studies than in poorly controlled studies. Evidence of publication bias was found for some drugs. The associations found cannot be interpreted as causal relationships, principally because most studies do not control very well for potentially confounding factors. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Validation of gamma irradiator controls for quality and regulatory compliance

    NASA Astrophysics Data System (ADS)

    Harding, Rorry B.; Pinteric, Francis J. A.

    1995-09-01

    Since 1978 the U.S. Food and Drug Administration (FDA) has had both the legal authority and the Current Good Manufacturing Practice (CGMP) regulations in place to require irradiator owners who process medical devices to produce evidence of Irradiation Process Validation. One of the key components of Irradiation Process Validation is the validation of the irradiator controls. However, it is only recently that FDA audits have focused on this component of the process validation. What is Irradiator Control System Validation? What constitutes evidence of control? How do owners obtain evidence? What is the irradiator supplier's role in validation? How does the ISO 9000 Quality Standard relate to the FDA's CGMP requirement for evidence of Control System Validation? This paper presents answers to these questions based on the recent experiences of Nordion's engineering and product management staff who have worked with several US-based irradiator owners. This topic — Validation of Irradiator Controls — is a significant regulatory compliance and operations issue within the irradiator suppliers' and users' community.

  20. Biopolymers as transdermal drug delivery systems in dermatology therapy.

    PubMed

    Basavaraj, K H; Johnsy, George; Navya, M A; Rashmi, R; Siddaramaiah

    2010-01-01

    The skin is considered a complex organ for drug delivery because of its structure. Drug delivery systems are designed for the controlled release of drugs through the skin into the systemic circulation, maintaining consistent efficacy and reducing the dose of the drugs and their related side effects. Transdermal drug delivery represents one of the most rapidly advancing areas of novel drug delivery. The excellent impervious nature of the skin is the greatest challenge that must be overcome for successful drug delivery. Today, polymers have been proven to be successful for long-term drug delivery applications as no single polymer can satisfy all of the requirements. Biopolymers in the field of dermal application are rare and the mechanisms that affect skin absorption are almost unknown. Biopolymers are widely used as drug delivery systems, but as such the use of biopolymers as drug delivery systems in dermatologic therapy is still in progress. Commonly used biopolymers include hydrocolloids, alginates, hydrogels, polyurethane, collagen, poly(lactic-co-glycolic acid), chitosan, proteins and peptides, pectin, siRNAs, and hyaluronic acid. These new and exciting methods for drug delivery are already increasing the number and quality of dermal and transdermal therapies. This article reviews current research on biopolymers and focuses on their potential as drug carriers, particularly in relation to the dermatologic aspects of their use.

  1. [Batch release of immunoglobulin and monoclonal antibody products].

    PubMed

    Gross, S

    2014-10-01

    The Paul-Ehrlich Institute (PEI) is an independent institution of the Federal Republic of Germany responsible for performing official experimental batch testing of sera. The institute decides about the release of each batch and performs experimental research in the field. The experimental quality control ensures the potency of the product and also the absence of harmful impurities. For release of an immunoglobulin batch the marketing authorization holder has to submit the documentation of the manufacture and the results of quality control measures together with samples of the batch to the PEI. Experimental testing is performed according to the approved specifications regarding the efficacy and safety. Since implementation of the 15th German drug law amendment, the source of antibody is not defined anymore. According to § 32 German drug law, all batches of sera need to be released by an official control laboratory. Sera are medicinal products, which contain antibodies, antibody fragments or fusion proteins with a functional antibody portion. Therefore, all batches of monoclonal antibodies and derivatives must also be released by the PEI and the marketing authorization holder has to submit a batch release application. Under certain circumstances a waiver for certain products can be issued with regard to batch release. The conditions for such a waiver apply to the majority of monoclonal antibodies.

  2. Drug quality in South Africa: perceptions of key players involved in medicines distribution.

    PubMed

    Patel, Aarti; Norris, Pauline; Gauld, Robin; Rades, Thomas

    2009-01-01

    Substandard medicines contribute to poor public health and affect development, especially in the developing world. However knowledge of how manufacturers, distributors and providers understand the concept of drug quality and what strategies they adopt to ensure drug quality is limited, particularly in the developing world. The purpose of this paper is to explore pharmaceutical manufacturers', distributors' and providers' perceptions of drug quality in South Africa and how they ensure the quality of drugs during the distribution process. The approach taken was qualitative data collection through key informant interviews using a semi-structured interview guide. Transcripts were analysed thematically in Johannesburg, Pretoria and Durban, South Africa. Participants were recruited purposefully from a South African pharmaceutical manufacturer, SA subsidiaries of international manufacturers, national distribution companies, national wholesaler, public and private sector pharmacists, and a dispensing doctor. In total, ten interviews were conducted. Participants described drug quality in terms of the product and the processes involved in manufacturing and handling the product. Participants identified purchasing registered medicines from licensed suppliers, use of standard operating procedures, and audits between manufacturer and distributor and/or provider as key strategies employed to protect medicine quality. Effective communication amongst all stakeholders, especially in terms of providing feedback regarding complaints about medicine quality, appears as a potential area of concern, which would benefit from further research. The paper hightlights that ensuring medicine quality should be a shared responsibility amongst all involved in the distribution process to prevent medicines moving from one distribution system (public) into another (private).

  3. 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.

  4. Cholinergic medication for antipsychotic-induced tardive dyskinesia.

    PubMed

    Tammenmaa-Aho, Irina; Asher, Rosie; Soares-Weiser, Karla; Bergman, Hanna

    2018-03-19

    Tardive dyskinesia (TD) remains a troublesome adverse effect of conventional antipsychotic (neuroleptic) medication. It has been proposed that TD could have a component of central cholinergic deficiency. Cholinergic drugs have been used to treat TD. To determine the effects of cholinergic drugs (arecoline, choline, deanol, lecithin, meclofenoxate, physostigmine, RS 86, tacrine, metoxytacrine, galantamine, ipidacrine, donepezil, rivastigmine, eptastigmine, metrifonate, xanomeline, cevimeline) for treating antipsychotic-induced TD in people with schizophrenia or other chronic mental illness. An electronic search of the Cochrane Schizophrenia Group's Study-Based Register of Trials (16 July 2015 and April 2017) was undertaken. This register is assembled by extensive searches for randomised controlled trials in many electronic databases, registers of trials, conference proceedings and dissertations. References of all identified studies were searched for further trial citations. We included reports identified by the search if they were of controlled trials involving people with antipsychotic-induced TD and chronic mental illness, who had been randomly allocated to either a cholinergic agent or to a placebo or no intervention. Two review authors independently assessed the methodological quality of the trials. Two review authors extracted data and, where possible, estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We analysed data on an intention-to-treat basis, with the assumption that people who left early had no improvement. We assessed risk of bias and created a 'Summary of findings' table using GRADE. We included 14 studies investigating the use of cholinergic drugs compared with placebo published between 1976 and 2014. All studies involved small numbers of participants (five to 60 people). Three studies that investigated the new cholinergic Alzheimer drugs for the treatment of TD are new to this update. Overall, the risk of bias in the included studies was unclear, mainly due to poor reporting; allocation concealment was not described, generation of the sequence was not explicit, studies were not clearly blinded, we are unsure if data are incomplete, and data were often poorly or selectively reported.We are uncertain about the effect of new or old cholinergic drugs on no clinically important improvement in TD symptoms when compared with placebo; the quality of evidence was very low (RR 0.89, 95% CI 0.65 to 1.23; 27 people, 4 RCTs). Eight trials found that cholinergic drugs may make little or no difference to deterioration of TD symptoms (low-quality evidence, RR 1.11, 95% CI 0.55 to 2.24; 147 people). Again, due to very low-quality evidence, we are uncertain about the effects on mental state (RR 0.50, 95% CI 0.10 to 2.61; 77 people, 5 RCTs), adverse events (RR 0.56, 95% CI 0.15 to 2.14; 106 people, 4 RCTs), and leaving the study early (RR 1.09,95% CI 0.56 to 2.10; 288 people 12 RCTs). No study reported on social confidence, social inclusion, social networks, or personalised quality of life. TD remains a major public health problem. The clinical effects of both older cholinergic drugs and new cholinergic agents, now used for treating Alzheimer's disease, are unclear, as too few, too small studies leave many questions unanswered. Cholinergic drugs should remain of interest to researchers and currently have little place in routine clinical work. However, with the advent of new cholinergic agents now used for treating Alzheimer's disease, scope exists for more informative trials. If these new cholinergic agents are to be investigated for treating people with TD, their effects should be demonstrated in large well-designed, conducted and reported randomised trials.

  5. Current Scenario of Spurious and Substandard Medicines in India: A Systematic Review

    PubMed Central

    Khan, A. N.; Khar, R. K.

    2015-01-01

    Globally, every country is the victim of substandard or spurious drugs, which result in life threatening issues, financial loss of consumer and manufacturer and loss in trust on health system. The aim of this enumerative review was to probe the extent on poor quality drugs with their consequences on public health and the preventive measures taken by the Indian pharmaceutical regulatory system. Government and non-government studies, literature and news were gathered from journals and authentic websites. All data from 2000 to 2013 were compiled and interpreted to reveal the real story of poor quality drugs in India. For minimizing spurious/falsely-labelled/falsified/counterfeit drugs or not of standard quality drugs, there is urgent requirement of more stringent regulation and legal action against the problem. However, India has taken some preventive steps in the country to fight against the poor quality drugs for protecting and promoting the public health. PMID:25767312

  6. The impact of outpatient chemotherapy-related adverse events on the quality of life of breast cancer patients.

    PubMed

    Tachi, Tomoya; Teramachi, Hitomi; Tanaka, Kazuhide; Asano, Shoko; Osawa, Tomohiro; Kawashima, Azusa; Yasuda, Masahiro; Mizui, Takashi; Nakada, Takumi; Noguchi, Yoshihiro; Tsuchiya, Teruo; Goto, Chitoshi

    2015-01-01

    The objective of our study was to clarify the impact of adverse events associated with the initial course of outpatient chemotherapy on the quality of life of breast cancer patients. We conducted a survey to assess the quality of life in 48 breast cancer patients before and after receiving their first course of outpatient chemotherapy at Gifu Municipal Hospital. Patients completed the European Quality of Life 5 Dimensions and Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs before and after 1 course of outpatient chemotherapy. European Quality of Life 5 Dimensions utility value and Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs total score decreased significantly after chemotherapy (p<0.001 and p = 0.018, respectively). The mean scores for the activity, physical condition, and psychological condition subscales of the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs decreased significantly after chemotherapy (p = 0.003, p<0.001, and p = 0.032, respectively), whereas the social relationships score increased significantly (p<0.001). Furthermore, in the evaluation of quality of life according to individual adverse events, the decrease in quality of life after chemotherapy in terms of the European Quality of Life 5 Dimensions utility value and the Quality of Life Questionnaire for Cancer Patients Treated with Anticancer Drugs total score was greater in anorexic patients than in non-anorexic patients (p = 0.009 and p<0.001, respectively). This suggests that anorexia greatly reduces quality of life. Our findings reveal that anticancer drug-related adverse events, particularly anorexia, reduce overall quality of life following the first course of outpatient chemotherapy in current breast cancer patients. These findings are extremely useful and important in understanding the impact of anticancer drug-related adverse events on quality of life.

  7. Managing healthcare costs within an integrated framework.

    PubMed

    Fernandes, Rudy

    2002-01-01

    Laupacis, Anderson and O'Brien's comprehensive diagnosis of the illness affecting the Canadian healthcare system is very insightful. In addition, their call for improving the quality of drug evidence and outcomes is a laudable goal. However, their prognosis of the negative impact on healthcare due to escalating drug costs appears to be rather pessimistic, as they fail to view drugs within an integrated framework. In part, their prescription for the perceived malady is rather impractical. Their recommendation for mandatory head-to-head randomized studies, as a prerequisite for achieving new drug listing in benefit formularies, suffers from many drawbacks. Such studies would be highly time-consuming, extremely costly, and given the fact that the choice of a drug comparator is a "moving target," the end result may not achieve the original intent. Growing anxieties about the rising healthcare costs in Canada, now forecast to reach C$100 billion in 2002, have led to implementation ofa variety of reforms aimed at cost-cutting. Shifts in drug utilization, demographics and prescribing have contributed to the authors' understandable concern about the rapid rise in drug plan expenditure, which has undeniably outpaced the increases of other healthcare components. However, drug plan costs represent only 7.7% of total provincial/territorial healthcare expenditures. Innovative medicines have played a significant role in reducing the burden of illness and overall healthcare costs. Drugs prevent, treat and cure disease, improve quality of life, control pain/suffering and save lives. Despite their great value, spending on drugs has received particular scrutiny from policy-makers, and pharmaceuticals have become the primary cost-containment target. The authors' goal-oriented concept of creating a clinical milieu that encourages cost-effective prescribing via "optimum" drug use is very attractive. One such approach is Disease Management, which relies on evidence-based, outcome-oriented performance indicators. It is highly regarded for promoting effective treatment options, improving patient care and optimizing healthcare resource utilization--hence deserving serious consideration for reducing overall costs while achieving improved outcomes.

  8. Practitioner Review: Use of Antiepileptic Drugs in Children

    ERIC Educational Resources Information Center

    Guerrini, Renzo; Parmeggiani, Lucio

    2006-01-01

    Background: The aim in treating epilepsy is to minimise or control seizures with full respect of quality-of-life issues, especially of cognitive functions. Optimal treatment first demands a correct recognition of the major type of seizures, followed by a correct diagnosis of the type of epilepsy or of the specific syndrome. Methods: Review of data…

  9. Nature's Pharmacy: Do You Have a Green Tongue?

    ERIC Educational Resources Information Center

    Vamos, Sandra

    2005-01-01

    The use of plants for healing purposes has been prevalent in all cultures throughout history and continues to play a role in medicine today. While herbal medicine has much to offer, adverse effects can result from lack of quality control and standardization, consuming an inadequate dose, using the wrong herb, and reactions with modern drugs. To…

  10. 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.

  11. 21 CFR 1271.160 - Establishment and maintenance of a quality program.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Establishment and maintenance of a quality program. 1271.160 Section 1271.160 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION...

  12. Strengthening of national capacity in implementation of antimalarial drug quality assurance in Thailand.

    PubMed

    Vijaykadga, Saowanit; Cholpol, Sawat; Sitthimongkol, Saipin; Pawaphutanan, Anusorn; Pinyoratanachot, Arunya; Rojanawatsirivet, Chaiporn; Kovithvattanapong, Rojana; Thimasarn, Krongthong

    2006-01-01

    Substandard and counterfeit pharmaceutical products, including antimalarial drugs, appear to be widespread internationally and affect both the developing and developed countries. The aim of the study was to investigate the quality of antimalarial drugs, ie, artesunate (ART), chloroquine (CHL), mefloquine (MEF), quinine (QUI), sulfadoxine/pyrimethamine (S/P) and tetracycline (TT) obtained from the government sector and private pharmacies in 4 Thai provinces: Mae Hong Son, Kanchanaburi, Ranong, and Chanthaburi. Three hundred sixty-nine samples of 6 antimalarial drugs from 27 government hospitals, 27 malaria clinics, and 53 drugstores, were collected. Drug quality was assessed by simple disintegration test and semi-quantitative thin-layer chromatography in each province; 10% passed, 100% failed and doubtful samples were sent to be verified by high performance liquid chromatography (HPLC) at the Thai National Drug Analysis Laboratory, (NL). Fifteen point four percent of ART, 11.1% of CHL and 29.4% of QUI were substandard. Based on the finding, drug regulatory authorities in the country took appropriate action against violators to ensure that antimalarial drugs consumed by malaria patients are of good quality.

  13. Direct infusion mass spectrometry metabolomics dataset: a benchmark for data processing and quality control

    PubMed Central

    Kirwan, Jennifer A; Weber, Ralf J M; Broadhurst, David I; Viant, Mark R

    2014-01-01

    Direct-infusion mass spectrometry (DIMS) metabolomics is an important approach for characterising molecular responses of organisms to disease, drugs and the environment. Increasingly large-scale metabolomics studies are being conducted, necessitating improvements in both bioanalytical and computational workflows to maintain data quality. This dataset represents a systematic evaluation of the reproducibility of a multi-batch DIMS metabolomics study of cardiac tissue extracts. It comprises of twenty biological samples (cow vs. sheep) that were analysed repeatedly, in 8 batches across 7 days, together with a concurrent set of quality control (QC) samples. Data are presented from each step of the workflow and are available in MetaboLights. The strength of the dataset is that intra- and inter-batch variation can be corrected using QC spectra and the quality of this correction assessed independently using the repeatedly-measured biological samples. Originally designed to test the efficacy of a batch-correction algorithm, it will enable others to evaluate novel data processing algorithms. Furthermore, this dataset serves as a benchmark for DIMS metabolomics, derived using best-practice workflows and rigorous quality assessment. PMID:25977770

  14. Are We Using Slow-Acting Symptomatic Chondroprotective Drugs Conscious Enough?

    PubMed

    Gumustas, Seyit Ali; Oznam, Kadir; Mutlu, Cagri Ata; Kaya, Yasin Emre; Yilmaz, Ibrahim; Isyar, Mehmet; Guzelant, Aliye Yıldırım; Guler, Olcay; Akkaya, Semih; Mahirogullari, Mahir

    2017-01-01

    Osteochondral injuries constitute an entity that is widespread and can be seen in patients of all ages. Actual treatment modalities aim to relieve pain, obtain full range of movement of the joint, and improve the quality of life. There are many slow-acting chondroprotective agents prevalently used in the United States that are classified as nutritional support but not as medicines . This study presents the importance of clinical adverse effect profiles as well as the pharmacological mechanism of action and application of combinations of drugs that are widely prescribed and not subjected to control. Electronic databases were searched with keywords about the chondroprotective drugs without any language restriction. Evaluations of the descriptive statistics were represented via Microsoft Office Excel 2010 lists in the form of a mean±standard deviation or frequency (%). The first evaluation showed that 1502 studies were potentially relevant. Following exclusion of the 1277 studies which were not clinical, full versions of the remaining 225 studies were subjected to further evaluation. No controlled, blinded, randomized and/or comparative studies met the inclusion criteria of the study, and no studies evaluated the comparative clinical results of the hyaluronan of different molecular weights. The findings of this study concluded that especially when prescribing drugs with ingredients like GS and CS, many patients' pre-existing conditions must be considered, such as whether the patient has a glucose intolerance or not. Additionally, mineral toxication should be considered since the drugs contain minerals, and after the application of injected hyaluronan, complications should be considered. Clinical, controlled and comparative studies about the use of chondroprotective drugs must be performed to define the benefits of these drugs, if any, in order to determine the most suitable time for operative intervention.

  15. Qualities of Sore Throat Index (QuaSTI): measuring descriptors of sore throat in a randomized, placebo-controlled trial.

    PubMed

    Schachtel, Bernard; Shephard, Adrian; Schachtel, Emily; Lorton, Mary Beth; Shea, Tim; Aspley, Sue

    2018-03-01

    Patients with pharyngitis often describe various sensory, affective and evaluative pain qualities. Using an 11-word/phrase index, the Qualities of Sore Throat Index (QuaSTI), we characterized throat symptoms and evaluated changes in a randomized controlled trial (NCT01986361). Patients received a single flurbiprofen 8.75 mg (n = 101) or placebo (n = 21) lozenge and rated throat soreness at baseline and regular intervals over 3 h, and the QuaSTI at baseline, 1, 2 and 3 h post-treatment. The QuaSTI distinguished active drug from placebo and detected clinically important (≥2-point) changes over 3 h. Mean change from baseline over 3 h was significantly greater for flurbiprofen (154%) than placebo (p < 0.05). The QuaSTI is a sensitive instrument for measuring therapeutic effects in patients with pharyngitis.

  16. Are mass-media campaigns effective in preventing drug use? A Cochrane systematic review and meta-analysis

    PubMed Central

    Allara, Elias; Ferri, Marica; Bo, Alessandra; Gasparrini, Antonio; Faggiano, Fabrizio

    2015-01-01

    Objective To determine whether there is evidence that mass-media campaigns can be effective in reducing illicit drug consumption and the intent to consume. Design Systematic review of randomised and non-randomised studies. Methods We searched four electronic databases (MEDLINE, EMBASE, ProQuest Dissertations & Theses A&I and CENTRAL) and further explored seven additional resources to obtain both published and unpublished materials. We appraised the quality of included studies using standardised tools. We carried out meta-analyses of randomised controlled trials and a pooled analysis of interrupted time-series and controlled before-and-after studies. Results We identified 19 studies comprising 184 811 participants. Pooled analyses and narrative synthesis provided mixed evidence of effectiveness. Eight interventions evaluated with randomised controlled trials leaned towards no evidence of an effect, both on drug use (standardised mean difference (SMD) −0.02; 95% CI −0.15 to 0.12) and the intention to use drugs (SMD −0.07; 95% CI −0.19 to 0.04). Four campaigns provided some evidence of beneficial effects in preventing drug use and two interventions provided evidence of iatrogenic effects. Conclusions Studies were considerably heterogeneous in type of mass-media intervention, outcome measures, underlying theory, comparison groups and design. Such factors can contribute to explaining the observed variability in results. Owing to the risk of adverse effects, caution is needed in disseminating mass-media campaigns tackling drug use. Large studies conducted with appropriate methodology are warranted to consolidate the evidence base. PMID:26338836

  17. Automatic indexing in a drug information portal.

    PubMed

    Sakji, Saoussen; Letord, Catherine; Dahamna, Badisse; Kergourlay, Ivan; Pereira, Suzanne; Joubert, Michel; Darmoni, Stéfan

    2009-01-01

    The objective of this work is to create a bilingual (French/English) Drug Information Portal (DIP), in a multi-terminological context and to emphasize its exploitation by an ATC automatic indexing allowing having more pertinent information about substances, organs or systems on which drugs act and their therapeutic and chemical characteristics. The development of the DIP was based on the CISMeF portal, which catalogues and indexes the most important and quality-controlled sources of institutional health information in French. DIP has created specific functionalities and uses specific drugs terminologies such as the ATC classification which used to automatic index the DIP resources. DIP is the result of collaboration between the CISMeF team and the VIDAL Company, specialized in drug information. DIP is conceived to facilitate the user information retrieval. The ATC automatic indexing provided relevant results in 76% of cases. Using multi-terminological context and in the framework of the drug field, indexing drugs with the appropriate codes or/and terms revealed to be very important to have the appropriate information storage and retrieval. The main challenge in the coming year is to increase the accuracy of the approach.

  18. Captopril as a replacement for multiple therapy in hypertension: a controlled study.

    PubMed

    Yodfat, Y; Fidel, J; Bloom, D S

    1985-11-01

    A controlled study was conducted in hypertensive patients to investigate whether captopril can be substituted for the various other antihypertensive drugs (not including diuretics) to reduce side effects and improve the quality of life. Captopril in a twice daily dose of 25-50 mg, was substituted and titrated in 54 patients. Fifty-two patients, matched by age and sex, comprised the control group, and were treated with a variety of agents. During a follow-up of 9 months, 44 of the patients receiving captopril (81%) achieved the goal of supine blood pressure less than 90 mmHg. Captopril was discontinued in two patients due to side effects. Mild proteinuria was observed in two patients. A significant reduction in scores or rates of side effects (numbness, blurred vision, insomnia, vivid dreams, cold extremities, sleepiness, sexual dysfunction and fatigue) and improvement in quality of life (general feeling, mood and concentration) was observed in the study group compared with the control group. Captopril alone in a twice daily dose of 25-50 mg, or in co-treatment with thiazide, provided sustained blood pressure control with minimal side effects and improvement in quality of life compared with the treatment of hypertension with beta-blockers, vasodilators or methyldopa.

  19. Issues and advances in the management and pathogenesis of cutaneous lupus erythematosus.

    PubMed

    Pelle, Michelle T

    2006-01-01

    Evidence-based therapy for cutaneous lupus is lacking. A new clinical assessment tool for cutaneous lupus, the CLASI score, will enable more standardized assessments of response to therapy. Anti-Ro autoantibodies are associated with photosensitive SLE and SCLE, and they play a role in cell survival following ultraviolet exposure. Ro also functions in quality control of small RNAs, important in the prevention of autoimmune disease. Drug-induced lupus erythematosus can be anti-Ro- or anti-dsDNA-associated; SCLE and photosensitivity are characteristic of Ro-positive drug-induced lupus. Biologic therapies and IVIg are being studied for the treatment of SLE and cutaneous lupus. Large, controlled trials are needed, not only to evaluate newer therapies, but also to substantiate and define the usage of traditional therapies for cutaneous lupus erythematosus.

  20. 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.

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