Science.gov

Sample records for biological drug products

  1. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug, antibiotic...

  2. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug, antibiotic...

  3. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug, antibiotic...

  4. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug, antibiotic...

  5. 37 CFR 1.775 - Calculation of patent term extension for a human drug, antibiotic drug or human biological product.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... extension for a human drug, antibiotic drug or human biological product. 1.775 Section 1.775 Patents... Review § 1.775 Calculation of patent term extension for a human drug, antibiotic drug or human biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a human drug, antibiotic...

  6. 78 FR 78796 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-27

    ... holders of an approved drug or biological product to change the product labeling to reflect certain types... biological product to change the product labeling to reflect certain types of newly acquired information in... Applications Proposing Labeling Changes for Approved Drugs and Biological Products; Correction and Extension of...

  7. 78 FR 12760 - Guidance for Industry on Labeling for Human Prescription Drug and Biological Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-25

    ...The Food and Drug Administration (FDA) is announcing the availability of a guidance for industry entitled ``Labeling for Human Prescription Drug and Biological Products--Implementing the PLR Content and Format Requirements.'' This guidance is intended to assist applicants in complying with the content and format requirements of labeling for human prescription drug and biological products. The......

  8. 75 FR 33312 - Indexing Structured Product Labeling for Human Prescription Drug and Biological Products; Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-11

    ... HUMAN SERVICES Food and Drug Administration Indexing Structured Product Labeling for Human Prescription... Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) are indexing certain... class as a top priority for indexing of product labeling information. FDA is now announcing that medical...

  9. 76 FR 66235 - Bar Code Technologies for Drugs and Biological Products; Retrospective Review Under Executive...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-26

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 201 and 610 Bar Code Technologies for Drugs and Biological Products; Retrospective Review Under Executive Order 13563; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for comments. SUMMARY: The Food and Drug...

  10. 21 CFR 201.56 - Requirements on content and format of labeling for human prescription drug and biological products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Requirements on content and format of labeling for human prescription drug and biological products. 201.56 Section 201.56 Food and Drugs FOOD AND DRUG... human prescription drug and biological products. (a) General requirements. Prescription drug labeling...

  11. Considerations of the chemical biology of microbial natural products provide an effective drug discovery strategy.

    PubMed

    Choi, Hyukjae; Oh, Dong-Chan

    2015-09-01

    Conventional approaches to natural product drug discovery rely mainly on random searches for bioactive compounds using bioassays. These traditional approaches do not incorporate a chemical biology perspective. Searching for bioactive molecules using a chemical and biological rationale constitutes a powerful search paradigm. Here, the authors review recent examples of the discovery of bioactive natural products based on chemical and biological interactions between hosts and symbionts, and propose this method provides a more effective means of exploring natural chemical diversity and eventually of discovering new drugs.

  12. Biological products for the treatment of psoriasis: therapeutic targets, pharmacodynamics and disease-drug-drug interaction implications.

    PubMed

    Wang, Jie; Wang, Yow-Ming C; Ahn, Hae-Young

    2014-09-01

    Psoriasis is a chronic inflammatory skin disease condition that involves altered expression of a broad spectrum of proinflammatory cytokines which are associated with activation of T cells and proliferation of keratinocytes. Currently approved biological products for psoriasis treatment fall into two main classes: cytokine modulators and biologics targeting T cells. In psoriatic patients, elevated levels of proinflammatory cytokines are observed. Elevated proinflammatory cytokines can suppress some cytochrome P450 (CYP) enzymes, and the treatment of psoriasis with biological products can reduce proinflammatory cytokine levels. Therefore, the exposure of CYP substrate drugs is anticipated to be affected by the psoriasis disease resulting in a higher exposure than in healthy state (named disease-drug interaction) as well as by the biological treatments due to disease improvements resulting in a decrease in exposure (named disease-drug-drug interaction, disease-DDI). However, the quantitative impact on CYP substrate exposure due to disease or due to treatment with biological products remains to be evaluated. The objective of the current review is to provide an overview of the therapeutic targets and cytokine-related pharmacodynamic effects of biological products in psoriasis treatment with a particular focus on their implications for disease-DDI. The clinical study design considerations for psoriasis disease-DDI evaluation are also discussed.

  13. Statistical and regulatory considerations in assessments of interchangeability of biological drug products.

    PubMed

    Tóthfalusi, Lászlo; Endrényi, László; Chow, Shein-Chung

    2014-05-01

    When the patent of a brand-name, marketed drug expires, new, generic products are usually offered. Small-molecule generic and originator drug products are expected to be chemically identical. Their pharmaceutical similarity can be typically assessed by simple regulatory criteria such as the expectation that the 90% confidence interval for the ratio of geometric means of some pharmacokinetic parameters be between 0.80 and 1.25. When such criteria are satisfied, the drug products are generally considered to exhibit therapeutic equivalence. They are then usually interchanged freely within individual patients. Biological drugs are complex proteins, for instance, because of their large size, intricate structure, sensitivity to environmental conditions, difficult manufacturing procedures, and the possibility of immunogenicity. Generic and brand-name biologic products can be expected to show only similarity but not identity in their various features and clinical effects. Consequently, the determination of biosimilarity is also a complicated process which involves assessment of the totality of the evidence for the close similarity of the two products. Moreover, even when biosimilarity has been established, it may not be assumed that the two biosimilar products can be automatically substituted by pharmacists. This generally requires additional, careful considerations. Without declaring interchangeability, a new product could be prescribed, i.e. it is prescribable. However, two products can be automatically substituted only if they are interchangeable. Interchangeability is a statistical term and it means that products can be used in any order in the same patient without considering the treatment history. The concepts of interchangeability and prescribability have been widely discussed in the past but only in relation to small molecule generics. In this paper we apply these concepts to biosimilars and we discuss: definitions of prescribability and interchangeability and

  14. Self in vivo production of a synthetic biological drug CTLA4Ig using a minicircle vector

    PubMed Central

    Rim, Yeri Alice; Yi, Hyoju; Kim, Youngkyun; Park, Narae; Jung, Hyerin; Kim, Juryun; Jung, Seung Min; Park, Sung-Hwan; Ju, Ji Hyeon

    2014-01-01

    Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA4Ig, abatacept) is a B7/CD28 costimulation inhibitor that can ward off the immune response by preventing the activation of naïve T cells. This therapeutic agent is administered to patients with autoimmune diseases such as rheumatoid arthritis. Its antiarthritic efficacy is satisfactory, but the limitations are the necessity for frequent injection and high cost. Minicircles can robustly express the target molecule and excrete it outside the cell as an indirect method to produce the protein of interest in vivo. We inserted the sequence of abatacept into the minicircle vector, and by successful in vivo injection the host was able to produce the synthetic protein drug. Intravenous infusion of the minicircle induced spontaneous production of CTLA4Ig in mice with collagen-induced arthritis. Self-produced CTLA4Ig significantly decreased the symptoms of arthritis. Injection of minicircle CTLA4Ig regulated Foxp3+ T cells and Th17 cells. Parental and mock vectors did not ameliorate arthritis or modify the T cell population. We have developed a new concept of spontaneous protein drug delivery using a minicircle vector. Self in vivo production of a synthetic protein drug may be useful when biological drugs cannot be injected because of manufacturing or practical problems. PMID:25374010

  15. Self in vivo production of a synthetic biological drug CTLA4Ig using a minicircle vector.

    PubMed

    Rim, Yeri Alice; Yi, Hyoju; Kim, Youngkyun; Park, Narae; Jung, Hyerin; Kim, Juryun; Jung, Seung Min; Park, Sung-Hwan; Ju, Ji Hyeon

    2014-11-06

    Cytotoxic T lymphocyte-associated antigen 4 immunoglobulin fusion protein (CTLA4Ig, abatacept) is a B7/CD28 costimulation inhibitor that can ward off the immune response by preventing the activation of naïve T cells. This therapeutic agent is administered to patients with autoimmune diseases such as rheumatoid arthritis. Its antiarthritic efficacy is satisfactory, but the limitations are the necessity for frequent injection and high cost. Minicircles can robustly express the target molecule and excrete it outside the cell as an indirect method to produce the protein of interest in vivo. We inserted the sequence of abatacept into the minicircle vector, and by successful in vivo injection the host was able to produce the synthetic protein drug. Intravenous infusion of the minicircle induced spontaneous production of CTLA4Ig in mice with collagen-induced arthritis. Self-produced CTLA4Ig significantly decreased the symptoms of arthritis. Injection of minicircle CTLA4Ig regulated Foxp3(+) T cells and Th17 cells. Parental and mock vectors did not ameliorate arthritis or modify the T cell population. We have developed a new concept of spontaneous protein drug delivery using a minicircle vector. Self in vivo production of a synthetic protein drug may be useful when biological drugs cannot be injected because of manufacturing or practical problems.

  16. Postmarketing safety reports for human drug and biological products; electronic submission requirements. Final rule.

    PubMed

    2014-06-10

    The Food and Drug Administration (FDA or we) is amending its postmarketing safety reporting regulations for human drug and biological products to require that persons subject to mandatory reporting requirements submit safety reports in an electronic format that FDA can process, review, and archive. FDA is taking this action to improve the Agency's systems for collecting and analyzing postmarketing safety reports. The change will help the Agency to more rapidly review postmarketing safety reports, identify emerging safety problems, and disseminate safety information in support of FDA's public health mission. In addition, the amendments will be a key element in harmonizing FDA's postmarketing safety reporting regulations with international standards for the electronic submission of safety information.

  17. The contribution of oxazolidinone frame to the biological activity of pharmaceutical drugs and natural products.

    PubMed

    Zappia, Giovanni; Menendez, Pilar; Monache, Giuliano Delle; Misiti, Domenico; Nevola, Laura; Botta, Bruno

    2007-04-01

    The development of resistance by the antibiotics in the Gram-positive pathogenic bacteria over the last twenty years and continuing today has created a need for new antibiotic classes, which may be unaffected by existing bacterial resistance. The oxazolidin-2-ones represent not only a new class with a novel mechanism of action, but also satisfy the requirement for overcoming the resistance mechanisms. Both linezolid and eperozolid, the first chemical candidates, arose from the piperazine subclass, with the first one being chosen further development because of its enhanced pharmacokinetic properties. The main attractive traits of the oxazolidinone series has encouraged further work in the area, and the patent literature reveals that extensive chemical investigation is currently being made. The unexpected early resistance development emphasizes the need for further exploration of features of the oxazolidinone to eliminate these deficiencies. Recently, several changes, involving the C5 side chain as well the N-phenyl heterocyclic ring, give promise for such improvement. Oxazolidinone antibacterial agents comprise also ketolides, derivatives of macrolides, such as erythromycin A, with a newly formed carbamate cycle, with a largely unexplored potential. The oxazolidinone nucleus does not appear only in the structures of antimicrobial drugs, but a number of biological activities are connected with frameworks including the oxazolidinone ring. A partial list of these activities comprises enzyme inhibitors, agonists and antagonists, with a particular citation for a new generation of selective monoamino oxidase inhibitors (befloxatone). The oxazolidinone moiety was found in the structure of few biologically active natural products, such as (-)-cytoxazone and streptazolin. Moreover, in some cases the oxazolidinone ring has been chosen for the preparation of isosteric aza analogues of natural compounds (podophyllotoxin, pilocarpine) that can be more easily synthesised and more

  18. Propolis: A Complex Natural Product with a Plethora of Biological Activities That Can Be Explored for Drug Development.

    PubMed

    Silva-Carvalho, Ricardo; Baltazar, Fátima; Almeida-Aguiar, Cristina

    2015-01-01

    The health industry has always used natural products as a rich, promising, and alternative source of drugs that are used in the health system. Propolis, a natural resinous product known for centuries, is a complex product obtained by honey bees from substances collected from parts of different plants, buds, and exudates in different geographic areas. Propolis has been attracting scientific attention since it has many biological and pharmacological properties, which are related to its chemical composition. Several in vitro and in vivo studies have been performed to characterize and understand the diverse bioactivities of propolis and its isolated compounds, as well as to evaluate and validate its potential. Yet, there is a lack of information concerning clinical effectiveness. The goal of this review is to discuss the potential of propolis for the development of new drugs by presenting published data concerning the chemical composition and the biological properties of this natural compound from different geographic origins.

  19. Propolis: A Complex Natural Product with a Plethora of Biological Activities That Can Be Explored for Drug Development

    PubMed Central

    Silva-Carvalho, Ricardo; Baltazar, Fátima; Almeida-Aguiar, Cristina

    2015-01-01

    The health industry has always used natural products as a rich, promising, and alternative source of drugs that are used in the health system. Propolis, a natural resinous product known for centuries, is a complex product obtained by honey bees from substances collected from parts of different plants, buds, and exudates in different geographic areas. Propolis has been attracting scientific attention since it has many biological and pharmacological properties, which are related to its chemical composition. Several in vitro and in vivo studies have been performed to characterize and understand the diverse bioactivities of propolis and its isolated compounds, as well as to evaluate and validate its potential. Yet, there is a lack of information concerning clinical effectiveness. The goal of this review is to discuss the potential of propolis for the development of new drugs by presenting published data concerning the chemical composition and the biological properties of this natural compound from different geographic origins. PMID:26106433

  20. 78 FR 67985 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-13

    ... labeling changes (e.g., boxed warnings and contraindications) for drug products with labeling in the PLR... for use and adequate warnings (see 21 U.S.C. 331(a) and (b) and 352(a), (f), and (j)). B. Current... strengthen a contraindication, warning, precaution, or adverse reaction for which the evidence of a causal...

  1. Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

    PubMed

    2010-09-29

    The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health.

  2. Lessons from the past and charting the future of marine natural products drug discovery and chemical biology

    PubMed Central

    Gerwick, William H.; Moore, Bradley S.

    2012-01-01

    Summary Marine life forms are an important source of structurally-diverse and biologically-active secondary metabolites, several of which have inspired the development of new classes of therapeutic agents. These success stories have had to overcome difficulties inherent to natural products-derived drugs, such as adequate sourcing of the agent and issues related to structural complexity. Nevertheless, several marine-derived agents are now approved, most as `first-in-class' drugs, with 5 of 7 appearing in the past few years. Additionally, there is a rich pipeline of clinical and pre-clinical marine compounds to suggest their continued application in human medicine. Understanding of how these agents are biosynthetically assembled has accelerated in recent years, especially through interdisciplinary approaches, and innovative manipulations and re-engineering of some of these gene clusters are yielding novel agents of enhanced pharmaceutical properties compared with the natural product. PMID:22284357

  3. 78 FR 65904 - Permanent Discontinuance or Interruption in Manufacturing of Certain Drug or Biological Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-04

    ... of the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Food and Drug...) significantly amended provisions in the FD&C Act related to drug shortages. Among other things, FDASIA amended section 506C of the FD&C Act (21 U.S.C. 356c) to require all manufacturers of certain drugs to notify...

  4. The Year's New Drugs & Biologics - 2009.

    PubMed

    Graul, Ann I; Sorbera, Lisa; Pina, Patricia; Tell, Montse; Cruces, Elisabet; Rosa, Esmeralda; Stringer, Mark; Castañer, Rosa; Revel, Laura

    2010-01-01

    This annual article presents new drugs and biologics that were launched or approved for the first time during the previous year. In 2009, 51 new medicines and vaccines reached their first markets. Line extensions (new indications, new formulations and new combinations of previously marketed products) accounted for more than 30% of the new products launched in 2009. In addition to providing an overview of all drugs and biologics launched or approved for the first time ever in the previous year, this article will also review in further depth the first-in-class drugs launched for the first time last year, providing a better understanding of their novel mechanisms of action; an analysis of the discovery and development periods for the year's new products; and a comprehensive overview of drug repositioning as a strategy for extending the life spans of medicines. We also provide a brief glimpse at selected drugs and biologics which could reach their first markets in the foreseeable future.

  5. 42 CFR 410.29 - Limitations on drugs and biologicals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Limitations on drugs and biologicals. 410.29... § 410.29 Limitations on drugs and biologicals. Medicare part B does not pay for the following: (a... factors, and except for EPO, any drug or biological that can be self-administered. (b) Any drug product...

  6. 21 CFR 201.56 - Requirements on content and format of labeling for human prescription drug and biological products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., mutagenesis, impairment of fertility 13.2 Animal toxicology and/or pharmacology 14 Clinical Studies 15... approved prescription drug products. This paragraph applies only to prescription drug products described in... substance 9.2 Abuse 9.3 Dependence 10 Overdosage 11 Description 12 Clinical Pharmacology 12.1 Mechanism of...

  7. 21 CFR 201.56 - Requirements on content and format of labeling for human prescription drug and biological products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... approved prescription drug products. This paragraph applies only to prescription drug products described in... substance 9.2 Abuse 9.3 Dependence 10 Overdosage 11 Description 12 Clinical Pharmacology 12.1 Mechanism of action 12.2 Pharmacodynamics 12.3 Pharmacokinetics 13 Nonclinical Toxicology 13.1 Carcinogenesis...

  8. 21 CFR 201.56 - Requirements on content and format of labeling for human prescription drug and biological products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., mutagenesis, impairment of fertility 13.2 Animal toxicology and/or pharmacology 14 Clinical Studies 15... approved prescription drug products. This paragraph applies only to prescription drug products described in... substance 9.2 Abuse 9.3 Dependence 10 Overdosage 11 Description 12 Clinical Pharmacology 12.1 Mechanism of...

  9. Drugs@FDA: FDA Approved Drug Products

    MedlinePlus

    ... Cosmetics Tobacco Products Home Drug Databases Drugs@FDA Drugs@FDA: FDA Approved Drug Products Share Tweet Linkedin Pin it More sharing options Linkedin Pin it Email Print Search by Drug Name, Active Ingredient, or Application Number Enter at ...

  10. Identification of transformation products of antiviral drugs formed during biological wastewater treatment and their occurrence in the urban water cycle.

    PubMed

    Funke, Jan; Prasse, Carsten; Ternes, Thomas A

    2016-07-01

    The fate of five antiviral drugs (abacavir, emtricitabine, ganciclovir, lamivudine and zidovudine) was investigated in biological wastewater treatment. Investigations of degradation kinetics were accompanied by the elucidation of formed transformation products (TPs) using activated sludge lab experiments and subsequent LC-HRMS analysis. Degradation rate constants ranged between 0.46 L d(-1) gSS(-1) (zidovudine) and 55.8 L d(-1) gSS(-1) (abacavir). Despite these differences of the degradation kinetics, the same main biotransformation reaction was observed for all five compounds: oxidation of the terminal hydroxyl-moiety to the corresponding carboxylic acid (formation of carboxy-TPs). In addition, the oxidation of thioether moieties to sulfoxides was observed for emtricitabine and lamivudine. Antiviral drugs were detected in influents of municipal wastewater treatment plants (WWTPs) with concentrations up to 980 ng L(-1) (emtricitabine), while in WWTP effluents mainly the TPs were found with concentration levels up to 1320 ng L(-1) (carboxy-abacavir). Except of zidovudine none of the original antiviral drugs were detected in German rivers and streams, whereas the concentrations of the TPs ranged from 16 ng L(-1) for carboxy-lamivudine up to 750 ng L(-1) for carboxy-acyclovir. These concentrations indicate an appreciable portion from WWTP effluents present in rivers and streams, as well as the high environmental persistence of the carboxy-TPs. As a result three of the carboxylic TPs were detected in finished drinking water. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. 77 FR 47397 - Request for Nominations of Specific Drug/Biologic Product(s) That Could Be Brought Before the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-08

    ... Agency to include the public in its decision-making processes. Significant public health and safety... Evaluation and Research, Food and Drug Administration, 10903 New Hampshire Ave., Bldg. 22, Rm. 2206, Silver...

  12. The year's new drugs & biologics - 2008.

    PubMed

    Graul, Ann I; Revel, Laura; Barrionuevo, Meritxell; Cruces, Elisabet; Rosa, Esmeralda; Verges, Clara; Lupone, Becky; Diaz, Nuria; Castaner, Rosa

    2009-01-01

    This annual article presents new drugs and biologics that were launched or approved for the first time during the previous year. In 2008, 31 new medicines-this figure includes both drugs and biologics for therapeutic use as well as new diagnostic agents-reached their first markets. Line extensions (new indications, new formulations and new combinations of previously marketed products) accounted for more than one-third of the new medicines launched in 2008. In addition to providing an overview of all drugs and biologics launched or approved for the first time ever in the previous year, this article will also review in further depth the first-in-class drugs launched for the first time last year, providing a better understanding of their novel mechanisms of action; an analysis of the discovery and development periods for the year's new products; and a comprehensive overview of drug repositioning as a strategy for extending the life spans of medicines. We also provide a brief glimpse at selected drugs and biologics which could reach their first markets in the foreseeable future.

  13. Molecular Phenotyping Combines Molecular Information, Biological Relevance, and Patient Data to Improve Productivity of Early Drug Discovery.

    PubMed

    Drawnel, Faye Marie; Zhang, Jitao David; Küng, Erich; Aoyama, Natsuyo; Benmansour, Fethallah; Araujo Del Rosario, Andrea; Jensen Zoffmann, Sannah; Delobel, Frédéric; Prummer, Michael; Weibel, Franziska; Carlson, Coby; Anson, Blake; Iacone, Roberto; Certa, Ulrich; Singer, Thomas; Ebeling, Martin; Prunotto, Marco

    2017-05-18

    Today, novel therapeutics are identified in an environment which is intrinsically different from the clinical context in which they are ultimately evaluated. Using molecular phenotyping and an in vitro model of diabetic cardiomyopathy, we show that by quantifying pathway reporter gene expression, molecular phenotyping can cluster compounds based on pathway profiles and dissect associations between pathway activities and disease phenotypes simultaneously. Molecular phenotyping was applicable to compounds with a range of binding specificities and triaged false positives derived from high-content screening assays. The technique identified a class of calcium-signaling modulators that can reverse disease-regulated pathways and phenotypes, which was validated by structurally distinct compounds of relevant classes. Our results advocate for application of molecular phenotyping in early drug discovery, promoting biological relevance as a key selection criterion early in the drug development cascade. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. FDA 101: Regulating Biological Products

    MedlinePlus

    ... Home For Consumers Consumer Updates FDA 101: Regulating Biological Products Share Tweet Linkedin Pin it More sharing ... and highly important field. back to top What biological products does FDA regulate? The Center for Biologics ...

  15. How to compare biologic drugs.

    PubMed

    Calvet, Xavier; Esplugues, Juan Vicente

    2014-01-01

    This consensus document reviews the evidence on the evaluation of biological drugs. The main conclusions of the group are: a) the current evidence on biological comparisons is based on indirect comparisons and is generally unreliable and with important methodological limitations. Therefore, b) it is considered necessary to amend the regulatory directives in the sense of strongly favoring randomized non-inferiority studies comparing face to face the new biological treatment with current standards, avoiding trials versus placebo, c) A key element in this process will be determined by consensus among regulatory agencies, scientific societies, the pharmaceutical industry and health authorities regarding the clinical differences that should be considered relevant in each of the conditions tested. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  16. 42 CFR 410.29 - Limitations on drugs and biologicals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... factors, and except for EPO, any drug or biological that can be self-administered. (b) Any drug product... determination by FDA, made under its efficacy review program, that there is a compelling justification of the drug product's medical need. (21 CFR 310.6 contains an explanation of the efficacy review program.)...

  17. 42 CFR 410.29 - Limitations on drugs and biologicals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... factors, and except for EPO, any drug or biological that can be self-administered. (b) Any drug product... determination by FDA, made under its efficacy review program, that there is a compelling justification of the drug product's medical need. (21 CFR 310.6 contains an explanation of the efficacy review program.)...

  18. 42 CFR 410.29 - Limitations on drugs and biologicals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... factors, and except for EPO, any drug or biological that can be self-administered. (b) Any drug product... determination by FDA, made under its efficacy review program, that there is a compelling justification of the drug product's medical need. (21 CFR 310.6 contains an explanation of the efficacy review program.)...

  19. 42 CFR 410.29 - Limitations on drugs and biologicals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... factors, and except for EPO, any drug or biological that can be self-administered. (b) Any drug product... determination by FDA, made under its efficacy review program, that there is a compelling justification of the drug product's medical need. (21 CFR 310.6 contains an explanation of the efficacy review program.)...

  20. Biological hydrogen production

    SciTech Connect

    Benemann, J.R.

    1995-11-01

    Biological hydrogen production can be accomplished by either thermochemical (gasification) conversion of woody biomass and agricultural residues or by microbiological processes that yield hydrogen gas from organic wastes or water. Biomass gasification is a well established technology; however, the synthesis gas produced, a mixture of CO and H{sub 2}, requires a shift reaction to convert the CO to H{sub 2}. Microbiological processes can carry out this reaction more efficiently than conventional catalysts, and may be more appropriate for the relatively small-scale of biomass gasification processes. Development of a microbial shift reaction may be a near-term practical application of microbial hydrogen production.

  1. Overview of drug product development.

    PubMed

    Narayan, Padma

    2011-12-01

    The process for developing drug delivery systems has evolved over the past two decades with more scientific rigor, involving a collaboration of various fields, i.e., biology, chemistry, engineering, and pharmaceutics. Drug products, also commonly known in the pharmaceutical industry as formulations or "dosage forms," are used for administering the active pharmaceutical ingredient (API) for purposes of assessing safety in preclinical models, early- to late-phase human clinical trials, and for routine clinical/commercial use. This overview discusses approaches for creating small-molecule API dosage forms, from preformulation to commercial manufacturing. © 2011 by John Wiley & Sons, Inc.

  2. Materials and methods for delivery of biological drugs

    NASA Astrophysics Data System (ADS)

    Zelikin, Alexander N.; Ehrhardt, Carsten; Healy, Anne Marie

    2016-11-01

    Biological drugs generated via recombinant techniques are uniquely positioned due to their high potency and high selectivity of action. The major drawback of this class of therapeutics, however, is their poor stability upon oral administration and during subsequent circulation. As a result, biological drugs have very low bioavailability and short therapeutic half-lives. Fortunately, tools of chemistry and biotechnology have been developed into an elaborate arsenal, which can be applied to improve the pharmacokinetics of biological drugs. Depot-type release systems are available to achieve sustained release of drugs over time. Conjugation to synthetic or biological polymers affords long circulating formulations. Administration of biological drugs through non-parenteral routes shows excellent performance and the first products have reached the market. This Review presents the main accomplishments in this field and illustrates the materials and methods behind existing and upcoming successful formulations and delivery strategies for biological drugs.

  3. Environmental assessment requirements for live biological drugs.

    PubMed

    Sutton, Ann

    2008-02-01

    Marketing approval of biological products by the US Food and Drug Administration must comply with requirements of Code of Federal Regulations title 21 part 25, "Environmental Impact Considerations." An environmental impact statement is usually not required. Environmental assessment is required unless excluded. As naturally occurring substances, biological products qualify for categorical exclusion if manufacture and use do not significantly alter their concentration or distribution in the human environment. The manufacturing process and establishment descriptions in the license application should include enough detail to ensure that waste is controlled and inactivated. During clinical development of a live biotherapeutic product, data should be collected regarding the shedding of live organisms from treated patients. The ability of the live organism to persist in the environment should be assessed, and instructions for safe handling by health care providers and consumers should be incorporated into the package insert.

  4. Synthetic biology for pharmaceutical drug discovery.

    PubMed

    Trosset, Jean-Yves; Carbonell, Pablo

    2015-01-01

    Synthetic biology (SB) is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell-cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity.

  5. Guide to Using Drugs, Biologics, and Other Chemicals in Aquaculture

    USDA-ARS?s Scientific Manuscript database

    The Guide to Using Drugs, Biologics, and Other Chemicals in Aquaculture (Guide) describes regulated products that are approved for use in U.S. aquaculture. The Guide also describes drugs that are not yet approved for use in the U. S. but that can be used under an Investigational New Animal Drug (INA...

  6. Electrophilic natural products and their biological targets.

    PubMed

    Gersch, Malte; Kreuzer, Johannes; Sieber, Stephan A

    2012-06-01

    The study of biologically active natural products has resulted in seminal contributions to our understanding of living systems. In the case of electrophilic natural products, the covalent nature of their interaction has largely facilitated the identification of their biological binding partners. In this review, we provide a comprehensive compilation of electrophilic natural products from all major chemical classes together with their biological targets. Covering Michael acceptor systems, ring-strained compounds and other electrophiles, such as esters or carbamates, we highlight representative and instructive examples for over 20 electrophilic moieties. The fruitful cooperation of natural product chemistry, medicinal chemistry and chemical biology has produced a collection of well-studied examples for how electrophilic natural products exert their biological functions that range from antibiotic to antitumor effects. Special emphasis is put on the elucidation of their respective biological targets via activity-based protein profiling, which together with the recent advancements in mass spectrometry has been crucial to the success of the field. The wealth of naturally occurring electrophilic moieties and their chemical complexity enables binding of a large variety of biological targets, such as enzymes of all classes, nonenzymatic proteins, DNA and other cellular compounds. With approximately 30,000 genes in the human genome but only 266 confirmed protein drug targets, the study of biologically active, electrophilic natural products has the potential to provide insights into fundamental biological processes and to greatly aid the discovery of new drug targets.

  7. Mechanisms of adverse drug reactions to biologics.

    PubMed

    Clarke, Janet B

    2010-01-01

    Biologics encompass a broad range of therapeutics that include proteins and other products derived from living systems. Although the multiplicity of target organs often seen with new chemical entities is generally not seen with biologics, they can produce significant adverse reactions. Examples include IL-12 and an anti-CD28 antibody that resulted in patient deaths and/or long stays in intensive care units. Mechanisms of toxicities can be categorized as pharmacological or nonpharmacological, with most, excepting hypersensitivity reactions, associated with the interaction of the agent with its planned target. Unexpected toxicities generally arise as a result of previously unknown biology. Manufacturing quality is a significant issue relative to the toxicity of biologics. The development of recombinant technology represented the single biggest advance leading to humanized products with minimal or no contaminants in comparison to products purified from animal tissues. Nevertheless, the type of manufacturing process including choice of cell type, culture medium, and purification method can result in changes to the protein. For example, a change to the closure system for erythropoietin led to an increase in aplastic anemia as a result of changing the immunogenicity characteristics of the protein. Monoclonal antibodies represent a major class of successful biologics. Toxicities associated with these agents include those associated with the binding of the complementary determining region (CDR) with the target. First dose reactions or infusion reactions are generally thought to be mediated via the Fc region of the antibody activating cytokine release, and have been observed with several antibodies. Usually, these effects (flu-like symptoms, etc.) are transient with subsequent dosing. Although biologics can have nonpharmacologic toxicities, these are less common than with small molecule drugs.

  8. 21 CFR 601.50 - Confidentiality of data and information in an investigational new drug notice for a biological...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... investigational new drug notice for a biological product. 601.50 Section 601.50 Food and Drugs FOOD AND DRUG... biological product. (a) The existence of an IND notice for a biological product will not be disclosed by the... availability for public disclosure of all data and information in an IND file for a biological product shall be...

  9. 21 CFR 201.56 - Requirements on content and format of labeling for human prescription drug and biological products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....3 Nursing mothers 8.4 Pediatric use 8.5 Geriatric use 9 Drug Abuse and Dependence 9.1 Controlled substance 9.2 Abuse 9.3 Dependence 10 Overdosage 11 Description 12 Clinical Pharmacology 12.1 Mechanism of..., mutagenesis, impairment of fertility 13.2 Animal toxicology and/or pharmacology 14 Clinical Studies...

  10. Biologically active peptides: prospects for drug development.

    PubMed

    Hughes, J

    1980-08-11

    Biologically active peptides aree typified by their unbiquity of distribution, their high receptor affinity and an almost infinite diversity of structure. For these reasons, considerable effort is now being expended to elucidate the possible role of peptides in brain function. This effort has been stimulated by the discovery of a number of new endogenous peptides, such as the enkephalins, endorphins, vasoactive intestinal peptide and neurotensin. At present, there is no clearly defined role for these peptides, although they may form an important basis for the chemical coding of various brain functions, including pain, mood and memory. At present, the potential for drug development of peptide agonists remains in fairly circumscribed areas such as analgesia, pituitary hormone control, and gastrointestinal motor and secretory control. Peptide antagonists may provide a vast field for future development, although only one area, that of antifertility drugs based on LHRH antagonists, shows any promise of immediate success. Industrial research approaches to new peptide agonists and antagonists mainly rely at present on rational drug design through structural analogies. Other fruitful approaches to be considered are the screening of natural microbial and plant products and the possible application of genetic engineering techniques.

  11. Plankton Production Biology

    DTIC Science & Technology

    2005-09-30

    information if it does not display a currently valid OMB control number. 1. REPORT DATE 30 SEP 2005 2. REPORT TYPE 3. DATES COVERED 00-00-2005 to 00-00... Crustacea ), the group that contributes the major part of the biomass of zooplankton collected with plankton nets in salt- and freshwater. The basis of...windows to the large Russian-language marine- biological literature by publishing this translation. The observations are not subject to becoming outdated

  12. Integrating systems biology sources illuminates drug action

    PubMed Central

    Gottlieb, Assaf; Altman, Russ B.

    2014-01-01

    There are significant gaps in our understanding of the pathways by which drugs act. This incomplete knowledge limits our ability to use mechanistic molecular information rationally to repurpose drugs, understand their side effects, and predict their interactions with other drugs. Here we present DrugRouter: a novel method for generating drug-specific pathways of action by linking target genes, disease genes and pharmacogenes using gene interaction networks. We construct pathways for over a hundred drugs, and show that the genes included in our pathways (1) co-occur with the query drug in the literature, (2) significantly overlap or are adjacent to known drug-response pathways, and (3) are adjacent to genes that are hits in genome wide association studies assessing drug response. Finally, these computed pathways suggest novel drug repositioning opportunities (e.g., statins for follicular thyroid cancer), gene-side effect associations, and gene-drug interactions. Thus, DrugRouter generates hypotheses about drug actions using systems biology data. PMID:24577151

  13. Plankton Production Biology

    DTIC Science & Technology

    2010-09-30

    studied. The book by Sazhina provides illustrated keys for all stages of the nauplii ( copepod larvae) of 85 species common in the oceans and is the...has to take precedence. 6 3. Sazhina’s (1985) keys for copepod nauplii still are the only ones anywhere. They will permit the study of stage...specific population dynamics (growth rate, production, mortality) of copepod larvae in mixed populations. TRANSITIONS The world’s oceanographic

  14. Biosynthesis of therapeutic natural products using synthetic biology.

    PubMed

    Awan, Ali R; Shaw, William M; Ellis, Tom

    2016-10-01

    Natural products are a group of bioactive structurally diverse chemicals produced by microorganisms and plants. These molecules and their derivatives have contributed to over a third of the therapeutic drugs produced in the last century. However, over the last few decades traditional drug discovery pipelines from natural products have become far less productive and far more expensive. One recent development with promise to combat this trend is the application of synthetic biology to therapeutic natural product biosynthesis. Synthetic biology is a young discipline with roots in systems biology, genetic engineering, and metabolic engineering. In this review, we discuss the use of synthetic biology to engineer improved yields of existing therapeutic natural products. We further describe the use of synthetic biology to combine and express natural product biosynthetic genes in unprecedented ways, and how this holds promise for opening up completely new avenues for drug discovery and production.

  15. 76 FR 59705 - Guidance for Industry on User Fee Waivers, Reductions, and Refunds for Drug and Biological...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-27

    ... Refunds for Drug and Biological Products; Availability AGENCY: Food and Drug Administration, HHS. ACTION... industry entitled ``User Fee Waivers, Reductions, and Refunds for Drug and Biological Products.'' This... a guidance for industry entitled ``User Fee Waivers, Reductions, and Refunds for Drug and Biological...

  16. Biological Processes for Hydrogen Production.

    PubMed

    van Niel, Ed W J

    Methane is produced usually from organic waste in a straightforward anaerobic digestion process. However, hydrogen production is technically more challenging as more stages are needed to convert all biomass to hydrogen because of thermodynamic constraints. Nevertheless, the benefit of hydrogen is that it can be produced, both biologically and thermochemically, in more than one way from either organic compounds or water. Research in biological hydrogen production is booming, as reflected by the myriad of recently published reviews on the topic. This overview is written from the perspective of how to transfer as much energy as possible from the feedstock into the gaseous products hydrogen, and to a lesser extent, methane. The status and remaining challenges of all the biological processes are concisely discussed.

  17. The year's new drugs & biologics 2015: Part I.

    PubMed

    Graul, A I; Cruces, E; Stringer, M

    2016-01-01

    Nearly 100 new drugs and biologics, including important new line extensions, were approved or launched for the first time globally in 2015. These products are covered in depth in part I of our annual review of the pharma and biotech industry.

  18. Biosimilars of biological drug therapies: regulatory, clinical and commercial considerations.

    PubMed

    Dranitsaris, George; Amir, Eitan; Dorward, Kristine

    2011-08-20

    Biologicals are distinct from small molecule drugs in that they are larger, more structurally complex agents. While the overall risk is modest, the active protein structure characteristic of biologicals makes them more prone to induce an acute and/or chronic immune response. Biosimilars are a new class of drugs intended to offer comparable safety and efficacy to the reference, off-patent biological. They are not generic alternatives per se and are generally not interchangeable. Given their structural complexity, multifaceted manufacturing process and risk for immunogenicity, unique regulatory pathways are required for biosimilars. In this article, we review the clinical, safety and submission requirements for biosimilars in several major markets. We also highlight issues of ongoing debate amongst key stakeholders and examine some of the commercial challenges faced by developers of biosimilars. As the leader of biosimilars drug approval and product uptake, the EU is highlighted.

  19. The year's new drugs & biologics, 2014: Part I.

    PubMed

    Graul, A I; Cruces, E; Stringer, M

    2015-01-01

    A year-end wrap-up of new drug approvals and launches reveals that activity in the pharmaceutical industry continues at a high level, with 55 new drugs and biologics introduced on their first markets in 2014 (as of December 23, 2014). Additionally, 29 important new line extensions (new formulations, new combinations or new indications for previously marketed products) also reached their first markets during the year. The most active therapeutic group in terms of new launches was anti-infective therapies, with 11 new drugs and biologics launched, most for the treatment of multidrug-resistant bacterial infections or hepatitis C. The most active market for new launches was again the U.S., site of more than half of all new launches in 2014. However new launch activity increased considerably last year in Japan, which actually pulled ahead of the E.U. for the first time in many years. In another important new development, 15 of the new drugs and biologics launched last year had orphan drug status, 5 had breakthrough therapy designation and 3 had Qualified Infectious Disease Product (QIDP) status. Another 19 products were approved for the first time during the year but not yet launched by close of this article; most are slated for launch in the first months of the new year.

  20. 75 FR 68802 - Report on the Performance of Drug and Biologics Firms in Conducting Postmarketing Requirements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-09

    ... clinical safety, clinical efficacy, clinical pharmacology, and nonclinical toxicology study/clinical trial.... The regulations apply only to human drug and biological products that are approved under NDAs, ANDAs, and BLAs. They do not apply to animal drugs or to biological products regulated under the medical...

  1. 77 FR 13339 - Report on the Performance of Drug and Biologics Firms in Conducting Postmarketing Requirements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-06

    ... clinical safety, clinical efficacy, clinical pharmacology, and nonclinical toxicology study/clinical trial... 30, 2001. The regulations apply only to human drug and biological products approved under NDAs, ANDAs, and BLAs. They do not apply to animal drugs or to biological products regulated under the medical...

  2. Canadian Drug Products Containing ASA

    PubMed Central

    Parker, William A.; Shearer, Cameron A.; Kirkpatrick, Susan L.

    1977-01-01

    A list of nearly 200 Canadian ASA-containing drug products is presented. Information was supplied by the major pharmaceutical companies and data were also obtained from various Canadian reference sources. This information should aid the physician and other health-related personnel in identifying ASA-containing products and counselling the salicylate-endangered patient. PMID:21304856

  3. Drugs and other product choices.

    PubMed

    Hyman, Paul M; Carvajal, Ricardo

    2009-01-01

    Dermatologists have at their disposal a wide range of products to recommend or prescribe to their patients, all of which are regulated in some way by the Food and Drug Administration (FDA). However, the degree to which FDA has confirmed the safety and efficacy of a dermatological product can vary widely. Most prescription and some over-the-counter drugs and medical devices are approved by the FDA based on scientific data. Most over-the-counter drugs are marketed in compliance with FDA regulations based on expert medical review. The FDA clears most medical devices based on their substantial equivalence to other legally marketed devices. Cosmetics, medical foods, and dietary supplements are subject only to general postmarket prohibitions against adulterated and misbranded products, although the FDA may review ingredient safety and specific claims for dietary supplements. Some product information is available on FDA's Web site, but the prudent physician should supplement that information by reviewing available scientific literature.

  4. 21 CFR 25.31 - Human drugs and biologics.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Human drugs and biologics. 25.31 Section 25.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENVIRONMENTAL IMPACT CONSIDERATIONS Categorical Exclusions § 25.31 Human drugs and biologics. The classes...

  5. 21 CFR 25.31 - Human drugs and biologics.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Human drugs and biologics. 25.31 Section 25.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENVIRONMENTAL IMPACT CONSIDERATIONS Categorical Exclusions § 25.31 Human drugs and biologics. The classes...

  6. 21 CFR 25.31 - Human drugs and biologics.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Human drugs and biologics. 25.31 Section 25.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENVIRONMENTAL IMPACT CONSIDERATIONS Categorical Exclusions § 25.31 Human drugs and biologics. The classes of...

  7. 21 CFR 25.31 - Human drugs and biologics.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Human drugs and biologics. 25.31 Section 25.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENVIRONMENTAL IMPACT CONSIDERATIONS Categorical Exclusions § 25.31 Human drugs and biologics. The classes...

  8. 21 CFR 25.31 - Human drugs and biologics.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Human drugs and biologics. 25.31 Section 25.31 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ENVIRONMENTAL IMPACT CONSIDERATIONS Categorical Exclusions § 25.31 Human drugs and biologics. The classes...

  9. Synthetic Biology Guides Biofuel Production

    PubMed Central

    Connor, Michael R.; Atsumi, Shota

    2010-01-01

    The advancement of microbial processes for the production of renewable liquid fuels has increased with concerns about the current fuel economy. The development of advanced biofuels in particular has risen to address some of the shortcomings of ethanol. These advanced fuels have chemical properties similar to petroleum-based liquid fuels, thus removing the need for engine modification or infrastructure redesign. While the productivity and titers of each of these processes remains to be improved, progress in synthetic biology has provided tools to guide the engineering of these processes through present and future challenges. PMID:20827393

  10. Drugs@FDA: FDA Approved Drug Products

    MedlinePlus

    ... by Month Approvals, tentative approvals, and supplements Original New Drug Approvals (NDAs and BLAs) by Month All applications ... FDA. Does not include tentative approvals. Original Abbreviated New Drug Approvals (ANDAs) by Month Generic Drug Approvals. Does ...

  11. The year's new drugs & biologics 2016: Part I.

    PubMed

    Graul, A I; Pina, P; Cruces, E; Stringer, M

    2017-01-01

    Nearly 90 new drugs and biologics, including important new line extensions, were approved or launched for the first time globally in 2016, a comparatively lower number with respect to previous years. Forty-four new drugs and biologics reached their first markets worldwide in 2016, nearly 10% fewer than the previous year. Seven of the new launches were first-in-class agents, meaning the first drug with a novel mechanism of action to be approved and launched anywhere in the world. In addition, 23 novel line extensions (i.e., new formulations, new combinations and new indications) were introduced last year. The remaining 21 products discussed in this article were approved for the first time during the year just passed, but had not yet been launched as of December 15, 2016. Information on these new arrivals is covered in depth in part I of our annual review of the pharma and biotech industry. Copyright 2017 Clarivate Analytics.

  12. 42 CFR 409.13 - Drugs and biologicals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Drugs and biologicals. 409.13 Section 409.13 Public... § 409.13 Drugs and biologicals. (a) Except as specified in paragraph (b) of this section, Medicare pays for drugs and biologicals as inpatient hospital or inpatient CAH services only if— (1) They...

  13. 42 CFR 409.13 - Drugs and biologicals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Drugs and biologicals. 409.13 Section 409.13 Public... § 409.13 Drugs and biologicals. (a) Except as specified in paragraph (b) of this section, Medicare pays for drugs and biologicals as inpatient hospital or inpatient CAH services only if— (1) They...

  14. 42 CFR 409.13 - Drugs and biologicals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Drugs and biologicals. 409.13 Section 409.13 Public... § 409.13 Drugs and biologicals. (a) Except as specified in paragraph (b) of this section, Medicare pays for drugs and biologicals as inpatient hospital or inpatient CAH services only if— (1) They...

  15. 42 CFR 409.13 - Drugs and biologicals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Drugs and biologicals. 409.13 Section 409.13 Public... § 409.13 Drugs and biologicals. (a) Except as specified in paragraph (b) of this section, Medicare pays for drugs and biologicals as inpatient hospital or inpatient CAH services only if— (1) They...

  16. 42 CFR 409.13 - Drugs and biologicals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Drugs and biologicals. 409.13 Section 409.13 Public... § 409.13 Drugs and biologicals. (a) Except as specified in paragraph (b) of this section, Medicare pays for drugs and biologicals as inpatient hospital or inpatient CAH services only if— (1) They represent...

  17. Are biological drugs safe in pregnancy?

    PubMed

    Calligaro, A; Hoxha, A; Ruffatti, A; Punzi, L

    2015-03-31

    The introduction of biological therapies has significantly improved the outcome of inflammatory rheumatic diseases. As most of these diseases affect women and men in childbearing age, some concerns have been voiced as to the safety of these drugs in relation to reproduction and pregnancy. Data from many hundreds of pregnancies in patients affected by inflammatory bowel disease and inflammatory arthritis have suggested that exposure to anti-TNF therapies at conception and/or during pregnancy is not associated with adverse pregnancy outcomes or any increase in congenital abnormalities. However, the exposure to anti-TNFα agents, particularly to monoclonal antibodies, in late pregnancy is associated with high drug levels in the newborn and their long-term effects on children remain unknown. Therefore, limiting the use of anti-TNFα to the first 30 weeks of pregnancy is recommended to reduce fetal exposure. Live-virus vaccines should be given only when levels of anti-TNFα drugs are undetectable in the serum of infants. Studies suggest that many of these drugs do enter breast milk in small amounts, but the extent to which the infant absorbs them is less clear. Limited reports have not suggested adverse pregnancy outcomes in women whose partners were exposed to anti-TNF therapies at the time of conception. Pregnancy data for rituximab, abatacept, anakinra, tocilizumab and belimumab are limited and their use in pregnancy cannot currently be recommended.

  18. Co-opting biology to deliver drugs

    PubMed Central

    Yousefpour, Parisa; Chilkoti, Ashutosh

    2014-01-01

    The goal of drug delivery is to improve the safety and therapeutic efficacy of drugs. This review focuses on delivery platforms that are either derived from endogenous pathways, long-circulating biomolecules and cells or that piggyback onto long-circulating biomolecules and cells. The first class of such platforms is protein-based delivery systems—albumin, transferrin, and fusion to the Fc domain of antibodies—that have a long-circulation half-life and are designed to transport different molecules. The second class is lipid-based delivery systems—lipoproteins and exosomes—that are naturally occurring circulating lipid particles. The third class is cell-based delivery systems—erythrocytes, macrophages, and platelets—that have evolved, for reasons central to their function, to exhibit a long life-time in the body. The last class is small molecule-based delivery systems that include folic acid. This paper reviews the biology of these systems, their application in drug delivery, and the promises and limitations of these endogenous systems for drug delivery. PMID:24916780

  19. Metabolic engineering of microorganisms: general strategies and drug production.

    PubMed

    Lee, Sang Yup; Kim, Hyun Uk; Park, Jin Hwan; Park, Jong Myung; Kim, Tae Yong

    2009-01-01

    Many drugs and drug precursors found in natural organisms are rather difficult to synthesize chemically and to extract in large amounts. Metabolic engineering is playing an increasingly important role in the production of these drugs and drug precursors. This is typically achieved by establishing new metabolic pathways leading to the product formation, and enforcing or removing the existing metabolic pathways toward enhanced product formation. Recent advances in system biology and synthetic biology are allowing us to perform metabolic engineering at the whole cell level, thus enabling optimal design of a microorganism for the efficient production of drugs and drug precursors. In this review, we describe the general strategies for the metabolic engineering of microorganisms for the production of drugs and drug precursors. As successful examples of metabolic engineering, the approaches taken toward strain development for the production of artemisinin, an antimalarial drug, and benzylisoquinoline alkaloids, a family of antibacterial and anticancer drugs, are described in detail. Also, systems metabolic engineering of Escherichia coli for the production of L-valine, an important drug precursor, is showcased as an important strategy of future metabolic engineering effort.

  20. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Biologics; products subject to license control. 310.4 Section 310.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (b) To obtain marketing approval for radioactive biological products for human use, as defined...

  1. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Biologics; products subject to license control. 310.4 Section 310.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (b) To obtain marketing approval for radioactive biological products for human use, as defined...

  2. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Biologics; products subject to license control. 310.4 Section 310.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN.... (b) To obtain marketing approval for radioactive biological products for human use, as defined...

  3. Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

    PubMed Central

    Crane, Erika A.

    2016-01-01

    Abstract Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody–drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products. PMID:26833854

  4. Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis.

    PubMed

    Crane, Erika A; Gademann, Karl

    2016-03-14

    Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody-drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products.

  5. Role of natural product diversity in chemical biology.

    PubMed

    Hong, Jiyong

    2011-06-01

    Through the natural selection process, natural products possess a unique and vast chemical diversity and have been evolved for optimal interactions with biological macromolecules. Owing to their diversity, target affinity, and specificity, natural products have demonstrated enormous potential as modulators of biomolecular function, been an essential source for drug discovery, and provided design principles for combinatorial library development.

  6. A New Strategy to Deliver Synthetic Protein Drugs: Self-reproducible Biologics Using Minicircles

    PubMed Central

    Yi, Hyoju; Kim, Youngkyun; Kim, Juryun; Jung, Hyerin; Rim, Yeri Alice; Jung, Seung Min; Park, Sung-Hwan; Ju, Ji Hyeon

    2014-01-01

    Biologics are the most successful drugs used in anticytokine therapy. However, they remain partially unsuccessful because of the elevated cost of their synthesis and purification. Development of novel biologics has also been hampered by the high cost. Biologics are made of protein components; thus, theoretically, they can be produced in vivo. Here we tried to invent a novel strategy to allow the production of synthetic drugs in vivo by the host itself. The recombinant minicircles encoding etanercept or tocilizumab, which are synthesized currently by pharmaceutical companies, were injected intravenously into animal models. Self-reproduced etanercept and tocilizumab were detected in the serum of mice. Moreover, arthritis subsided in mice that were injected with minicircle vectors carrying biologics. Self-reproducible biologics need neither factory facilities for drug production nor clinical processes, such as frequent drug injection. Although this novel strategy is in its very early conceptual stage, it seems to represent a potential alternative method for the delivery of biologics. PMID:25091294

  7. Applying systems biology in drug discovery and development.

    PubMed

    Galizzi, Jean-Pierre; Lockhart, Brian Paul; Bril, Antoine

    2013-01-01

    Translational research is a continuum between clinical and basic research where the patient is the center of the research process. It brings clinical research to a starting point for the drug discovery process, permitting the generation of a more robust pathophysiological hypothesis essential for a better selection of drug targets and candidate optimization. It also establishes the basis of early proof for clinical concept studies, preferably in phase I, for which biomarkers and surrogate endpoints can often be used. Systems biology is a prerequisite approach to translational research where technologies and expertise are integrated and articulated to support efficient and productive realization of this concept. The first component of systems biology relies on omics-based technologies and integrates the changes in variables, such as genes, proteins and metabolites, into networks that are responsible for an organism's normal and diseased state. The second component of systems biology is in the domain of computational methods, where simulation and modeling create hypotheses of signaling pathways, transcription networks, physiological processes or even cell- or organism-based models. The simulations aim to show the origin of perturbations of the system that lead to pathological states and what treatment could be achieved to ameliorate or normalize the system. This review discusses how translational research and systems biology together could improve global understanding of drug targets, suggest new targets and approaches for therapeutics, and provide a deeper understanding of drug effects. Taken together, these types of analyses can lead to new therapeutic options while improving the safety and efficacy of new and existing medications.

  8. 9 CFR 114.4 - Identification of biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Identification of biological products... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.4 Identification of biological products. Suitable tags or labels of... biological products, all component parts to be combined to form a biological product, all biological products...

  9. 9 CFR 114.4 - Identification of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Identification of biological products... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.4 Identification of biological products. Suitable tags or labels of... biological products, all component parts to be combined to form a biological product, all biological products...

  10. 21 CFR 601.50 - Confidentiality of data and information in an investigational new drug notice for a biological...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Confidentiality of data and information in an investigational new drug notice for a biological product. 601.50 Section 601.50 Food and Drugs FOOD AND DRUG... Information § 601.50 Confidentiality of data and information in an investigational new drug notice for...

  11. Design control considerations for biologic-device combination products.

    PubMed

    Anderson, Dave; Liu, Roger; Anand Subramony, J; Cammack, Jon

    2017-01-11

    Combination products are therapeutic and diagnostic medical products that combine drugs, devices, and/or biological products with one another. Historically, biologics development involved identifying efficacious doses administered to patients intravenously or perhaps by a syringe. Until fairly recently, there has been limited focus on developing an accompanying medical device, such as a prefilled syringe or auto-injector, to enable easy and more efficient delivery. For the last several years, and looking forward, where there may be little to distinguish biologics medicines with relatively similar efficacy profiles, the biotechnology market is beginning to differentiate products by patient-focused, biologic-device based combination products. As innovative as biologic-device combination products are, they can pose considerable development, regulatory, and commercialization challenges due to unique physicochemical properties and special clinical considerations (e.g., dosing volumes, frequency, co-medications, etc.) of the biologic medicine. A biologic-device combination product is a marriage between two partners with "cultural differences," so to speak. There are clear differences in the development, review, and commercialization processes of the biologic and the device. When these two cultures come together in a combination product, developers and reviewers must find ways to address the design controls and risk management processes of both the biologic and device, and knit them into a single entity with supporting product approval documentation. Moreover, digital medicine and connected health trends are pushing the boundaries of combination product development and regulations even further. Despite an admirable cooperation between industry and FDA in recent years, unique product configurations and design features have resulted in review challenges. These challenges have prompted agency reviewers to modernize consultation processes, while at the same time, promoting

  12. Chemical and biological production of cyclotides

    PubMed Central

    Li, Yilong; Bi, Tao; Camarero, Julio A.

    2016-01-01

    Cyclotides are fascinating naturally occurring micro-proteins (≈30 residues long) present in several plant families, and display various biological properties such as protease inhibitory, anti-microbial, insecticidal, cytotoxic, anti-HIV and hormone-like activities. Cyclotides share a unique head-to-tail circular knotted topology of three disulfide bridges, with one disulfide penetrating through a macrocycle formed by the two other disulfides and interconnecting peptide backbones, forming what is called a cystine knot topology. This cyclic cystine knot (CCK) framework gives the cyclotides exceptional rigidity, resistance to thermal and chemical denaturation, and enzymatic stability against degradation. Interestingly, cyclotides have been shown to be orally bioavailable, and other cyclotides have been shown to cross the cell membranes. Moreover, recent reports have also shown that engineered cyclotides can be efficiently used to target extracellular and intracellular protein-protein interactions, therefore making cyclotides ideal tools for drug development to selectively target protein-protein interactions. In this work we will review all the available methods for production of these interesting proteins using chemical or biological methods. PMID:27064329

  13. Natural products with health benefits from marine biological resources

    USDA-ARS?s Scientific Manuscript database

    The ocean is the cradle of lives, which provides a diverse array of intriguing natural products that has captured scientists’ attention in the past few decades due to their significant and extremely potent biological activities. In addition to being rich sources for pharmaceutical drugs, marine nat...

  14. Biological production of products from waste gases

    DOEpatents

    Gaddy, James L.

    2002-01-22

    A method and apparatus are designed for converting waste gases from industrial processes such as oil refining, and carbon black, coke, ammonia, and methanol production, into useful products. The method includes introducing the waste gases into a bioreactor where they are fermented to various products, such as organic acids, alcohols, hydrogen, single cell protein, and salts of organic acids by anaerobic bacteria within the bioreactor. These valuable end products are then recovered, separated and purified.

  15. Initial steps in the regulation of generic biological drugs: a comparison of U.S. and Canadian regimes.

    PubMed

    Szeto, Kenneth J; Wolanski, Marian

    2012-01-01

    Biological drug products are poised to overtake traditional pharmaceuticals as the best selling products in the pharmaceutical industry. Accordingly, both innovator and generic drug companies have a vested interest in the rules and regulations governing the approval and market entry of follow-on ("generic") biologic drug products as well as relevant procedures for litigating disputes involving biologic drug products. The U.S. and Canada both regulate the development and sale of traditional generic drugs through complex legal and regulatory schemes that seek to maintain a balance of interests between the innovator and generic sectors of the pharmaceutical industry. With the continued emergence of biological drugs, both countries have recently set forth legal and regulatory schemes to address the unique issues presented by generic biologic drug products. These issues include the requirements needed to submit an application for a generic biologic; biosimilarity vs. interchangeability designations; market and data exclusivity; and procedures for litigating disputes involving biologic drugs. Like the respective rules governing traditional pharmaceuticals, the recent U.S. and Canadian regulations addressing biological drugs contain both similarities and differences. As such, an understanding of both countries regulatory schemes will help both innovators and generics in decision making and legal strategy related to biological drugs. This article provides a comparative overview of the two systems to assist in such an understanding.

  16. [Special features of biological drug therapy in children].

    PubMed

    Aalto, Kristiina; Leinonen, Sanna; Kolho, Kaija-Leena; Lahdenne, Pekka

    2016-01-01

    Several new biological drugs, of which TNFα blockers are being used most extensively, have in recent years been adopted for the treatment of pediatric inflammatory diseases such as juvenile arthritis and associated chronic iritis, and inflammatory bowel diseases. In special situations the children will be prescribed off-label also other drugs affecting cytokines, e.g. IL-1 and IL-6 blockers. Tailoring of the treatment is possible today with the help of drug level measurements and anti-drug antibody determinations. Severe safety hazards associated with biological drug therapy in children are very rare.

  17. Genetic and biological markers in drug abuse and alcoholism

    SciTech Connect

    Braude, M.C.; Chao, H.M.

    1986-01-01

    This book contains 11 selections. Some of the titles are: Polymorphic Gene Marker Studies; Pharmacogenetic Approaches to the Prediction of Drug Response; Genetic Markers of Drug Abuse in Mouse Models; Genetics as a Tool for Identifying Biological Markers of Drug Abuse; and Studies of an Animal Model of Alcoholism.

  18. Pharmacogenomic Biomarkers: an FDA Perspective on Utilization in Biological Product Labeling.

    PubMed

    Schuck, Robert N; Grillo, Joseph A

    2016-05-01

    Precision medicine promises to improve both the efficacy and safety of therapeutic products by better informing why some patients respond well to a drug, and some experience adverse reactions, while others do not. Pharmacogenomics is a key component of precision medicine and can be utilized to select optimal doses for patients, more precisely identify individuals who will respond to a treatment and avoid serious drug-related toxicities. Since pharmacogenomic biomarker information can help inform drug dosing, efficacy, and safety, pharmacogenomic data are critically reviewed by FDA staff to ensure effective use of pharmacogenomic strategies in drug development and appropriate incorporation into product labels. Pharmacogenomic information may be provided in drug or biological product labeling to inform health care providers about the impact of genotype on response to a drug through description of relevant genomic markers, functional effects of genomic variants, dosing recommendations based on genotype, and other applicable genomic information. The format and content of labeling for biologic drugs will generally follow that of small molecule drugs; however, there are notable differences in pharmacogenomic information that might be considered useful for biologic drugs in comparison to small molecule drugs. Furthermore, the rapid entry of biologic drugs for treatment of rare genetic diseases and molecularly defined subsets of common diseases will likely lead to increased use of pharmacogenomic information in biologic drug labels in the near future. In this review, we outline the general principles of therapeutic product labeling and discuss the utilization of pharmacogenomic information in biologic drug labels.

  19. Raman Barcode for Counterfeit Drug Product Detection.

    PubMed

    Lawson, Latevi S; Rodriguez, Jason D

    2016-05-03

    Potential infiltration of counterfeit drug products-containing the wrong or no active pharmaceutical ingredient (API)-into the bona fide drug supply poses a significant threat to consumers worldwide. Raman spectroscopy offers a rapid, nondestructive avenue to screen a high throughput of samples. Traditional qualitative Raman identification is typically done with spectral correlation methods that compare the spectrum of a reference sample to an unknown. This is often effective for pure materials but is quite challenging when dealing with drug products that contain different formulations of active and inactive ingredients. Typically, reliable identification of drug products using common spectral correlation algorithms can only be made if the specific product under study is present in the library of reference spectra, thereby limiting the scope of products that can be screened. In this paper, we introduce the concept of the Raman barcode for identification of drug products by comparing the known peaks in the API reference spectrum to the peaks present in the finished drug product under study. This method requires the transformation of the Raman spectra of both API and finished drug products into a barcode representation by assigning zero intensity to every spectral frequency except the frequencies that correspond to Raman peaks. By comparing the percentage of nonzero overlap between the expected API barcode and finished drug product barcode, the identity of API present can be confirmed. In this study, 18 approved finished drug products and nine simulated counterfeits were successfully identified with 100% accuracy utilizing this method.

  20. 76 FR 52669 - Report on the Performance of Drug and Biologics Firms in Conducting Postmarketing Requirements...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ...The Food and Drug Administration (FDA) is correcting a notice of availability that appeared in the Federal Register of August 4, 2011 (76 FR 47211). The Agency is required to report annually in the Federal Register on the status of postmarketing requirements and commitments required of, or agreed upon by, holders of approved drug and biological products. The August 4, 2011, notice is the......

  1. 21 CFR 510.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS General Provisions § 510.4 Biologics; products subject to license control. An animal drug produced and distributed in full conformance with the animal virus, serum, and toxin law of March 4, 1913 (37 Stat. 832; 21 U.S.C. 151 et seq. )...

  2. 21 CFR 510.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS NEW ANIMAL DRUGS General Provisions § 510.4 Biologics; products subject to license control. An animal drug produced and distributed in full conformance with the animal virus, serum, and toxin law of March 4, 1913 (37 Stat. 832; 21 U.S.C. 151 et seq. )...

  3. 76 FR 52668 - Vaccines and Related Biological Products Advisory Committee; Amendment of Notice

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-23

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... Administration (FDA) is announcing an amendment to the notice of meeting of the Vaccines and Related Biological... announced that a meeting of the Vaccines and Related Biological Products Advisory Committee would be held on...

  4. 76 FR 13646 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-14

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological... Products, Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, FDA. In the...

  5. Drug-device combination products: regulatory landscape and market growth.

    PubMed

    Bayarri, L

    2015-08-01

    Combination products are therapeutic and diagnostic products that combine drugs, devices and/or biological products, leading to safer and more effective treatments thanks to careful and precise drug targeting, local administration and individualized therapy. These technologies can especially benefit patients suffering from serious diseases and conditions such as cancer, heart disease, multiple sclerosis and diabetes, among others. On the other hand, drug-device combination products have also introduced a new dynamic in medical product development, regulatory approval and corporate interaction. Due to the increasing integration of drugs and devices observed in the latest generation of combination products, regulatory agencies have developed specific competences and regulations over the last decade. Manufacturers are required to fully understand the specific requirements in each country in order to ensure timely and accurate market access of new combination products, and the development of combination products involves a very specific pattern of interactions between manufacturers and regulatory agencies. The increased sophistication of the products brought to market over the last couple of decades has accentuated the need to develop drugs and devices collaboratively using resources from both industries, fostering the need of business partnering and technology licensing. This review will provide a global overview of the market trends, as well as (in the last section) an analysis of the drug-device combination products approved by the FDA during the latest 5 years. Copyright 2015 Prous Science, S.A.U. or its licensors. All rights reserved.

  6. Synthetic biology advances for pharmaceutical production

    PubMed Central

    Breitling, Rainer; Takano, Eriko

    2015-01-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems. PMID:25744872

  7. Marine Natural Products: A Way to New Drugs

    PubMed Central

    2009-01-01

    The investigation of marine natural products (low molecular weight bioregulators) is a rapidly developing scientific field at the intersection of biology and chemistry. Investigations aimed at detecting, identifying, and understanding the structure of marine natural products have led to the discovery of 20,000 new substances, including those characterized by an extremely high physiological activity. Some results and prospects of works aimed at creating new drugs on the basis of marine natural products are discussed herein. PMID:22649599

  8. Marine natural products: a way to new drugs.

    PubMed

    Stonik, V A

    2009-07-01

    The investigation of marine natural products (low molecular weight bioregulators) is a rapidly developing scientific field at the intersection of biology and chemistry. Investigations aimed at detecting, identifying, and understanding the structure of marine natural products have led to the discovery of 20,000 new substances, including those characterized by an extremely high physiological activity. Some results and prospects of works aimed at creating new drugs on the basis of marine natural products are discussed herein.

  9. The similarity question for biologicals and non-biological complex drugs.

    PubMed

    Crommelin, Daan J A; Shah, Vinod P; Klebovich, Imre; McNeil, Scott E; Weinstein, Vera; Flühmann, Beat; Mühlebach, Stefan; de Vlieger, Jon S B

    2015-08-30

    For small - low molecular weight - molecule medicines a robust regulatory system has evolved over the years. This system guarantees high and constant quality of our (generic) medicines. Pharmaceutical equivalence and bioequivalence assessment are the pillars under that system. But there are complex medicines where the question of equivalence is more challenging to answer. For biologicals the paradigm of similarity rather than equality (the emergence of 'biosimilars') was developed in the past decade. This has been a program where an evolutionary, science based approach has been chosen by the frontrunner regulatory body, the EMA, with a 'learn and confirm' character. In addition, there is another group of complex drugs, the non-biological complex drugs, NBCDs, where the generic paradigm can be challenged as well. The NBCDs are defined as: 1. consisting of a complex multitude of closely related structures; 2. the entire multitude is the active pharmaceutical ingredient; 3. the properties cannot be fully characterized by physicochemical analysis and 4. the consistent, tightly controlled manufacturing process is fundamental to reproduce the product. NBCDs encompass product families such as the glatiramoids, liposomes, iron-carbohydrate colloids and many candidates of the group of the upcoming nanoparticulate systems. Following the main principles of regulatory pathways for biologicals (with appropriate product-by-product adjustments), instead of that for small molecules, would be the more logical strategy for these NBCDs. The status and outstanding regulatory issues for biosimilars and NBCD-similars/follow on versions were discussed at a conference in Budapest, Hungary (October 2014) and this commentary touches upon the issues brought up in the presentations, deliberations and conclusions.

  10. Advances in the development of biologics to treat drug addictions and overdose.

    PubMed

    Montoya, Iván D

    2012-01-01

    Drug addictions are complex disorders that require multiple approaches, including the use of pharmacotherapies. Currently, these therapies are based on "small" molecules or chemicals that penetrate the blood-brain barrier, reach the brain, and produce their effects on neurotransmitter systems. Unfortunately, they often do not have the desired efficacy or may cause undesirable side effects, especially at the central nervous system (CNS) level. A novel approach is the use of biologics to treat drug addictions. Biologics are usually complex and "large" molecules, which do not cross the blood-brain barrier and, thus, have no CNS effects. In principle, it appears that the efficacy of biologics to treat drug addiction is by preventing the access of the drug of abuse to the brain, preventing the activation of brain reward systems, and eventually producing the extinction of addiction. Biologic therapeutics includes immunotherapies, such as vaccines or antibodies, as well as enzymes. New products as well as new and more efficient methods of production, are offering vast opportunities to advance the discovery and development of biologics to treat addictions as well as drug overdose. These products include new vaccines with greater specificity and ability to produce antibodies, new methods and techniques to produce vaccines and antibodies, as well as new enzymes with high efficiency to metabolize cocaine. The purpose of the article is to provide a general overview of the development of biologics for the treatment of drug addictions and overdose.

  11. The year's new drugs & biologics 2014 - Part II: trends & challenges.

    PubMed

    Graul, A I; Serebrov, M; Cruces, E; Tracy, M; Dulsat, C

    2015-02-01

    2014 was a year of continued high activity in the pharma and biotech industry, as evidenced in part I of this annual two-part review article published last month in this journal (1). As of December 23, 2014, a total of 55 new chemical and biological entities had reached their first markets worldwide, together with another 29 important new line extensions. Another 19 products were approved for the first time during the year but not yet launched by December 23. Furthermore, during the now-traditional year-end sprint, several regulatory agencies issued last-minute approvals for other compounds that missed the deadline for inclusion in that article, bringing the total of new approvals for the year to a somewhat higher number. In addition to the successful development, registration and launch of new drugs and biologics, there are various other trends and tendencies that serve as indicators of the overall health and status of the industry. These include the pursuit of novel programs designed by regulators to stimulate the development of drugs for diseases that are currently under-treated; the regular and pragmatic culling by companies of their R&D pipelines; and the decision to unify pipelines, portfolios and sales forces through mergers and acquisitions.

  12. Nanoparticle iron medicinal products - Requirements for approval of intended copies of non-biological complex drugs (NBCD) and the importance of clinical comparative studies.

    PubMed

    Borchard, Gerrit; Flühmann, Beat; Mühlebach, Stefan

    2012-11-01

    Currently, most countries apply the standard generic approach for the approval of intended copies of originator nanoparticle iron medicinal products, requiring only demonstration of bioequivalence to a reference medicinal product by bioavailability studies. However, growing evidence suggests that this regulatory approach is not appropriate. Clinical and non-clinical studies have shown that intended copy preparations of nanoparticle iron medicinal products can differ substantially from the originator product in their efficacy and potentially in their safety profile. An adapted regulatory pathway (separate from the standard generic approach) with defined data requirements is needed for approval of intended copies of iron medicinal products. Here, we discuss the difficulties involved in assessing therapeutic equivalence of nanoparticle iron medicinal products and suggest key concepts of a regulatory approach. Standardized non-clinical comparative studies are necessary but, as demonstrated in the reported clinical data, they may not be sufficient to demonstrate a comparable efficacy and safety profile. Validated, prospective, comparative clinical studies might be needed, in addition to non-clinical studies, in order to enable appropriate assessment of therapeutic equivalence. Furthermore, including brand names in addition to the International Non-proprietary Names (INNs) in safety reports could enable effective safety monitoring of intended copies and originator products.

  13. Requirements for Foreign and Domestic Establishment Registration and Listing for Human Drugs, Including Drugs That Are Regulated Under a Biologics License Application, and Animal Drugs. Final rule.

    PubMed

    2016-08-31

    The Food and Drug Administration (FDA) is amending its regulations governing drug establishment registration and drug listing. These amendments reorganize, modify, and clarify current regulations concerning who must register establishments and list human drugs, human drugs that are also biological products, and animal drugs. The final rule requires electronic submission, unless waived in certain circumstances, of registration and listing information. This rulemaking pertains to finished drug products and to active pharmaceutical ingredients (APIs) alone or together with one or more other ingredients. The final rule describes how and when owners or operators of establishments at which drugs are manufactured or processed must register their establishments with FDA and list the drugs they manufacture or process. In addition, the rule makes certain changes to the National Drug Code (NDC) system. We are taking this action to improve management of drug establishment registration and drug listing requirements and make these processes more efficient and effective for industry and for us. This action also supports implementation of the electronic prescribing provisions of the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA) and the availability of current drug labeling information through DailyMed, a computerized repository of drug information maintained by the National Library of Medicine.

  14. Natural product leads for drug discovery: isolation, synthesis and biological evaluation of 6-cyano-5-methoxyindolo[2,3-a]carbazole based ligands as antibacterial agents.

    PubMed

    Guo, Songpo; Tipparaju, Suresh K; Pegan, Scott D; Wan, Baojie; Mo, Shunyan; Orjala, Jimmy; Mesecar, Andrew D; Franzblau, Scott G; Kozikowski, Alan P

    2009-10-15

    Indolo[2,3-a]carbazole based inhibitors were synthesized from readily available indigo via a seven-step linear synthetic sequence with a moderate overall yield. The inhibitors were selectively and readily functionalized at the nitrogen on the indole portion of the carbazole unit. The synthesized analogs displayed moderate inhibitory activities toward Bacillus anthracis and Mycobacterium tuberculosis, indicating that indolo[2,3-a]carbazoles could serve as promising leads in the development of new drugs to combat anthrax and tuberculosis infections.

  15. Natural Product Leads for Drug Discovery: Isolation, Synthesis and Biological Evaluation of 6-Cyano-5-methoxyindolo[2,3-a]carbazole Based Ligands as Antibacterial Agents

    PubMed Central

    Guo, Songpo; Tipparaju, Suresh K.; Pegan, Scott D.; Wan, Baojie; Mo, Shunyan; Orjala, Jimmy; Mesecar, Andrew D.; Franzblau, Scott G.; Kozikowski, Alan P.

    2010-01-01

    Indolo[2,3-a]carbazole based inhibitors were synthesized from readily available indigo via a seven-step linear synthetic sequence with a moderate overall yield. The inhibitors were selectively and readily functionalized at the nitrogen on the indole portion of the carbazole unit. The synthesized analogs displayed moderate inhibitory activities toward B. anthracis and M. tuberculosis, indicating that indolo[2,3-a]carbazoles could serve as promising leads in the development of new drugs to combat anthrax and tuberculosis infections. PMID:19783449

  16. Biologically active proteins from natural product extracts.

    PubMed

    O'Keefe, B R

    2001-10-01

    The term "biologically active proteins" is almost redundant. All proteins produced by living creatures are, by their very nature, biologically active to some extent in their homologous species. In this review, a subset of these proteins will be discussed that are biologically active in heterologous systems. The isolation and characterization of novel proteins from natural product extracts including those derived from microorganisms, plants, insects, terrestrial vertebrates, and marine organisms will be reviewed and grouped into several distinct classes based on their biological activity and their structure.

  17. Advanced systems biology methods in drug discovery and translational biomedicine.

    PubMed

    Zou, Jun; Zheng, Ming-Wu; Li, Gen; Su, Zhi-Guang

    2013-01-01

    Systems biology is in an exponential development stage in recent years and has been widely utilized in biomedicine to better understand the molecular basis of human disease and the mechanism of drug action. Here, we discuss the fundamental concept of systems biology and its two computational methods that have been commonly used, that is, network analysis and dynamical modeling. The applications of systems biology in elucidating human disease are highlighted, consisting of human disease networks, treatment response prediction, investigation of disease mechanisms, and disease-associated gene prediction. In addition, important advances in drug discovery, to which systems biology makes significant contributions, are discussed, including drug-target networks, prediction of drug-target interactions, investigation of drug adverse effects, drug repositioning, and drug combination prediction. The systems biology methods and applications covered in this review provide a framework for addressing disease mechanism and approaching drug discovery, which will facilitate the translation of research findings into clinical benefits such as novel biomarkers and promising therapies.

  18. Biological production of organic compounds

    DOEpatents

    Yu, Jianping; Paddock, Troy; Carrieri, Damian; Maness, Pin-Ching; Seibert, Michael

    2016-04-12

    Strains of cyanobacteria that produce high levels of alpha ketoglutarate (AKG) and pyruvate are disclosed herein. Methods of culturing these cyanobacteria to produce AKG or pyruvate and recover AKG or pyruvate from the culture are also described herein. Nucleic acid sequences encoding polypeptides that function as ethylene-forming enzymes and their use in the production of ethylene are further disclosed herein. These nucleic acids may be expressed in hosts such as cyanobacteria, which in turn may be cultured to produce ethylene.

  19. Regulatory Requirements for PET Drug Production.

    PubMed

    Schwarz, Sally W; Dick, David; VanBrocklin, Henry F; Hoffman, John M

    2014-07-01

    The Food and Drug Administration (FDA) issued the final rule for title 21 of Code of Federal Regulations part 212 regarding the regulations on current good manufacturing practice for PET drugs. The regulations are intended to ensure that PET drugs meet the safety and quality assurance requirements of the Federal Food, Drug, and Cosmetic Act. The new regulation became effective December 12, 2011, but the FDA used regulatory discretion to allow new drug applications and abbreviated new drug applications to be filed until June 12, 2012, without interruption of the existing PET drug production for human use. The production of PET drugs for both clinical use and clinical research use are outlined in this continuing education module, including an overview of specific requirements for compliance. Additionally, FDA preapproval inspections and postapproval reporting requirements are reviewed. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  20. Transporter biology in drug approval: regulatory aspects.

    PubMed

    Maeda, Kazuya; Sugiyama, Yuichi

    2013-01-01

    Previous in vitro and clinical research have indicated that a wide variety of drug transporters as well as metabolic enzymes dominate the pharmacokinetics of drugs and that some drugs modified the expression/function of drug transporters in humans, which lead to the altered pharmacokinetics and subsequent pharmacological/toxicological effects. Thus, regulatory authorities in US and EU have recently emphasized the needs to evaluate the risk of transporter-mediated drug-drug interactions (DDIs) in the (draft) guidance for pharmaceutical industries. The revised guidance includes the key transporters governing pharmacokinetics of drugs and decision trees to determine whether NMEs are substrates or inhibitors of each key transporter and when an in vivo clinical study is needed. In the evaluation of the potency of clinical DDIs, estimation of the inhibitor concentration at the target site is essential, but difficult since its direct measurement is almost impossible. Thus, people are now discussing what kind of inhibitor concentration should be used and how much is the appropriate cutoff value of the ratio of plasma AUC in the presence of inhibitor drugs to that in its absence (AUCR) to avoid false-negative predictions and maximize prediction accuracy. This minireview briefly summarizes the current status of the criteria for risk management of transporter-mediated DDIs in the regulatory guidelines, and describes scientific achievements that may affect regulatory decisions. Target transporters include OATP1B1 (SLCO1B1) and OATP1B3 (SLCO1B3) in the liver, and OAT1 (SLC22A6), OAT3 (SLC22A8), OCT2 (SLC22A2), MATE1 (SLC47A1), and MATE2-K (SLC47A2) in the kidney, and MDR1 (ABCB1) in the intestine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  1. Industrial natural product chemistry for drug discovery and development.

    PubMed

    Bauer, Armin; Brönstrup, Mark

    2014-01-01

    Covering: up to March 2013. In addition to their prominent role in basic biological and chemical research, natural products are a rich source of commercial products for the pharmaceutical and other industries. Industrial natural product chemistry is of fundamental importance for successful product development, as the vast majority (ca. 80%) of commercial drugs derived from natural products require synthetic efforts, either to enable economical access to bulk material, and/or to optimize drug properties through structural modifications. This review aims to illustrate issues on the pathway from lead to product, and how they have been successfully addressed by modern natural product chemistry. It is focused on natural products of current relevance that are, or are intended to be, used as pharmaceuticals.

  2. Natural production of biological optical systems

    NASA Astrophysics Data System (ADS)

    Choi, Seung Ho; Kim, Young L.

    2015-03-01

    Synthesis and production in nature often provide ideas to design and fabricate advanced biomimetic photonic materials and structures, leading to excellent physical properties and enhanced performance. In addition, the recognition and utilization of natural or biological substances have been typical routes to develop biocompatible and biodegradable materials for medical applications. In this respect, biological lasers utilizing such biomaterials and biostructures have been received considerable attention, given a variety of implications and potentials for bioimaging, biosensing, implantation, and therapy. However, without relying on industrial facilities, eco-friendly massive production of such optical components or systems has not yet been investigated. We show examples of bioproduction of biological lasers using agriculture and fisheries. We anticipate that such approaches will open new possibilities for scalable eco-friendly `green' production of biological photonics components and systems.

  3. [System biology and synthetic biology modify drug discovery and development].

    PubMed

    Haiech, Jacques; Ranjeva, Raoul; Kilhoffer, Marie-Claude

    2012-02-01

    Life Sciences are built on observations. Right now, a more systemic approach allowing to integrate the different organizational levels in Biology is emerging. Such an approach uses a set of technologies and strategies allowing to build models that appear to be more and more predictive (omics, bioinformatics, integrative biology, computational biology…). Those models accelerate the rational development of new therapies avoiding an engineering based only on trials and errors. This approach both holistic and predictive radically modifies the discovery and development modalities used today in health industries. Moreover, because of the apparition of new jobs at the interface of disciplines, of private and public sectors and of life sciences and engineering sciences, this implies to rethink the training programs in both their contents and their pedagogical tools.

  4. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... requirements for biological products held by the Strategic National Stockpile. 610.68 Section 610.68 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS GENERAL BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.68 Exceptions or alternatives to labeling...

  5. Natural product synthesis at the interface of chemistry and biology

    PubMed Central

    2014-01-01

    Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences. PMID:25043880

  6. Natural product synthesis at the interface of chemistry and biology.

    PubMed

    Hong, Jiyong

    2014-08-11

    Nature has evolved to produce unique and diverse natural products that possess high target affinity and specificity. Natural products have been the richest sources for novel modulators of biomolecular function. Since the chemical synthesis of urea by Wöhler, organic chemists have been intrigued by natural products, leading to the evolution of the field of natural product synthesis over the past two centuries. Natural product synthesis has enabled natural products to play an essential role in drug discovery and chemical biology. With the introduction of novel, innovative concepts and strategies for synthetic efficiency, natural product synthesis in the 21st century is well poised to address the challenges and complexities faced by natural product chemistry and will remain essential to progress in biomedical sciences. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. 9 CFR 114.6 - Mixing biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Mixing biological products. 114.6 Section 114.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... BIOLOGICAL PRODUCTS § 114.6 Mixing biological products. Each biological product, when in liquid form, shall...

  8. Is biological aging accelerated in drug addiction?

    PubMed

    Bachi, Keren; Sierra, Salvador; Volkow, Nora D; Goldstein, Rita Z; Alia-Klein, Nelly

    2017-02-01

    Drug-addiction may trigger early onset of age-related disease, due to drug-induced multi-system toxicity and perilous lifestyle, which remains mostly undetected and untreated. We present the literature on pathophysiological processes that may hasten aging and its relevance to addiction, including: oxidative stress and cellular aging, inflammation in periphery and brain, decline in brain volume and function, and early onset of cardiac, cerebrovascular, kidney, and liver disease. Timely detection of accelerated aging in addiction is crucial for the prevention of premature morbidity and mortality.

  9. Novel opportunities for computational biology and sociology in drug discovery☆

    PubMed Central

    Yao, Lixia; Evans, James A.; Rzhetsky, Andrey

    2013-01-01

    Current drug discovery is impossible without sophisticated modeling and computation. In this review we outline previous advances in computational biology and, by tracing the steps involved in pharmaceutical development, explore a range of novel, high-value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery. These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use. Computation can also be used to model research teams and innovative regions and to estimate the value of academy–industry links for scientific and human benefit. Attention to these opportunities could promise punctuated advance and will complement the well-established computational work on which drug discovery currently relies. PMID:20349528

  10. Novel opportunities for computational biology and sociology in drug discovery

    PubMed Central

    Yao, Lixia

    2009-01-01

    Drug discovery today is impossible without sophisticated modeling and computation. In this review we touch on previous advances in computational biology and by tracing the steps involved in pharmaceutical development, we explore a range of novel, high value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery. These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use. Computation can also be used to model research teams and innovative regions and to estimate the value of academy-industry ties for scientific and human benefit. Attention to these opportunities could promise punctuated advance, and will complement the well-established computational work on which drug discovery currently relies. PMID:19674801

  11. Novel opportunities for computational biology and sociology in drug discovery.

    PubMed

    Yao, Lixia; Evans, James A; Rzhetsky, Andrey

    2009-09-01

    Current drug discovery is impossible without sophisticated modeling and computation. In this review we outline previous advances in computational biology and, by tracing the steps involved in pharmaceutical development, explore a range of novel, high-value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery. These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use. Computation can also be used to model research teams and innovative regions and to estimate the value of academy-industry links for scientific and human benefit. Attention to these opportunities could promise punctuated advance and will complement the well-established computational work on which drug discovery currently relies.

  12. Novel opportunities for computational biology and sociology in drug discovery.

    PubMed

    Yao, Lixia; Evans, James A; Rzhetsky, Andrey

    2010-04-01

    Current drug discovery is impossible without sophisticated modeling and computation. In this review we outline previous advances in computational biology and, by tracing the steps involved in pharmaceutical development,explore a range of novel, high-value opportunities for computational innovation in modeling the biological process of disease and the social process of drug discovery.These opportunities include text mining for new drug leads, modeling molecular pathways and predicting the efficacy of drug cocktails, analyzing genetic overlap between diseases and predicting alternative drug use.Computation can also be used to model research teams and innovative regions and to estimate the value of academy-industry links for scientific and human benefit. Attention to these opportunities could promise punctuated advance and will complement the well-established computational work on which drug discovery currently relies.

  13. On the biological activity of drug molecules: Busulfan and nabumetone

    NASA Astrophysics Data System (ADS)

    Novak, Igor; Kovač, Branka

    2010-10-01

    The electronic structures of drug molecules busulfan (BSU) and nabumetone (NAB) have been investigated by HeI and HeII UV photoelectron spectroscopy (UPS), quantum chemical calculations and virtual docking studies. Their biological activities are discussed in the framework of their electronic and molecular structures, reactivity and drug-enzyme binding.

  14. Synthetic biology advances for pharmaceutical production.

    PubMed

    Breitling, Rainer; Takano, Eriko

    2015-12-01

    Synthetic biology enables a new generation of microbial engineering for the biotechnological production of pharmaceuticals and other high-value chemicals. This review presents an overview of recent advances in the field, describing new computational and experimental tools for the discovery, optimization and production of bioactive molecules, and outlining progress towards the application of these tools to pharmaceutical production systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. 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.

  16. Synthetic biology of avermectin for production improvement and structure diversification.

    PubMed

    Zhuo, Ying; Zhang, Tao; Wang, Qi; Cruz-Morales, Pablo; Zhang, Buchang; Liu, Mei; Barona-Gómez, Francisco; Zhang, Lixin

    2014-03-01

    Natural products are still key sources of current clinical drugs and innovative therapeutic agents. Since wild-type microorganisms only produce natural products in very small quantities, yields of production strains need to be improved by breaking down the precise genetic and biochemical circuitry. Herein, we use avermectins as an example of production improvement and chemical structure diversification by synthetic biology. Avermectins are macrocyclic lactones produced by Streptomyces avermitilis and are well known and widely used for antiparasitic therapy. Given the importance of this molecule and its derivatives, many efforts and strategies were employed to improve avermectin production and generate new active analogues. This review describes the current status of synthetic strategies successfully applied for developing natural-product-producing strains and discusses future prospects for the application of enhanced avermectin production. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Drug Development Against Viral Diseases (Biological Testing)

    DTIC Science & Technology

    1992-02-01

    any. sip of infection or disese (11. Also, laboratory work with CCHF has beeni limited because accidental infections which have had serious or even fata...were unldrgoir. i,,¢rois. No leb’ons were found in submaxillary or sublingual salivary gland, kidney , heart, eye, lacrimal gland, thyroid, trachea, or...examined including kidney , lung, liver and brain. e. Active chemotherapeutic agents in the vaccinia tail lesion model. Most drugs tested in thit model gave

  18. The effect of network biology on drug toxicology.

    PubMed

    Gautier, Laurent; Taboureau, Olivier; Audouze, Karine

    2013-11-01

    The high failure rate of drug candidates due to toxicity, during clinical trials, is a critical issue in drug discovery. Network biology has become a promising approach, in this regard, using the increasingly large amount of biological and chemical data available and combining it with bioinformatics. With this approach, the assessment of chemical safety can be done across multiple scales of complexity from molecular to cellular and system levels in human health. Network biology can be used at several levels of complexity. This review describes the strengths and limitations of network biology. The authors specifically assess this approach across different biological scales when it is applied to toxicity. There has been much progress made with the amount of data that is generated by various omics technologies. With this large amount of useful data, network biology has the opportunity to contribute to a better understanding of a drug's safety profile. The authors believe that considering a drug action and protein's function in a global physiological environment may benefit our understanding of the impact some chemicals have on human health and toxicity. The next step for network biology will be to better integrate differential and quantitative data.

  19. [Interchangeability of biological drugs: considerations about the approval of biogeneric formulations in Chile].

    PubMed

    Saavedra S, Iván; Quiñones S, Luis

    2006-12-01

    Once drug patents expire, the health authorities can approve the registry of similar products. They must request to the manufacturer, the bibliographic background of the original product and the analytical results that certify drug quality. An inspection of the premises of the manufacturer is also required. The main goal of this approval is to decrease cost, considering that the original product is usually more expensive. This is a current situation due to the imminent expiration of the patents of many biopharmaceutical products. Therefore, in Chile, the Public Health (ISP) and the Ministry of Health should consider that for this kind of products, until now, there are no interchangeable generic drugs, and that the similar drugs that are offered have a different chemical composition, since they have been manufactured through different processes. In the case of biological drugs (e.g. erythropoietir, somatotropin, heparin) the quality and homogeneity depend from the manufacture process. Its complete composition can not be absolutely elucidated; therefore small impurities or conformational variants can elicit an altered immune response or unexpected adverse reactions. This indicates that the approval of a biogeneric drug requires in addition to pharmacokinetic studies, preclinical and clinical analytical studies such as physicochemical assays, biological and immunological test. This issues have been established by WHO and have been incorporated for the main drug registry entities all over the world (FDA, EMEA, ANVISA) to approve biogeneric products.

  20. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Packaging biological products. 112.6... § 112.6 Packaging biological products. (a) Each multiple-dose final container of a biological product... equipment. (e) Final containers of biological product prepared at a licensed establishment, or imported, in...

  1. Biological engineering for sustainable biomass production

    SciTech Connect

    Shen, S.

    1986-09-01

    A new discipline has evolved in efforts to engineer photosynthetic production systems that produce biomass feedstocks efficiently, economically and with minimal adverse environmental impact. In this talk an overview is given of how biological engineering systems are designed to produce energy and novel material products within the framework of existing market infrastructure. Practical examples of biological engineering systems which employ components based on genetic engineering, species propagation, modern agricultural techniques, chemical engineering, and mechanical engineering are analyzed for worldwide materials application and environmental conservation. 9 refs., 6 figs.

  2. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Reporting of biological product deviations by licensed manufacturers. 600.14 Section 600.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... addresses in § 600.2), or an electronic filing through CBER's Web site at http://www.fda.gov/cber/biodev...

  3. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Reporting of biological product deviations by licensed manufacturers. 600.14 Section 600.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... addresses in § 600.2), or an electronic filing through CBER's Web site at...

  4. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Reporting of biological product deviations by licensed manufacturers. 600.14 Section 600.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... addresses in § 600.2), or an electronic filing through CBER's Web site at...

  5. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Reporting of biological product deviations by licensed manufacturers. 600.14 Section 600.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... addresses in § 600.2), or an electronic filing through CBER's Web site at...

  6. 21 CFR 600.14 - Reporting of biological product deviations by licensed manufacturers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Reporting of biological product deviations by licensed manufacturers. 600.14 Section 600.14 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... addresses in § 600.2), or an electronic filing through CBER's Web site at...

  7. Orphan drugs: the question of products liability.

    PubMed

    Scharf, S F

    1985-01-01

    Orphan drugs, essential for the treatment of persons with rare diseases, generally are unprofitable for manufacturers to develop and market. While congressional and administrative efforts to promote the development of orphan drugs have met with modest success, application of products liability doctrine to orphan drug sponsors could subvert those efforts. This Note describes the provisions of the Orphan Drug Act and analyzes products liability law with respect to orphan drug litigation. It argues that the goals of tort law support the imposition of liability for design defect, failure to warn and negligence in testing. Finally, the Note acknowledges that liability costs create disincentives for orphan drug development and suggests mechanisms for reducing manufacturers' liability concerns.

  8. 75 FR 47605 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological..., Office of Vaccines Research and Review, Center for Biologics Evaluation and Research, FDA. FDA intends to...

  9. Pregnane X receptor and natural products: beyond drug-drug interactions.

    PubMed

    Staudinger, Jeff L; Ding, Xunshan; Lichti, Kristin

    2006-12-01

    The pregnane X receptor (PXR, NR1I2) is a member of the nuclear receptor superfamily that is activated by a myriad of compounds and natural products in clinical use. Activation of PXR represents the basis for several clinically important drug-drug interactions. Although PXR activation has undesirable effects in patients on combination therapy, it also mediates the hepatoprotective effects exhibited by some herbal remedies. This review focuses on PXR activation by natural products and the potential therapeutic opportunities presented. In particular, the biological effects of St. John's Wort, gugulipid, kava kava, Coleus forskolii, Hypoxis, Sutherlandia, qing hao, wu wei zi, gan cao and other natural products are discussed. The impact of these natural products on drug metabolism and hepatoprotection is highlighted in the context of activation and antagonism of PXR.

  10. Translating Stem Cell Biology Into Drug Discovery

    PubMed Central

    Singeç, Ilyas; Simeonov, Anton

    2016-01-01

    Pluripotent stem cell research has made extraordinary progress over the last decade. The robustness of nuclear reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) has created entirely novel opportunities for drug discovery and personalized regenerative medicine. Patient- and disease-specific iPSCs can be expanded indefinitely and differentiated into relevant cell types of different organ systems. As the utilization of iPSCs is becoming a key enabling technology across various scientific disciplines, there are still important challenges that need to be addressed. Here we review the current state and reflect on the issues that the stem cell and translational communities are facing in bringing iPSCs closer to clinical application. PMID:27774310

  11. Examining the production costs of antiretroviral drugs.

    PubMed

    Pinheiro, Eloan; Vasan, Ashwin; Kim, Jim Yong; Lee, Evan; Guimier, Jean Marc; Perriens, Joseph

    2006-08-22

    To present direct manufacturing costs and price calculations of individual antiretroviral drugs, enabling those responsible for their procurement to have a better understanding of the cost structure of their production, and to indicate the prices at which these antiretroviral drugs could be offered in developing country markets. Direct manufacturing costs and factory prices for selected first and second-line antiretroviral drugs were calculated based on cost structure data from a state-owned company in Brazil. Prices for the active pharmaceutical ingredients (API) were taken from a recent survey by the World Health Organization (WHO). The calculated prices for antiretroviral drugs are compared with quoted prices offered by privately-owned, for-profit manufacturers. The API represents the largest component of direct manufacturing costs (55-99%), while other inputs, such as salaries, equipment costs, and scale of production, have a minimal impact. The calculated prices for most of the antiretroviral drugs studied fall within the lower quartile of the range of quoted prices in developing country markets. The exceptions are those drugs, primarily for second-line therapy, for which the API is either under patent, in short supply, or in limited use in developing countries (e.g. abacavir, lopinavir/ritonavir, nelfinavir, saquinavir). The availability of data on the cost of antiretroviral drug production and calculation of factory prices under a sustainable business model provide benchmarks that bulk purchasers of antiretroviral drugs could use to negotiate lower prices. While truly significant price decreases for antiretroviral drugs will depend largely on the future evolution of API prices, the present study demonstrates that for several antiretroviral drugs price reduction is currently possible. Whether or not these reductions materialize will depend on the magnitude of indirect cost and profit added by each supplier over the direct production costs. The ability to

  12. 77 FR 30887 - Amendments to Sterility Test Requirements for Biological Products; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-24

    ...The Food and Drug Administration (FDA) is correcting a final rule that appeared in the Federal Register of May 3, 2012. (77 FR 26162). The final rule provides manufacturers of biological products greater flexibility, as appropriate, and encourages use of the most appropriate and state-of-the-art test methods for assuring the safety of biological products. The rule was published with an......

  13. 78 FR 5465 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-25

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... strains to be included in the influenza virus vaccine for the 2013- 2014 influenza season. FDA intends to...

  14. 78 FR 60884 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological... of Retroviruses and Laboratory of Immunoregulation, Division of Viral Products, Office of Vaccines...

  15. 75 FR 17929 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-08

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... circovirus type 1 (PCV 1) in Rotarix, a U.S. licensed vaccine manufactured by GlaxoSmithKline and indicated...

  16. 75 FR 2876 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-19

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... selection of strains to be included in the influenza virus vaccine for the 2010 - 2011 influenza season. FDA...

  17. 76 FR 44016 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-22

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... portion of the meeting will be closed to the public. Name of Committee: Vaccines and Related Biological..., Division of Bacterial, Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center...

  18. 77 FR 63839 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-17

    ... HUMAN SERVICES Food and Drug Administration Vaccines and Related Biological Products Advisory Committee... be open to the public. Name of Committee: Vaccines and Related Biological Products Advisory Committee... immunogenicity of an Influenza A (H5N1) Virus Monovalent Vaccine manufactured by GlaxoSmithKline. On November 15...

  19. Microbial Production of Isoprenoids Enabled by Synthetic Biology

    PubMed Central

    Immethun, Cheryl M.; Hoynes-O’Connor, Allison G.; Balassy, Andrea; Moon, Tae Seok

    2013-01-01

    Microorganisms transform inexpensive carbon sources into highly functionalized compounds without toxic by-product generation or significant energy consumption. By redesigning the natural biosynthetic pathways in an industrially suited host, microbial cell factories can produce complex compounds for a variety of industries. Isoprenoids include many medically important compounds such as antioxidants and anticancer and antimalarial drugs, all of which have been produced microbially. While a biosynthetic pathway could be simply transferred to the production host, the titers would become economically feasible when it is rationally designed, built, and optimized through synthetic biology tools. These tools have been implemented by a number of research groups, with new tools pledging further improvements in yields and expansion to new medically relevant compounds. This review focuses on the microbial production of isoprenoids for the health industry and the advancements though synthetic biology. PMID:23577007

  20. Design of future rabies biologics and antiviral drugs.

    PubMed

    Smith, Todd G; Wu, Xianfu; Franka, Richard; Rupprecht, Charles E

    2011-01-01

    In recent years, no major paradigm shifts have occurred in the utilization of new products for the prevention and control of rabies. Development of new cost-effective rabies biologics and antiviral drugs is critical in continuing to prevent and reduce disease. Current rabies vaccines are highly effective but have developed largely based on technical improvements in the vaccine industry. In the future, alternative approaches for improved vaccines, including novel avirulent rabies virus (RABV) vectors, should be pursued. Any rabies vaccine that is effective without the need for rabies immune globulin (RIG) will contribute fundamentally to disease prevention by reducing the cost and complexity of postexposure prophylaxis (PEP). The lack of high quality, affordable RIG is a continuing problem. Virus-specific monoclonal antibodies (mAbs) will soon fulfill the PEP requirement for passive immunity, currently met with RIG. Several relevant strategies for mAb production, including use of transgenic mice, humanization of mouse mAbs, and generation of human immune libraries, are underway. As a result of successful PEP and pre-exposure prophylaxis in developed countries, until recently, no significant focused efforts have been devoted to RABV-specific antiviral agents. To date, combination therapy including broad spectrum antiviral agents has been successful in only one case, and reports of antiviral activity are often conflicting. Current antiviral strategies target either the nucleoprotein or phosphoprotein, but drugs targeting the viral polymerase should be considered. Considering the lag from creation of new concepts to experimental development and clinical trials, many years will likely elapse between today's ideas and tomorrow's practices. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. RNA interference: from biology to drugs and therapeutics.

    PubMed

    Appasani, Krishnarao

    2004-07-01

    RNA interference (RNAi) is a newly discovered and popular technology platform among researchers not only in the fields of RNA biology and molecular cell biology. It has created excitement in clinical sciences such as oncology, neurology, endocrinology, infectious diseases and drug discovery. There is an urgent need to educate and connect academic and industry researchers for the purpose of knowledge transfer. Thus, GeneExpression Systems of Waltham organized its Second International Conference in Waltham City (May 2-4, 2004, MA, USA) on the theme of 'RNA interference: From Biology to Drugs & Therapeutics.' About 200 participants and 32 speakers attended this two and half-day event which was arranged in six scientific and three technology sessions and ended with a panel discussion. This report covers a few representative talks from academia, biotech and the drug industry.

  2. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Preparation of experimental biological... PRODUCTION, DISTRIBUTION, AND EVALUATION OF BIOLOGICAL PRODUCTS PRIOR TO LICENSING § 103.1 Preparation of experimental biological products. Except as otherwise provided in this section, experimental biological...

  3. Counting on natural products for drug design

    NASA Astrophysics Data System (ADS)

    Rodrigues, Tiago; Reker, Daniel; Schneider, Petra; Schneider, Gisbert

    2016-06-01

    Natural products and their molecular frameworks have a long tradition as valuable starting points for medicinal chemistry and drug discovery. Recently, there has been a revitalization of interest in the inclusion of these chemotypes in compound collections for screening and achieving selective target modulation. Here we discuss natural-product-inspired drug discovery with a focus on recent advances in the design of synthetically tractable small molecules that mimic nature's chemistry. We highlight the potential of innovative computational tools in processing structurally complex natural products to predict their macromolecular targets and attempt to forecast the role that natural-product-derived fragments and fragment-like natural products will play in next-generation drug discovery.

  4. 21 CFR 211.134 - Drug product inspection.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Drug product inspection. 211.134 Section 211.134 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... § 211.134 Drug product inspection. (a) Packaged and labeled products shall be examined during...

  5. 21 CFR 211.134 - Drug product inspection.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Drug product inspection. 211.134 Section 211.134 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... § 211.134 Drug product inspection. (a) Packaged and labeled products shall be examined during...

  6. 21 CFR 211.134 - Drug product inspection.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Drug product inspection. 211.134 Section 211.134 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS... § 211.134 Drug product inspection. (a) Packaged and labeled products shall be examined during...

  7. 21 CFR 332.30 - Labeling of antiflatulent drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of antiflatulent drug products. 332.30 Section 332.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 332.30 Labeling of antiflatulent drug products....

  8. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... for biological products held by the Strategic National Stockpile. 610.68 Section 610.68 Food and Drugs... BIOLOGICAL PRODUCTS STANDARDS Labeling Standards § 610.68 Exceptions or alternatives to labeling requirements for biological products held by the Strategic National Stockpile. (a) The appropriate FDA Center...

  9. Nanomaterial Drug Products: Manufacturing and Analytical Perspectives.

    PubMed

    Sayes, Christie M; Aquino, Grace V; Hickey, Anthony J

    2017-01-01

    The increasing use of nanotechnology, including nanoparticles, in the preparation of drug products requires both manufacturing and analytical considerations in order to establish the quality metrics suitable for performance and risk assessment. A range of different nanoparticle systems exists including (but not limited to) nano-drugs, nano-additives, and nano-carriers. These systems generally require more complex production and characterization strategies than conventional pharmaceutical dosage forms. The advantage of using nanoparticle systems in pharmaceutical science is that the effective and desired function of the material can be designed through modern manufacturing processes. This paper offers a systematic nomenclature which allows for greater understanding of the drug product under evaluation based on available data from other nanoparticle reports. Analytical considerations of nano-drugs, nano-additives, and nano-carriers and the way in which they are measured are directly connected to quality control. Ultimately, the objective is to consider the entire nano-drug, nano-additive, and nano-carrier product life cycle with respect to its manufacture, use, and eventual fate. The tools and approaches to address the needs of these products exist; it should be the task of the pharmaceutical scientists and those in related disciplines to increase their understanding of nanomedicine and its novel products.

  10. Drug product selection and the law.

    PubMed

    Fink, J L

    1979-01-01

    Pharmacists are reported to be concerned about their liability exposure when engaging in drug product selection. A review of the elements of a suit for negligence is presented along with a brief application of those principles to a suit for negligence in drug product selection. The role of the manufacturer in assuring product integrity is emphasized. A liability suit also could be based on contract law principles, which are discussed. A few reasons that may explain why no suit has been successfully maintained in this area to date are presented. Finally, discussion of legislative provisions that attempt to contain the pharmacist's liability exposure are considered.

  11. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Exceptions or alternatives to labeling requirements for biological products held by the Strategic National Stockpile. 610.68 Section 610.68 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS...

  12. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Exceptions or alternatives to labeling requirements for biological products held by the Strategic National Stockpile. 610.68 Section 610.68 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS...

  13. 21 CFR 610.68 - Exceptions or alternatives to labeling requirements for biological products held by the Strategic...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Exceptions or alternatives to labeling requirements for biological products held by the Strategic National Stockpile. 610.68 Section 610.68 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS...

  14. Systems biology solutions for biochemical production challenges.

    PubMed

    Hansen, Anne Sofie Lærke; Lennen, Rebecca M; Sonnenschein, Nikolaus; Herrgård, Markus J

    2017-06-01

    There is an urgent need to significantly accelerate the development of microbial cell factories to produce fuels and chemicals from renewable feedstocks in order to facilitate the transition to a biobased society. Methods commonly used within the field of systems biology including omics characterization, genome-scale metabolic modeling, and adaptive laboratory evolution can be readily deployed in metabolic engineering projects. However, high performance strains usually carry tens of genetic modifications and need to operate in challenging environmental conditions. This additional complexity compared to basic science research requires pushing systems biology strategies to their limits and often spurs innovative developments that benefit fields outside metabolic engineering. Here we survey recent advanced applications of systems biology methods in engineering microbial production strains for biofuels and -chemicals. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Biological products; exemption. 106.1... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR BIOLOGICAL PRODUCTS USED IN DEPARTMENT PROGRAMS OR UNDER DEPARTMENT CONTROL OR SUPERVISION § 106.1 Biological products...

  16. 9 CFR 114.17 - Rebottling of biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Rebottling of biological products. 114.17 Section 114.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.17 Rebottling of biological products. The Administrator may...

  17. 9 CFR 114.18 - Reprocessing of biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Reprocessing of biological products. 114.18 Section 114.18 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.18 Reprocessing of biological products. The Administrator may...

  18. 9 CFR 114.18 - Reprocessing of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Reprocessing of biological products. 114.18 Section 114.18 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... REQUIREMENTS FOR BIOLOGICAL PRODUCTS § 114.18 Reprocessing of biological products. The Administrator may...

  19. Aging Biology and Novel Targets for Drug Discovery

    PubMed Central

    McLachlan, Andrew J.; Quinn, Ronald J.; Simpson, Stephen J.; de Cabo, Rafael

    2012-01-01

    Despite remarkable technological advances in genetics and drug screening, the discovery of new pharmacotherapies has slowed and new approaches to drug development are needed. Research into the biology of aging is generating many novel targets for drug development that may delay all age-related diseases and be used long term by the entire population. Drugs that successfully delay the aging process will clearly become “blockbusters.” To date, the most promising leads have come from studies of the cellular pathways mediating the longevity effects of caloric restriction (CR), particularly target of rapamycin and the sirtuins. Similar research into pathways governing other hormetic responses that influence aging is likely to yield even more targets. As aging becomes a more attractive target for drug development, there will be increasing demand to develop biomarkers of aging as surrogate outcomes for the testing of the effects of new agents on the aging process. PMID:21693687

  20. Marine natural products: a new wave of drugs?

    PubMed Central

    Montaser, Rana; Luesch, Hendrik

    2011-01-01

    The largely unexplored marine world that presumably harbors the most biodiversity may be the vastest resource to discover novel ‘validated’ structures with novel modes of action that cover biologically relevant chemical space. Several challenges, including the supply problem and target identification, need to be met for successful drug development of these often complex molecules; however, approaches are available to overcome the hurdles. Advances in technologies such as sampling strategies, nanoscale NMR for structure determination, total chemical synthesis, fermentation and biotechnology are all crucial to the success of marine natural products as drug leads. We illustrate the high degree of innovation in the field of marine natural products, which in our view will lead to a new wave of drugs that flow into the market and pharmacies in the future. PMID:21882941

  1. Yeast Synthetic Biology Platform Generates Novel Chemical Structures as Scaffolds for Drug Discovery

    PubMed Central

    2014-01-01

    Synthetic biology has been heralded as a new bioengineering platform for the production of bulk and specialty chemicals, drugs, and fuels. Here, we report for the first time a series of 74 novel compounds produced using a combinatorial genetics approach in baker’s yeast. Based on the concept of “coevolution” with target proteins in an intracellular primary survival assay, the identified, mostly scaffold-sized (200–350 MW) compounds, which displayed excellent biological activity, can be considered as prevalidated hits. Of the molecules found, >75% have not been described previously; 20% of the compounds exhibit novel scaffolds. Their structural and physicochemical properties comply with established rules of drug- and fragment-likeness and exhibit increased structural complexities compared to synthetically produced fragments. In summary, the synthetic biology approach described here represents a completely new, complementary strategy for hit and early lead identification that can be easily integrated into the existing drug discovery process. PMID:24742115

  2. Data-intensive drug development in the information age: applications of Systems Biology/Pharmacology/Toxicology.

    PubMed

    Kiyosawa, Naoki; Manabe, Sunao

    2016-01-01

    Pharmaceutical companies continuously face challenges to deliver new drugs with true medical value. R&D productivity of drug development projects depends on 1) the value of the drug concept and 2) data and in-depth knowledge that are used rationally to evaluate the drug concept's validity. A model-based data-intensive drug development approach is a key competitive factor used by innovative pharmaceutical companies to reduce information bias and rationally demonstrate the value of drug concepts. Owing to the accumulation of publicly available biomedical information, our understanding of the pathophysiological mechanisms of diseases has developed considerably; it is the basis for identifying the right drug target and creating a drug concept with true medical value. Our understanding of the pathophysiological mechanisms of disease animal models can also be improved; it can thus support rational extrapolation of animal experiment results to clinical settings. The Systems Biology approach, which leverages publicly available transcriptome data, is useful for these purposes. Furthermore, applying Systems Pharmacology enables dynamic simulation of drug responses, from which key research questions to be addressed in the subsequent studies can be adequately informed. Application of Systems Biology/Pharmacology to toxicology research, namely Systems Toxicology, should considerably improve the predictability of drug-induced toxicities in clinical situations that are difficult to predict from conventional preclinical toxicology studies. Systems Biology/Pharmacology/Toxicology models can be continuously improved using iterative learn-confirm processes throughout preclinical and clinical drug discovery and development processes. Successful implementation of data-intensive drug development approaches requires cultivation of an adequate R&D culture to appreciate this approach.

  3. 21 CFR 341.72 - Labeling of antihistamine drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of antihistamine drug products. 341.72 Section 341.72 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  4. 21 CFR 341.76 - Labeling of bronchodilator drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of bronchodilator drug products. 341.76 Section 341.76 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  5. 21 CFR 341.76 - Labeling of bronchodilator drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of bronchodilator drug products. 341.76 Section 341.76 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  6. 21 CFR 341.72 - Labeling of antihistamine drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Labeling of antihistamine drug products. 341.72 Section 341.72 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  7. 21 CFR 341.72 - Labeling of antihistamine drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of antihistamine drug products. 341.72 Section 341.72 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  8. 21 CFR 341.72 - Labeling of antihistamine drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of antihistamine drug products. 341.72 Section 341.72 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  9. 21 CFR 341.72 - Labeling of antihistamine drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of antihistamine drug products. 341.72 Section 341.72 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS...

  10. 21 CFR 333.350 - Labeling of acne drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Labeling of acne drug products. 333.350 Section 333.350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  11. 21 CFR 333.350 - Labeling of acne drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of acne drug products. 333.350 Section 333.350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  12. Biological Markers of Drug Use in the Club Setting*

    PubMed Central

    Miller, Brenda A.; Furr-Holden, Debra; Johnson, Mark B.; Holder, Harold; Voas, Robert; Keagy, Carolyn

    2009-01-01

    Objective: The prevalence of drug and alcohol use among patrons of clubs featuring electronic music dance events was determined by using biological assays at entrance and exit. Method: Using a portal methodology that randomly selects groups of patrons on arrival at clubs, oral assays for determining level and type of drug use and level of alcohol use were obtained anonymously. Patrons provided self-reported data on their personal characteristics. A total of 362 patrons were interviewed at entrance and provided oral assay data, and 277 provided data at both entrance and exit. Results: Overall, one quarter of all patrons surveyed at entrance were positive for some type of drug use. Based on our exit sample, one quarter of the sample was positive at exit. Individual drugs most prevalent at entrance or exit included cocaine, marijuana, and amphetamines/stimulants. Only the amphetamine/stimulant category increased significantly from entrance to exit. Drug-using patrons arrive at the club already using drugs; few patrons arrive with no drug use and leave with detectable levels of drug use. Clubs vary widely in drug-user prevalence at entrance and exit, suggesting that both events and club policies and practices may attract different types of patrons. Approximately one half of the total entrance sample arrived with detectable alcohol use, and nearly one fifth arrived with an estimated blood alcohol concentration of .08 or greater. Based on our exit sample data, one third of patrons were intoxicated, and slightly less than one fifth were using both drugs and alcohol at exit. Clubs attract a wide array of emerging adults, with both genders and all ethnicities well represented. Clubs also attract emerging adults who are not in college and who are working full time. Conclusions: At clubs featuring electronic music dance events, drug use and/or high levels of alcohol use were detected using biological assays from patrons at entrance and exit from the clubs. Thus, these clubs

  13. 9 CFR 113.50 - Ingredients of biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Ingredients of biological products... REQUIREMENTS Ingredient Requirements § 113.50 Ingredients of biological products. All ingredients used in a licensed biological product shall meet accepted standards of purity and quality; shall be sufficiently...

  14. 9 CFR 113.50 - Ingredients of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Ingredients of biological products... REQUIREMENTS Ingredient Requirements § 113.50 Ingredients of biological products. All ingredients used in a licensed biological product shall meet accepted standards of purity and quality; shall be sufficiently...

  15. Antroquinonol A: Scalable Synthesis and Preclinical Biology of a Phase 2 Drug Candidate

    PubMed Central

    2015-01-01

    The fungal-derived Taiwanese natural product antroquinonol A has attracted both academic and commercial interest due to its reported exciting biological properties. This reduced quinone is currently in phase II trials (USA and Taiwan) for the treatment of non-small-cell lung carcinoma (NSCLC) and was recently granted orphan drug status by the FDA for the treatment of pancreatic cancer and acute myeloid leukemia. Pending successful completion of human clinical trials, antroquinonol is expected to be commercialized under the trade name Hocena. A synthesis-enabled biological re-examination of this promising natural product, however, reveals minimal in vitro and in vivo antitumor activity in preclinical models. PMID:27163023

  16. Drug discovery in advanced prostate cancer: translating biology into therapy.

    PubMed

    Yap, Timothy A; Smith, Alan D; Ferraldeschi, Roberta; Al-Lazikani, Bissan; Workman, Paul; de Bono, Johann S

    2016-10-01

    Castration-resistant prostate cancer (CRPC) is associated with a poor prognosis and poses considerable therapeutic challenges. Recent genetic and technological advances have provided insights into prostate cancer biology and have enabled the identification of novel drug targets and potent molecularly targeted therapeutics for this disease. In this article, we review recent advances in prostate cancer target identification for drug discovery and discuss their promise and associated challenges. We review the evolving therapeutic landscape of CRPC and discuss issues associated with precision medicine as well as challenges encountered with immunotherapy for this disease. Finally, we envision the future management of CRPC, highlighting the use of circulating biomarkers and modern clinical trial designs.

  17. [Chronopharmacology--importance of the biological clock in drug treatment].

    PubMed

    Lemmer, Björn

    2009-11-01

    Nearly all functions of living creatures including man exhibit significant daily variations. Today, internal biological clocks are traced down to the molecular level. In man pathophysiological events such as coronary infarction, angina pectoris, asthma attacks and gastro-intestinal ulcers do not occur at random but exhibit a clear-cut daily rhythmic pattern. It is, therefore, not surprising that the pharmacokinetics as well the effects and side-effects of drugs can vary significantly with the time of day as has been documented in many clinical studies. Thus, "time-of-day" has to be regarded as an important factor to evaluate drug efficacy and its therapeutic window.

  18. 75 FR 61497 - Approval Pathway for Biosimilar and Interchangeable Biological Products; Public Hearing; Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-05

    ... drug, thereby saving time and resources and avoiding unnecessary duplication of human or animal testing.... Most biological products are produced in a living system such as a microorganism, or plant or animal cells, whereas small molecule drugs are typically manufactured through chemical synthesis. Section 351(k...

  19. Synthetic Biological Approaches to Natural Product Biosynthesis

    PubMed Central

    Winter, Jaclyn M; Tang, Yi

    2012-01-01

    Small molecules produced in Nature continue to be an inspiration for the development of new therapeutic agents. These natural products possess exquisite chemical diversity, which gives rise to their wide range of biological activities. In their host organism, natural products are assembled and modified by dedicated biosynthetic pathways that Nature has meticulously developed. Often times, the complex structures or chemical modifications instated by these pathways are difficult to replicate using traditional synthetic methods. An alternative approach for creating or enhancing the structural variation of natural products is through combinatorial biosynthesis. By rationally reprogramming and manipulating the biosynthetic machinery responsible for their production, unnatural metabolites that were otherwise inaccessible can be obtained. Additionally, new chemical structures can be synthesized or derivatized by developing the enzymes that carry out these complicated chemical reactions into biocatalysts. In this review, we will discuss a variety of combinatorial biosynthetic strategies, their technical challenges, and highlight some recent (since 2007) examples of rationally designed unnatural metabolites, as well as platforms that have been established for the production and modification of clinically important pharmaceutical compounds. PMID:22221832

  20. Prescription Drugs, Over-the-Counter Drugs, Supplements and Herbal Products

    MedlinePlus

    ... at risk? Zika virus and pregnancy Folic acid Medicine safety and pregnancy Birth defects prevention Learn how ... the-counter drugs, supplements and herbal products Prescription drugs, over-the-counter drugs, supplements and herbal products ...

  1. Production and marketing of drugs in Brazil.

    PubMed

    Castelo, A; Colombo, A L; Holbrook, A M

    1991-01-01

    Brazil is typical of many developing countries in its struggle to provide basic healthcare for its citizens in face of national economic instability. Since pharmaceuticals represent a major component of modern healthcare, their production, regulation and use become an area of concern. It appears that any change in the current production patterns will require a major commitment from governments, understanding external economic pressures. There are pros and cons in a policy directed towards pharmaceutical self-sufficiency. Aside from production, efforts directed towards extending access to essential drugs and improving the appropriateness of use, would appear to be warranted.

  2. Defining Patient Centric Pharmaceutical Drug Product Design.

    PubMed

    Stegemann, Sven; Ternik, Robert L; Onder, Graziano; Khan, Mansoor A; van Riet-Nales, Diana A

    2016-09-01

    The term "patient centered," "patient centric," or "patient centricity" is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved.

  3. Influencing upon Mammalian Radioresistance with Biologically Active Drug Respistim Plus

    DTIC Science & Technology

    2009-10-01

    RTO-MP-HFM-181 3 - 1 Influencing upon Mammalian Radioresistance with Biologically Active Drug Respistim Plus Leut . Iv. Kindekov MD Vl...Vasilieva Assoc. Prof. M. Aljakov MD PhD, Coll. Assoc. Prof. Pl. Petrunov MD, PhD ivankindekov@gmail.com ABSTRACT Radiobiology is a medical...success. Protection of the hematopoietic and immune systems is a critical area for restoring organism after irradiation. Some radioprotective

  4. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL... products which are neither composed of nor prepared with organisms or antigens used in biologicals...

  5. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... spray) and products used in automatic vaccinating systems (including but not limited to pneumatic beak... apply to licensed veterinary practitioners administering or dispensing biological products in the course...

  6. Antimycobacterial Metabolism: Illuminating Mycobacterium tuberculosis Biology and Drug Discovery.

    PubMed

    Awasthi, Divya; Freundlich, Joel S

    2017-09-01

    Bacteria are capable of performing a number of biotransformations that may activate or deactivate xenobiotics. Recent efforts have utilized metabolomics techniques to study the fate of small-molecule antibacterials within the targeted organism. Examples involving Mycobacterium tuberculosis are reviewed and analyzed with regard to the insights they provide as to both activation and deactivation of the antibacterial. The studies, in particular, shed light on biosynthetic transformations performed by M. tuberculosis while suggesting avenues for the evolution of chemical tools, highlighting potential areas for drug discovery, and mechanisms of approved drugs. A two-pronged approach investigating the metabolism of antibacterials within both the host and bacterium is outlined and will be of value to both the chemical biology and drug discovery fields. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Electrophoretic deposition of biological macromolecules, drugs, and cells.

    PubMed

    Seuss, Sigrid; Boccaccini, Aldo R

    2013-10-14

    The use of biological entities in biotechnology and the biomedical field is of great interest as the biocompatibility and the functionality of naturally occurring is usually higher compared to other biomaterials, for example, synthetic polymers. Processing of natural biomolecules, including proteins like collagen and also living cells and bacteria, to develop medical devices, bioactive coatings, functionalized implants, tissue scaffolds, or biosensors, is however challenging. Electrophoretic deposition, a technique that takes advantage of the presence of charged particles or molecules in suitable solvents, is a low-temperature process suitable for manipulating a wide range of biomolecules and biological entities preserving their bioactivity, which could be otherwise lost by processing at high temperatures. Another advantage of EPD is the possibility to use aqueous suspensions to process biological entities given that organic solvents also could lead to degradation of biomolecules. This paper gives an overview of the available literature on the application of EPD to process different biomolecules and biological entities, like proteins, bacteria cells, hyaluronic acid, and therapeutic drugs, aiming at using such biomaterials in numerous applications ranging from biosensors to orthopedic implants, tissue scaffolds, and drug delivery devices.

  8. [Key technologies in synthetic biology of natural products].

    PubMed

    Kuang, Xue-Jun; Zou, Li-Qiu; Li, Ying; Sun, Chao; Chen, Shi-Lin

    2016-11-01

    Natural products with complex and diverse structures are the major sources of new drugs. The biosynthesis of natural products is considered to be one of the best ways to solve the problems of complex and scarce natural products. DNA assembly technology and genome editing technology are two key technologies in the emerging interdisciplinary field of synthetic biology. A number of novel DNA assembly methods developed in the last few years have paved the way for the engineering of high molecular weight DNA molecules, including whole genomes, hence, it can realize the reconstruction of the metabolic pathways and speed up optimization process. A wide variety of new tools for microbial genome editing will be applied widely to modify the chassis genome to increase its adaptation with the exogenetic pathways. This article summarized the latest advance with respect to DNA assembly and genome editing, which aims to provide help for reconstruction and optimization of the synthetic biological systems of natural products. Copyright© by the Chinese Pharmaceutical Association.

  9. Systems Biology of Microbial Exopolysaccharides Production

    PubMed Central

    Ates, Ozlem

    2015-01-01

    Exopolysaccharides (EPSs) produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture, and medicine. EPSs are mainly associated with high-value applications, and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However, only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover, a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore, a systems-based approach constitutes an important step toward understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism, and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan, and dextran. PMID:26734603

  10. Systems Biology of Microbial Exopolysaccharides Production.

    PubMed

    Ates, Ozlem

    2015-01-01

    Exopolysaccharides (EPSs) produced by diverse group of microbial systems are rapidly emerging as new and industrially important biomaterials. Due to their unique and complex chemical structures and many interesting physicochemical and rheological properties with novel functionality, the microbial EPSs find wide range of commercial applications in various fields of the economy such as food, feed, packaging, chemical, textile, cosmetics and pharmaceutical industry, agriculture, and medicine. EPSs are mainly associated with high-value applications, and they have received considerable research attention over recent decades with their biocompatibility, biodegradability, and both environmental and human compatibility. However, only a few microbial EPSs have achieved to be used commercially due to their high production costs. The emerging need to overcome economic hurdles and the increasing significance of microbial EPSs in industrial and medical biotechnology call for the elucidation of the interrelations between metabolic pathways and EPS biosynthesis mechanism in order to control and hence enhance its microbial productivity. Moreover, a better understanding of biosynthesis mechanism is a significant issue for improvement of product quality and properties and also for the design of novel strains. Therefore, a systems-based approach constitutes an important step toward understanding the interplay between metabolism and EPS biosynthesis and further enhances its metabolic performance for industrial application. In this review, primarily the microbial EPSs, their biosynthesis mechanism, and important factors for their production will be discussed. After this brief introduction, recent literature on the application of omics technologies and systems biology tools for the improvement of production yields will be critically evaluated. Special focus will be given to EPSs with high market value such as xanthan, levan, pullulan, and dextran.

  11. Biological factors that impinge on Chagas disease drug development.

    PubMed

    Francisco, Amanda F; Jayawardhana, Shiromani; Lewis, Michael D; Taylor, Martin C; Kelly, John M

    2017-08-23

    Chagas disease is caused by infection with the insect-transmitted protozoan Trypanosoma cruzi, and is the most important parasitic infection in Latin America. The current drugs, benznidazole and nifurtimox, are characterized by limited efficacy and toxic side-effects, and treatment failures are frequently observed. The urgent need for new therapeutic approaches is being met by a combined effort from the academic and commercial sectors, together with major input from not-for-profit drug development consortia. With the disappointing outcomes of recent clinical trials against chronic Chagas disease, it has become clear that an incomplete understanding of parasite biology and disease pathogenesis is impacting negatively on the development of more effective drugs. In addition, technical issues, including difficulties in establishing parasitological cure in both human patients and animal models, have greatly complicated the assessment of drug efficacy. Here, we outline the major questions that need to be addressed and discuss technical innovations that can be exploited to accelerate the drug development pipeline.

  12. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1992-12-01

    Due to the abundant supply of coal in the United States, significant research efforts have occurred over the past 15 years concerning the conversion of coal to liquid fuels. Researchers at the University of Arkansas have concentrated on a biological approach to coal liquefaction, starting with coal-derived synthesis gas as the raw material. Synthesis gas, a mixture of CO, H[sub 2], CO[sub 2], CH[sub 4] and sulfur gases, is first produced using traditional gasification techniques. The CO, CO[sub 2] and H[sub 2] are then converted to ethanol using a bacterial culture of Clostridium 1jungdahlii. Ethanol is the desired product if the resultant product stream is to be used as a liquid fuel. However, under normal operating conditions, the wild strain'' produces acetate in favor of ethanol in conjunction with growth in a 20:1 molar ratio. Research was performed to determine the conditions necessary to maximize not only the ratio of ethanol to acetate, but also to maximize the concentration of ethanol resulting in the product stream.

  13. The challenging definition of naïve patient for biological drug use.

    PubMed

    Biggioggero, Martina; Danova, Marco; Genovese, Umberto; Locatelli, Francesco; Meroni, Pier Luigi; Pane, Fabrizio; Scaglione, Francesco

    2015-06-01

    Biosimilar is defined by The European Medical Agency as a biological medicinal product, which is similar but not identical to the biological drug already authorized. The biosimilar and its reference product are expected to display the same safety and efficacy profile and are generally used to treat the same conditions. The Italian Medicines Agency considers biosimilars as a valid therapeutic option with an economic advantage, especially in primary naïve patients with no previous exposure to the originator or with a sufficiently long wash-out period ("secondary naïve"). The identification of "secondary naïve" is not well defined and can be subjected to different variables, mainly the drug biologic effect and its immunogenicity. The first one depends on the type of biologics and on their mechanism of action. The second one is related to the fact that biologicals may be immunogenic and can trigger an anti-drug antibody response (ADA). ADA may behave as neutralizing antibodies blocking the active site of the biological but can also recognize other epitopes favoring the formation of immune-complexes that eventually affect the pharmacodynamics. Moreover, the concomitant immune-suppressive treatment can affect the immunogenicity, even if the exact mechanism remains unknown. In conclusion, the development and use of biosimilars represent a tool for increasing health system sustainability. However it is of paramount importance to distinguish between the pharmacodynamics of a given drug and its immunogenicity being the two aspects unrelated. Thus a detailed definition of "secondary naïve" patients is challenging, and may be related to both the two parameters. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Antibacterial Cleaning Products and Drug Resistance

    PubMed Central

    Marshall, Bonnie; Levy, Stuart B.; Della-Latta, Phyllis; Lin, Susan X.; Larson, Elaine

    2005-01-01

    We examined whether household use of antibacterial cleaning and hygiene products is an emerging risk factor for carriage of antimicrobial drug–resistant bacteria on hands of household members. Households (N = 224) were randomized to use of antibacterial or nonantibacterial cleaning and hygiene products for 1 year. Logistic regression was used to assess the influence of antibacterial product use in homes. Antibacterial product use did not lead to a significant increase in antimicrobial drug resistance after 1 year (odds ratio 1.33, 95% confidence interval 0.74–2.41), nor did it have an effect on bacterial susceptibility to triclosan. However, more extensive and longer term use of triclosan might provide a suitable environment for emergence of resistant species. Further research on this issue is needed. PMID:16318697

  15. Biological response modifiers: interferons, interleukins, recombinant products, liposomal products.

    PubMed

    Kruth, S A

    1998-03-01

    The concept of enhancing the normal immune response against infections and neoplasms has been considered for decades. The administration of various natural and synthetic products to simulate systemic infections has largely given over to the idea that specific cytokines can be used effectively when administered systemically. Interferons, interleukins, and hematopoietic growth factors may offer substantial clinical benefit in chronic viral infections, and cancers such as osteosarcoma, melanoma, and lymphosarcoma. Erythropoietin has been shown to have great utility in the management of chronic renal failure. At this point in time, only recombinant products derived from humans are commercially available, and they are expensive and not licensed for use in companion animals. Nevertheless, these products may have significant clinical impact on several highly fatal disorders of dogs and cats. When administered systemically, cytokines perturb complex regulatory pathways, and serious side effects may occur. Innovative delivery methods, such as liposomes, gene therapy, and even oral administration may increase the therapeutic index of these molecules. Biological response modification, cytokine biology, and associated delivery systems are rapidly changing fields, and the small animal veterinarian will need to watch for significant advances in these areas over the next several years.

  16. DNA tetrahedron nanostructures for biological applications: biosensors and drug delivery.

    PubMed

    Xie, Nuli; Liu, Shiyuan; Yang, Xiaohai; He, Xiaoxiao; Huang, Jin; Wang, Kemin

    2017-09-08

    With the rapid development of DNA nanotechnology, various DNA nanostructures with different shapes and sizes have been self-assembled using "bottom-up" fabrication strategies and applied to a wide range of fields such as biosensors, drug delivery and tools for molecular biology. As a classical and simple polyhedron, DNA tetrahedron can be easily synthesised by a one-step assembly. Due to the excellent biocompatibility and cellular permeability, it provides a universal and promising platform to construct a series of biosensors and drug delivery systems for living cells studies. Moreover, the high programmability of DNA tetrahedron determines its capability to perform artful design and combine with other materials. Herein, we review and summarise the development and applications of DNA tetrahedron in living cell studies. We mainly focus on two parts, cellular biosensors for the detection of nucleic acids, proteins, small molecules and cancer cells and drug delivery systems for chemotherapy, immunotherapy, photodynamic therapy and gene silencing. With the rapid progress in DNA tetrahedron as well as DNA nanotechnology, new avenues and opportunities have opened up in analytical chemistry, molecular biology and medicine.

  17. Genetics of rheumatoid arthritis contributes to biology and drug discovery.

    PubMed

    Okada, Yukinori; Wu, Di; Trynka, Gosia; Raj, Towfique; Terao, Chikashi; Ikari, Katsunori; Kochi, Yuta; Ohmura, Koichiro; Suzuki, Akari; Yoshida, Shinji; Graham, Robert R; Manoharan, Arun; Ortmann, Ward; Bhangale, Tushar; Denny, Joshua C; Carroll, Robert J; Eyler, Anne E; Greenberg, Jeffrey D; Kremer, Joel M; Pappas, Dimitrios A; Jiang, Lei; Yin, Jian; Ye, Lingying; Su, Ding-Feng; Yang, Jian; Xie, Gang; Keystone, Ed; Westra, Harm-Jan; Esko, Tõnu; Metspalu, Andres; Zhou, Xuezhong; Gupta, Namrata; Mirel, Daniel; Stahl, Eli A; Diogo, Dorothée; Cui, Jing; Liao, Katherine; Guo, Michael H; Myouzen, Keiko; Kawaguchi, Takahisa; Coenen, Marieke J H; van Riel, Piet L C M; van de Laar, Mart A F J; Guchelaar, Henk-Jan; Huizinga, Tom W J; Dieudé, Philippe; Mariette, Xavier; Bridges, S Louis; Zhernakova, Alexandra; Toes, Rene E M; Tak, Paul P; Miceli-Richard, Corinne; Bang, So-Young; Lee, Hye-Soon; Martin, Javier; Gonzalez-Gay, Miguel A; Rodriguez-Rodriguez, Luis; Rantapää-Dahlqvist, Solbritt; Arlestig, Lisbeth; Choi, Hyon K; Kamatani, Yoichiro; Galan, Pilar; Lathrop, Mark; Eyre, Steve; Bowes, John; Barton, Anne; de Vries, Niek; Moreland, Larry W; Criswell, Lindsey A; Karlson, Elizabeth W; Taniguchi, Atsuo; Yamada, Ryo; Kubo, Michiaki; Liu, Jun S; Bae, Sang-Cheol; Worthington, Jane; Padyukov, Leonid; Klareskog, Lars; Gregersen, Peter K; Raychaudhuri, Soumya; Stranger, Barbara E; De Jager, Philip L; Franke, Lude; Visscher, Peter M; Brown, Matthew A; Yamanaka, Hisashi; Mimori, Tsuneyo; Takahashi, Atsushi; Xu, Huji; Behrens, Timothy W; Siminovitch, Katherine A; Momohara, Shigeki; Matsuda, Fumihiko; Yamamoto, Kazuhiko; Plenge, Robert M

    2014-02-20

    A major challenge in human genetics is to devise a systematic strategy to integrate disease-associated variants with diverse genomic and biological data sets to provide insight into disease pathogenesis and guide drug discovery for complex traits such as rheumatoid arthritis (RA). Here we performed a genome-wide association study meta-analysis in a total of >100,000 subjects of European and Asian ancestries (29,880 RA cases and 73,758 controls), by evaluating ∼10 million single-nucleotide polymorphisms. We discovered 42 novel RA risk loci at a genome-wide level of significance, bringing the total to 101 (refs 2 - 4). We devised an in silico pipeline using established bioinformatics methods based on functional annotation, cis-acting expression quantitative trait loci and pathway analyses--as well as novel methods based on genetic overlap with human primary immunodeficiency, haematological cancer somatic mutations and knockout mouse phenotypes--to identify 98 biological candidate genes at these 101 risk loci. We demonstrate that these genes are the targets of approved therapies for RA, and further suggest that drugs approved for other indications may be repurposed for the treatment of RA. Together, this comprehensive genetic study sheds light on fundamental genes, pathways and cell types that contribute to RA pathogenesis, and provides empirical evidence that the genetics of RA can provide important information for drug discovery.

  18. The impact of natural products upon modern drug discovery.

    PubMed

    Ganesan, A

    2008-06-01

    In the period 1970-2006, a total of 24 unique natural products were discovered that led to an approved drug. We analyze these successful leads in terms of drug-like properties, and show that they can be divided into two equal subsets. The first falls in the 'Lipinski universe' and complies with the Rule of Five. The second is a 'parallel universe' that violates the rules. Nevertheless, the latter compounds remain largely compliant in terms of logP and H-bond donors, highlighting the importance of these two metrics in predicting bioavailability. Natural products are often cited as an exception to Lipinski's rules. We believe this is because nature has learned to maintain low hydrophobicity and intermolecular H-bond donating potential when it needs to make biologically active compounds with high molecular weight and large numbers of rotatable bonds. In addition, natural products are more likely than purely synthetic compounds to resemble biosynthetic intermediates or endogenous metabolites, and hence take advantage of active transport mechanisms. Interestingly, the natural product leads in the Lipinski and parallel universe had an identical success rate (50%) in delivering an oral drug.

  19. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Biological products; exemption. 106.1 Section 106.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR BIOLOGICAL...

  20. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Biological products; exemption. 106.1 Section 106.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR BIOLOGICAL...

  1. Mold Control and Detection In Biological Drug Substance Manufacturing Facilities: An Industry Perspective.

    PubMed

    Bawa, Anita; Asefi, Sophia; Ramsey, Stephanie; Arbesser-Rastburg, Christine; Paul, Mousumi; Leira, Francisco; McFarland, Kim; Landeryou, Tracy; Reddy, Bindhu; Murphy, Marie; Daddis, Barbara; Baine, David; Willison-Parry, Derek

    2017-06-16

    The biopharmaceutical industry produces non-sterile and/or low-bioburden intermediates and bulk biologics (i.e. Drug Substances) using bioburden controlled processes in accordance to Q7A and Annex 2. In many cases, single mold isolation events have received a high level of scrutiny; the goal of this paper is to challenge this paradigm and provide the rationale for an enhanced control approach that focuses on trending of mold species as microbial indicators rather than on single isolation events. Molds, can also be part (in much lower numbers) of the normal microbial population of a biologics manufacturing facility and, therefore, mold isolation is not an unexpected event in non-aseptic processing environments. This presentation provides recommendations from a biopharmaceutical industry perspective on mold monitoring in biologics drug substance facilities and processes. Additionally, recommendations on subjects commonly encountered in the establishment of a monitoring program, such as mold trending, responding to mold isolation events and best practices on mold prevention, are included. These recommendations assist biologic manufacturers in refining their current mold control strategy, as well as developing control strategies for new processes, facilities and products. Establishing appropriate mold control programs is a key element of overall microbial control plans in biologics manufacturing facilities. Copyright © 2017, Parenteral Drug Association.

  2. Regulatory considerations for raw materials used in biological products.

    PubMed

    Khan, A S

    2010-01-01

    Raw materials are critical components of product manufacture; these include source materials such as cell substrates, tissues, and biological fluids required for product manufacture, as well as biological materials required for cell growth, propagation, differentiation, and selection. Adventitious viruses are a major safety concern in biological raw materials. This paper discusses the specific concerns related to different types of biological materials and presents the Center for Biologics Evaluation and Research's perspective on the qualification and management of raw materials for purposes of developing a safety program for the manufacture of biological products.

  3. Comparison of Biologic Disease-Modifying Antirheumatic Drug Therapy Persistence Between Biologics Among Rheumatoid Arthritis Patients Switching from Another Biologic.

    PubMed

    Johnston, Stephen S; McMorrow, Donna; Farr, Amanda M; Juneau, Paul; Ogale, Sarika

    2015-06-01

    To compare biologic disease-modifying antirheumatic drug therapy persistence between biologics among patients with rheumatoid arthritis (RA) who previously used ≥1 other biologic. Using a large United States administrative claims dataset, we identified adult patients with RA initiating abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, or tocilizumab between January 1, 2010 and January 1, 2012 (initiation date = index). Patients were required to have used ≥1 other biologic before index. Outcomes were biologic persistence, defined in two alternative ways: (1) time from initiation until switching to a different biologic (time to switch) and (2) time from initiation until switching or the first occurrence of a 90-day gap in treatment with the initiated biologic (time to switch/discontinuation). Rituximab was excluded from analyses due to retreatment based on clinical evaluation, which complicates the measurement of persistence. Multivariable survival analyses compared persistence outcomes between tocilizumab and the other biologics, adjusting for patient characteristics. The sample comprised 9,782 biologic initiations; mean age 54 years and 82% female. Compared with tocilizumab, the hazards of switching biologic therapy were significantly higher for abatacept [hazard ratio (HR) = 1.19, P = 0.041], adalimumab (HR = 1.39, P < 0.001), certolizumab (HR = 1.39, P < 0.001), golimumab (HR = 1.20, P = 0.047), and infliximab (HR = 1.33, P < 0.001), but not significantly different for etanercept (HR = 1.19, P = 0.095); the hazards of switching/discontinuing biologic therapy were significantly higher for adalimumab (HR = 1.16, P = 0.014) and certolizumab (HR = 1.15, P < 0.012), but not significantly different for abatacept (HR = 1.08, P = 0.229), etanercept (HR = 0.97, P = 0.644), golimumab (HR = 0.99, P = 0.829), and infliximab (HR = 0.97, P = 0.721). This is one of the first studies of biologic

  4. The chemistry-biology-medicine continuum and the drug discovery and development process in academia.

    PubMed

    Nicolaou, K C

    2014-09-18

    Admirable as it is, the drug discovery and development process is continuously undergoing changes and adjustments in search of further improvements in efficiency, productivity, and profitability. Recent trends in academic-industrial partnerships promise to provide new opportunities for advancements of this process through transdisciplinary collaborations along the entire spectrum of activities involved in this complex process. This perspective discusses ways to promote the emerging academic paradigm of the chemistry-biology-medicine continuum as a means to advance the drug discovery and development process.

  5. Neurotrophic Natural Products: Chemistry and Biology

    PubMed Central

    Xu, Jing; Lacoske, Michelle H.

    2014-01-01

    Neurodegenerative diseases and spinal cord injury affect approximately 50 million people worldwide, bringing the total healthcare cost to over 600 billion dollars per year. Nervous system growth factors, that is, neurotrophins, are a potential solution to these disorders, since they could promote nerve regeneration. An average of 500 publications per year attests to the significance of neurotrophins in biomedical sciences and underlines their potential for therapeutic applications. Nonetheless, the poor pharmacokinetic profile of neurotrophins severely restricts their clinical use. On the other hand, small molecules that modulate neurotrophic activity offer a promising therapeutic approach against neurological disorders. Nature has provided an impressive array of natural products that have potent neurotrophic activities. This Review highlights the current synthetic strategies toward these compounds and summarizes their ability to induce neuronal growth and rehabilitation. It is anticipated that neurotrophic natural products could be used not only as starting points in drug design but also as tools to study the next frontier in biomedical sciences: the brain activity map project. PMID:24353244

  6. Monascus secondary metabolites: production and biological activity.

    PubMed

    Patakova, Petra

    2013-02-01

    The genus Monascus, comprising nine species, can reproduce either vegetatively with filaments and conidia or sexually by the formation of ascospores. The most well-known species of genus Monascus, namely, M. purpureus, M. ruber and M. pilosus, are often used for rice fermentation to produce red yeast rice, a special product used either for food coloring or as a food supplement with positive effects on human health. The colored appearance (red, orange or yellow) of Monascus-fermented substrates is produced by a mixture of oligoketide pigments that are synthesized by a combination of polyketide and fatty acid synthases. The major pigments consist of pairs of yellow (ankaflavin and monascin), orange (rubropunctatin and monascorubrin) and red (rubropunctamine and monascorubramine) compounds; however, more than 20 other colored products have recently been isolated from fermented rice or culture media. In addition to pigments, a group of monacolin substances and the mycotoxin citrinin can be produced by Monascus. Various non-specific biological activities (antimicrobial, antitumor, immunomodulative and others) of these pigmented compounds are, at least partly, ascribed to their reaction with amino group-containing compounds, i.e. amino acids, proteins or nucleic acids. Monacolins, in the form of β-hydroxy acids, inhibit hydroxymethylglutaryl-coenzyme A reductase, a key enzyme in cholesterol biosynthesis in animals and humans.

  7. Genetics of Psoriasis and Pharmacogenetics of Biological Drugs

    PubMed Central

    Prieto-Pérez, Rocío; Cabaleiro, Teresa; Daudén, Esteban; Ochoa, Dolores; Roman, Manuel; Abad-Santos, Francisco

    2013-01-01

    Psoriasis is a chronic inflammatory disease of the skin. The causes of psoriasis are unknown, although family and twin studies have shown genetic factors to play a key role in its development. The many genes associated with psoriasis and the immune response include TNFα, IL23, and IL12. Advances in knowledge of the pathogenesis of psoriasis have enabled the development of new drugs that target cytokines (e.g., etanercept, adalimumab, and infliximab, which target TNFα, and ustekinumab, which targets the p40 subunit of IL23 and IL12). These drugs have improved the safety and efficacy of treatment in comparison with previous therapies. However, not all patients respond equally to treatment, possibly owing to interindividual genetic variability. In this review, we describe the genes associated with psoriasis and the immune response, the biological drugs used to treat chronic severe plaque psoriasis, new drugs in phase II and III trials, and current knowledge on the implications of pharmacogenomics in predicting response to these treatments. PMID:24069534

  8. What does systems biology mean for drug development?

    PubMed

    Schrattenholz, André; Soskić, Vukić

    2008-01-01

    The complexity and flexibility of cellular architectures is increasingly recognized by impressive progress on the side of molecular analytics, i.e. proteomics, genomics and metabolomics. One of the messages from systems biology is that the number of molecular species in cellular networks is orders of magnitude bigger than anticipated by genomic analysis, in particular by fast posttranslational modifications of proteins. The requirements to manage external signals, integrate spatiotemporal signal transduction inside an organism and at the same time optimizing networks of biochemical and chemical reactions result in chemically extremely fine tuned molecular entities. Chemical side reactions of enzymatic activity, like e.g. random oxidative damage of proteins by free radicals during aging constantly introduce epigenetic alterations of protein targets. These events gradually and on an individual stochastic scale, keep modifying activities of these targets, and their affinities and selectivities towards biological and pharmacological ligands. One further message is that many of the key reactions in living systems are essentially based on interactions of low affinities and even low selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. So, in complex disorders like cancer or neurodegenerative diseases, which are rooted in relatively subtle and multimodal dysfunction of important physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which still dominate the pharmaceutical industry increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade and the treatment of "complex diseases" remains a most pressing medical need. Currently a change of paradigm can be observed with

  9. Effective integration of systems biology, biomarkers, biosimulation and modelling in streamlining drug development.

    PubMed

    Krishna, Rajesh; Schaefer, Hans Guenter; Bjerrum, Ole J

    2007-05-01

    The European Federation of Pharmaceutical Sciences (EUFEPS) has long established itself as leaders in the field of interdisciplinary meetings to discuss issues that face drug development. It's ever popular and well attended "Optimizing Drug Development" series has tackled numerous issues, most recent of which have been drug interactions, getting the dose right, candidate selection, and biomarkers (Lesko et al., 2000; Rolan et al., 2003; Stanski et al., 2005; Tucker et al., 2001). Over a course of 3 productive days, the meeting on "Effective Integration of Systems Biology, Biomarkers, Biosimulation and Modelling in Streamlining Drug Development", held in Basel, Switzerland was jointly sponsored by EUFEPS, European Biosimulation Network of Excellence (BioSim), American College of Clinical Pharmacology (ACCP), European Centre of Pharmaceutical Medicine (ECPM), and Swiss Society of Pharmaceutical Sciences (SGRW). The meeting was focused on emerging aspects related to the quantitative understanding of underlying pathways in drug discovery and clinical development, i.e. moving from an empirical to a model-based, quantitative drug development process. The objectives of the meeting were: (1) to highlight the current state of the art on biomarkers (as they relate to quantitative fingerprinting of disease), systems biology, modelling and simulation; (2) to illustrate the applications of these emerging tools in increasing the efficiency and productivity of new drug development by case examples; (3) to understand the gaps in the technology and organizational implementations in governance, and (4) allow an opportunity for cross-disciplinary interaction, i.e., scientists with more theoretical and technical modelling and simulation expertise of the BioSim network and researchers experienced in applying modelling and simulation techniques in day-to-day drug development were drawn together. This report summarizes the outcome from this meeting.

  10. 21 CFR 336.50 - Labeling of antiemetic drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... chronic bronchitis or who have glaucoma, without first consulting the child's doctor.” (2) For products... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of antiemetic drug products. 336.50 Section 336.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  11. 21 CFR 211.204 - Returned drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Returned drug products. 211.204 Section 211.204 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Returned and Salvaged...

  12. 21 CFR 211.94 - Drug product containers and closures.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Drug product containers and closures. 211.94 Section 211.94 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Control...

  13. 21 CFR 211.94 - Drug product containers and closures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drug product containers and closures. 211.94 Section 211.94 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Control...

  14. 21 CFR 211.94 - Drug product containers and closures.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Drug product containers and closures. 211.94 Section 211.94 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Control...

  15. 21 CFR 211.204 - Returned drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Returned drug products. 211.204 Section 211.204 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Returned and Salvaged...

  16. 21 CFR 211.94 - Drug product containers and closures.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Drug product containers and closures. 211.94 Section 211.94 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Control...

  17. 21 CFR 335.50 - Labeling of antidiarrheal drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of antidiarrheal drug products. 335.50 Section 335.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... section 502 of the Federal Food, Drug, and Cosmetic Act (the act) relating to misbranding and...

  18. 21 CFR 333.350 - Labeling of acne drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of acne drug products. 333.350 Section 333.350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 330.1(c)(2) of this chapter, subject to the provisions of section 502 of the Federal Food, Drug,...

  19. 21 CFR 335.50 - Labeling of antidiarrheal drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Labeling of antidiarrheal drug products. 335.50 Section 335.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... section 502 of the Federal Food, Drug, and Cosmetic Act (the act) relating to misbranding and...

  20. 21 CFR 314.108 - New drug product exclusivity.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... investigation means any experiment other than a bioavailability study in which a drug is administered or... 21 Food and Drugs 5 2014-04-01 2014-04-01 false New drug product exclusivity. 314.108 Section 314.108 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  1. 21 CFR 211.204 - Returned drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Returned drug products. 211.204 Section 211.204 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Returned and Salvaged...

  2. 21 CFR 211.204 - Returned drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Returned drug products. 211.204 Section 211.204 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Returned and Salvaged...

  3. 21 CFR 211.208 - Drug product salvaging.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Drug product salvaging. 211.208 Section 211.208 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Returned and Salvaged...

  4. 21 CFR 211.208 - Drug product salvaging.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Drug product salvaging. 211.208 Section 211.208 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Returned and Salvaged...

  5. 21 CFR 211.208 - Drug product salvaging.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Drug product salvaging. 211.208 Section 211.208 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Returned and Salvaged...

  6. 21 CFR 211.204 - Returned drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Returned drug products. 211.204 Section 211.204 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Returned and Salvaged...

  7. 21 CFR 211.134 - Drug product inspection.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Drug product inspection. 211.134 Section 211.134 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Packaging and Labeling Control...

  8. 21 CFR 341.76 - Labeling of bronchodilator drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of bronchodilator drug products. 341.76 Section 341.76 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... § 330.1(c)(2) of this chapter, subject to the provisions of section 502 of the Federal Food, Drug, and...

  9. 21 CFR 332.30 - Labeling of antiflatulent drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... states, “Keep this and all drugs out of the reach of children.” ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of antiflatulent drug products. 332.30 Section 332.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  10. 21 CFR 332.30 - Labeling of antiflatulent drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... states, “Keep this and all drugs out of the reach of children.” ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of antiflatulent drug products. 332.30 Section 332.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  11. 21 CFR 332.30 - Labeling of antiflatulent drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... states, “Keep this and all drugs out of the reach of children.” ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of antiflatulent drug products. 332.30 Section 332.30 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  12. Assessment of the Biological Effects of a Multifunctional Nano-Drug-Carrier and Its Encapsulated Drugs.

    PubMed

    Song, Yipeng; Zhao, Ruifang; Hu, Yili; Hao, Fuhua; Li, Ning; Nie, Guangjun; Tang, Huiru; Wang, Yulan

    2015-12-04

    Polymer-nanoparticle-encapsulated doxorubicin (DOX) and paclitaxel (TAX) have the potential for novel therapeutic use against cancer in the clinic. However, the systemic biological effect of the nanoparticle material, namely, methoxypoly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA), and its encapsulated drugs have not been fully studied. We have applied NMR-based metabonomics methodology to characterize and analyze the systemic metabolic changes in mice after being exposed to mPEG-PLGA, mPEG-PLGA-encapsulated DOX and TAX (NP-D/T), and their free forms. The study revealed that mPEG-PLGA exposure only induces temporary and slight metabolic alternations and that there are detoxification effects of nanoparticle packed with D/T drugs on the heart when comparing with free-form D/T drugs. Both NP-D/T and their free forms induce a shift in energy metabolism, stimulate antioxidation pathways, and disturb the gut microbial activity of the host. However, mPEG-PLGA packaging can relieve the energy metabolism inhibition and decrease the activation of antioxidation pathways caused by D/T exposure. These findings provide a holistic insight into the biological effect of polymer nanoparticle and nanoparticle-encapsulated drugs. This study also furthers our understanding of the molecular mechanisms involved in the amelioration effects of mPEG-PLGA packaging on the toxicity of the incorporated drugs.

  13. Use of Natural Products as Chemical Library for Drug Discovery and Network Pharmacology

    PubMed Central

    Gu, Jiangyong; Gui, Yuanshen; Chen, Lirong; Yuan, Gu; Lu, Hui-Zhe; Xu, Xiaojie

    2013-01-01

    Background Natural products have been an important source of lead compounds for drug discovery. How to find and evaluate bioactive natural products is critical to the achievement of drug/lead discovery from natural products. Methodology We collected 19,7201 natural products structures, reported biological activities and virtual screening results. Principal component analysis was employed to explore the chemical space, and we found that there was a large portion of overlap between natural products and FDA-approved drugs in the chemical space, which indicated that natural products had large quantity of potential lead compounds. We also explored the network properties of natural product-target networks and found that polypharmacology was greatly enriched to those compounds with large degree and high betweenness centrality. In order to make up for a lack of experimental data, high throughput virtual screening was employed. All natural products were docked to 332 target proteins of FDA-approved drugs. The most potential natural products for drug discovery and their indications were predicted based on a docking score-weighted prediction model. Conclusions Analysis of molecular descriptors, distribution in chemical space and biological activities of natural products was conducted in this article. Natural products have vast chemical diversity, good drug-like properties and can interact with multiple cellular target proteins. PMID:23638153

  14. [Dangerous drugs: products containing synthetic chemicals].

    PubMed

    Kamijo, Yoshito

    2016-02-01

    When the patients poisoned with "dangerous drugs", that is, products containing synthetic chemicals such as synthetic cannabinoids and cathinones, are transferred to the emergency facilities, the chemicals really consumed cannot be determined there. So, supportive care may be the most important strategy for treating them. For example, those with serious consciousness disturbance should be supported with ventilator after intubation. Those with remarkable excitatory CNS or sympathetic symptoms, benzodiazepines such as diazepam and midazolam, should be administered. Those with hallucination or delusion, antipsychotics such as haloperidol or risperidone should be administered. Those with rhabdomyolysis, hypermyoglobinemia and acute kidney injury, intravenous fluids and hemodialysis should be introduced.

  15. Biological treatment of shrimp production wastewater.

    PubMed

    Boopathy, Raj

    2009-07-01

    Over the last few decades, there has been an increase in consumer demand for shrimp, which has resulted in its worldwide aquaculture production. In the United States, the stringent enforcement of environmental regulations encourages shrimp farmers to develop new technologies, such as recirculating raceway systems. This is a zero-water exchange system capable of producing high-density shrimp yields. The system also produces wastewater characterized by high levels of ammonia, nitrate, nitrite, and organic carbon, which make waste management costs prohibitive. Shrimp farmers have a great need for a waste management method that is effective and economical. One such method is the sequencing batch reactor (SBR). A SBR is a variation of the activated sludge biological treatment process. This process uses multiple steps in the same reactor to take the place of multiple reactors in a conventional treatment system. The SBR accomplishes equalization, aeration, and clarification in a timed sequence in a single reactor system. This is achieved through reactor operation in sequences, which includes fill, react, settle, decant, and idle. A laboratory scale SBR was successfully operated using shrimp aquaculture wastewater. The wastewater contained high concentrations of carbon and nitrogen. By operating the reactors sequentially, namely, aerobic and anoxic modes, nitrification and denitrification were achieved as well as removal of carbon. Ammonia in the waste was nitrified within 4 days. The denitrification of nitrate was achieved by the anoxic process, and 100% removal of nitrate was observed within 15 days of reactor operation.

  16. Parasite neuropeptide biology: Seeding rational drug target selection?

    PubMed Central

    McVeigh, Paul; Atkinson, Louise; Marks, Nikki J.; Mousley, Angela; Dalzell, Johnathan J.; Sluder, Ann; Hammerland, Lance; Maule, Aaron G.

    2011-01-01

    The rationale for identifying drug targets within helminth neuromuscular signalling systems is based on the premise that adequate nerve and muscle function is essential for many of the key behavioural determinants of helminth parasitism, including sensory perception/host location, invasion, locomotion/orientation, attachment, feeding and reproduction. This premise is validated by the tendency of current anthelmintics to act on classical neurotransmitter-gated ion channels present on helminth nerve and/or muscle, yielding therapeutic endpoints associated with paralysis and/or death. Supplementary to classical neurotransmitters, helminth nervous systems are peptide-rich and encompass associated biosynthetic and signal transduction components – putative drug targets that remain to be exploited by anthelmintic chemotherapy. At this time, no neuropeptide system-targeting lead compounds have been reported, and given that our basic knowledge of neuropeptide biology in parasitic helminths remains inadequate, the short-term prospects for such drugs remain poor. Here, we review current knowledge of neuropeptide signalling in Nematoda and Platyhelminthes, and highlight a suite of 19 protein families that yield deleterious phenotypes in helminth reverse genetics screens. We suggest that orthologues of some of these peptidergic signalling components represent appealing therapeutic targets in parasitic helminths. PMID:24533265

  17. Discovery of novel drug targets and their functions using phenotypic screening of natural products.

    PubMed

    Chang, Junghwa; Kwon, Ho Jeong

    2016-03-01

    Natural products are valuable resources that provide a variety of bioactive compounds and natural pharmacophores in modern drug discovery. Discovery of biologically active natural products and unraveling their target proteins to understand their mode of action have always been critical hurdles for their development into clinical drugs. For effective discovery and development of bioactive natural products into novel therapeutic drugs, comprehensive screening and identification of target proteins are indispensable. In this review, a systematic approach to understanding the mode of action of natural products isolated using phenotypic screening involving chemical proteomics-based target identification is introduced. This review highlights three natural products recently discovered via phenotypic screening, namely glucopiericidin A, ecumicin, and terpestacin, as representative case studies to revisit the pivotal role of natural products as powerful tools in discovering the novel functions and druggability of targets in biological systems and pathological diseases of interest.

  18. 77 FR 71803 - Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-04

    ... HUMAN SERVICES Food and Drug Administration Guidance on Food and Drug Administration Oversight of Positron Emission Tomography Drug Products--Questions and Answers; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing...

  19. Biology and technology for photochemical fuel production.

    PubMed

    Hambourger, Michael; Moore, Gary F; Kramer, David M; Gust, Devens; Moore, Ana L; Moore, Thomas A

    2009-01-01

    Sunlight is the ultimate energy source for the vast majority of life on Earth, and organisms have evolved elegant machinery for energy capture and utilization. Solar energy, whether converted to wind, rain, biomass or fossil fuels, is also the primary energy source for human-engineered energy transduction systems. This tutorial review draws parallels between biological and technological energy systems. Aspects of biology that might be advantageously incorporated into emerging technologies are highlighted, as well as ways in which technology might improve upon the principles found in biological systems. Emphasis is placed upon artificial photosynthesis, as well as the use of protonmotive force in biology.

  20. Drug diffusion and biological responses of arteries using a drug-eluting stent with nonuniform coating

    PubMed Central

    Saito, Noboru; Mori, Yuhei; Uchiyama, Sayaka

    2016-01-01

    The purpose of this study was to determine the effect of a nonuniform coating, abluminal-gradient coating (AGC), which leaves the abluminal surface of the curves and links parts of the stent free from the drug coating, on the diffusion direction of the drug and the biological responses of the artery to drug-eluting stent (DES) by comparing the AGC-sirolimus stent and the conventional full-surface coating (CFC) sirolimus stent. The study aimed to verify whether the AGC approach was appropriate for the development of a safer DES, minimizing the risks of stent thrombosis due to delayed endothelialization by the drug and distal embolization due to cracking of the coating layer on the hinge parts of the DES on stent expansion. In the in vitro local drug diffusion study, we used rhodamine B as a model drug, and rhodamine B released from the AGC stent diffused predominantly into the abluminal side of the alginate artery model. Conversely, rhodamine B released from the CFC stent quickly spread to the luminal side of the artery model, where endothelial cell regeneration is required. In the biological responses study, the luminal surface of the iliac artery implanted with the AGC-sirolimus stent in a rabbit iliac artery for 2 weeks was completely covered with endothelial-like cells. On the other hand, the luminal surface of the iliac artery implanted with the CFC-sirolimus stent for 2 weeks only showed partial coverage with endothelial-like cells. While thrombosis was observed in two of the three CFC-sirolimus stents, it was observed in only one of the three AGC-sirolimus stents. Taken together, these findings indicate that the designed nonuniform coating (AGC) is an appropriate approach to ensure a safer DES. However, the number of studies is limited and a larger study should be conducted to reach a statistically significant conclusion. PMID:27051322

  1. [Application of systems biology and synthetic biology in strain improvement for biofuel production].

    PubMed

    Zhao, Xinqing; Bai, Fengwu; Li, Yin

    2010-07-01

    Biofuels are renewable and environmentally friendly, but high production cost makes them economically not competitive, and the development of robust strains is thus one of the prerequisites. In this article, strain improvement studies based on the information from systems biology studies are reviewed, with a focus on their applications on stress tolerance improvement. Furthermore, the contribution of systems biology, synthetic biology and metabolic engineering in strain development for biofuel production is discussed, with an expectation for developing more robust strains for biofuel production.

  2. Prescription Drugs, Over-the-Counter Drugs, Supplements and Herbal Products

    MedlinePlus

    ... herbal products Prescription drugs, over-the-counter drugs, supplements and herbal products Now playing: E-mail to a friend ... care provider says it’s OK. Not all drugs, herbal products or supplements are safe to take during pregnancy. If you’ ...

  3. 75 FR 73108 - Guidance for Industry on Abbreviated New Drug Applications: Impurities in Drug Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-29

    ... degradation products and updates the draft guidance ``ANDAs: Impurities in Drug Products'' announced in... final guidance to: (1) Update information on listing of degradation products, setting acceptance criteria, and qualifying degradation products (thresholds and procedures) in abbreviated new...

  4. Natural products as leads in schistosome drug discovery.

    PubMed

    Neves, Bruno J; Andrade, Carolina H; Cravo, Pedro V L

    2015-01-23

    Schistosomiasis is a neglected parasitic tropical disease that claims around 200,000 human lives every year. Praziquantel (PZQ), the only drug recommended by the World Health Organization for the treatment and control of human schistosomiasis, is now facing the threat of drug resistance, indicating the urgent need for new effective compounds to treat this disease. Therefore, globally, there is renewed interest in natural products (NPs) as a starting point for drug discovery and development for schistosomiasis. Recent advances in genomics, proteomics, bioinformatics, and cheminformatics have brought about unprecedented opportunities for the rapid and more cost-effective discovery of new bioactive compounds against neglected tropical diseases. This review highlights the main contributions that NP drug discovery and development have made in the treatment of schistosomiasis and it discusses how integration with virtual screening (VS) strategies may contribute to accelerating the development of new schistosomidal leads, especially through the identification of unexplored, biologically active chemical scaffolds and structural optimization of NPs with previously established activity.

  5. An automated biological assay to determine levels of the trypanocidal drug melarsoprol in biological fluids.

    PubMed

    Onyango, J D; Burri, C; Brun, R

    2000-01-05

    For the investigation of the pharmacokinetic properties of a drug, methods for sensitive and precise quantification are a prerequisite. Only few functional methods exist for the determination of the trypanocidal drug melarsoprol in biological fluids: A bioassay which requires microscopical evaluation and two HPLC methods, which require sample extraction and are difficult to automatize due to the drug's properties. We report the development of an automated biological assay, based on the fluorescent dye Alamar blue. To validate the assay for melarsoprol, 108 serum and 37 cerebrospinal fluid (CSF) samples were spiked with melarsoprol at concentrations of 17-92 ng/ml for CSF and 17 ng/ml-2.2 microg/ml for serum. The precision (repeatability) expressed as the interday average coefficient of variation was 9.9% for serum and 18.8% for CSF samples over the respective concentration range. The accuracy (measurement for the systematic error) of the test was 99.4% for serum and 96.4% for CSF. The assay's limit of quantitation with the use of the trypanosome stock STI 704 BABA was 4 ng/ml for both serum and CSF samples.

  6. 9 CFR 114.17 - Rebottling of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Rebottling of biological products. 114.17 Section 114.17 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PRODUCTION...

  7. The year's new drugs & biologics, 2013: Part II.

    PubMed

    Graul, A I; Navarro, D; Dulsat, C; Cruces, E; Tracy, M

    2014-02-01

    The demise of the pharmaceutical industry, so pessimistically predicted by many in recent years, has not come to pass and in fact the patient is alive and well. New programs enacted by drug regulators have been enthusiastically taken up by the industry, including the FDA's breakthrough therapy and qualified infectious disease product (QIDP) designations, as well as the now-consolidated orphan drug programs in many countries. Pharma companies pragmatically wean nonperformers from the pipeline in an efficient manner, resulting in somewhat leaner but higher-quality pipelines. Mergers and acquisitions also continue to drive consolidation and efficiency in the industry, a trend that continued during 2013. This article provides an updated review of these and other trends in the pharmaceutical industry in the year just passed.

  8. Evaluation of the microbial growth potential of pharmaceutical drug products and quality by design.

    PubMed

    Lolas, Anastasia G; Metcalfe, John W

    2011-01-01

    The microbial growth potential of a pharmaceutical drug product refers to the ability of microorganisms to survive and proliferate in the product. Each drug formulation possesses a different potential for supporting or inhibiting microbial growth. Understanding this microbial growth potential can have a significant effect on the development and design of the drug manufacturing process. This article describes how this attribute can exert this effect on manufacturing process development and design through real examples and case studies obtained from the regulatory review of new drug and biologics license applications. In addition, this article describes how understanding the microbial growth potential of a pharmaceutical drug product is an element of the Quality by Design paradigm and how this understanding can simplify the drug development process and lead to better process design. The microbial growth potential of a pharmaceutical drug product refers to the ability of microorganisms to survive and proliferate in the product formulation. Each drug product formulation possesses a different potential for supporting or inhibiting microbial growth depending on its components. Understanding this microbial growth potential can have a significant effect on the development and design of the drug manufacturing process. This article describes how this attribute can affect manufacturing process development and design through real examples and case studies obtained from the regulatory review of new drug and biologics license applications. In addition, this article describes how understanding the microbial growth potential of a pharmaceutical drug product is an element of the Quality by Design paradigm and how this understanding can simplify the drug development process and lead to better process design.

  9. Alcohol and Drug Prevention Curriculum Resource Guide Grades 10-12: Science--Biology.

    ERIC Educational Resources Information Center

    North Carolina State Dept. of Public Instruction, Raleigh. Alcohol and Drug Defense Program.

    This curriculum resource guide on alcohol and drug prevention provides suggested activities for teachers of grades 10 through 12. Three integrated learning activities for science/biology and healthful living are presented. The science/biology goal is understanding the biology of humans. Healthful living goals include analyzing drug and alcohol use…

  10. 9 CFR 103.3 - Shipment of experimental biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... name and address; number, species, class and location of animals involved; date shipment is anticipated... biological products for the purpose of evaluating such experimental products by treating limited numbers of...

  11. 9 CFR 103.3 - Shipment of experimental biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... name and address; number, species, class and location of animals involved; date shipment is anticipated... biological products for the purpose of evaluating such experimental products by treating limited numbers of...

  12. 9 CFR 103.3 - Shipment of experimental biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... name and address; number, species, class and location of animals involved; date shipment is anticipated... biological products for the purpose of evaluating such experimental products by treating limited numbers of...

  13. 9 CFR 103.3 - Shipment of experimental biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... name and address; number, species, class and location of animals involved; date shipment is anticipated... biological products for the purpose of evaluating such experimental products by treating limited numbers of...

  14. Learning from biology: synthetic lipoproteins for drug delivery.

    PubMed

    Huang, Huang; Cruz, William; Chen, Juan; Zheng, Gang

    2015-01-01

    Synthetic lipoproteins represent a relevant tool for targeted delivery of biological/chemical agents (chemotherapeutics, siRNAs, photosensitizers, and imaging contrast agents) into various cell types. These nanoparticles offer a number of advantages for drugs delivery over their native counterparts while retaining their natural characteristics and biological functions. Their ultra-small size (<30 nm), high biocompatibility, favorable circulation half-life, and natural ability to bind specific lipoprotein receptors, i.e., low-density lipoprotein receptor (LDLR) and Scavenger receptor class B member 1 (SRB1) that are found in a number of pathological conditions (e.g., cancer, atherosclerosis), make them superior delivery strategies when compared with other nanoparticle systems. We review the various approaches that have been developed for the generation of synthetic lipoproteins and their respective applications in vitro and in vivo. More specifically, we summarize the approaches employed to address the limitation on use of reconstituted lipoproteins by means of natural or recombinant apolipoproteins, as well as apolipoprotein mimetic molecules. Finally, we provide an overview of the advantages and disadvantages of these approaches and discuss future perspectives for clinical translation of these nanoparticles. © 2014 Wiley Periodicals, Inc.

  15. Learning from Biology: Synthetic Lipoproteins for Drug Delivery

    PubMed Central

    Huang, Huang; Cruz, William; Chen, Juan; Zheng, Gang

    2014-01-01

    Synthetic lipoproteins represent a relevant tool for targeted delivery of biological/chemical agents (chemotherapeutics, siRNAs, photosensitizers and imaging contrast agents) into various cell types. These nanoparticles offer a number of advantages on drugs delivery over their native counterparts while retaining their natural characteristics and biological functions. Their ultra-small size (<30nm), high biocompatibility, favorable circulation half-life and natural ability to bind specific lipoprotein receptors i.e. low-density lipoprotein receptor (LDLR) and Scavenger receptor class B member 1 (SRB1) that are found in a number of pathological conditions (e.g. cancer, atherosclerosis), make them superior delivery strategies when compared to other nanoparticle systems. We review the various approaches that have been developed for the generation of synthetic lipoproteins and their respective applications in vitro and in vivo. More specifically, we summarize the way to address the limitation on use of reconstituted lipoproteins by means of natural or recombinant apolipoproteins, as well as apolipoprotein mimetic molecules. Finally, we provide an overview of the advantages and disadvantages of these approaches and discuss future perspectives for clinical translation of these nanoparticles. PMID:25346461

  16. Mixed fermentation for natural product drug discovery.

    PubMed

    Pettit, Robin K

    2009-05-01

    Natural products continue to play a major role in drug discovery and development. However, chemical redundancy is an ongoing problem. Genomic studies indicate that certain groups of bacteria and fungi have dozens of secondary metabolite pathways that are not expressed under standard laboratory growth conditions. One approach to more fully access the metabolic potential of cultivatable microbes is mixed fermentation, where the presence of neighboring microbes may induce secondary metabolite synthesis. Research to date indicates that mixed fermentation can result in increased antibiotic activity in crude extracts, increased yields of previously described metabolites, increased yields of previously undetected metabolites, analogues of known metabolites resulting from combined pathways and, importantly, induction of previously unexpressed pathways for bioactive constituents.

  17. Presence and biological activity of antibiotics used in fuel ethanol and corn co-product production.

    PubMed

    Compart, D M Paulus; Carlson, A M; Crawford, G I; Fink, R C; Diez-Gonzalez, F; Dicostanzo, A; Shurson, G C

    2013-05-01

    Antibiotics are used in ethanol production to control bacteria from competing with yeast for nutrients during starch fermentation. However, there is no published scientific information on whether antibiotic residues are present in distillers grains (DG), co-products from ethanol production, or whether they retain their biological activity. Therefore, the objectives of this study were to quantify concentrations of various antibiotic residues in DG and determine whether residues were biologically active. Twenty distillers wet grains and 20 distillers dried grains samples were collected quarterly from 9 states and 43 ethanol plants in the United States. Samples were analyzed for DM, CP, NDF, crude fat, S, P, and pH to describe the nutritional characteristics of the samples evaluated. Samples were also analyzed for the presence of erythromycin, penicillin G, tetracycline, tylosin, and virginiamycin M1, using liquid chromatography and mass spectrometry. Additionally, virginiamycin residues were determined, using a U.S. Food and Drug Administration-approved bioassay method. Samples were extracted and further analyzed for biological activity by exposing the sample extracts to 10(4) to 10(7) CFU/mL concentrations of sentinel bacterial strains Escherichia coli ATCC 8739 and Listeria monocytogenes ATCC 19115. Extracts that inhibited bacterial growth were considered to have biological activity. Physiochemical characteristics varied among samples but were consistent with previous findings. Thirteen percent of all samples contained low (≤1.12 mg/kg) antibiotic concentrations. Only 1 sample extract inhibited growth of Escherichia coli at 10(4) CFU/mL, but this sample contained no detectable concentrations of antibiotic residues. No extracts inhibited Listeria monocytogenes growth. These data indicate that the likelihood of detectable concentrations of antibiotic residues in DG is low; and if detected, they are found in very low concentrations. The inhibition in only 1 DG

  18. 9 CFR 114.6 - Mixing biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Mixing biological products. 114.6 Section 114.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... be mixed thoroughly in a single container. During bottling operations, the product shall be...

  19. 9 CFR 114.6 - Mixing biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Mixing biological products. 114.6 Section 114.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... be mixed thoroughly in a single container. During bottling operations, the product shall be...

  20. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Packaging biological products. 112.6 Section 112.6 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS PACKAGING AND...

  1. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Inspections of biological products. 115.2 Section 115.2 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS...

  2. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Preparation of experimental biological products. 103.1 Section 103.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL...

  3. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Biological products and related terms. 101.3 Section 101.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS DEFINITIONS...

  4. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Biological products and related terms. 101.3 Section 101.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS DEFINITIONS...

  5. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Preparation of experimental biological products. 103.1 Section 103.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXPERIMENTAL...

  6. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Biological products; exemption. 106.1 Section 106.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR...

  7. 9 CFR 101.3 - Biological products and related terms.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Biological products and related terms. 101.3 Section 101.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT...) Product Code Number. A number assigned by Animal and Plant Health Inspection Service to each type of...

  8. Biological control and sustainable food production.

    PubMed

    Bale, J S; van Lenteren, J C; Bigler, F

    2008-02-27

    The use of biological control for the management of pest insects pre-dates the modern pesticide era. The first major successes in biological control occurred with exotic pests controlled by natural enemy species collected from the country or area of origin of the pest (classical control). Augmentative control has been successfully applied against a range of open-field and greenhouse pests, and conservation biological control schemes have been developed with indigenous predators and parasitoids. The cost-benefit ratio for classical biological control is highly favourable (1:250) and for augmentative control is similar to that of insecticides (1:2-1:5), with much lower development costs. Over the past 120 years, more than 5000 introductions of approximately 2000 non-native control agents have been made against arthropod pests in 196 countries or islands with remarkably few environmental problems. Biological control is a key component of a 'systems approach' to integrated pest management, to counteract insecticide-resistant pests, withdrawal of chemicals and minimize the usage of pesticides. Current studies indicate that genetically modified insect-resistant Bt crops may have no adverse effects on the activity or function of predators or parasitoids used in biological control. The introduction of rational approaches for the environmental risk assessment of non-native control agents is an essential step in the wider application of biological control, but future success is strongly dependent on a greater level of investment in research and development by governments and related organizations that are committed to a reduced reliance on chemical control.

  9. Dynamic enhancement of drug product labels to support drug safety, efficacy, and effectiveness

    PubMed Central

    2013-01-01

    Out-of-date or incomplete drug product labeling information may increase the risk of otherwise preventable adverse drug events. In recognition of these concerns, the United States Federal Drug Administration (FDA) requires drug product labels to include specific information. Unfortunately, several studies have found that drug product labeling fails to keep current with the scientific literature. We present a novel approach to addressing this issue. The primary goal of this novel approach is to better meet the information needs of persons who consult the drug product label for information on a drug’s efficacy, effectiveness, and safety. Using FDA product label regulations as a guide, the approach links drug claims present in drug information sources available on the Semantic Web with specific product label sections. Here we report on pilot work that establishes the baseline performance characteristics of a proof-of-concept system implementing the novel approach. Claims from three drug information sources were linked to the Clinical Studies, Drug Interactions, and Clinical Pharmacology sections of the labels for drug products that contain one of 29 psychotropic drugs. The resulting Linked Data set maps 409 efficacy/effectiveness study results, 784 drug-drug interactions, and 112 metabolic pathway assertions derived from three clinically-oriented drug information sources (ClinicalTrials.gov, the National Drug File – Reference Terminology, and the Drug Interaction Knowledge Base) to the sections of 1,102 product labels. Proof-of-concept web pages were created for all 1,102 drug product labels that demonstrate one possible approach to presenting information that dynamically enhances drug product labeling. We found that approximately one in five efficacy/effectiveness claims were relevant to the Clinical Studies section of a psychotropic drug product, with most relevant claims providing new information. We also identified several cases where all of the drug-drug

  10. 21 CFR 341.76 - Labeling of bronchodilator drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR..., pseudoephedrine, ephedrine, or caffeine (such as for allergy, cough-cold, or pain)”. (4) The following...

  11. 21 CFR 341.76 - Labeling of bronchodilator drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR..., pseudoephedrine, ephedrine, or caffeine (such as for allergy, cough-cold, or pain)”. (4) The following...

  12. Marinopyrroles: Unique Drug Discoveries Based on Marine Natural Products.

    PubMed

    Li, Rongshi

    2016-01-01

    Natural products provide a successful supply of new chemical entities (NCEs) for drug discovery to treat human diseases. Approximately half of the NCEs are based on natural products and their derivatives. Notably, marine natural products, a largely untapped resource, have contributed to drug discovery and development with eight drugs or cosmeceuticals approved by the U.S. Food and Drug Administration and European Medicines Agency, and ten candidates undergoing clinical trials. Collaborative efforts from drug developers, biologists, organic, medicinal, and natural product chemists have elevated drug discoveries to new levels. These efforts are expected to continue to improve the efficiency of natural product-based drugs. Marinopyrroles are examined here as a case study for potential anticancer and antibiotic agents. © 2015 Wiley Periodicals, Inc.

  13. Systems biology approaches for identifying adverse drug reactions and elucidating their underlying biological mechanisms.

    PubMed

    Boland, Mary Regina; Jacunski, Alexandra; Lorberbaum, Tal; Romano, Joseph D; Moskovitch, Robert; Tatonetti, Nicholas P

    2016-01-01

    Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and postmarket surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, whereas postmarket surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. © 2015 Wiley Periodicals, Inc.

  14. Systems Biology Approaches for Identifying Adverse Drug Reactions and Elucidating Their Underlying Biological Mechanisms

    PubMed Central

    Boland, Mary Regina; Jacunski, Alexandra; Lorberbaum, Tal; Romano, Joseph; Moskovitch, Robert; Tatonetti, Nicholas P.

    2015-01-01

    Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and post-market surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, while post-market surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. PMID:26559926

  15. Drug Discovery Prospect from Untapped Species: Indications from Approved Natural Product Drugs

    PubMed Central

    Qin, Chu; Tao, Lin; Liu, Xin; Shi, Zhe; Zhang, Cun Long; Tan, Chun Yan; Chen, Yu Zong; Jiang, Yu Yang

    2012-01-01

    Due to extensive bioprospecting efforts of the past and technology factors, there have been questions about drug discovery prospect from untapped species. We analyzed recent trends of approved drugs derived from previously untapped species, which show no sign of untapped drug-productive species being near extinction and suggest high probability of deriving new drugs from new species in existing drug-productive species families and clusters. Case histories of recently approved drugs reveal useful strategies for deriving new drugs from the scaffolds and pharmacophores of the natural product leads of these untapped species. New technologies such as cryptic gene-cluster exploration may generate novel natural products with highly anticipated potential impact on drug discovery. PMID:22808057

  16. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 9 2013-04-01 2013-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

  17. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 9 2012-04-01 2012-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

  18. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 9 2011-04-01 2011-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

  19. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 9 2014-04-01 2014-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT... Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. (a) The...

  20. Regulation of drug-metabolizing enzymes in infectious and inflammatory disease: implications for biologics-small molecule drug interactions.

    PubMed

    Mallick, Pankajini; Taneja, Guncha; Moorthy, Bhagavatula; Ghose, Romi

    2017-06-01

    Drug-metabolizing enzymes (DMEs) are primarily down-regulated during infectious and inflammatory diseases, leading to disruption in the metabolism of small molecule drugs (smds), which are increasingly being prescribed therapeutically in combination with biologics for a number of chronic diseases. The biologics may exert pro- or anti-inflammatory effect, which may in turn affect the expression/activity of DMEs. Thus, patients with infectious/inflammatory diseases undergoing biologic/smd treatment can have complex changes in DMEs due to combined effects of the disease and treatment. Areas covered: We will discuss clinical biologics-SMD interaction and regulation of DMEs during infection and inflammatory diseases. Mechanistic studies will be discussed and consequences on biologic-small molecule combination therapy on disease outcome due to changes in drug metabolism will be highlighted. Expert opinion: The involvement of immunomodulatory mediators in biologic-SMDs is well known. Regulatory guidelines recommend appropriate in vitro or in vivo assessments for possible interactions. The role of cytokines in biologic-SMDs has been documented. However, the mechanisms of drug-drug interactions is much more complex, and is probably multi-factorial. Studies aimed at understanding the mechanism by which biologics effect the DMEs during inflammation/infection are clinically important.

  1. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false U.S. Veterinary Biological Product... BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary Biological Product License. (a) Authorization to produce each biological product shall be specified on a U.S. Veterinary Biological Product License, issued by...

  2. 9 CFR 102.5 - U.S. Veterinary Biological Product License.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false U.S. Veterinary Biological Product... BIOLOGICAL PRODUCTS § 102.5 U.S. Veterinary Biological Product License. (a) Authorization to produce each biological product shall be specified on a U.S. Veterinary Biological Product License, issued by the...

  3. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Preparation of experimental biological products. 103.1 Section 103.1 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE... submitted to the Administrator. Research facilities that are entirely separate and apart from facilities...

  4. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Sampling of biological products. 113.3 Section 113.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... market by a Animal and Plant Health Inspection Service representative. (a) Either an employee of the...

  5. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Sampling of biological products. 113.3 Section 113.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF... market by a Animal and Plant Health Inspection Service representative. (a) Either an employee of the...

  6. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1990-01-01

    Previous results have shown that the medium pH, the composition of the medium and concentration of medium constituents significantly affect the ratio of ethanol to acetate in the product stream when fermenting CO, CO{sub 2} and H{sub 2} in synthesis gas to products by Clostridium ljungdahlii. An additional batch study was carried out varying the agitation rate at pH 4, 4.5 and 5.0. It was speculated that increased agitation rates in combination with low pH might result in increased ethanol production while, at the same time, yielding higher cell concentrations which could eventually result in higher ethanol concentrations.

  7. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1990-01-01

    A batch kinetic study involving Clostridium lungdahlii in a mineral medium was carried out in order to provide baseline data for the effects of nutrients on product ratio and kinetics. The use of this minimal medium containing vitamins, minerals, select amino acids and salts showed both a lower maximum specific growth rate and a lower maximum specific uptake rate than found when using a complex medium supplemented with 0.01% yeast extract. At the same time, the product ratio was improved slightly in favor of ethanol over acetate. Future experiments will measure the effects of ammonia and phosphate limitation on product ratio and process kinetics.

  8. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1991-01-01

    Previously studies have shown the importance of both medium composition and concentration and medium pH on ethanol production of Clostridium ljungdahlii in fermenting CO, CO{sub 2} and H{sub 2} in synthesis gas. Four additional batch experiments involving medium composition and concentration were carried out in modified basal medium without yeast extract at pH 4.0. These experiments indicate that basal medium with only small amounts of B-vitamins can yield significant cell growth while yielding ethanol as the major product. Product ratios as high as 11.0 g ethanol per g acetate were obtained with half strength B-vitamins. Further experiments indicates that Ca-pantothenate may be necessary for the growth of C. ljungdahlii and that growth and ethanol production can occur simultaneously.

  9. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1992-01-01

    Research is continuing in an attempt to increase both the ethanol concentration and product ratio using C. ljungdahlii. The purpose of this report is to present data utilizing a medium prepared especially for C. ljungdahlii. Medium development studies are presented, as well as reactor studies with the new medium in batch reactors. CSTRs and CSTRs with cell recycle. The use of this new medium has resulted in significant improvements in cell concentration, ethanol concentration and product ratio.

  10. Biological production of ethanol fom coal

    SciTech Connect

    Not Available

    1992-05-01

    Research is continuing in an attempt to increase both the ethanol concentration and product ratio using C. ljungdahlii. The purpose of this report is to present data (acetate to ethanol) utilizing a medium prepared especially for C. ljungdahlii. Medium development studies are presented, as well as reactor studies with the new medium in batch reactors. Continuous stirred tank reactor (CSTR) with cell recycle. The use of this new medium has resulted in significant improvements in cell concentration, ethanol concentration and product ratio.

  11. Assessment of the quality and structural integrity of a complex glycoprotein mixture following extraction from the formulated biopharmaceutical drug product.

    PubMed

    Liu, Cuihua; Dong, Shiming; Xu, Xiao-Jin; Yin, Yan; Shriver, Zachary; Capila, Ishan; Myette, James; Venkataraman, Ganesh

    2011-01-05

    Biological drugs represent an important and rapidly growing class of therapeutics useful in the treatment of a variety of disorders ranging from cancer to inflammation to infectious diseases. Unlike single chemical entities, the recombinant production of these drugs in living cells confers considerable structural and chemical heterogeneity to the biologically derived protein product that constitutes the active pharmaceutical ingredient (API). In mammalian based expression systems, much of this diversity is conferred through heterogeneous protein glycosylation. These post-translational modifications can have significant effects on the structure, biological function, and pharmacological properties of the API. In addition, the bulk proteins that comprise the API are further formulated through the use of multiple excipients designed to ensure product stability, solubility, and lot-to-lot consistency. Unfortunately, these matrices can interfere with commonly available analytical methods used in the thorough chemical characterization of the biological drug product. At the same time, a demonstration of the suitable extraction of the bulk drug substance in a manner and form that does not destabilize the active ingredient or introduce any structural bias with direct reference to the original drug product is both critical and necessary. Here, we use recombinant human follicle stimulating hormone (follitropin alpha for injection) from a pharmaceutical source as an example to illustrate a suitable purification strategy to effectively extract the bulk drug substance from the formulated drug product with high purity and yield. We assess the suitability of this extraction method in preserving the structural integrity and overall quality of the drug substance relative to the formulated drug product, placing a particular emphasis on glycosylation as a key product attribute. In so doing, we demonstrate that it is possible to effectively extract the active pharmaceutical ingredient

  12. "Pruning of biomolecules and natural products (PBNP)": an innovative paradigm in drug discovery.

    PubMed

    Bathula, Surendar Reddy; Akondi, Srirama Murthy; Mainkar, Prathama S; Chandrasekhar, Srivari

    2015-06-21

    The source or inspiration of many marketed drugs can be traced back to natural product research. However, the chemical structure of natural products covers a wide spectrum from very simple to complex. With more complex structures it is often desirable to simplify the molecule whilst retaining the desired biological activity. This approach seeks to identify the structural unit or pharmacophore responsible for the desired activity. Such pharmacophores have been the start point for a wide range of lead generation and optimisation programmes using techniques such as Biology Oriented Synthesis, Diversity Oriented Synthesis, Diverted Total Synthesis, and Fragment Based Drug Discovery. This review discusses the literature precedence of simplification strategies in four areas of natural product research: proteins, polysaccharides, nucleic acids, and compounds isolated from natural product extracts, and their impact on identifying therapeutic products.

  13. 42 CFR 409.25 - Drugs, biologicals, supplies, appliances, and equipment.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... equipment. 409.25 Section 409.25 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF... Drugs, biologicals, supplies, appliances, and equipment. (a) Drugs and biologicals. Except as specified... only if— (1) They represent a cost to the facility; (2) They are ordinarily furnished by the facility...

  14. 9 CFR 115.2 - Inspections of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... United States veterinary license number or a United States veterinary permit number or other mark...) When notified to stop distribution and sale of a serial or subserial of a veterinary biological product by the Secretary, veterinary biologics licensees or permittees shall: (1) Stop the...

  15. Biological Activity of Recently Discovered Halogenated Marine Natural Products

    PubMed Central

    Gribble, Gordon W.

    2015-01-01

    This review presents the biological activity—antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity—of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included. PMID:26133553

  16. Compatibility and stability of polygeline (Haemaccel) with different drug products.

    PubMed

    Ahmad, Mansoor; Adil, Nudrat

    2014-11-01

    Compatibility and stability of the polygeline-based blood plasma expander/plasma substitute Haemaccel with different drug products i.e., Profenid, Stemetil, and Lasix were examined in the context of its potential use in surgical, spinal, septic shock and in circulatory insufficiency, because treatment, safety, acceptability and efficacy of drug product may be affected by drug instability or incompatibility. Therefore, drug stability and compatibility are critical elements in accurate and appropriate delivery of drug therapy to patients. This study was initiated to specifically and critically assess the compatibility of Haemaccel with different drug products with the aim of delivering safe, suitable, acceptable and efficacious administration of two different drug products simultaneously in emergency conditions. All of these different brands of drug products were physically and chemically compatible with Haemaccel and all of the test results were almost similar before and after mixing different drugs in Haemaccel. This study revealed that Lasix, Profenid and Stemetil can be administered/co-administered with Haemaccel safely. Different drug product must be studies in detail before it's co-administration with Haemaccel.

  17. Drug discovery in pharmaceutical industry: productivity challenges and trends.

    PubMed

    Khanna, Ish

    2012-10-01

    Low productivity, rising R&D costs, dissipating proprietary products and dwindling pipelines are driving the pharmaceutical industry to unprecedented challenges and scrutiny. In this article I reflect on the current status of the pharmaceutical industry and reasons for continued low productivity. An emerging 'symbiotic model of innovation', that addresses underlying issues in drug failure and attempts to narrow gaps in current drug discovery processes, is discussed to boost productivity. The model emphasizes partnerships in innovation to deliver quality products in a cost-effective system. I also discuss diverse options to build a balanced research portfolio with higher potential for persistent delivery of drug molecules.

  18. Production of hydrogen using an anaerobic biological process

    DOEpatents

    Kramer, Robert; Pelter, Libbie S.; Patterson, John A.

    2016-11-29

    Various embodiments of the present invention pertain to methods for biological production of hydrogen. More specifically, embodiments of the present invention pertain to a modular energy system and related methods for producing hydrogen using organic waste as a feed stock.

  19. Retention of Preservative Levels of Formaldehyde in Desiccated Biological Products

    PubMed Central

    Pemberton, John R.

    1975-01-01

    Concentrations ranging from 8 to 100% of the preservative level of formalin (37% formaldehyde solution) were retained by desiccated biologics, with most products retaining about 50% regardless of the amount originally present. PMID:972183

  20. Natural Products as Tools for Neuroscience: Discovery and Development of Novel Agents to Treat Drug Abuse⊥

    PubMed Central

    Prisinzano, Thomas E.

    2009-01-01

    Much of what we know about the neurosciences is the direct result of studying psychoactive natural products. Unfortunately, there are many gaps in our understanding of the basic biological processes that contribute to the etiology of many CNS disorders. The investigation of psychoactive natural products offers an excellent approach to identify novel agents to treat CNS disorders and to find new chemical tools to better elucidate their biological mechanisms. This review will detail recent progress in a program directed towards investigating psychoactive natural products with the goal of treating drug abuse by targeting κ opioid receptors. PMID:19099466

  1. A Two-Layer Mathematical Modelling of Drug Delivery to Biological Tissues

    NASA Astrophysics Data System (ADS)

    Chakravarty, Koyel; Dalal, D. C.

    2016-10-01

    Local drug delivery has received much recognition in recent years, yet it is still unpredictable how drug efficacy depends on physicochemical properties and delivery kinetics. The purpose of the current study is to provide a useful mathematical model for drug release from a drug delivery device and consecutive drug transport in biological tissue, thereby aiding the development of new therapeutic drug by a systemic approach. In order to study the complete process, a two-layer spatio-temporal model depicting drug transport between the coupled media is presented. Drug release is described by considering solubilisation dynamics of drug particle, diffusion of the solubilised drug through porous matrix and also some other processes like reversible dissociation / recrystallization, drug particle-receptor binding and internalization phenomena. The model has led to a system of partial differential equations describing the important properties of drug kinetics. This model contributes towards the perception of the roles played by diffusion, mass-transfer, particle binding and internalization parameters.

  2. Implementation of mechanism of action biology-driven early drug development for children with cancer.

    PubMed

    Pearson, Andrew D J; Herold, Ralf; Rousseau, Raphaël; Copland, Chris; Bradley-Garelik, Brigid; Binner, Debbie; Capdeville, Renaud; Caron, Hubert; Carleer, Jacqueline; Chesler, Louis; Geoerger, Birgit; Kearns, Pamela; Marshall, Lynley V; Pfister, Stefan M; Schleiermacher, Gudrun; Skolnik, Jeffrey; Spadoni, Cesare; Sterba, Jaroslav; van den Berg, Hendrick; Uttenreuther-Fischer, Martina; Witt, Olaf; Norga, Koen; Vassal, Gilles

    2016-07-01

    An urgent need remains for new paediatric oncology drugs to cure children who die from cancer and to reduce drug-related sequelae in survivors. In 2007, the European Paediatric Regulation came into law requiring industry to create paediatric drug (all types of medicinal products) development programmes alongside those for adults. Unfortunately, paediatric drug development is still largely centred on adult conditions and not a mechanism of action (MoA)-based model, even though this would be more logical for childhood tumours as these have much fewer non-synonymous coding mutations than adult malignancies. Recent large-scale sequencing by International Genome Consortium and Paediatric Cancer Genome Project has further shown that the genetic and epigenetic repertoire of driver mutations in specific childhood malignancies differs from more common adult-type malignancies. To bring about much needed change, a Paediatric Platform, ACCELERATE, was proposed in 2013 by the Cancer Drug Development Forum, Innovative Therapies for Children with Cancer, the European Network for Cancer Research in Children and Adolescents and the European Society for Paediatric Oncology. The Platform, comprising multiple stakeholders in paediatric oncology, has three working groups, one with responsibility for promoting and developing high-quality MoA-informed paediatric drug development programmes, including specific measures for adolescents. Key is the establishment of a freely accessible aggregated database of paediatric biological tumour drug targets to be aligned with an aggregated pipeline of drugs. This will enable prioritisation and conduct of early phase clinical paediatric trials to evaluate these drugs against promising therapeutic targets and to generate clinical paediatric efficacy and safety data in an accelerated time frame. Through this work, the Platform seeks to ensure that potentially effective drugs, where the MoA is known and thought to be relevant to paediatric

  3. Lipophilic drug transfer between liposomal and biological membranes: what does it mean for parenteral and oral drug delivery?

    PubMed

    Fahr, Alfred; van Hoogevest, Peter; Kuntsche, Judith; Leigh, Mathew L S

    2006-01-01

    This review presents the current knowledge on the interaction of lipophilic, poorly water soluble drugs with liposomal and biological membranes. The center of attention will be on drugs having the potential to dissolve in a lipid membrane without perturbing them too much. The degree of interaction is described as solubility of a drug in phospholipid membranes and the kinetics of transfer of a lipophilic drug between membranes. Finally, the consequences of these two factors on the design of lipid-based carriers for oral, as well as parenteral use, for lipophilic drugs and lead selection of oral lipophilic drugs is described. Since liposomes serve as model-membranes for natural membranes, the assessment of lipid solubility and transfer kinetics of lipophilic drug using liposome formulations may additionally have predictive value for bioavailability and biodistribution and the pharmacokinetics of lipophilic drugs after parenteral as well as oral administration.

  4. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1990-01-01

    Previous results have shown that the yeast extract concentration and the medium pH significantly affect the ratio of ethanol to acetate in the product stream when fermenting CO, CO{sub 2} and H{sub 2} in synthesis gas to products by Clostridium ljungdahlii. Further experimentation has demonstrated the impact of eliminating yeast extract from the medium (except for the slight quantity transferred with the inoculm), especially when coupled with low pH. An ethanol to acetate product ratio of 4.0 was obtained at pH 4.5 without yeast extract present in the medium when using culture previously exposed to growth-limiting H{sub 2}S. The product ratio was 2.0 at pH 4.0 (nearly three times the value of pH 4.5 and nine times the value of pH 5.0) without yeast extract present in the media when using the standard (unexposed) culture.

  5. Equivalence of complex drug products: advances in and challenges for current regulatory frameworks.

    PubMed

    Hussaarts, Leonie; Mühlebach, Stefan; Shah, Vinod P; McNeil, Scott; Borchard, Gerrit; Flühmann, Beat; Weinstein, Vera; Neervannan, Sesha; Griffiths, Elwyn; Jiang, Wenlei; Wolff-Holz, Elena; Crommelin, Daan J A; de Vlieger, Jon S B

    2017-04-26

    Biotechnology and nanotechnology provide a growing number of innovator-driven complex drug products and their copy versions. Biologics exemplify one category of complex drugs, but there are also nonbiological complex drug products, including many nanomedicines, such as iron-carbohydrate complexes, drug-carrying liposomes or emulsions, and glatiramoids. In this white paper, which stems from a 1-day conference at the New York Academy of Sciences, we discuss regulatory frameworks in use worldwide (e.g., the U.S. Food and Drug Administration, the European Medicines Agency, the World Health Organization) to approve these complex drug products and their follow-on versions. One of the key questions remains how to assess equivalence of these complex products. We identify a number of points for which consensus was found among the stakeholders who were present: scientists from innovator and generic/follow-on companies, academia, and regulatory bodies from different parts of the world. A number of topics requiring follow-up were identified: (1) assessment of critical attributes to establish equivalence for follow-on versions, (2) the need to publish scientific findings in the public domain to further progress in the field, (3) the necessity to develop worldwide consensus regarding nomenclature and labeling of these complex products, and (4) regulatory actions when substandard complex drug products are identified. © 2017 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals, Inc. on behalf of New York Academy of Sciences.

  6. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1990-01-01

    The fermentation pH has been observed to be the key parameter affecting the ratio of ethanol to acetate produced by Clostridium ljungdahlii. The effects of controlled pH on cell growth and product formation by C. ljungdahlii were measured. It was found that cell concentration and acetate concentration increased with pH, while the ethanol concentration was highest at the lower pH. The molar product ratio of ethanol to acetate was 0.74 at pH 4.0, 0.39 at pH 4.5 and 0.12 at pH 5.0. Future experiments will concentrate on studying other important parameters such as agitation rate and nutrients concentrations with controlled pH as a preclude to continuous reactor studies.

  7. Biological production of liquid fuels from biomass

    SciTech Connect

    1982-01-01

    A scheme for the production of liquid fuels from renewable resources such as poplar wood and lignocellulosic wastes from a refuse hydropulper was investigated. The particular scheme being studied involves the conversion of a cellulosic residue, resulting from a solvent delignified lignocellulosic feed, into either high concentration sugar syrups or into ethyl and/or butyl alcohol. The construction of a pilot apparatus for solvent delignifying 150 g samples of lignocellulosic feeds was completed. Also, an analysis method for characterizing the delignified product has been selected and tested. This is a method recommended in the Forage Fiber Handbook. Delignified samples are now being prepared and tested for their extent of delignification and susceptibility to enzyme hydrolysis. Work is continuing on characterizing the cellulase and cellobiase enzyme systems derived from the YX strain of Thermomonospora.

  8. Systems biology brings new dimensions for structure-based drug design.

    PubMed

    Pei, Jianfeng; Yin, Ning; Ma, Xiaomin; Lai, Luhua

    2014-08-20

    In this Perspective, we focus on new, systems-centric views of structure-based drug design (SBDD) that we believe will impact future drug discovery research and development. We will first discuss new ways to identify drug targets based on systems intervention analysis, and then we will introduce emerging SBDD methods driven by advancements in systems biology.

  9. Biological production of ethanol from coal

    SciTech Connect

    Not Available

    1991-01-01

    Research is continuing in attempting to increase both the ethanol concentration and product ratio from the C. ljungdahlii fermentation. Both batch and continuous reactors are being used for this purpose. The purpose of this report is four-fold. First, the data presented in PETC Report No. 2-4-91 (June--September 1991) are analyzed and interpreted using normalized specific growth and production rates. This technique eliminates experimental variation due to the differences in inoculum history. Secondly, the effects of the sulfur gases H{sub 2}S and COS on the performance of C. ljungdahlii are presented and discussed. Although these are preliminary results, they illustrate the tolerance of the bacterium to low levels of sulfur gases. Thirdly, the results of continuous stirred tank reactor studies are presented, where cell and product concentrations are shown as a function of agitation rate and gas flow rate. Finally, additional data are presented showing the performance of C. ljungdahlii in a CSTR with cell recycle.

  10. Protein Complex Production from the Drug Discovery Standpoint.

    PubMed

    Moarefi, Ismail

    2016-01-01

    Small molecule drug discovery critically depends on the availability of meaningful in vitro assays to guide medicinal chemistry programs that are aimed at optimizing drug potency and selectivity. As it becomes increasingly evident, most disease relevant drug targets do not act as a single protein. In the body, they are instead generally found in complex with protein cofactors that are highly relevant for their correct function and regulation. This review highlights selected examples of the increasing trend to use biologically relevant protein complexes for rational drug discovery to reduce costly late phase attritions due to lack of efficacy or toxicity.

  11. The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Product (PODP).

    PubMed

    Paskiet, Diane; Jenke, Dennis; Ball, Douglas; Houston, Christopher; Norwood, Daniel L; Markovic, Ingrid

    2013-01-01

    The Product Quality Research Institute (PQRI) is a non-profit consortium of organizations working together to generate and share timely, relevant, and impactful information that advances drug product quality and development. The collaborative activities of PQRI participants have, in the case of orally inhaled and nasal drug products (OINDPs), resulted in comprehensive and widely-accepted recommendations for leachables assessments to help ensure patient safety with respect to this class of packaged drug products. These recommendations, which include scientifically justified safety thresholds for leachables, represent a significant milestone towards establishing standardized approaches for safety qualification of leachables in OINDP. To build on the success of the OINDP effort, PQRI's Parenteral and Ophthalmic Drug Products (PODP) Leachables and Extractables Working Group was formed to extrapolate the OINDP threshold concepts and best practice recommendations to other dosage forms with high concern for interaction with packaging/delivery systems. This article considers the general aspects of leachables and their safety assessment, introduces the PODP Work Plan and initial study Protocol, discusses the laboratory studies being conducted by the PODP Chemistry Team, outlines the strategy being developed by the PODP Toxicology Team for the safety qualification of PODP leachables, and considers the issues associated with application of the safety thresholds, particularly with respect to large-volume parenterals. Lastly, the unique leachables issues associated with biologics are described. The Product Quality Research Institute (PQRI) is a non-profit consortium involving industry organizations, academia, and regulatory agencies that together provide recommendations in support of regulatory guidance to advance drug product quality. The collaborative activities of the PQRI Orally Inhaled and Nasal Drug Products Leachables and Extractables Working Group resulted in a

  12. Biology of PXR: role in drug-hormone interactions

    PubMed Central

    Wang, Jing; Dai, Shu; Guo, Yan; Xie, Wen; Zhai, Yonggong

    2014-01-01

    Hormonal homeostasis is essential for a variety of physiological and pathological processes. Elimination and detoxification of xenobiotics, such as drugs introduced into the human body, could disrupt the balance of hormones due to the induction of drug metabolizing enzymes (DMEs) and transporters. Pregnane X receptor (PXR, NR1I2) functions as a master xenobiotic receptor involved in drug metabolism and drug-drug interactions by its coordinated transcriptional regulation of phase I and phase II DMEs and transporters. Recently, increasing evidences indicate that PXR can also mediate the endocrine disruptor function and thus impact the integrity of the endocrine system. This review focuses primarily on the recent advances in our understanding of the function of PXR in glucocorticoid, mineralocorticoid, androgen and estrogen homeostasis. The elucidation of PXR-mediated drug-hormone interactions might have important therapeutic implications in dealing with hormone-dependent diseases and safety assessment of drugs. PMID:26417296

  13. Stabilization of Protein-Protein Interactions in chemical biology and drug discovery.

    PubMed

    Bier, David; Thiel, Philipp; Briels, Jeroen; Ottmann, Christian

    2015-10-01

    More than 300,000 Protein-Protein Interactions (PPIs) can be found in human cells. This number is significantly larger than the number of single proteins, which are the classical targets for pharmacological intervention. Hence, specific and potent modulation of PPIs by small, drug-like molecules would tremendously enlarge the "druggable genome" enabling novel ways of drug discovery for essentially every human disease. This strategy is especially promising in diseases with difficult targets like intrinsically disordered proteins or transcription factors, for example neurodegeneration or metabolic diseases. Whereas the potential of PPI modulation has been recognized in terms of the development of inhibitors that disrupt or prevent a binary protein complex, the opposite (or complementary) strategy to stabilize PPIs has not yet been realized in a systematic manner. This fact is rather surprising given the number of impressive natural product examples that confer their activity by stabilizing specific PPIs. In addition, in recent years more and more examples of synthetic molecules are being published that work as PPI stabilizers, despite the fact that in the majority they initially have not been designed as such. Here, we describe examples from both the natural products as well as the synthetic molecules advocating for a stronger consideration of the PPI stabilization approach in chemical biology and drug discovery. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Physicochemical Characterization of Iron Carbohydrate Colloid Drug Products.

    PubMed

    Zou, Peng; Tyner, Katherine; Raw, Andre; Lee, Sau

    2017-07-31

    Iron carbohydrate colloid drug products are intravenously administered to patients with chronic kidney disease for the treatment of iron deficiency anemia. Physicochemical characterization of iron colloids is critical to establish pharmaceutical equivalence between an innovator iron colloid product and generic version. The purpose of this review is to summarize literature-reported techniques for physicochemical characterization of iron carbohydrate colloid drug products. The mechanisms, reported testing results, and common technical pitfalls for individual characterization test are discussed. A better understanding of the physicochemical characterization techniques will facilitate generic iron carbohydrate colloid product development, accelerate products to market, and ensure iron carbohydrate colloid product quality.

  15. Natural Products as a Foundation for Drug Discovery

    PubMed Central

    Beutler, John A.

    2009-01-01

    Natural products have contributed to the development of many drugs for diverse indications. While most U.S. pharmaceutical companies have reduced or eliminated their in-house natural product groups, new paradigms and new enterprises have evolved to carry on a role for natural products in the pharmaceutical industry. Many of the reasons for the decline in popularity of natural products are being addressed by the development of new techniques for screening and production. This overview aims to inform pharmacologists of current strategies and techniques that make natural products a viable strategic choice for inclusion in drug discovery programs. PMID:20161632

  16. [New drugs for horses and production animals in 2011].

    PubMed

    Emmerich, I U

    2012-10-17

    In 2011, three newly developed active pharmaceutical ingredients for horses and food producing animals were released on the German market for veterinary drug products. Two of these new products represent different drug classes of antibiotics, the polypeptide antibiotic Bacitracin (Bacivet™) and the macrolide antibiotic Clorsulon (Levatum®). The third product represents an anticestodal antiparasitic (Tildipirosin, Zuprevo®). Furthermore, three established veterinary active pharmaceutical ingredients were modified to allow their application for additional species. Thus the nonsteroidal anti-inflammatory drug sodium salicylate is now additionally authorised for turkeys and both the macrolide antibiotic Tilmicosin and the anticoccidial drug Toltrazuril are currently available for sheep. Additionally, two veterinary drugs with a new formulation as well as a veterinary drug for horses and food producing animals with a resourceful new combination of active pharmaceutical ingredients have recently been released.

  17. Integration of Regulatory Guidelines into Protein Drug Product Development.

    PubMed

    Wang, Wei

    2016-01-01

    The drug product development process for proteins went through its infancy in the early eighties of last century and is in its maturity today. This has been driven largely by the rapid growth of the biotechnology industry, which led to the development and issuance of many regulatory guidelines/directories, especially those through the International Conference of Harmonization (ICH). These guidelines have certainly guided different aspects of a drug product development process. On the other hand, they were issued separately on different topics and in different time periods. An integration of all relevant guidelines into the corresponding areas in drug product development would greatly facilitate the development process. The purpose of this short review is to integrate the relevant (mainly ICH) regulatory guidelines into protein drug product development and to discuss remaining issues, which may lead to further revision of existing guidelines or development of new ones. Drug product development scientists need to collect adequate and relevant development data for a successful product registration. The key is the ability to justify the final drug product in terms of choice of the drug product formulation, container closure system, and manufacturing process. The drug product development process for proteins has matured today, largely due to the rapid growth of the biotechnology industry. In this process, many regulatory guidelines/directories were developed and issued, especially through the International Conference of Harmonization (ICH). However, they were issued separately on different topics and in different time periods. An integration of all relevant guidelines into the corresponding areas in drug product development would greatly facilitate the development process. The purpose of this short review is to integrate the relevant (mainly ICH) regulatory guidelines into protein drug product development and to discuss remaining issues, which may lead to further

  18. Recent advances in biological production of erythritol.

    PubMed

    Rzechonek, Dorota A; Dobrowolski, Adam; Rymowicz, Waldemar; Mirończuk, Aleksandra M

    2017-09-27

    Erythritol is a natural sweetener commonly used in the food and pharmaceutical industries. Produced by microorganisms as an osmoprotectant, it is an ideal sucrose substitute for diabetics or overweight persons due to its almost zero calorie content. Currently, erythritol is produced on an industrial scale through the fermentation of sugars by some yeasts, such as Moniliella sp. However, the popularity of erythritol as a sweetener is still small because of its high retail price. This creates an opportunity for further process improvement. Recent years have brought the rapid development of erythritol biosynthesis methods from the low-cost substrates, and a better understanding of the metabolic pathways leading to erythritol synthesis. The yeast Yarrowia lipolytica emerges as an organism effectively producing erythritol from pure or crude glycerol. Moreover, novel erythritol producing organisms and substrates may be taken into considerations due to metabolic engineering. This review focuses on the modification of erythritol production to use low-cost substrates and metabolic engineering of the microorganisms in order to improve yield and productivity.

  19. Linking neuroethology to the chemical biology of natural products: interactions between cone snails and their fish prey, a case study.

    PubMed

    Olivera, Baldomero M; Raghuraman, Shrinivasan; Schmidt, Eric W; Safavi-Hemami, Helena

    2017-05-27

    From a biological perspective, a natural product can be defined as a compound evolved by an organism for chemical interactions with another organism including prey, predator, competitor, pathogen, symbiont or host. Natural products hold tremendous potential as drug leads and have been extensively studied by chemists and biochemists in the pharmaceutical industry. However, the biological purpose for which a natural product evolved is rarely addressed. By focusing on a well-studied group of natural products-venom components from predatory marine cone snails-this review provides a rationale for why a better understanding of the evolution, biology and biochemistry of natural products will facilitate both neuroscience and the potential for drug leads. The larger goal is to establish a new sub-discipline in the broader field of neuroethology that we refer to as "Chemical Neuroethology", linking the substantial work carried out by chemists on natural products with accelerating advances in neuroethology.

  20. Improvement of FK506 production by synthetic biology approaches.

    PubMed

    Fu, Li-Feng; Tao, Yang; Jin, Mei-Ying; Jiang, Hui

    2016-12-01

    Synthetic biology has been applied to direct improvement of valuable metabolite productions. Tacrolimus (FK506), a clinically used immunosuppressive agent isolated from many Streptomyces, is produced by fermentation in industry. Here we chose FK506 as an example to review recent progress in improving FK506 production, including enhancing transcription levels of biosynthetic genes, accelerating post-translational modification levels of biosynthetic enzymes, increasing activities of rate limiting enzymes, and rational supplement of limited precursors. FK506 production was increased from 25 % to sevenfold by these synthetic biology approaches.

  1. Comorbidity as a predictor for drug survival of biologic therapy in patients with psoriasis.

    PubMed

    Jacobi, Arnd; Rustenbach, Stephan J; Augustin, Matthias

    2016-03-01

    Psoriasis often requires lifelong therapy, and adherence to treatment is considered a marker for treatment success. Data on the drug survival of biologics in psoriasis patients with comorbidities are lacking. This study was designed to estimate the long-term drug survival rates of different biologic agents in a cohort of psoriasis patients and to evaluate reasons and predictors for treatment adherence. Drug survival rates and outcome parameters in psoriasis patients treated with biologic agents were analyzed. A total of 125 treatment periods with adalimumab (n = 37), efalizumab (n = 9), etanercept (n = 55), infliximab (n = 13), and ustekinumab (n = 11) were administered to 67 psoriasis patients. Patients with psoriatic arthritis (P = 0.010) and without comorbidity (P = 0.033) demonstrated significantly greater rates of drug survival. The overall efficacy of biologic agents is reduced with time. Patients with the comorbidity of metabolic syndrome demonstrate a loss of adherence to biologic treatment. © 2015 The International Society of Dermatology.

  2. Predicting potential drug-drug interactions by integrating chemical, biological, phenotypic and network data.

    PubMed

    Zhang, Wen; Chen, Yanlin; Liu, Feng; Luo, Fei; Tian, Gang; Li, Xiaohong

    2017-01-05

    Drug-drug interactions (DDIs) are one of the major concerns in drug discovery. Accurate prediction of potential DDIs can help to reduce unexpected interactions in the entire lifecycle of drugs, and are important for the drug safety surveillance. Since many DDIs are not detected or observed in clinical trials, this work is aimed to predict unobserved or undetected DDIs. In this paper, we collect a variety of drug data that may influence drug-drug interactions, i.e., drug substructure data, drug target data, drug enzyme data, drug transporter data, drug pathway data, drug indication data, drug side effect data, drug off side effect data and known drug-drug interactions. We adopt three representative methods: the neighbor recommender method, the random walk method and the matrix perturbation method to build prediction models based on different data. Thus, we evaluate the usefulness of different information sources for the DDI prediction. Further, we present flexible frames of integrating different models with suitable ensemble rules, including weighted average ensemble rule and classifier ensemble rule, and develop ensemble models to achieve better performances. The experiments demonstrate that different data sources provide diverse information, and the DDI network based on known DDIs is one of most important information for DDI prediction. The ensemble methods can produce better performances than individual methods, and outperform existing state-of-the-art methods. The datasets and source codes are available at https://github.com/zw9977129/drug-drug-interaction/ .

  3. 21 CFR 216.24 - Drug products withdrawn or removed from the market for reasons of safety or effectiveness.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... Bromfenac sodium: All drug products containing bromfenac sodium. Butamben: All parenteral drug products... use as a patient preoperative skin preparation. Chlormadinone acetate: All drug products containing chlormadinone acetate. Chloroform: All drug products containing chloroform. Cobalt: All drug products containing...

  4. 21 CFR 216.24 - Drug products withdrawn or removed from the market for reasons of safety or effectiveness.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... Bromfenac sodium: All drug products containing bromfenac sodium. Butamben: All parenteral drug products... use as a patient preoperative skin preparation. Chlormadinone acetate: All drug products containing chlormadinone acetate. Chloroform: All drug products containing chloroform. Cobalt: All drug products containing...

  5. 21 CFR 216.24 - Drug products withdrawn or removed from the market for reasons of safety or effectiveness.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... Bromfenac sodium: All drug products containing bromfenac sodium. Butamben: All parenteral drug products... use as a patient preoperative skin preparation. Chlormadinone acetate: All drug products containing chlormadinone acetate. Chloroform: All drug products containing chloroform. Cobalt: All drug products containing...

  6. 21 CFR 216.24 - Drug products withdrawn or removed from the market for reasons of safety or effectiveness.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... Bromfenac sodium: All drug products containing bromfenac sodium. Butamben: All parenteral drug products... use as a patient preoperative skin preparation. Chlormadinone acetate: All drug products containing chlormadinone acetate. Chloroform: All drug products containing chloroform. Cobalt: All drug products containing...

  7. 21 CFR 216.24 - Drug products withdrawn or removed from the market for reasons of safety or effectiveness.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... Bromfenac sodium: All drug products containing bromfenac sodium. Butamben: All parenteral drug products... use as a patient preoperative skin preparation. Chlormadinone acetate: All drug products containing chlormadinone acetate. Chloroform: All drug products containing chloroform. Cobalt: All drug products containing...

  8. The Interstellar Production of Biologically Important Organics

    NASA Technical Reports Server (NTRS)

    Sandford, Scott A.; Bernstein, Max P.; Dworkin, Jason; Allamandola, Louis J.

    2000-01-01

    One of the primary tasks of the Astrochemistry Laboratory at Ames Research Center is to use laboratory simulations to study the chemical processes that occur in dense interstellar clouds. Since new stars are formed in these clouds, their materials may be responsible for the delivery of organics to new habitable planets and may play important roles in the origin of life. These clouds are extremely cold (less than 50 kelvin), and most of the volatiles in these clouds are condensed onto dust grains as thin ice mantles. These ices are exposed to cosmic rays and ultraviolet (UV) photons that break chemical bonds and result in the production of complex molecules when the ices are warmed (as they would be when incorporated into a star-forming region). Using cryovacuum systems and UV lamps, this study simulates the conditions of these clouds and studies the resulting chemistry. Some of the areas of progress made in 1999 are described below. It shows some of the types of molecules that may be formed in the interstellar medium. Laboratory simulations have already confirmed that many of these compounds are made under these conditions.

  9. Harnessing Polypharmacology with Computer-Aided Drug Design and Systems Biology.

    PubMed

    Wathieu, Henri; Issa, Naiem T; Byers, Stephen W; Dakshanamurthy, Sivanesan

    2016-01-01

    The ascent of polypharmacology in drug development has many implications for disease therapy, most notably in the efforts of drug discovery, drug repositioning, precision medicine and combination therapy. The single- target approach to drug development has encountered difficulties in predicting drugs that are both clinically efficacious and avoid toxicity. By contrast, polypharmacology offers the possibility of a controlled distribution of effects on a biological system. This review addresses possibilities and bottlenecks in the efficient computational application of polypharmacology. The two major areas we address are the discovery and prediction of multiple protein targets using the tools of computer-aided drug design, and the use of these protein targets in predicting therapeutic potential in the context of biological networks. The successful application of polypharmacology to systems biology and pharmacology has the potential to markedly accelerate the pace of development of novel therapies for multiple diseases, and has implications for the intellectual property landscape, likely requiring targeted changes in patent law.

  10. Acinetobacter baumannii: biology and drug resistance - role of carbapenemases.

    PubMed

    Nowak, Pawel; Paluchowska, Paulina

    2016-01-01

    Acinetobacter baumannii is a Gram-negative, glucose-non-fermenting, oxidase-negative coccobacillus, most commonly associated with the hospital settings. The ability to survive in adverse environmental conditions as well as high level of natural and acquired antimicrobial resistance make A. baumannii one of the most important nosocomial pathogens. While carbapenems have long been considered as antimicrobials of last-resort, the rates of clinical A. baumannii strains resistant to these antibiotics are increasing worldwide. Carbapenem resistance among A. baumannii is conferred by coexisting mechanisms including: decrease in permeability of the outer membrane, efflux pumps, production of beta-lactamases, and modification of penicillin-binding proteins. The most prevalent mechanism of carbapenem resistance among A. baumannii is associated with carbapenem-hydro-lysing enzymes that belong to Ambler class D and B beta-lactamases. In addition, there have also been reports of resistance mediated by selected Ambler class A carbapenemases among A. baumannii strains. Resistance determinants in A. baumannii are located on chromosome and plasmids, while acquisition of new mechanisms can be mediated by insertion sequences, integrons, transposons, and plasmids. Clinical relevance of carbapen-em resistance among strains isolated from infected patients, carriers and hospital environment underlines the need for carbapenemase screening. Currently available methods vary in principle, accuracy and efficiency. The techniques that deserve particular attention belong to both easily accessible unsophisticated methods as well as advanced techniques based on mass spectrometry or molecular biology. While carbapenemases limit the therapeutic options in A. baumannii infections, studies concerning novel beta-lactamase inhibitors offer a new insight into effective therapy.

  11. Effect of biological pretreatments in enhancing corn straw biogas production.

    PubMed

    Zhong, Weizhang; Zhang, Zhongzhi; Luo, Yijing; Sun, Shanshan; Qiao, Wei; Xiao, Meng

    2011-12-01

    A biological pretreatment with new complex microbial agents was used to pretreat corn straw at ambient temperature (about 20°C) to improve its biodegradability and anaerobic biogas production. A complex microbial agent dose of 0.01% (w/w) and pretreatment time of 15 days were appropriate for biological pretreatment. These treatment conditions resulted in 33.07% more total biogas yield, 75.57% more methane yield, and 34.6% shorter technical digestion time compared with the untreated sample. Analyses of chemical compositions showed 5.81-25.10% reductions in total lignin, cellulose, and hemicellulose contents, and 27.19-80.71% increases in hot-water extractives; these changes contributed to the enhancement of biogas production. Biological pretreatment could be an effective method for improving biodegradability and enhancing the highly efficient biological conversion of corn straw into bioenergy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Systems Biology Approaches to Understand Natural Products Biosynthesis.

    PubMed

    Licona-Cassani, Cuauhtemoc; Cruz-Morales, Pablo; Manteca, Angel; Barona-Gomez, Francisco; Nielsen, Lars K; Marcellin, Esteban

    2015-01-01

    Actinomycetes populate soils and aquatic sediments that impose biotic and abiotic challenges for their survival. As a result, actinomycetes metabolism and genomes have evolved to produce an overwhelming diversity of specialized molecules. Polyketides, non-ribosomal peptides, post-translationally modified peptides, lactams, and terpenes are well-known bioactive natural products with enormous industrial potential. Accessing such biological diversity has proven difficult due to the complex regulation of cellular metabolism in actinomycetes and to the sparse knowledge of their physiology. The past decade, however, has seen the development of omics technologies that have significantly contributed to our better understanding of their biology. Key observations have contributed toward a shift in the exploitation of actinomycete's biology, such as using their full genomic potential, activating entire pathways through key metabolic elicitors and pathway engineering to improve biosynthesis. Here, we review recent efforts devoted to achieving enhanced discovery, activation, and manipulation of natural product biosynthetic pathways in model actinomycetes using genome-scale biological datasets.

  13. A Synthetic Biology Project - Developing a single-molecule device for screening drug-target interactions.

    PubMed

    Firman, Keith; Evans, Luke; Youell, James

    2012-07-16

    This review describes a European-funded project in the area of Synthetic Biology. The project seeks to demonstrate the application of engineering techniques and methodologies to the design and construction of a biosensor for detecting drug-target interactions at the single-molecule level. Production of the proteins required for the system followed the principle of previously described "bioparts" concepts (a system where a database of biological parts - promoters, genes, terminators, linking tags and cleavage sequences - is used to construct novel gene assemblies) and cassette-type assembly of gene expression systems (the concept of linking different "bioparts" to produce functional "cassettes"), but problems were quickly identified with these approaches. DNA substrates for the device were also constructed using a cassette-system. Finally, micro-engineering was used to build a magnetoresistive Magnetic Tweezer device for detection of single molecule DNA modifying enzymes (motors), while the possibility of constructing a Hall Effect version of this device was explored. The device is currently being used to study helicases from Plasmodium as potential targets for anti-malarial drugs, but we also suggest other potential uses for the device. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  14. Drug Development Process

    MedlinePlus

    ... Products Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products ... Research Drugs undergo laboratory and animal testing to answer basic questions about safety. More Information ...

  15. Natural products as a foundation for drug discovery.

    PubMed

    Beutler, John A

    2009-09-01

    Natural products have provided chemical leads for the development of many drugs for diverse indications. While most U.S. pharmaceutical firms have reduced or eliminated their in-house natural product groups, there is a renewed interest in this source of new chemical entities. Many of the reasons for the past decline in popularity of natural products are being addressed by the development of new techniques for screening and production. The aim of this unit is to review current strategies and techniques that increase the value of natural products as a source for novel drug candidates.

  16. Prediction of novel drug indications using network driven biological data prioritization and integration

    PubMed Central

    2014-01-01

    Background With the rapid development of high-throughput genomic technologies and the accumulation of genome-wide datasets for gene expression profiling and biological networks, the impact of diseases and drugs on gene expression can be comprehensively characterized. Drug repositioning offers the possibility of reduced risks in the drug discovery process, thus it is an essential step in drug development. Results Computational prediction of drug-disease interactions using gene expression profiling datasets and biological networks is a new direction in drug repositioning that has gained increasing interest. We developed a computational framework to build disease-drug networks using drug- and disease-specific subnetworks. The framework incorporates protein networks to refine drug and disease associated genes and prioritize genes in disease and drug specific networks. For each drug and disease we built multiple networks using gene expression profiling and text mining. Finally a logistic regression model was used to build functional associations between drugs and diseases. Conclusions We found that representing drugs and diseases by genes with high centrality degree in gene networks is the most promising representation of drug or disease subnetworks. PMID:24397863

  17. 21 CFR 347.50 - Labeling of skin protectant drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of skin protectant drug products. 347.50... (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 347.50 Labeling of skin protectant drug products. A skin protectant drug product may have more than...

  18. 21 CFR 349.50 - Labeling of ophthalmic drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., discard.” (3) For ophthalmic drug products containing mercury compounds used as a preservative. “This product contains (name and quantity of mercury-containing ingredient) as a preservative. Do not use this product if you are sensitive to” (select one of the following: “mercury” or “(insert name of mercury...

  19. 21 CFR 349.50 - Labeling of ophthalmic drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., discard.” (3) For ophthalmic drug products containing mercury compounds used as a preservative. “This product contains (name and quantity of mercury-containing ingredient) as a preservative. Do not use this product if you are sensitive to” (select one of the following: “mercury” or “(insert name of...

  20. 21 CFR 349.50 - Labeling of ophthalmic drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., discard.” (3) For ophthalmic drug products containing mercury compounds used as a preservative. “This product contains (name and quantity of mercury-containing ingredient) as a preservative. Do not use this product if you are sensitive to” (select one of the following: “mercury” or “(insert name of...

  1. The generation of "unnatural" products: synthetic biology meets synthetic chemistry.

    PubMed

    Goss, Rebecca J M; Shankar, Sreejith; Fayad, Antoine Abou

    2012-08-01

    Natural product analogue generation is important, providing tools for chemical biology, enabling structure activity relationship determination and insight into the way in which natural products interact with their target biomolecules. The generation of analogues is also often necessary in order to improve bioavailability and to fine tune compounds' activity. This review provides an overview of the catalogue of approaches available for accessing series of analogues. Over the last few years there have been major advances in genome sequencing and the development of tools for biosynthetic pathway engineering; it is therefore becoming increasingly easy to combine molecular biology and synthetic organic chemistry in order to enable expeditious access to series of natural products. This review outlines the various ways of combining biology and chemistry that have been applied to analogue generation, drawing upon a series of examples to illustrate each approach.

  2. Milk kefir: composition, microbial cultures, biological activities, and related products

    PubMed Central

    Prado, Maria R.; Blandón, Lina Marcela; Vandenberghe, Luciana P. S.; Rodrigues, Cristine; Castro, Guillermo R.; Thomaz-Soccol, Vanete; Soccol, Carlos R.

    2015-01-01

    In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir’s exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir’s microflora and the importance of kefiran as a beneficial health substance. PMID:26579086

  3. Milk kefir: composition, microbial cultures, biological activities, and related products.

    PubMed

    Prado, Maria R; Blandón, Lina Marcela; Vandenberghe, Luciana P S; Rodrigues, Cristine; Castro, Guillermo R; Thomaz-Soccol, Vanete; Soccol, Carlos R

    2015-01-01

    In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir's exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir's microflora and the importance of kefiran as a beneficial health substance.

  4. Assessment of biological Hydrogen production processes: A review

    NASA Astrophysics Data System (ADS)

    Najafpour, G. D.; Shahavi, M. H.; Neshat, S. A.

    2016-06-01

    Energy crisis created a special attention on renewable energy sources. Among these sources; hydrogen through biological processes is well-known as the most suitable and renewable energy sources. In terms of process yield, hydrogen production from various sources was evaluated. A summary of microorganisms as potential hydrogen producers discussed along with advantages and disadvantages of several bioprocesses. The pathway of photo-synthetic and dark fermentative organisms was discussed. In fact, the active enzymes involved in performance of biological processes for hydrogen generation were identified and their special functionalities were discussed. The influential factors affecting on hydrogen production were known as enzymes assisting liberation specific enzymes such as nitrogenase, hydrogenase and uptake hydrogenase. These enzymes were quite effective in reduction of proton and form active molecular hydrogen. Several types of photosynthetic systems were evaluated with intension of maximum hydrogen productivities. In addition dark fermentative and light intensities on hydrogen productions were evaluated. The hydrogen productivities of efficient hydrogen producing strains were evaluated.

  5. 78 FR 38053 - Determination That OPANA ER (Oxymorphone Hydrochloride) Drug Products Covered by New Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-25

    ...The Food and Drug Administration (FDA) has determined that OPANA ER (oxymorphone hydrochloride (HCl)) Extended-Release Tablet products approved under new drug application (NDA) 21-610 were not withdrawn from sale for reasons of safety or effectiveness. This determination means that FDA will not begin procedures to withdraw approval of abbreviated new drug applications (ANDAs) that refer to these drug products, and it will allow FDA to continue to approve ANDAs for oxymorphone HCl extended-release tablets if all other legal and regulatory requirements are met.

  6. Stacking-cyclodextrin-microchip electrokinetic chromatographic determination of gabapentinoid drugs in pharmaceutical and biological matrices.

    PubMed

    Zeid, Abdallah M; Kaji, Noritada; Nasr, Jenny Jeehan M; Belal, Fathalla F; Baba, Yoshinobu; Walash, Mohamed I

    2017-06-23

    A facile, rapid, and highly sensitive microchip-based electrokinetic chromatographic method was developed for the simultaneous analysis of two gabapentinoid drugs, gabapentin (GPN) and pregabalin (PGN). Both drugs were first reacted with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) via nucleophilic substitution reactions to yield highly fluorescent products with λex/em 470/540nm. Analyses of both fluorescently labeled compounds were achieved within 200s in a poly(methyl methacrylate) (PMMA) microchip with a 30mm separation channel. Optimum separation was achieved using a borate buffer (pH 9.0) solution containing methylcellulose and β-cyclodextrin (β-CD) as buffer additives. Methylcellulose acted as a dynamic coating to prevent adsorption of the studied compounds on the inner surfaces of the microchannels, while β-CD acted as a pseudo-stationary phase to improve the separation efficiency between the labeled drugs with high resolution (Rs>7). The fluorescence intensities of the labeled drugs were measured using a light emitting diode-induced fluorescence detector at 540nm after excitation at 470nm. The sensitivity of the method was enhanced 14- and 17-fold for PGN and GPN, respectively by field-amplified stacking relative to traditional pinched injection so that it could quantify 10ngmL(-1) for both analytes, with a detection limit lower than 3ngmL(-1). The developed method was efficiently applied to analyze PGN and GPN in their pharmaceutical dosage forms and in biological fluids. The extraction recoveries of the studied drugs from plasma and urine samples were more than 89% with%RSD values lower than 6.2. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Yeast synthetic biology toolbox and applications for biofuel production.

    PubMed

    Tsai, Ching-Sung; Kwak, Suryang; Turner, Timothy L; Jin, Yong-Su

    2015-02-01

    Yeasts are efficient biofuel producers with numerous advantages outcompeting bacterial counterparts. While most synthetic biology tools have been developed and customized for bacteria especially for Escherichia coli, yeast synthetic biological tools have been exploited for improving yeast to produce fuels and chemicals from renewable biomass. Here we review the current status of synthetic biological tools and their applications for biofuel production, focusing on the model strain Saccharomyces cerevisiae We describe assembly techniques that have been developed for constructing genes, pathways, and genomes in yeast. Moreover, we discuss synthetic parts for allowing precise control of gene expression at both transcriptional and translational levels. Applications of these synthetic biological approaches have led to identification of effective gene targets that are responsible for desirable traits, such as cellulosic sugar utilization, advanced biofuel production, and enhanced tolerance against toxic products for biofuel production from renewable biomass. Although an array of synthetic biology tools and devices are available, we observed some gaps existing in tool development to achieve industrial utilization. Looking forward, future tool development should focus on industrial cultivation conditions utilizing industrial strains.

  8. Success rates for product development strategies in new drug development.

    PubMed

    Dahlin, E; Nelson, G M; Haynes, M; Sargeant, F

    2016-04-01

    While research has examined the likelihood that drugs progress across phases of clinical trials, no research to date has examined the types of product development strategies that are the most likely to be successful in clinical trials. This research seeks to identify the strategies that are most likely to reach the market-those generated using a novel product development strategy or strategies that combine a company's expertise with both drugs and indications, which we call combined experience strategies. We evaluate the success of product development strategies in the drug development process for a sample of 2562 clinical trials completed by 406 US pharmaceutical companies. To identify product development strategies, we coded each clinical trial according to whether it consisted of an indication or a drug that was new to the firm. Accordingly, a clinical trial that consists of both an indication and a drug that were both new to the firm represents a novel product development strategy; indication experience is a product development strategy that consists of an indication that a firm had tested previously in a clinical trial, but with a drug that was new to the firm; drug experience is a product development strategy that consists of a drug that the firm had prior experience testing in clinical trials, but with an indication that was new to the firm; combined experience consists of both a drug and an indication that the firm had experience testing in clinical trials. Success rates for product development strategies across clinical phases were calculated for the clinical trials in our sample. Combined experience strategies had the highest success rate. More than three and a half percent (0·036) of the trials that combined experience with drugs and indications eventually reached the market. The next most successful strategy is drug experience (0·025) with novel strategies trailing closely (0·024). Indication experience strategies are the least successful (0·008

  9. United States Food and Drug Administration Product Label Changes.

    PubMed

    Kircik, Leon; Sung, Julie C; Stein-Gold, Linda; Goldenberg, Gary

    2017-02-01

    Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug.

  10. United States Food and Drug Administration Product Label Changes.

    PubMed

    Kircik, Leon; Sung, Julie C; Stein-Gold, Linda; Goldenberg, Gary

    2016-01-01

    Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug.

  11. United States Food and Drug Administration Product Label Changes

    PubMed Central

    Sung, Julie C.; Stein-Gold, Linda; Goldenberg, Gary

    2016-01-01

    Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug. PMID:26962391

  12. United States Food and Drug Administration Product Label Changes

    PubMed Central

    Sung, Julie C.; Stein-Gold, Linda; Goldenberg, Gary

    2017-01-01

    Once a drug has been approved by the United States Food and Drug Administration and is on the market, the Food and Drug Administration communicates new safety information through product label changes. Most of these label changes occur after a spontaneous report to either the drug manufacturing companies or the Food and Drug Administration MedWatch program. As a result, 400 to 500 label changes occur every year. Actinic keratosis treatments exemplify the commonality of label changes throughout the postmarket course of a drug. Diclofenac gel, 5-fluorouracil cream, imiquimod, and ingenol mebutate are examples of actinic keratosis treatments that have all undergone at least one label revision. With the current system of spontaneous reports leading to numerous label changes, each occurrence does not necessarily signify a radical change in the safety of a drug. PMID:28367259

  13. 21 CFR 314.108 - New drug product exclusivity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule... Administration. New chemical entity means a drug that contains no active moiety that has been approved by FDA in...) application. (1) (2) If a drug product that contains a new chemical entity was approved after September...

  14. 21 CFR 314.108 - New drug product exclusivity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule... Administration. New chemical entity means a drug that contains no active moiety that has been approved by FDA in...) application. (1) (2) If a drug product that contains a new chemical entity was approved after September...

  15. 21 CFR 314.108 - New drug product exclusivity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule... Administration. New chemical entity means a drug that contains no active moiety that has been approved by FDA in...) application. (1) (2) If a drug product that contains a new chemical entity was approved after September...

  16. 21 CFR 314.108 - New drug product exclusivity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule... Administration. New chemical entity means a drug that contains no active moiety that has been approved by FDA in...) application. (1) (2) If a drug product that contains a new chemical entity was approved after September...

  17. 21 CFR 341.78 - Labeling of expectorant drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...,” and “make coughs more productive”). Other truthful and nonmisleading statements, describing only the... persistent cough may be a sign of a serious condition. If cough persists for more than 1 week, tends to...

  18. 21 CFR 341.78 - Labeling of expectorant drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...,” and “make coughs more productive”). Other truthful and nonmisleading statements, describing only the... persistent cough may be a sign of a serious condition. If cough persists for more than 1 week, tends to...

  19. 21 CFR 341.78 - Labeling of expectorant drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...,” and “make coughs more productive”). Other truthful and nonmisleading statements, describing only the... persistent cough may be a sign of a serious condition. If cough persists for more than 1 week, tends to...

  20. 21 CFR 341.78 - Labeling of expectorant drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...,” and “make coughs more productive”). Other truthful and nonmisleading statements, describing only the... persistent cough may be a sign of a serious condition. If cough persists for more than 1 week, tends to...

  1. 21 CFR 341.78 - Labeling of expectorant drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...,” and “make coughs more productive”). Other truthful and nonmisleading statements, describing only the... persistent cough may be a sign of a serious condition. If cough persists for more than 1 week, tends to...

  2. 21 CFR 347.52 - Labeling of astringent drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 347... monohydrate identified in § 347.20(b). “For temporary relief of minor skin irritations due to: .” (2) For... witch hazel identified in § 347.12(c). “Relieves minor skin irritations due to: .” (c) Warnings....

  3. 21 CFR 347.52 - Labeling of astringent drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 347... monohydrate identified in § 347.20(b). “For temporary relief of minor skin irritations due to: .” (2) For... witch hazel identified in § 347.12(c). “Relieves minor skin irritations due to: .” (c) Warnings....

  4. 21 CFR 347.52 - Labeling of astringent drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 347... monohydrate identified in § 347.20(b). “For temporary relief of minor skin irritations due to: .” (2) For... witch hazel identified in § 347.12(c). “Relieves minor skin irritations due to: .” (c) Warnings....

  5. 21 CFR 347.52 - Labeling of astringent drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 347... monohydrate identified in § 347.20(b). “For temporary relief of minor skin irritations due to: .” (2) For... witch hazel identified in § 347.12(c). “Relieves minor skin irritations due to: .” (c) Warnings....

  6. 21 CFR 347.52 - Labeling of astringent drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... (CONTINUED) DRUGS FOR HUMAN USE SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 347... monohydrate identified in § 347.20(b). “For temporary relief of minor skin irritations due to: .” (2) For... witch hazel identified in § 347.12(c). “Relieves minor skin irritations due to: .” (c) Warnings....

  7. 78 FR 78366 - Draft Guidance for Industry on Naming of Drug Products Containing Salt Drug Substances; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-26

    ...The Food and Drug Administration (FDA) is announcing the availability of a draft guidance for industry entitled ``Naming of Drug Products Containing Salt Drug Substances.'' The United States Pharmacopeial (U.S.P.) Convention has adopted a monograph naming policy that changed the nomenclature for compendial drug products that contain a salt. Under the new policy, drug names and strengths for......

  8. Inflammatory cytokine production in tumor cells upon chemotherapy drug exposure or upon selection for drug resistance.

    PubMed

    Edwardson, Derek W; Boudreau, Justin; Mapletoft, Jonathan; Lanner, Carita; Kovala, A Thomas; Parissenti, Amadeo M

    2017-01-01

    Tumor Necrosis Factor alpha (TNF-α) has been shown to be released by tumor cells in response to docetaxel, and lipopolysaccharides (LPS), the latter through activation of toll-like receptor 4 (TLR4). However, it is unclear whether the former involves TLR4 receptor activation through direct binding of the drug to TLR4 at the cell surface. The current study was intended to better understand drug-induced TNF-α production in tumor cells, whether from short-term drug exposure or in cells selected for drug resistance. ELISAs were employed to measure cytokine release from breast and ovarian tumor cells in response to several structurally distinct chemotherapy agents and/or TLR4 agonists or antagonists. Drug uptake and drug sensitivity studies were also performed. We observed that several drugs induced TNF-αrelease from multiple tumor cell lines. Docetaxel-induced cytokine production was distinct from that of LPS in both MyD88-positive (MCF-7) and MyD88-deficient (A2780) cells. The acquisition of docetaxel resistance was accompanied by increased constitutive production of TNF-αand CXCL1, which waned at higher levels of resistance. In docetaxel-resistant MCF-7 and A2780 cell lines, the production of TNF-α could not be significantly augmented by docetaxel without the inhibition of P-gp, a transporter protein that promotes drug efflux from tumor cells. Pretreatment of tumor cells with LPS sensitized MyD88-positive cells (but not MyD88-deficient) to docetaxel cytotoxicity in both drug-naive and drug-resistant cells. Our findings suggest that taxane-induced inflammatory cytokine production from tumor cells depends on the duration of exposure, requires cellular drug-accumulation, and is distinct from the LPS response seen in breast tumor cells. Also, stimulation of the LPS-induced pathway may be an attractive target for treatment of drug-resistant disease.

  9. 21 CFR 211.94 - Drug product containers and closures.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS Control of... product containers and closures shall not be reactive, additive, or absorptive so as to alter the safety...

  10. Molecular Biology of Drug Resistance in Mycobacterium tuberculosis

    PubMed Central

    Smith, Tasha; Wolff, Kerstin A.; Nguyen, Liem

    2014-01-01

    Tuberculosis (TB) has become a curable disease thanks to the discovery of antibiotics. However, it has remained one of the most difficult infections to treat. Most current TB regimens consist of six to nine months of daily doses of four drugs that are highly toxic to patients. The purpose of these lengthy treatments is to completely eradicate Mycobacterium tuberculosis, notorious for its ability to resist most antibacterial agents, thereby preventing the formation of drug resistant mutants. On the contrary, the prolonged therapies have led to poor patient adherence. This, together with a severe limit of drug choices, has resulted in the emergence of strains that are increasingly resistant to the few available antibiotics. Here we review our current understanding of molecular mechanisms underlying the profound drug resistance of M. tuberculosis. This knowledge is essential for the development of more effective antibiotics that not only are potent against drug resistant M. tuberculosis strains but also help shorten the current treatment courses required for drug susceptible TB. PMID:23179675

  11. Enhancement of biological activities of nanostructured hydrophobic drug species

    NASA Astrophysics Data System (ADS)

    Han, Qiusen; Yang, Rong; Li, Jingying; Liang, Wei; Zhang, Ying; Dong, Mingdong; Besenbacher, Flemming; Wang, Chen

    2012-03-01

    We report a study of nanoribbons of quercetin, a phase I clinical trial anticancer drug, and their inhibitory effects on cancer cell proliferation. Novel quercetin nanoribbons have been prepared by atmospheric pressure physical vapor deposition (PVD). The nanostructures have been characterized by optical microscopy, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy, etc. Significantly enhanced solubility in PBS solution and increased drug release rate have been observed for quercetin nanoribbons in comparison to those of quercetin powder. The observed increase of inhibitory effects of quercetin nanoribbons on 4T1 cancel cell growth is correlated with an improvement in their solubility and drug release behavior.We report a study of nanoribbons of quercetin, a phase I clinical trial anticancer drug, and their inhibitory effects on cancer cell proliferation. Novel quercetin nanoribbons have been prepared by atmospheric pressure physical vapor deposition (PVD). The nanostructures have been characterized by optical microscopy, scanning electron microscopy, transmission electron microscopy, and Raman spectroscopy, etc. Significantly enhanced solubility in PBS solution and increased drug release rate have been observed for quercetin nanoribbons in comparison to those of quercetin powder. The observed increase of inhibitory effects of quercetin nanoribbons on 4T1 cancel cell growth is correlated with an improvement in their solubility and drug release behavior. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr12013e

  12. Interactions of dendrimers with biological drug targets: reality or mystery - a gap in drug delivery and development research.

    PubMed

    Ahmed, Shaimaa; Vepuri, Suresh B; Kalhapure, Rahul S; Govender, Thirumala

    2016-07-21

    Dendrimers have emerged as novel and efficient materials that can be used as therapeutic agents/drugs or as drug delivery carriers to enhance therapeutic outcomes. Molecular dendrimer interactions are central to their applications and realising their potential. The molecular interactions of dendrimers with drugs or other materials in drug delivery systems or drug conjugates have been extensively reported in the literature. However, despite the growing application of dendrimers as biologically active materials, research focusing on the mechanistic analysis of dendrimer interactions with therapeutic biological targets is currently lacking in the literature. This comprehensive review on dendrimers over the last 15 years therefore attempts to identify the reasons behind the apparent lack of dendrimer-receptor research and proposes approaches to address this issue. The structure, hierarchy and applications of dendrimers are briefly highlighted, followed by a review of their various applications, specifically as biologically active materials, with a focus on their interactions at the target site. It concludes with a technical guide to assist researchers on how to employ various molecular modelling and computational approaches for research on dendrimer interactions with biological targets at a molecular level. This review highlights the impact of a mechanistic analysis of dendrimer interactions on a molecular level, serves to guide and optimise their discovery as medicinal agents, and hopes to stimulate multidisciplinary research between scientific, experimental and molecular modelling research teams.

  13. Legal, workplace, and treatment drug testing with alternate biological matrices on a global scale.

    PubMed

    Cone, E J

    2001-09-15

    Global trends in drug trafficking and drug usage patterns indicate a continuing pattern of escalation throughout the world. Over the last two decades, urinalysis has evolved into a highly accurate means for determining whether individuals have been exposed to illicit drugs of abuse. Advances have also been made in the use of alternate biological matrices such as hair, oral fluids and sweat for drug testing. Often, these new matrices demonstrate some distinct advantages over urinalysis, e.g. less invasive procedures, different time course of drug detection. They may even indicate impairment. National and local laws of each country provide the underpinnings of drug-testing programs, but most countries have not addressed use of these alternate matrices. Currently, only a few countries have statutes that specifically mention use of alternate biological matrices, e.g. United States (Florida state law), Germany, Ireland, Poland and the Czech Republic. Conversely, few countries have prohibited collection of alternate biological specimens or drug test devices that utilize such specimens. In addition, guidelines for implementing drug testing programs have been slow to emerge and most deal primarily with workplace drug testing programs, e.g. United States. Currently, scientific technology utilized in drug testing is advancing rapidly, but there is a clear need for parallel development of guidelines governing the use of alternate matrices for drug testing. This article provides an overview of global drug trafficking patterns and drug use, and results from a survey of legal statutes in 20 countries covering use of alternate matrices for drug testing. In addition, elements needed for the development of guidelines for alternate matrices testing for drugs of abuse are discussed, and specific examples of use of alternate matrices in treatment monitoring are provided.

  14. Lipid-lipid and lipid-drug interactions in biological membranes

    NASA Astrophysics Data System (ADS)

    Martynowycz, Michael W.

    Interactions between lipids and drug molecules in biological membranes help govern proper biological function in organisms. The mechanisms responsible for hydrophobic drug permeation remain elusive. Many small molecule drugs are hydrophobic. These drugs inhibit proteins in the cellular interior. The rise of antibiotic resistance in bacteria is thought to be caused by mutations in protein structure, changing drug kinetics to favor growth. However, small molecule drugs have been shown to have different mechanisms depending in the structure of the lipid membrane of the target cell. Biological membranes are investigated using Langmuir monolayers at the air-liquid interface. These offer the highest level of control in the mimetic system and allow them to be investigated using complementary techniques. Langmuir isotherms and insertion assays are used to determine the area occupied by each lipid in the membrane and the change in area caused by the introduction of a drug molecule, respectively. Specular X-ray reflectivity is used to determine the electron density of the monolayer, and grazing incidence X-ray diffraction is used to determine the in-plane order of the monolayer. These methods determine the affinity of the drug and the mechanism of action. Studies are presented on hydrophobic drugs with mammalian membrane mimics using warfarin along with modified analogues, called superwarfarins. Data shows that toxicity of these modified drugs are modulated by the membrane cholesterol content in cells; explaining several previously unexplained effects of the drugs. Membrane mimics of bacteria are investigated along with their interactions with a hydrophobic antibiotic, novobiocin. Data suggests that permeation of the drug is mediated by modifications to the membrane lipids, and completely ceases translocation under certain circumstances. Circumventing deficiencies in small, hydrophobic drugs is approached by using biologically mimetic oligomers. Peptoids, mimetic of host

  15. Importance of systems biology in engineering microbes for biofuel production.

    PubMed

    Mukhopadhyay, Aindrila; Redding, Alyssa M; Rutherford, Becky J; Keasling, Jay D

    2008-06-01

    Microorganisms have been rich sources for natural products, some of which have found use as fuels, commodity chemicals, specialty chemicals, polymers, and drugs, to name a few. The recent interest in production of transportation fuels from renewable resources has catalyzed numerous research endeavors that focus on developing microbial systems for production of such natural products. Eliminating bottlenecks in microbial metabolic pathways and alleviating the stresses due to production of these chemicals are crucial in the generation of robust and efficient production hosts. The use of systems-level studies makes it possible to comprehensively understand the impact of pathway engineering within the context of the entire host metabolism, to diagnose stresses due to product synthesis, and provides the rationale to cost-effectively engineer optimal industrial microorganisms.

  16. Importance of systems biology in engineering microbes for biofuel production

    SciTech Connect

    Mukhopadhyay, Aindrila; Redding, Alyssa M.; Rutherford, Becky J.; Keasling, Jay D.

    2009-12-02

    Microorganisms have been rich sources for natural products, some of which have found use as fuels, commodity chemicals, specialty chemicals, polymers, and drugs, to name a few. The recent interest in production of transportation fuels from renewable resources has catalyzed numerous research endeavors that focus on developing microbial systems for production of such natural products. Eliminating bottlenecks in microbial metabolic pathways and alleviating the stresses due to production of these chemicals are crucial in the generation of robust and efficient production hosts. The use of systems-level studies makes it possible to comprehensively understand the impact of pathway engineering within the context of the entire host metabolism, to diagnose stresses due to product synthesis, and provides the rationale to cost-effectively engineer optimal industrial microorganisms.

  17. Membrane transporters and drug development: relevance to pharmacogenomics, nutrigenomics, epigenetics, and systems biology.

    PubMed

    Yan, Qing

    2010-01-01

    The study of membrane transporters may result in breakthroughs in the discovery of new drugs and the development of safer drugs. Membrane transporters are essential for fundamental cellular functions and normal physiological processes. These molecules influence drug absorption and distribution and play key roles in drug therapeutic effects. A primary goal of current research in drug discovery and development is to fully understand the interactions between transporters and drugs at both the system levels in the human body and the individual level for personalized therapy. Systematic studies of membrane transporters will help in not only better understanding of diseases from the systems biology point of view but also better drug design and development. The exploration of both pharmacogenomics and systems biology in transporters is necessary to connect individuals' genetic profiles with systematic drug responses in the human body. Understanding of gene-diet interactions and the effects of epigenetic changes on transporter gene expression may help improve clinical drug efficacy. The integration of pharmacogenomics, nutrigenomics, epigenetics, and systems biology may enable us to move from disease treatment to disease prevention and optimal health. The key issues in such integrative understanding include the correlations between structure and function, genotype and phenotype, and systematic interactions among transporters, other proteins, nutrients, drugs, and the environment. The exploration in these key issues may ultimately contribute to personalized medicine with high efficacy but less toxicity.

  18. Continuous downstream processing for high value biological products: A Review.

    PubMed

    Zydney, Andrew L

    2016-03-01

    There is growing interest in the possibility of developing truly continuous processes for the large-scale production of high value biological products. Continuous processing has the potential to provide significant reductions in cost and facility size while improving product quality and facilitating the design of flexible multi-product manufacturing facilities. This paper reviews the current state-of-the-art in separations technology suitable for continuous downstream bioprocessing, focusing on unit operations that would be most appropriate for the production of secreted proteins like monoclonal antibodies. This includes cell separation/recycle from the perfusion bioreactor, initial product recovery (capture), product purification (polishing), and formulation. Of particular importance are the available options, and alternatives, for continuous chromatographic separations. Although there are still significant challenges in developing integrated continuous bioprocesses, recent technological advances have provided process developers with a number of attractive options for development of truly continuous bioprocessing operations.

  19. Synthetic and systems biology for microbial production of commodity chemicals.

    PubMed

    Chubukov, Victor; Mukhopadhyay, Aindrila; Petzold, Christopher J; Keasling, Jay D; Martín, Héctor García

    2016-01-01

    The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.

  20. Synthetic and systems biology for microbial production of commodity chemicals

    SciTech Connect

    Chubukov, Victor; Mukhopadhyay, Aindrila; Petzold, Christopher J.; Keasling, Jay D.; Martín, Héctor Garcia

    2016-04-07

    The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.

  1. Synthetic and systems biology for microbial production of commodity chemicals

    PubMed Central

    Chubukov, Victor; Mukhopadhyay, Aindrila; Petzold, Christopher J; Keasling, Jay D; Martín, Héctor García

    2016-01-01

    The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges start at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering. PMID:28725470

  2. Biological and photochemical degradation of cytostatic drugs under laboratory conditions.

    PubMed

    Franquet-Griell, Helena; Medina, Andrés; Sans, Carme; Lacorte, Silvia

    2017-02-05

    Cytostatic drugs, used in chemotherapy, have emerged as new environmental contaminants due to their recurrent presence in surface waters and genotoxic effects. Yet, their degradability and environmental fate is largely unknown. The aim of this study was to determine the degradation kinetics of 16 cytostatic drugs, prioritized according to their usage and occurrence in hospital and wastewater treatment plants (WWTP) effluents, through the following laboratory scale processes: hydrolysis, aerobic biodegradation, UV-C photolysis, UV-C/H2O2 and simulated solar radiation. Some drugs were unstable in milli-Q water (vincristine, vinblastine, daunorubicin, doxorubicin and irinotecan); others were photodegraded under UV-C light (melphalan and etoposide) but some others were found to be recalcitrant to biodegradation and/or UV-C, making necessary the use of advanced oxidation processes (AOPs) such as UV-C/H2O2 for complete elimination (cytarabine, ifosfamide and cyclophosphamide). Finally, radiation in a solar box was used to simulate the fate of cytostatic drugs in surface waters under natural radiation and complete removal was not observed for any drug. The degradation process was monitored using liquid chromatography coupled to high resolution mass spectrometry and pseudo-first order kinetic degradation constants were calculated. This study provides new data on the degradability of cytostatic compounds in water, thus contributing to the existing knowledge on their fate and risk in the environment.

  3. Natural products from plants as drug candidates and lead compounds against leishmaniasis and trypanosomiasis.

    PubMed

    Salem, Manar M; Werbovetz, Karl A

    2006-01-01

    Millions of people in the developing world are affected by diseases caused by the kinetoplastid parasites: the leishmaniases, African trypanosomiasis, and Chagas disease. In many cases the drugs employed for treatment are toxic, marginally effective, given by injection, and/or compromised by the development of resistance. Since safe, effective, and affordable chemotherapeutic agents for leishmaniasis and trypanosomiasis are clearly needed, the identification of new antikinetoplastid drug candidates should be an urgent priority. Numerous plant-derived natural products from different structural classes have been investigated as antileishmanial and antitrypanosomal candidates, including various alkaloids, terpenoids, flavonoids, and quinonoids. This review outlines the antikinetoplastid activities of plant-derived natural products reported in the literature and also provides an overview of mechanistic studies that have been conducted with these compounds. Given the activities of these agents and their diverse range of effects on parasite biology, natural products are a potentially rich source of drug candidates and leads against leishmaniasis and trypanosomiasis.

  4. Packaging biological cargoes in mesoporous materials: opportunities for drug delivery.

    PubMed

    Siefker, Justin; Karande, Pankaj; Coppens, Marc-Olivier

    2014-11-01

    Confinement of biomolecules in structured nanoporous materials offers several desirable features ranging from chemical and thermal stability, to resistance to degradation from the external environment. A new generation of mesoporous materials presents exciting new possibilities for the formulation and controlled release of biological agents. Such materials address niche applications in enteral and parenteral delivery of biologics, such as peptides, polypeptides, enzymes and proteins for use as therapeutics, imaging agents, biosensors, and adjuvants. Mesoporous silica Santa Barbara Amorphous-15 (SBA-15), with its unique, tunable pore diameter, and easily functionalized surface, provides a representative example of this new generation of materials. Here, we review recent advances in the design and synthesis of nanostructured mesoporous materials, focusing on SBA-15, and highlight opportunities for the delivery of biological agents to various organ and tissue compartments. The SBA-15 platform provides a delivery carrier that is inherently separated from the active biologic due to distinct intra and extra-particle environments. This permits the SBA-15 platform to not require direct modification of the active biological therapeutic. Additionally, this makes the platform universal and allows for its application independent of the desired methods of discovery and development. The SBA-15 platform also directly addresses issues of targeted delivery and controlled release, although future challenges in the implementation of this platform reside in particle design, biocompatibility, and the tunability of the internal and external material properties. Examples illustrating the flexibility in the application of the SBA-15 platform are also discussed.

  5. Evaluation of anti-inflammatory drug-conjugated silicon quantum dots: their cytotoxicity and biological effect.

    PubMed

    Hanada, Sanshiro; Fujioka, Kouki; Futamura, Yasuhiro; Manabe, Noriyoshi; Hoshino, Akiyoshi; Yamamoto, Kenji

    2013-01-10

    Silicon quantum dots (Si-QDs) have great potential for biomedical applications, including their use as biological fluorescent markers and carriers for drug delivery systems. Biologically inert Si-QDs are less toxic than conventional cadmium-based QDs, and can modify the surface of the Si-QD with covalent bond. We synthesized water-soluble alminoprofen-conjugated Si-QDs (Ap-Si). Alminoprofen is a non-steroid anti-inflammatory drug (NSAID) used as an analgesic for rheumatism. Our results showed that the "silicon drug" is less toxic than the control Si-QD and the original drug. These phenomena indicate that the condensed surface integration of ligand/receptor-type drugs might reduce the adverse interaction between the cells and drug molecules. In addition, the medicinal effect of the Si-QDs (i.e., the inhibition of COX-2 enzyme) was maintained compared to that of the original drug. The same drug effect is related to the integration ratio of original drugs, which might control the binding interaction between COX-2 and the silicon drug. We conclude that drug conjugation with biocompatible Si-QDs is a potential method for functional pharmaceutical drug development.

  6. Biological evaluation of layered double hydroxides as efficient drug vehicles.

    PubMed

    Li, Yan; Liu, Dan; Ai, Hanhua; Chang, Qing; Liu, Dandan; Xia, Ying; Liu, Shuwen; Peng, Nanfang; Xi, Zhuge; Yang, Xu

    2010-03-12

    Recently there has been a rapid expansion of the development of bioinorganic hybrid systems for safe drug delivery. Layered double hydroxides (LDH), a variety of available inorganic matrix, possess great promise for this purpose. In this study, an oxidative stress biomarker system, including measurement of reactive oxygen species, glutathione content, endogenous nitric oxide, carbonyl content in proteins, DNA strand breaks and DNA-protein crosslinks, was designed to evaluate the biocompatibility of different concentrations of nano-Zn/Al-LDH with a Hela cell line. The drug delivery activity of the LDH-folic-acid complex was also assessed. The resulting data clearly demonstrated that nano-LDH could be applied as a relatively safe drug vehicle with good delivery activity, but with the caveat that the effects of high dosages observed here should not be ignored when attempting to maximize therapeutic activity by increasing LDH concentration.

  7. Irradiation of advanced health care products - Tissues and biologics

    NASA Astrophysics Data System (ADS)

    Winters, Martell

    2014-12-01

    Radiation sterilization of tissues and biologics has become more common in recent years. As a result it has become critical to understand how to adapt the typical test methods and validation approaches to a tissue or biological product scenario. Also data evaluation sometimes becomes more critical than with traditional medical devices because for many tissues and biologics a low radiation dose is required. It is the intent behind this paper to provide information on adapting bioburden tests used in radiation validations such that the data can be most effectively used on tissues and biologics. In addition challenges with data evaluation are discussed, particularly the use of less-than values for bioburden results in radiation validation studies.

  8. Lessons from innovation in drug-device combination products.

    PubMed

    Couto, Daniela S; Perez-Breva, Luis; Saraiva, Pedro; Cooney, Charles L

    2012-01-01

    Drug-device combination products introduced a new dynamic on medical product development, regulatory approval, and corporate interaction that provide valuable lessons for the development of new generations of combination products. This paper examines the case studies of drug-eluting stents and transdermal patches to facilitate a detailed understanding of the challenges and opportunities introduced by combination products when compared to previous generations of traditional medical or drug delivery devices. Our analysis indicates that the largest barrier to introduce a new kind of combination products is the determination of the regulatory center that is to oversee its approval. The first product of a new class of combination products offers a learning opportunity for the regulator and the sponsor. Once that first product is approved, the leading regulatory center is determined, and the uncertainty about the entire class of combination products is drastically reduced. The sponsor pioneering a new class of combination products assumes a central role in reducing this uncertainty by advising the decision on the primary function of the combination product. Our analysis also suggests that this decision influences the nature (pharmaceutical, biotechnology, or medical devices) of the companies that will lead the introduction of these products into the market, and guide the structure of corporate interaction thereon.

  9. De Novo Fragment Design for Drug Discovery and Chemical Biology.

    PubMed

    Rodrigues, Tiago; Reker, Daniel; Welin, Martin; Caldera, Michael; Brunner, Cyrill; Gabernet, Gisela; Schneider, Petra; Walse, Björn; Schneider, Gisbert

    2015-12-07

    Automated molecular de novo design led to the discovery of an innovative inhibitor of death-associated protein kinase 3 (DAPK3). An unprecedented crystal structure of the inactive DAPK3 homodimer shows the fragment-like hit bound to the ATP pocket. Target prediction software based on machine learning models correctly identified additional macromolecular targets of the computationally designed compound and the structurally related marketed drug azosemide. The study validates computational de novo design as a prime method for generating chemical probes and starting points for drug discovery.

  10. Systems biology-embedded target validation: improving efficacy in drug discovery.

    PubMed

    Vandamme, Drieke; Minke, Benedikt A; Fitzmaurice, William; Kholodenko, Boris N; Kolch, Walter

    2014-01-01

    The pharmaceutical industry is faced with a range of challenges with the ever-escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment.

  11. 42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Transitional pass-through payments: Drugs and... DEPARTMENT SERVICES Transitional Pass-through Payments § 419.64 Transitional pass-through payments: Drugs and biologicals. (a) Eligibility for pass-through payment. CMS makes a transitional pass-through payment for...

  12. 42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Transitional pass-through payments: Drugs and... HOSPITAL OUTPATIENT DEPARTMENT SERVICES Transitional Pass-through Payments § 419.64 Transitional pass-through payments: Drugs and biologicals. (a) Eligibility for pass-through payment. CMS makes a...

  13. 42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Transitional pass-through payments: Drugs and... HOSPITAL OUTPATIENT DEPARTMENT SERVICES Transitional Pass-through Payments § 419.64 Transitional pass-through payments: Drugs and biologicals. (a) Eligibility for pass-through payment. CMS makes a...

  14. 42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Transitional pass-through payments: Drugs and... DEPARTMENT SERVICES Transitional Pass-through Payments § 419.64 Transitional pass-through payments: Drugs and biologicals. (a) Eligibility for pass-through payment. CMS makes a transitional pass-through payment for the...

  15. 42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 3 2013-10-01 2013-10-01 false Transitional pass-through payments: Drugs and... HOSPITAL OUTPATIENT DEPARTMENT SERVICES Transitional Pass-through Payments § 419.64 Transitional pass-through payments: Drugs and biologicals. (a) Eligibility for pass-through payment. CMS makes a...

  16. Network-based drug discovery by integrating systems biology and computational technologies

    PubMed Central

    Leung, Elaine L.; Cao, Zhi-Wei; Jiang, Zhi-Hong; Zhou, Hua

    2013-01-01

    Network-based intervention has been a trend of curing systemic diseases, but it relies on regimen optimization and valid multi-target actions of the drugs. The complex multi-component nature of medicinal herbs may serve as valuable resources for network-based multi-target drug discovery due to its potential treatment effects by synergy. Recently, robustness of multiple systems biology platforms shows powerful to uncover molecular mechanisms and connections between the drugs and their targeting dynamic network. However, optimization methods of drug combination are insufficient, owning to lacking of tighter integration across multiple ‘-omics’ databases. The newly developed algorithm- or network-based computational models can tightly integrate ‘-omics’ databases and optimize combinational regimens of drug development, which encourage using medicinal herbs to develop into new wave of network-based multi-target drugs. However, challenges on further integration across the databases of medicinal herbs with multiple system biology platforms for multi-target drug optimization remain to the uncertain reliability of individual data sets, width and depth and degree of standardization of herbal medicine. Standardization of the methodology and terminology of multiple system biology and herbal database would facilitate the integration. Enhance public accessible databases and the number of research using system biology platform on herbal medicine would be helpful. Further integration across various ‘-omics’ platforms and computational tools would accelerate development of network-based drug discovery and network medicine. PMID:22877768

  17. Predicting Drug Use at Electronic Music Dance Events: Self-Reports and Biological Measurement

    ERIC Educational Resources Information Center

    Johnson, Mark B.; Voas, Robert A.; Miller, Brenda A.; Holder, Harold D.

    2009-01-01

    Most information on the prevalence of drug use comes from self-report surveys. The sensitivity of such information is cause for concern about the accuracy of self-report measures. In this study, self-reported drug use in the last 48 hr is compared to results from biological assays of saliva samples from 371 young adults entering clubs. The…

  18. Network-based drug discovery by integrating systems biology and computational technologies.

    PubMed

    Leung, Elaine L; Cao, Zhi-Wei; Jiang, Zhi-Hong; Zhou, Hua; Liu, Liang

    2013-07-01

    Network-based intervention has been a trend of curing systemic diseases, but it relies on regimen optimization and valid multi-target actions of the drugs. The complex multi-component nature of medicinal herbs may serve as valuable resources for network-based multi-target drug discovery due to its potential treatment effects by synergy. Recently, robustness of multiple systems biology platforms shows powerful to uncover molecular mechanisms and connections between the drugs and their targeting dynamic network. However, optimization methods of drug combination are insufficient, owning to lacking of tighter integration across multiple '-omics' databases. The newly developed algorithm- or network-based computational models can tightly integrate '-omics' databases and optimize combinational regimens of drug development, which encourage using medicinal herbs to develop into new wave of network-based multi-target drugs. However, challenges on further integration across the databases of medicinal herbs with multiple system biology platforms for multi-target drug optimization remain to the uncertain reliability of individual data sets, width and depth and degree of standardization of herbal medicine. Standardization of the methodology and terminology of multiple system biology and herbal database would facilitate the integration. Enhance public accessible databases and the number of research using system biology platform on herbal medicine would be helpful. Further integration across various '-omics' platforms and computational tools would accelerate development of network-based drug discovery and network medicine.

  19. 41 CFR 101-42.1102-5 - Drugs, biologicals, and reagents other than controlled substances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... UTILIZATION AND DISPOSAL 42-UTILIZATION AND DISPOSAL OF HAZARDOUS MATERIALS AND CERTAIN CATEGORIES OF PROPERTY 42.11-Special Types of Hazardous Materials and Certain Categories of Property § 101-42.1102-5 Drugs... 41 Public Contracts and Property Management 2 2013-07-01 2012-07-01 true Drugs, biologicals,...

  20. 41 CFR 101-42.1102-5 - Drugs, biologicals, and reagents other than controlled substances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... UTILIZATION AND DISPOSAL 42-UTILIZATION AND DISPOSAL OF HAZARDOUS MATERIALS AND CERTAIN CATEGORIES OF PROPERTY 42.11-Special Types of Hazardous Materials and Certain Categories of Property § 101-42.1102-5 Drugs... 41 Public Contracts and Property Management 2 2011-07-01 2007-07-01 true Drugs, biologicals,...

  1. Predicting Drug Use at Electronic Music Dance Events: Self-Reports and Biological Measurement

    ERIC Educational Resources Information Center

    Johnson, Mark B.; Voas, Robert A.; Miller, Brenda A.; Holder, Harold D.

    2009-01-01

    Most information on the prevalence of drug use comes from self-report surveys. The sensitivity of such information is cause for concern about the accuracy of self-report measures. In this study, self-reported drug use in the last 48 hr is compared to results from biological assays of saliva samples from 371 young adults entering clubs. The…

  2. 9 CFR 106.1 - Biological products; exemption.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS EXEMPTION FOR BIOLOGICAL... control of the Department in the prevention, control or eradication of animal diseases in connection with (a) an official USDA program; or (b) an emergency animal disease situation, or (c) a...

  3. PRODUCTION AND BIOLOGICAL SIGNIFICANCE OF METHYLATED TRIVALENT ARSENICALS

    EPA Science Inventory

    PRODUCTION AND BIOLOGICAL SIGNIFICANCE OF METHYLATED TRIVALENT ARSENICALS

    Miroslav Styblo1,2,*, Zuzana Drobna1, Felecia S. Walton1, Ilona Jaspers1,2, Shan Lin3,
    Stephen B. Waters3, David J. Thomas4

    1Department of Pediatrics, 2Center for Environmental Medicine an...

  4. PRODUCTION AND BIOLOGICAL SIGNIFICANCE OF METHYLATED TRIVALENT ARSENICALS

    EPA Science Inventory

    PRODUCTION AND BIOLOGICAL SIGNIFICANCE OF METHYLATED TRIVALENT ARSENICALS

    Miroslav Styblo1,2,*, Zuzana Drobna1, Felecia S. Walton1, Ilona Jaspers1,2, Shan Lin3,
    Stephen B. Waters3, David J. Thomas4

    1Department of Pediatrics, 2Center for Environmental Medicine an...

  5. Biological cleaning of soil and reservoirs from oil products

    SciTech Connect

    Zinberg, M.B.; Ivanovskaya, I.B.; Gafarov, N.A.

    1996-12-31

    The production of oil and gas condensate invariably involves environmental hazards: water and soil contamination due to miscellaneous breakdowns of technological equipment and pipeline damage. Among many existing contamination methods biological cleaning has become more popular lately. It took us some years to make investigations and to carry out a number of field tests in order to develop biological methods of cleaning soil and reservoirs from oil and gas condensate products. Our method is based on the use of special biological agents containing various active hydrocarbon oxidizing bacteria. It has been experimentally proved that biological agents of {open_quotes}Devouroil{close_quotes} possess the greatest oxidizing properties. {open_quotes}Devouroil{close_quotes} contains five kinds of hydrocarbon oxidizing bacteria of Pseudomonas, Rodococcus, Candida genera. These bacteria are extracted from natural ecosystems: underground waters, soils, reservoirs. As the agents are grown on oil distillate, they are very destructive to different oil products. We also proved the described microorganisms ability to oxidize sulfate oil and hydrocarbon condensate, which are the most toxic components. For four years our colleagues have been cleaning soil and reservoirs contaminated with oil, black oil, gas condensate and other products of hydrocarbon origin. This method was used to treat different kinds of soil and ground (grass and arable land, swamp and forest) in actual hazardous situations involving oil and gas condensate spills. Besides it was successfully applied to clean sludge storage which had been filled with oil process sewage for several years.

  6. Predicting neurological Adverse Drug Reactions based on biological, chemical and phenotypic properties of drugs using machine learning models.

    PubMed

    Jamal, Salma; Goyal, Sukriti; Shanker, Asheesh; Grover, Abhinav

    2017-04-13

    Adverse drug reactions (ADRs) have become one of the primary reasons for the failure of drugs and a leading cause of deaths. Owing to the severe effects of ADRs, there is an urgent need for the generation of effective models which can accurately predict ADRs during early stages of drug development based on integration of various features of drugs. In the current study, we have focused on neurological ADRs and have used various properties of drugs that include biological properties (targets, transporters and enzymes), chemical properties (substructure fingerprints), phenotypic properties (side effects (SE) and therapeutic indications) and a combinations of the two and three levels of features. We employed relief-based feature selection technique to identify relevant properties and used machine learning approach to generated learned model systems which would predict neurological ADRs prior to preclinical testing. Additionally, in order to explain the efficiency and applicability of the models, we tested them to predict the ADRs for already existing anti-Alzheimer drugs and uncharacterized drugs, respectively in side effect resource (SIDER) database. The generated models were highly accurate and our results showed that the models based on chemical (accuracy 93.20%), phenotypic (accuracy 92.41%) and combination of three properties (accuracy 94.18%) were highly accurate while the models based on biological properties (accuracy 82.11%) were highly informative.

  7. 21 CFR 201.312 - Magnesium sulfate heptahydrate; label declaration on drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Magnesium sulfate heptahydrate; label declaration on drug products. 201.312 Section 201.312 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Drug Products § 201.312 Magnesium sulfate heptahydrate; label declaration on drug products....

  8. 21 CFR 201.312 - Magnesium sulfate heptahydrate; label declaration on drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Magnesium sulfate heptahydrate; label declaration on drug products. 201.312 Section 201.312 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Drug Products § 201.312 Magnesium sulfate heptahydrate; label declaration on drug products....

  9. 21 CFR 200.51 - Aqueous-based drug products for oral inhalation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Aqueous-based drug products for oral inhalation... SERVICES (CONTINUED) DRUGS: GENERAL GENERAL Requirements for Specific Classes of Drugs § 200.51 Aqueous-based drug products for oral inhalation. (a) All aqueous-based drug products for oral inhalation must be...

  10. 21 CFR 200.51 - Aqueous-based drug products for oral inhalation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Aqueous-based drug products for oral inhalation... SERVICES (CONTINUED) DRUGS: GENERAL GENERAL Requirements for Specific Classes of Drugs § 200.51 Aqueous-based drug products for oral inhalation. (a) All aqueous-based drug products for oral inhalation must be...

  11. 21 CFR 200.51 - Aqueous-based drug products for oral inhalation.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false Aqueous-based drug products for oral inhalation... SERVICES (CONTINUED) DRUGS: GENERAL GENERAL Requirements for Specific Classes of Drugs § 200.51 Aqueous-based drug products for oral inhalation. (a) All aqueous-based drug products for oral inhalation must be...

  12. 21 CFR 200.51 - Aqueous-based drug products for oral inhalation.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Aqueous-based drug products for oral inhalation... SERVICES (CONTINUED) DRUGS: GENERAL GENERAL Requirements for Specific Classes of Drugs § 200.51 Aqueous-based drug products for oral inhalation. (a) All aqueous-based drug products for oral inhalation must be...

  13. 21 CFR 200.51 - Aqueous-based drug products for oral inhalation.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Aqueous-based drug products for oral inhalation... SERVICES (CONTINUED) DRUGS: GENERAL GENERAL Requirements for Specific Classes of Drugs § 200.51 Aqueous-based drug products for oral inhalation. (a) All aqueous-based drug products for oral inhalation must be...

  14. 21 CFR 201.312 - Magnesium sulfate heptahydrate; label declaration on drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false Magnesium sulfate heptahydrate; label declaration on drug products. 201.312 Section 201.312 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Drug Products § 201.312 Magnesium sulfate heptahydrate; label declaration on drug products. Magnesium...

  15. 21 CFR 201.312 - Magnesium sulfate heptahydrate; label declaration on drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 4 2012-04-01 2012-04-01 false Magnesium sulfate heptahydrate; label declaration on drug products. 201.312 Section 201.312 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Drug Products § 201.312 Magnesium sulfate heptahydrate; label declaration on drug products. Magnesium...

  16. 21 CFR 201.312 - Magnesium sulfate heptahydrate; label declaration on drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false Magnesium sulfate heptahydrate; label declaration on drug products. 201.312 Section 201.312 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... Drug Products § 201.312 Magnesium sulfate heptahydrate; label declaration on drug products. Magnesium...

  17. Evaluating and Reporting the Immunogenicity Impacts for Biological Products--a Clinical Pharmacology Perspective.

    PubMed

    Wang, Yow-Ming C; Wang, Jie; Hon, Yuen Yi; Zhou, Lin; Fang, Lanyan; Ahn, Hae Young

    2016-03-01

    Immunogenicity assessment is important for biological products due to potential impacts of immunogenicity on safety and efficacy. We reviewed the prescribing information and the FDA's clinical pharmacology review of 121 approved biological products for evaluating and reporting of immunogenicity data. Of the 121 products, 89% (n = 108) reported the incidence of immunogenicity and 49% (n = 59) reported immunogenicity impact on efficacy. However, only 26% (n = 31) reported whether the immunogenicity affected pharmacokinetics. A subset of 16 products reported effects of anti-drug antibodies (ADA) on both systemic clearance and efficacy; 8 of 16 products had increased systemic clearance coinciding with reduced efficacy, and 6 of 16 products had no changes in either clearance or efficacy. Factors contributing to infrequent reporting of the ADA effect on exposure and methods for determining the effect of ADA on exposure are summarized. Measuring ADA and drug concentrations concurrently over time enables the evaluation of ADA impact on pharmacokinetics. Within-subject comparison of concentration data (before vs. after ADA formation) is a useful alternative to between-subject (ADA+ vs. ADA-) comparison when sample size is limited or when the majority of subjects developed ADA. The biological complexity of immune responses presents challenges to quantifying the ADA impact on pharmacokinetics using model-based methods. Our findings support that pharmacokinetic exposure is more sensitive than efficacy endpoints for evaluating ADA effects. A decrease in drug concentration due to formation of ADA during treatment can serve as an early indicator for potential reduced efficacy occurring at a later time.

  18. Stability profiles of drug products extended beyond labeled expiration dates.

    PubMed

    Lyon, Robbe C; Taylor, Jeb S; Porter, Donna A; Prasanna, Hullahalli R; Hussain, Ajaz S

    2006-07-01

    The American Medical Association has questioned whether expiration dating markedly underestimates the actual shelf life of drug products. Results from the shelf life extension program (SLEP) have been evaluated to provide extensive data to address this issue. The SLEP has been administered by the Food and Drug Administration for the United States Department of Defense (DOD) for 20 years. This program probably contains the most extensive source of pharmaceutical stability data extant. This report summarizes extended stability profiles for 122 different drug products (3,005 different lots). The drug products were categorized into five groups based on incidence of initial extension failures and termination failures (extended lot eventually failed upon re-testing). Based on testing and stability assessment, 88% of the lots were extended at least 1 year beyond their original expiration date for an average extension of 66 months, but the additional stability period was highly variable. The SLEP data supports the assertion that many drug products, if properly stored, can be extended past the expiration date. Due to the lot-to-lot variability, the stability and quality of extended drug products can only be assured by periodic testing and systematic evaluation of each lot.

  19. A Historical Overview of Natural Products in Drug Discovery

    PubMed Central

    Dias, Daniel A.; Urban, Sylvia; Roessner, Ute

    2012-01-01

    Historically, natural products have been used since ancient times and in folklore for the treatment of many diseases and illnesses. Classical natural product chemistry methodologies enabled a vast array of bioactive secondary metabolites from terrestrial and marine sources to be discovered. Many of these natural products have gone on to become current drug candidates. This brief review aims to highlight historically significant bioactive marine and terrestrial natural products, their use in folklore and dereplication techniques to rapidly facilitate their discovery. Furthermore a discussion of how natural product chemistry has resulted in the identification of many drug candidates; the application of advanced hyphenated spectroscopic techniques to aid in their discovery, the future of natural product chemistry and finally adopting metabolomic profiling and dereplication approaches for the comprehensive study of natural product extracts will be discussed. PMID:24957513

  20. Interfacing materials science and biology for drug carrier design.

    PubMed

    Such, Georgina K; Yan, Yan; Johnston, Angus P R; Gunawan, Sylvia T; Caruso, Frank

    2015-04-08

    Over the last ten years, there has been considerable research interest in the development of polymeric carriers for biomedicine. Such delivery systems have the potential to significantly reduce side effects and increase the bioavailability of poorly soluble therapeutics. The design of carriers has relied on harnessing specific variations in biological conditions, such as pH or redox potential, and more recently, by incorporating specific peptide cleavage sites for enzymatic hydrolysis. Although much progress has been made in this field, the specificity of polymeric carriers is still limited when compared with their biological counterparts. To synthesize the next generation of carriers, it is important to consider the biological rationale for materials design. This requires a detailed understanding of the cellular microenvironments and how these can be harnessed for specific applications. In this review, several important physiological cues in the cellular microenvironments are outlined, with a focus on changes in pH, redox potential, and the types of enzymes present in specific regions. Furthermore, recent studies that use such biologically inspired triggers to design polymeric carriers are highlighted, focusing on applications in the field of therapeutic delivery.

  1. 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.

  2. 21 CFR 310.509 - Parenteral drug products in plastic containers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Parenteral drug products in plastic containers... Parenteral drug products in plastic containers. (a) Any parenteral drug product packaged in a plastic... parenteral drug product for intravenous use in humans that is packaged in a plastic immediate container on or...

  3. 21 CFR 310.509 - Parenteral drug products in plastic containers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Parenteral drug products in plastic containers... Parenteral drug products in plastic containers. (a) Any parenteral drug product packaged in a plastic... parenteral drug product for intravenous use in humans that is packaged in a plastic immediate container on or...

  4. 21 CFR 310.509 - Parenteral drug products in plastic containers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Parenteral drug products in plastic containers... Parenteral drug products in plastic containers. (a) Any parenteral drug product packaged in a plastic... parenteral drug product for intravenous use in humans that is packaged in a plastic immediate container on or...

  5. 21 CFR 310.509 - Parenteral drug products in plastic containers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Parenteral drug products in plastic containers... Parenteral drug products in plastic containers. (a) Any parenteral drug product packaged in a plastic... parenteral drug product for intravenous use in humans that is packaged in a plastic immediate container on or...

  6. Biological background knowledge and learning from a drug and alcohol education program.

    PubMed

    Sigelman, Carol K; Bridges, Lisa J; Sorongon, Alberto G; Rinehart, Cheryl S; Brewster, Albert B; Wirtz, Philip

    2003-06-01

    The authors asked whether having a base of relevant biological knowledge put school children in a better position to understand the effects of alcohol and cocaine and to learn about these effects when exposed to a curriculum presenting a physiological theory of drug action. Participants were 337 ethnically diverse 3rd- through 6th-grade students who were pretested, trained, and posttested. Multiple regression analyses revealed that knowledge of the basic functions of the heart, blood, and brain predicted certain drug-knowledge variables. Students with greater biological background knowledge also learned more from instruction, a finding with implications for enhancing drug and other health education programs.

  7. Using Nonexperts for Annotating Pharmacokinetic Drug-Drug Interaction Mentions in Product Labeling: A Feasibility Study

    PubMed Central

    Ning, Yifan; Hernandez, Andres; Horn, John R; Jacobson, Rebecca; Boyce, Richard D

    2016-01-01

    Background Because vital details of potential pharmacokinetic drug-drug interactions are often described in free-text structured product labels, manual curation is a necessary but expensive step in the development of electronic drug-drug interaction information resources. The use of nonexperts to annotate potential drug-drug interaction (PDDI) mentions in drug product label annotation may be a means of lessening the burden of manual curation. Objective Our goal was to explore the practicality of using nonexpert participants to annotate drug-drug interaction descriptions from structured product labels. By presenting annotation tasks to both pharmacy experts and relatively naïve participants, we hoped to demonstrate the feasibility of using nonexpert annotators for drug-drug information annotation. We were also interested in exploring whether and to what extent natural language processing (NLP) preannotation helped improve task completion time, accuracy, and subjective satisfaction. Methods Two experts and 4 nonexperts were asked to annotate 208 structured product label sections under 4 conditions completed sequentially: (1) no NLP assistance, (2) preannotation of drug mentions, (3) preannotation of drug mentions and PDDIs, and (4) a repeat of the no-annotation condition. Results were evaluated within the 2 groups and relative to an existing gold standard. Participants were asked to provide reports on the time required to complete tasks and their perceptions of task difficulty. Results One of the experts and 3 of the nonexperts completed all tasks. Annotation results from the nonexpert group were relatively strong in every scenario and better than the performance of the NLP pipeline. The expert and 2 of the nonexperts were able to complete most tasks in less than 3 hours. Usability perceptions were generally positive (3.67 for expert, mean of 3.33 for nonexperts). Conclusions The results suggest that nonexpert annotation might be a feasible option for comprehensive

  8. New natural products as new leads for antibacterial drug discovery.

    PubMed

    Brown, Dean G; Lister, Troy; May-Dracka, Tricia L

    2014-01-15

    Natural products have been a rich source of antibacterial drugs for many decades, but investments in this area have declined over the past two decades. The purpose of this review article is to provide a recent survey of new natural product classes and the mechanisms by which they work.

  9. 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.

  10. Potential biological targets for bioassay development in drug discovery of Sturge-Weber syndrome.

    PubMed

    Mohammadipanah, Fatemeh; Salimi, Fatemeh

    2017-09-21

    Sturge-Weber Syndrome (SWS) is a neurocutaneous disease with clinical manifestations including ocular (glaucoma), cutaneous (port-wine birthmark), neurologic (seizures), and vascular problems. Molecular mechanisms of SWS pathogenesis are initiated by the somatic mutation in GNAQ. Therefore, no definite treatments exist for SWS and treatment options only mitigate the intensity of its clinical manifestations. Biological assay design for drug discovery against this syndrome demands comprehensive knowledge on mechanisms which are involved in its pathogenesis. By analysis of the interrelated molecular targets of SWS, some in vitro bioassay systems can be allotted for drug screening against its progression. Development of such platforms of bioassay can bring along the implementation of high-throughput screening of natural or synthetic compounds in drug discovery programs. Regarding the fact that study of molecular targets and their integration in biological assay design can facilitate the process of effective drug discovery; some potential biological targets and their respective biological assay for SWS drug discovery are propounded in this review. For this purpose, some biological targets for SWS drug discovery such as acetylcholinesterase, alkaline phosphatase, GABAergic receptors, Hypoxia-Inducible Factor (HIF)-1α and 2α are suggested. © 2017 John Wiley & Sons A/S.

  11. NATURAL PRODUCTS: A CONTINUING SOURCE OF NOVEL DRUG LEADS

    PubMed Central

    Cragg, Gordon M.; Newman, David J.

    2013-01-01

    1. Background Nature has been a source of medicinal products for millennia, with many useful drugs developed from plant sources. Following discovery of the penicillins, drug discovery from microbial sources occurred and diving techniques in the 1970s opened the seas. Combinatorial chemistry (late 1980s), shifted the focus of drug discovery efforts from Nature to the laboratory bench. 2. Scope of Review This review traces natural products drug discovery, outlining important drugs from natural sources that revolutionized treatment of serious diseases. It is clear Nature will continue to be a major source of new structural leads, and effective drug development depends on multidisciplinary collaborations. 3. Major Conclusions The explosion of genetic information led not only to novel screens, but the genetic techniques permitted the implementation of combinatorial biosynthetic technology and genome mining. The knowledge gained has allowed unknown molecules to be identified. These novel bioactive structures can be optimized by using combinatorial chemistry generating new drug candidates for many diseases. 4 General Significance: The advent of genetic techniques that permitted the isolation / expression of biosynthetic cassettes from microbes may well be the new frontier for natural products lead discovery. It is now apparent that biodiversity may be much greater in those organisms. The numbers of potential species involved in the microbial world are many orders of magnitude greater than those of plants and multi-celled animals. Coupling these numbers to the number of currently unexpressed biosynthetic clusters now identified (>10 per species) the potential of microbial diversity remains essentially untapped. PMID:23428572

  12. High-throughput electronic biology: mining information for drug discovery.

    PubMed

    Loging, William; Harland, Lee; Williams-Jones, Bryn

    2007-03-01

    The vast range of in silico resources that are available in life sciences research hold much promise towards aiding the drug discovery process. To fully realize this opportunity, computational scientists must consider the practical issues of data integration and identify how best to apply these resources scientifically. In this article we describe in silico approaches that are driven towards the identification of testable laboratory hypotheses; we also address common challenges in the field. We focus on flexible, high-throughput techniques, which may be initiated independently of 'wet-lab' experimentation, and which may be applied to multiple disease areas. The utility of these approaches in drug discovery highlights the contribution that in silico techniques can make and emphasizes the need for collaboration between the areas of disease research and computational science.

  13. Targeted Protein Degradation: from Chemical Biology to Drug Discovery.

    PubMed

    Cromm, Philipp M; Crews, Craig M

    2017-09-21

    Traditional pharmaceutical drug discovery is almost exclusively focused on directly controlling protein activity to cure diseases. Modulators of protein activity, especially inhibitors, are developed and applied at high concentration to achieve maximal effects. Thereby, reduced bioavailability and off-target effects can hamper compound efficacy. Nucleic acid-based strategies that control protein function by affecting expression have emerged as an alternative. However, metabolic stability and broad bioavailability represent development hurdles that remain to be overcome for these approaches. More recently, utilizing the cell's own protein destruction machinery for selective degradation of essential drivers of human disorders has opened up a new and exciting area of drug discovery. Small-molecule-induced proteolysis of selected substrates offers the potential of reaching beyond the limitations of the current pharmaceutical paradigm to expand the druggable target space. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Biological Drugs in Guillain-Barré Syndrome: An Update.

    PubMed

    Motamed-Gorji, Nazgol; Matin, Nassim; Tabatabaie, Omidreza; Pavone, Piero; Romano, Catia; Falsaperla, Raffaele; Vitaliti, Giovanna

    2017-01-01

    Guillain-Barré Syndrome (GBS) is currently considered the most common global cause of acute flaccid paralysis. Currently, standard therapy for Guillain-Barré Syndrome includes intravenous immunoglobulin or plasma exchange. Despite medical advances regarding these treatments, many treated patients do not reach full recovery. Therefore several biological agents have attracted the attentions from researchers during the last decades, and various studies have investigated their role in Guillain-Barré Syndrome. The present study aims to address emerging biological approaches to GBS while considering their efficiency and safety in treating the disease. An extensive electronic literature search was conducted by two researchers from April 2016 to July 2016. Original articles, clinical trials, systematic reviews (with or without meta-analysis) and case reports were selected. Titles and abstracts of papers were screened by reviewers to determine whether they met the eligibility criteria, and full texts of the selected articles were retrieved. Herein authors focused on the literature data concerning emerging biological therapeutic agents, namely anti-C5 monoclonal antibody (Eculizumab), anti-C1q monoclonal antibody, anti-T cell monoclonal antibody, anti-CD2 monoclonal antibody, anti L-selectin monoclonal antibody, anti- CD20 monoclonal antibody (Rituximab), anti-CD52 monoclonal antibody (Alemtuzumab) and cytokine targets. By far, none of these agents have been approved for the treatment of GBS by FDA. Literature findings represented in current review herald promising results for using these biological targets. Current review represents a summary of what is already in regards and what progress is required to improve the immunotherapeutic approach of treating GBS via future studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Methods in systems biology of experimental methamphetamine drug abuse.

    PubMed

    Kobeissy, Firas H; Sadasivan, Shankar; Buchanan, Melinda; Zhang, Zhiqun; Gold, Mark S; Wang, Kevin K W

    2010-01-01

    The use of methamphetamine (METH) as recreational drugs is a growing problem worldwide with recent concerns that it might cause long-lasting harmful effects to the human brain. METH is an illicit drug that is known to exert neurotoxic effects on both dopaminergic and serotonergic neural systems. Our laboratory has been studying the biochemical mechanisms underlying METH-induced neurotoxic effects both in vivo and in vitro. Our psychoproteomics METH abuse research focuses on the global alteration of cortical protein expression in rats treated with acute METH. In our analysis, an altered protein expression was identified using a multistep protein separation/proteomic platform. Differential changes of the selected proteins were further confirmed by quantitative immunoblotting. Our study identified 82 differentially expressed proteins, 40 of which were downregulated and 42 of which were upregulated post acute METH treatment. In this chapter, we describe the current protocols for the neuronal cell culture in vitro and the in vivo rat model of acute METH treatment (4 x 10 mg/kg) coupled with the description current bioinformatics analysis utilized to analyze the different implicated interaction protein/gene maps that reflected on the altered functions observed. These methods and protocols are discussed in the paradigm of the acute model of METH drug abuse and neuronal cell culture and can be applied on other models of substance abuse such as on MDMA or cocaine.

  16. Chemical biology 2012: from drug targets to biological systems and back.

    PubMed

    Socher, Elke; Grossmann, Tom N

    2013-01-02

    Multiple sites sharing a common target: This year's EMBO conference on chemical biology encouraged over 340 researchers to come to Heidelberg, Germany, and discuss the use of diverse chemical strategies and tools to investigate biological questions and better understand cellular processes. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Pregnane X receptor and natural products: beyond drug–drug interactions

    PubMed Central

    Staudinger, Jeff L; Ding, Xunshan; Lichti, Kristin

    2010-01-01

    The pregnane X receptor (PXR, NR1I2) is a member of the nuclear receptor superfamily that is activated by a myriad of compounds and natural products in clinical use. Activation of PXR represents the basis for several clinically important drug–drug interactions. Although PXR activation has undesirable effects in patients on combination therapy, it also mediates the hepatoprotective effects exhibited by some herbal remedies. This review focuses on PXR activation by natural products and the potential therapeutic opportunities presented. In particular, the biological effects of St. John’s Wort, gugulipid, kava kava, Coleus forskolii, Hypoxis, Sutherlandia, qing hao, wu wei zi, gan cao and other natural products are discussed. The impact of these natural products on drug metabolism and hepatoprotection is highlighted in the context of activation and antagonism of PXR. PMID:17125405

  18. The potential of plants as a system for the development and production of human biologics

    PubMed Central

    Chen, Qiang; Davis, Keith R.

    2016-01-01

    The growing promise of plant-made biologics is highlighted by the success story of ZMapp™ as a potentially life-saving drug during the Ebola outbreak of 2014-2016. Current plant expression platforms offer features beyond the traditional advantages of low cost, high scalability, increased safety, and eukaryotic protein modification. Novel transient expression vectors have been developed that allow the production of vaccines and therapeutics at unprecedented speed to control potential pandemics or bioterrorism attacks. Plant-host engineering provides a method for producing proteins with unique and uniform mammalian post-translational modifications, providing opportunities to develop biologics with increased efficacy relative to their mammalian cell-produced counterparts. Recent demonstrations that plant-made proteins can function as biocontrol agents of foodborne pathogens further exemplify the potential utility of plant-based protein production. However, resolving the technical and regulatory challenges of commercial-scale production, garnering acceptance from large pharmaceutical companies, and obtaining U.S. Food and Drug Administration approval for several major classes of biologics are essential steps to fulfilling the untapped potential of this technology. PMID:27274814

  19. Cell culture media impact on drug product solution stability.

    PubMed

    Purdie, Jennifer L; Kowle, Ronald L; Langland, Amie L; Patel, Chetan N; Ouyang, Anli; Olson, Donald J

    2016-07-08

    To enable subcutaneous administration of monoclonal antibodies, drug product solutions are often needed at high concentrations. A significant risk associated with high drug product concentrations is an increase in aggregate level over the shelf-life dating period. While much work has been done to understand the impact of drug product formulation on aggregation, there is limited understanding of the link between cell culture process conditions and soluble aggregate growth in drug product. During cell culture process development, soluble aggregates are often measured at harvest using cell-free material purified by Protein A chromatography. In the work reported here, cell culture media components were evaluated with respect to their impact on aggregate levels in high concentration solution drug product during accelerated stability studies. Two components, cysteine and ferric ammonium citrate, were found to impact aggregate growth rates in our current media (version 1) leading to the development of new chemically defined media and concentrated feed formulations. The new version of media and associated concentrated feeds (version 2) were evaluated across four cell lines producing recombinant IgG4 monoclonal antibodies and a bispecific antibody. In all four cell lines, the version 2 media reduced aggregate growth over the course of a 12 week accelerated stability study compared with the version 1 media, although the degree to which aggregate growth decreased was cell line dependent. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:998-1008, 2016. © 2016 American Institute of Chemical Engineers.

  20. Anti-infectious drug repurposing using an integrated chemical genomics and structural systems biology approach.

    PubMed

    Ng, Clara; Hauptman, Ruth; Zhang, Yinliang; Bourne, Philip E; Xie, Lei

    2014-01-01

    The emergence of multi-drug and extensive drug resistance of microbes to antibiotics poses a great threat to human health. Although drug repurposing is a promising solution for accelerating the drug development process, its application to anti-infectious drug discovery is limited by the scope of existing phenotype-, ligand-, or target-based methods. In this paper we introduce a new computational strategy to determine the genome-wide molecular targets of bioactive compounds in both human and bacterial genomes. Our method is based on the use of a novel algorithm, ligand Enrichment of Network Topological Similarity (ligENTS), to map the chemical universe to its global pharmacological space. ligENTS outperforms the state-of-the-art algorithms in identifying novel drug-target relationships. Furthermore, we integrate ligENTS with our structural systems biology platform to identify drug repurposing opportunities via target similarity profiling. Using this integrated strategy, we have identified novel P. falciparum targets of drug-like active compounds from the Malaria Box, and suggest that a number of approved drugs may be active against malaria. This study demonstrates the potential of an integrative chemical genomics and structural systems biology approach to drug repurposing.

  1. Difficulties in the production of identical drug products from a pharmaceutical technology viewpoint.

    PubMed

    Genazzani, Armando A; Pattarino, Franco

    2008-01-01

    Generic products reduce healthcare expenditure and create market competition, and it is broadly assumed that these drugs are identical to the original branded reference drug product. In practice, despite legislation demanding demonstration of pharmaceutical equivalence and bioequivalence, thereby ensuring the safety and efficacy of the product, generic products can differ significantly from the reference drug and amongst themselves, particularly in terms of pharmacokinetic properties. These differences most often relate to pharmaceutical technical differences in production of the active principle ingredient (e.g. different crystalline forms or particle size), to use of excipients (such as sugars) or to the manufacturing process itself (such as tablet manufacture). Furthermore, from the patient's perspective, changing from branded to generic drugs can give rise to concerns about switching. Although sufficient safeguards exist to ensure patient safety and generic drug efficacy, it should not be assumed that all generics are entirely identical.

  2. Systems Biology of Recombinant Protein Production in Bacillus megaterium

    NASA Astrophysics Data System (ADS)

    Biedendieck, Rebekka; Bunk, Boyke; Fürch, Tobias; Franco-Lara, Ezequiel; Jahn, Martina; Jahn, Dieter

    Over the last two decades the Gram-positive bacterium Bacillus megaterium was systematically developed to a useful alternative protein production host. Multiple vector systems for high yield intra- and extracellular protein production were constructed. Strong inducible promoters were combined with DNA sequences for optimised ribosome binding sites, various leader peptides for protein export and N- as well as C-terminal affinity tags for affinity chromatographic purification of the desired protein. High cell density cultivation and recombinant protein production were successfully tested. For further system biology based control and optimisation of the production process the genomes of two B. megaterium strains were completely elucidated, DNA arrays designed, proteome, fluxome and metabolome analyses performed and all data integrated using the bioinformatics platform MEGABAC. Now, solid theoretical and experimental bases for primary modeling attempts of the production process are available.

  3. Therapy with immunosuppressive drugs and biological agents and use of contraception in patients with rheumatic disease.

    PubMed

    Østensen, Monika; von Esebeck, Mathias; Villiger, Peter M

    2007-06-01

    To investigate the attitude of patients towards immunosuppressive and biological drugs in relation to reproduction and the outcome of pregnancies exposed to these drugs. We performed 2 postal surveys in regard to immunosuppressive drugs and reproduction, one in patients with rheumatic disease, the second in Swiss rheumatologists. Among the 237 female patients and the 189 male patients contacted for the survey, 72% of women and 40% of men returned the questionnaire. Ninety-four women and 47 men had received one or several immunosuppressive or biological agents during the years 2000-2005. Correct advice in regard to drugs and necessary birth control had been given to 84% of women. Advice to men was more inconsistent. One-third of women and 50% of men treated with potentially teratogenic drugs methotrexate (MTX) or leflunomide had not practiced birth control. The surveys of rheumatologists and patients disclosed 66 pregnancies under therapy with immunosuppressive and biological drugs with successful outcomes in 73%. However, 20% of pregnancies in women occurred under treatment with MTX and leflunomide. Issues regarding drugs and reproduction are not always sufficiently discussed with female and male patients. The increasing use of combination therapies containing MTX necessitates ensuring that advice regarding birth control is followed in order to avoid pregnancies exposed to potentially fetotoxic drugs.

  4. Synthesis and biological response of size-specific, monodisperse drug-silica nanoconjugates.

    PubMed

    Tang, Li; Fan, Timothy M; Borst, Luke B; Cheng, Jianjun

    2012-05-22

    Drug-containing nanoparticles (NPs) with monodisperse, controlled particle sizes are highly desirable for drug delivery. Accumulating evidence suggests that NPs with sizes less than 50 nm demonstrate superior performance in vitro and in vivo. However, it is difficult to fabricate monodisperse, drug-containing NPs with discrete sizes required for studying and characterizing existing relationships among particle size, biologic processing, and therapeutic functionality. Here, we report a scalable process of fabricating drug-silica conjugated nanoparticles, termed drug-silica nanoconjugates (drug-NCs), which possess monodisperse size distributions and desirable particle sizes as small as 20 nm. We find that 20 nm NCs are superior to their 50 and 200 nm NC analogues by 2-5- and 10-20-fold, respectively, with regard to tumor accumulation and penetration and cellular internalization. These fundamental findings underscore the importance and necessity of further miniaturizing nanomedicine size for optimized drug delivery applications.

  5. Synthesis and Biological Response of Size-Specific, Monodisperse Drug-Silica Nanoconjugates

    PubMed Central

    Tang, Li; Fan, Timothy M.; Borst, Luke B.; Cheng, Jianjun

    2012-01-01

    Drug-containing nanoparticles (NPs) with monodisperse, controlled particle sizes are highly desirable for drug delivery. Accumulating evidence suggests that NPs with sizes less than 50 nm demonstrate superior performance in vitro and in vivo. However, it is difficult to fabricate monodisperse, drug-containing NPs with discrete and incremental difference in sizes required for studying and characterizing existing relationships among particle size, biologic processing, and therapeutic functionality. Here, we report a scalable process of fabricating drug-silica conjugated nanoparticles, termed drug-silica nanoconjugates (drug-NCs), which possess monodisperse size distributions and desirable particle sizes as small as 20 nm. We found that 20-nm NCs are superior to their 50-nm and 200-nm NC analogues by 2–5 and 10–20 folds, respectively, with regard to tumor accumulation and penetration, and cellular internalization. These fundamental findings underscore the importance and necessity of further miniaturizing nanomedicine size for optimized drug delivery applications. PMID:22494403

  6. Synthetic biology and microbioreactor platforms for programmable production of biologics at the point-of-care

    PubMed Central

    Perez-Pinera, Pablo; Han, Ningren; Cleto, Sara; Cao, Jicong; Purcell, Oliver; Shah, Kartik A.; Lee, Kevin; Ram, Rajeev; Lu, Timothy K.

    2016-01-01

    Current biopharmaceutical manufacturing systems are not compatible with portable or distributed production of biologics, as they typically require the development of single biologic-producing cell lines followed by their cultivation at very large scales. Therefore, it remains challenging to treat patients in short time frames, especially in remote locations with limited infrastructure. To overcome these barriers, we developed a platform using genetically engineered Pichia pastoris strains designed to secrete multiple proteins on programmable cues in an integrated, benchtop, millilitre-scale microfluidic device. We use this platform for rapid and switchable production of two biologics from a single yeast strain as specified by the operator. Our results demonstrate selectable and near-single-dose production of these biologics in <24 h with limited infrastructure requirements. We envision that combining this system with analytical, purification and polishing technologies could lead to a small-scale, portable and fully integrated personal biomanufacturing platform that could advance disease treatment at point-of-care. PMID:27470089

  7. 21 CFR 333.150 - Labeling of first aid antibiotic drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product...

  8. 21 CFR 333.150 - Labeling of first aid antibiotic drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product...

  9. 21 CFR 333.150 - Labeling of first aid antibiotic drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product...

  10. 21 CFR 333.150 - Labeling of first aid antibiotic drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Labeling of first aid antibiotic drug products... First Aid Antibiotic Drug Products § 333.150 Labeling of first aid antibiotic drug products. (a... identifies the product as a “first aid antibiotic.” (b) Indications. The labeling of the product...

  11. Transfer of lipophilic drugs between liposomal membranes and biological interfaces: consequences for drug delivery.

    PubMed

    Fahr, Alfred; van Hoogevest, Peter; May, Sylvio; Bergstrand, Nill; S Leigh, Mathew L

    2005-11-01

    This review paper describes the present knowledge on the interaction of lipophilic, poorly water soluble, drugs with liposomal membranes and the reversibility of this interaction. This interaction is discussed in the context of equilibrium and spontaneous transfer kinetics of the drug, when the liposomes are brought in co-dispersion with other artificial or natural phospholipid membranes in an aqueous medium. The focus is on drugs, which have the potential to partition (dissolve) in a lipid membrane but do not perturb membranes. The degree of interaction is described as solubility of a drug in phospholipid membranes and the kinetics of transfer of a lipophilic drug between membranes. Finally, the consequences of these two factors on the design of lipid based carriers for oral, as well as parenteral use, for lipophilic drugs and lead selection of oral lipophilic drugs is described. Since liposomes serve as model-membranes for natural membranes, the assessment of lipid solubility and transfer kinetics of lipophilic drug using liposome formulations may additionally have predictive value for bioavailability and biodistribution and the pharmacokinetics of lipophilic drugs after parenteral as well as oral administration.

  12. Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development

    PubMed Central

    Tomar, Dheeraj S.; Kumar, Sandeep; Singh, Satish K.; Goswami, Sumit; Li, Li

    2016-01-01

    ABSTRACT Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored. PMID:26736022

  13. Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development.

    PubMed

    Tomar, Dheeraj S; Kumar, Sandeep; Singh, Satish K; Goswami, Sumit; Li, Li

    2016-01-01

    Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored.

  14. 21 CFR 341.74 - Labeling of antitussive drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...”) (select one of the following: “A cold” or “the common cold”) “or inhaled irritants.” (2) “Temporarily...,” or “occurring with”) (select one of the following: “A cold,” “the common cold,” or “inhaled irritants... (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  15. 21 CFR 341.74 - Labeling of antitussive drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...”) (select one of the following: “A cold” or “the common cold”) “or inhaled irritants.” (2) “Temporarily...,” or “occurring with”) (select one of the following: “A cold,” “the common cold,” or “inhaled irritants... (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  16. 21 CFR 341.74 - Labeling of antitussive drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...”) (select one of the following: “A cold” or “the common cold”) “or inhaled irritants.” (2) “Temporarily...,” or “occurring with”) (select one of the following: “A cold,” “the common cold,” or “inhaled irritants... (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  17. 21 CFR 341.74 - Labeling of antitussive drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...”) (select one of the following: “A cold” or “the common cold”) “or inhaled irritants.” (2) “Temporarily...,” or “occurring with”) (select one of the following: “A cold,” “the common cold,” or “inhaled irritants... (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  18. 21 CFR 341.74 - Labeling of antitussive drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...”) (select one of the following: “A cold” or “the common cold”) “or inhaled irritants.” (2) “Temporarily...,” or “occurring with”) (select one of the following: “A cold,” “the common cold,” or “inhaled irritants... (CONTINUED) DRUGS FOR HUMAN USE COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR...

  19. 21 CFR 1310.11 - Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Reinstatement of exemption for drug products distributed under the Food, Drug and Cosmetic Act. 1310.11 Section 1310.11 Food and Drugs DRUG ENFORCEMENT ADMINISTRATION, DEPARTMENT OF JUSTICE RECORDS AND REPORTS OF LISTED CHEMICALS AND CERTAIN MACHINES § 1310.11...

  20. 76 FR 16533 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-24

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Part 558 Animal Drugs, Feeds, and Related Products... medicated feed. This correction is being made to improve the accuracy of the animal drug regulations. DATES... removing cross references for use of the withdrawn drugs in combination ] drug medicated feed. This...

  1. 75 FR 65565 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-26

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 520, 556, and 558 Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of New Animal Drug Applications; Aklomide; Levamisole...: The Food and Drug Administration (FDA) is amending the animal drug regulations by removing those...

  2. Key Findings from Preclinical and Clinical Drug Interaction Studies Presented in New Drug and Biological License Applications Approved by the Food and Drug Administration in 2014.

    PubMed

    Yu, Jingjing; Ritchie, Tasha K; Zhou, Zhu; Ragueneau-Majlessi, Isabelle

    2016-01-01

    Regulatory approval documents contain valuable information, often not published, to assess the drug-drug interaction (DDI) profile of newly marketed drugs. This analysis aimed to systematically review all drug metabolism, transport, pharmacokinetics, and DDI data available in the new drug applications and biologic license applications approved by the U.S. Food and Drug Administration in 2014, using the University of Washington Drug Interaction Database, and to highlight the significant findings. Among the 30 new drug applications and 11 biologic license applications reviewed, 35 new molecular entities (NMEs) were well characterized with regard to drug metabolism, transport, and/or organ impairment and were fully analyzed in this review. In vitro, a majority of the NMEs were found to be substrates or inhibitors/inducers of at least one drug metabolizing enzyme or transporter. In vivo, when NMEs were considered as victim drugs, 16 NMEs had at least one in vivo DDI study with a clinically significant change in exposure (area under the time-plasma concentration curve or Cmax ratio ≥2 or ≤0.5), with 6 NMEs shown to be sensitive substrates of cytochrome P450 enzymes (area under the time-plasma concentration curve ratio ≥5 when coadministered with potent inhibitors): paritaprevir and naloxegol (CYP3A), eliglustat (CYP2D6), dasabuvir (CYP2C8), and tasimelteon and pirfenidone (CYP1A2). As perpetrators, seven NMEs showed clinically significant inhibition involving both enzymes and transporters, although no clinically significant induction was observed. Physiologically based pharmacokinetic modeling and pharmacogenetics studies were used for six and four NMEs, respectively, to optimize dosing recommendations in special populations and/or multiple impairment situations. In addition, the pharmacokinetic evaluations in patients with hepatic or renal impairment provided useful quantitative information to support drug administration in these fragile populations.

  3. Synthetic and systems biology for microbial production of commodity chemicals

    DOE PAGES

    Chubukov, Victor; Mukhopadhyay, Aindrila; Petzold, Christopher J.; ...

    2016-04-07

    The combination of synthetic and systems biology is a powerful framework to study fundamental questions in biology and produce chemicals of immediate practical application such as biofuels, polymers, or therapeutics. However, we cannot yet engineer biological systems as easily and precisely as we engineer physical systems. In this review, we describe the path from the choice of target molecule to scaling production up to commercial volumes. We present and explain some of the current challenges and gaps in our knowledge that must be overcome in order to bring our bioengineering capabilities to the level of other engineering disciplines. Challenges startmore » at molecule selection, where a difficult balance between economic potential and biological feasibility must be struck. Pathway design and construction have recently been revolutionized by next-generation sequencing and exponentially improving DNA synthesis capabilities. Although pathway optimization can be significantly aided by enzyme expression characterization through proteomics, choosing optimal relative protein expression levels for maximum production is still the subject of heuristic, non-systematic approaches. Toxic metabolic intermediates and proteins can significantly affect production, and dynamic pathway regulation emerges as a powerful but yet immature tool to prevent it. Host engineering arises as a much needed complement to pathway engineering for high bioproduct yields; and systems biology approaches such as stoichiometric modeling or growth coupling strategies are required. A final, and often underestimated, challenge is the successful scale up of processes to commercial volumes. Sustained efforts in improving reproducibility and predictability are needed for further development of bioengineering.« less

  4. Overcome Cancer Cell Drug Resistance Using Natural Products

    PubMed Central

    Wang, Pu; Yang, Hua Li; Yang, Ying Juan; Wang, Lan; Lee, Shao Chin

    2015-01-01

    Chemotherapy is one of the major treatment methods for cancer. However, failure in chemotherapy is not uncommon, mainly due to dose-limiting toxicity associated with drug resistance. Management of drug resistance is important towards successful chemotherapy. There are many reports in the Chinese literature that natural products can overcome cancer cell drug resistance, which deserve sharing with scientific and industrial communities. We summarized the reports into four categories: (1) in vitro studies using cell line models; (2) serum pharmacology; (3) in vivo studies using animal models; and (4) clinical studies. Fourteen single compounds were reported to have antidrug resistance activity for the first time. In vitro, compounds were able to overcome drug resistance at nontoxic or subtoxic concentrations, in a dose-dependent manner, by inhibiting drug transporters, cell detoxification capacity, or cell apoptosis sensitivity. Studies in vivo showed that single compounds, herbal extract, and formulas had potent antidrug resistance activities. Importantly, many single compounds, herbal extracts, and formulas have been used clinically to treat various diseases including cancer. The review provides comprehensive data on use of natural compounds to overcome cancer cell drug resistance in China, which may facilitate the therapeutic development of natural products for clinical management of cancer drug resistance. PMID:26421052

  5. The Impact of Conventional and Biological Disease Modifying Antirheumatic Drugs on Bone Biology. Rheumatoid Arthritis as a Case Study.

    PubMed

    Barreira, Sofia Carvalho; Fonseca, João Eurico

    2016-08-01

    The bone and the immune system have a very tight interaction. Systemic immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA), induce bone loss, leading to a twofold increase in osteoporosis and an increase of fragility fracture risk of 1.35-2.13 times. This review focuses on the effects of conventional and biological disease modifying antirheumatic drugs (DMARDs) on bone biology, in the context of systemic inflammation, with a focus on RA. Published evidence supports a decrease in osteoclastic activity induced by DMARDs, which leads to positive effects on bone mineral density (BMD). It is unknown if this effect could be translated into fracture risk reduction. The combination with antiosteoclastic drugs can have an additional benefit.

  6. The effect of globalization of drug manufacturing, production, and sourcing and challenges for American drug safety.

    PubMed

    Woo, J; Wolfgang, S; Batista, H

    2008-03-01

    Americans benefit from one of the safest drug supplies and one of the highest standards of consumer protection in the world. Over the past decade, though, a general trend toward globalization of the supply chains for finished pharmaceutical products and active pharmaceutical ingredients has created new challenges for the Food and Drug Administration (FDA) in ensuring the safety and quality of the drug supply. Explosive growth in pharmaceutical manufacturing for the US market is particularly evident in the developing regions of Asia. Manufacturing sites in China and India now comprise approximately 40% of all FDA-registered foreign sites, having increased from 30% in 2002. (In 2001, when legislation first went into effect requiring registration of all foreign drug manufacturing sites, 140 registered sites in China listed 797 drug items for potential importation; as of 1 October 2007, that number had grown to 815 registered sites and well over 3,000 listed items.) In total in 2006, the United States received >145,000 line entries of imported drug products from >160 countries, up from only 1,300 line entries in 2000. FDA regulatory oversight resources (e.g., those allocated to inspection and testing of imports) are being challenged to keep up with the explosive growth of imported drugs. (In 2006, the FDA performed inspections at 212 foreign drug firms. This number has remained relatively consistent over the past 6 years, starting at 249 in 2001 and ranging from 190 to 260 on an annual basis.)

  7. 21 CFR 601.26 - Reclassification procedures to determine that licensed biological products are safe, effective...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... shall provide that the biologics license application for that biological product will not be revoked... licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or... OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS LICENSING Biologics Licensing § 601.26...

  8. Biological anti-TNF drugs: immunogenicity underlying treatment failure and adverse events.

    PubMed

    Prado, Mônica Simon; Bendtzen, Klaus; Andrade, Luis Eduardo Coelho

    2017-09-01

    Genetically engineered monoclonal antibodies and fusion proteins directed against cytokines or their receptors represent a breakthrough in the treatment of various chronic immune-inflammatory diseases. Areas covered: Studies show high remission rates in several diseases, but clinical practice shows a significant percentage of individuals who do not exhibit the desired response. Loss of therapeutic benefit after initial successful response is designated secondary failure. Immune-biological agents are not self-antigens and are therefore potentially immunogenic. Secondary failure is frequently caused by antibodies against immune-biologicals, known as anti-drug antibodies (ADA). ADA that neutralize circulating immune-biologicals and/or promote their clearance can reduce treatment efficacy. Furthermore, ADA can induce adverse events by diverse immunological mechanisms. This review provides a comprehensive overview of ADA in rheumatoid arthritis patients treated with anti-TNF immune-biologicals, and explores the concept of therapeutic drug monitoring (TDM) as an effective strategy to improve therapeutic management. Expert opinion: Monitoring circulating ADA and therapeutic immune-biological drugs is helpful when evaluating patients with secondary failure. However, immunological tests for ADA vary considerably regarding their ability to detect different types of ADA. Several assays are not designed to determine ADA-induced drug neutralizing capacity, and they may report clinically non-relevant data, especially if drug is present in test samples.

  9. Systems Biology Approaches to Understand Natural Products Biosynthesis

    PubMed Central

    Licona-Cassani, Cuauhtemoc; Cruz-Morales, Pablo; Manteca, Angel; Barona-Gomez, Francisco; Nielsen, Lars K.; Marcellin, Esteban

    2015-01-01

    Actinomycetes populate soils and aquatic sediments that impose biotic and abiotic challenges for their survival. As a result, actinomycetes metabolism and genomes have evolved to produce an overwhelming diversity of specialized molecules. Polyketides, non-ribosomal peptides, post-translationally modified peptides, lactams, and terpenes are well-known bioactive natural products with enormous industrial potential. Accessing such biological diversity has proven difficult due to the complex regulation of cellular metabolism in actinomycetes and to the sparse knowledge of their physiology. The past decade, however, has seen the development of omics technologies that have significantly contributed to our better understanding of their biology. Key observations have contributed toward a shift in the exploitation of actinomycete’s biology, such as using their full genomic potential, activating entire pathways through key metabolic elicitors and pathway engineering to improve biosynthesis. Here, we review recent efforts devoted to achieving enhanced discovery, activation, and manipulation of natural product biosynthetic pathways in model actinomycetes using genome-scale biological datasets. PMID:26697425

  10. Current advances in biological production of propionic acid.

    PubMed

    Eş, Ismail; Khaneghah, Amin Mousavi; Hashemi, Seyed Mohammad Bagher; Koubaa, Mohamed

    2017-02-01

    Propionic acid and its derivatives are considered "Generally Recognized As Safe" food additives and are generally used as an anti-microbial and anti-inflammatory agent, herbicide, and artificial flavor in diverse industrial applications. It is produced via biological pathways using Propionibacterium and some anaerobic bacteria. However, its commercial chemical synthesis from the petroleum-based feedstock is the conventional production process bit results in some environmental issues. Novel biological approaches using microorganisms and renewable biomass have attracted considerable recent attention due to economic advantages as well as great adaptation with the green technology. This review provides a comprehensive overview of important biotechnological aspects of propionic acid production using recent technologies such as employment of co-culture, genetic and metabolic engineering, immobilization technique and efficient bioreactor systems.

  11. [Kinetic analysis of drug disposition and biological response].

    PubMed

    Koizumi, T

    2000-05-01

    This review deals with pharmacokinetic/pharmacodynamic analysis of drugs. For the analysis of antipyretics, it was assumed that: (1) The rat body is divided into two compartments, core and skin. (2) Metabolic heat (M) is generated in the core compartment. (3) Heat loss by vaporization (V) is mainly originated from a respiratory effect and occurs in the core compartment. (4) At the skin compartment, heat is gained from the core compartment by conduction (K) and is transferred to the ambient air by radiation and convection. (5) Central nervous system commands efferent signals for M, K and V to change their values according to changes in afferent signals from core and skin temperatures. (6) The effect of antipyretics is shown as afferent signals to the controller. For loop diuretics, it was assumed that: (1) The diuretic rate can be correlated with the urinary excretion rate of diuretics. (2) If there is no intervention in a body fluid regulation system, the relationship between the diuretic rate and the corresponding urinary excretion rate can be described by a Hill equation. (3) Intensity of the body fluid regulation is also described by the Hill equation, in which the intensity is correlated with cumulative amount of drugs excreted in the urine. For neuromuscular blockade, assumptions were: (1) There exists an acetylcholine (ACh) compartment at a motor nerve terminal. (2) ACh in the compartment is eliminated by a first-order rate process. (3) All of the ACh in the compartment is released by one electrical stimulus. (4) The compartment is replenished by two kinds of ACh mobilization. One is a slow mobilization with a constant rate and the other is a momentary mobilization which takes place just after the release of ACh. (5) The released ACh is metabolized immediately after binding to receptors and causing a twitch response. For centrally acting drugs, the quantitative electroencephalographic (EEG) method was used as a surrogate measure of a pharmacological response

  12. 21 CFR 212.110 - How must I maintain records of my production of PET drugs?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH... EMISSION TOMOGRAPHY DRUGS Records § 212.110 How must I maintain records of my production of PET drugs? (a) Record availability. Records must be maintained at the PET drug production facility or another location...

  13. 21 CFR 355.70 - Testing procedures for fluoride dentifrice drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Testing procedures for fluoride dentifrice drug... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ANTICARIES DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Testing Procedures § 355.70 Testing procedures for fluoride dentifrice drug products. (a) A fluoride dentifrice drug...

  14. 21 CFR 357.850 - Labeling of deodorant drug products for internal use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of deodorant drug products for internal use. 357.850 Section 357.850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE MISCELLANEOUS INTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER...

  15. 21 CFR 358.350 - Labeling of ingrown toenail relief drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of ingrown toenail relief drug products. 358.350 Section 358.350 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE MISCELLANEOUS EXTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN...

  16. 21 CFR 357.850 - Labeling of deodorant drug products for internal use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of deodorant drug products for internal use. 357.850 Section 357.850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE MISCELLANEOUS INTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER...

  17. 21 CFR 357.850 - Labeling of deodorant drug products for internal use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of deodorant drug products for internal use. 357.850 Section 357.850 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE MISCELLANEOUS INTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER...

  18. Microfluidics-assisted in vitro drug screening and carrier production

    PubMed Central

    Tsui, Jonathan H.; Lee, Woohyuk; Pun, Suzie H.; Kim, Jungkyu; Kim, Deok-Ho

    2013-01-01

    Microfluidic platforms provide several unique advantages for drug development. In the production of drug carriers, physical properties such as size and shape, and chemical properties such as drug composition and pharmacokinetic parameters, can be modified simply and effectively by tuning the flow rate and geometries. Large numbers of carriers can then be fabricated with minimal effort and with little to no batch-to-batch variation. Additionally, cell or tissue culture models in microfluidic systems can be used as in vitro drug screening tools. Compared to in vivo animal models, microfluidic drug screening platforms allow for high-throughput and reproducible screening at a significantly lower cost, and when combined with current advances in tissue engineering, are also capable of mimicking native tissues. In this review, various microfluidic platforms for drug and gene carrier fabrication are reviewed to provide guidelines for designing appropriate carriers. In vitro microfluidic drug screening platforms designed for high-throughput analysis and replication of in vivo conditions are also reviewed to highlight future directions for drug research and development. PMID:23856409

  19. Microfluidics-assisted in vitro drug screening and carrier production.

    PubMed

    Tsui, Jonathan H; Lee, Woohyuk; Pun, Suzie H; Kim, Jungkyu; Kim, Deok-Ho

    2013-11-01

    Microfluidic platforms provide several unique advantages for drug development. In the production of drug carriers, physical properties such as size and shape, and chemical properties such as drug composition and pharmacokinetic parameters, can be modified simply and effectively by tuning the flow rate and geometries. Large numbers of carriers can then be fabricated with minimal effort and with little to no batch-to-batch variation. Additionally, cell or tissue culture models in microfluidic systems can be used as in vitro drug screening tools. Compared to in vivo animal models, microfluidic drug screening platforms allow for high-throughput and reproducible screening at a significantly lower cost, and when combined with current advances in tissue engineering, are also capable of mimicking native tissues. In this review, various microfluidic platforms for drug and gene carrier fabrication are reviewed to provide guidelines for designing appropriate carriers. In vitro microfluidic drug screening platforms designed for high-throughput analysis and replication of in vivo conditions are also reviewed to highlight future directions for drug research and development. © 2013.

  20. Illicit drugs in alternative biological specimens: a case report.

    PubMed

    Margalho, Cláudia; Franco, João; Corte-Real, Francisco; Vieira, Duarte Nuno

    2011-04-01

    Postmortem tissues (e.g. liver, kidney) have been long used in forensic applications especially in those cases where blood is unavailable. The aim of this paper is to demonstrate the importance of the information provided to the forensic toxicologist at the time of carrying out the toxicological analysis, especially in cases where the samples commonly used in forensic toxicology are unavailable. This work describes the toxicological findings in a violent death resulting from a man who was hit by a train. Vitreous humor, liver and kidney were sent for toxicological analysis, once it was not possible to obtain blood and urine. The validated procedures used in the routine casework of Forensic Toxicology Laboratory of the Centre Branch of the National Institute of Legal Medicine, were applied in the analysis of liver, kidney and vitreous humor, using gas chromatography-mass spectrometry after solid-phase extraction and gas chromatography-flame ionization detector for the analysis of drugs of abuse and ethanol, respectively. Morphine, codeine, cocaine, benzoylecgonine and ecgonine methyl ester were found in the liver and in the kidney and no ethanol was found in the vitreous humor. The method validation included the study of specificity, selectivity, limits of detection, recovery and carryover. Although blood and urine are the most common and preferred matrices used for toxicological studies involving drugs of abuse, sometimes the choice of specimen is determined by the case under investigation. The forensic pathologist must be aware that relevant information must be provided so that the toxicological analysis can be conducted in accordance with case history, particularly when the only samples available for analysis are these "unconventional" specimens, since the interpretation of the obtained results is more difficult. Copyright © 2011 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.