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, 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,...

  2. 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,...

  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,...

  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,...

  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,...

  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

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

  7. 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

    ... HUMAN SERVICES Food and Drug Administration Request for Nominations of Specific Drug/Biologic Product(s) That Could Be Brought Before the Food and Drug Administration's Pediatric Subcommittee of the Oncologic Drugs Advisory Committee AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for...

  8. 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...

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 75 FR 59935 - Investigational New Drug Safety Reporting Requirements for Human Drug and Biological Products and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-29

    .... Unblinding G. Information Sufficient to Consider Product Administration Changes--Proposed Sec. 312.32(c)(1... product administration changes,'' Make it clear that safety reports of overall findings or data in the... of this document) and other revisions, including editorial changes to clarify provisions and...

  14. 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

    ... Management (HFA- 305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. All... concepts completed to date for each active ingredient associated with approved human prescription drug and... section of labeling. The current intent is to index the basic indication concepts without the...

  15. 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

  16. 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

    ...(D) Immune Globulin and Hepatitis B Immune Globulin; Coagulation Factor VIIa (Recombinant); and..., or mitigate shortages of these products. b. Vaccines. We are proposing to apply section 506C of the FD&C Act to all biological products, including vaccines. Under section 506C(i)(3)(B) of the FD&C...

  17. 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

  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. 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.

  20. 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

  1. 78 FR 67985 - Supplemental Applications Proposing Labeling Changes for Approved Drugs and Biological Products

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-13

    ... device in section 201(h) of the FD&C Act (21 U.S.C. 321(h)). All drugs have risks, and health care... previously approved under section 505(c) of the FD&C Act (the RLD) with respect to active ingredient(s... Labeling B. Current Requirements Related to Changes to Approved Drug Labeling C. Specific...

  2. 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.

  3. 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 ...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  10. 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.

  11. 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...

  12. 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

    ... evidence of effectiveness. Conclusions based on animal data but necessary for safe and effective use of the....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...

  13. 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

    ... evidence of effectiveness. Conclusions based on animal data but necessary for safe and effective use of the....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...

  14. 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

    ... evidence of effectiveness. Conclusions based on animal data but necessary for safe and effective use of the....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...

  15. 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

    ... evidence of effectiveness. Conclusions based on animal data but necessary for safe and effective use of the....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...

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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.

  8. 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 ...

  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. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Biologics; products subject to license control. 310.4 Section 310.4 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS General Provisions § 310.4 Biologics; products subject to license control. (a) If a drug has an...

  15. 21 CFR 310.4 - Biologics; products subject to license control.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. 42 CFR 410.29 - Limitations on drugs and biologicals.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICES MEDICARE PROGRAM SUPPLEMENTARY MEDICAL INSURANCE (SMI) BENEFITS Medical and Other Health Services... factors, and except for EPO, any drug or biological that can be self-administered. (b) Any drug...

  4. 42 CFR 410.29 - Limitations on drugs and biologicals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...) Except as provided in § 410.28(a) for outpatient diagnostic services and § 410.63(b) for blood clotting factors, and except for EPO, any drug or biological that can be self-administered. (b) Any drug...

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

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...) Except as provided in § 410.28(a) for outpatient diagnostic services and § 410.63(b) for blood clotting factors, and except for EPO, any drug or biological that can be self-administered. (b) Any drug...

  6. 42 CFR 410.29 - Limitations on drugs and biologicals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) Except as provided in § 410.28(a) for outpatient diagnostic services and § 410.63(b) for blood clotting factors, and except for EPO, any drug or biological that can be self-administered. (b) Any drug...

  7. 42 CFR 410.29 - Limitations on drugs and biologicals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...) Except as provided in § 410.28(a) for outpatient diagnostic services and § 410.63(b) for blood clotting factors, and except for EPO, any drug or biological that can be self-administered. (b) Any drug...

  8. 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...

  9. 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

  10. Natural products with health benefits from marine biological resources

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  11. [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.

  12. 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.

  13. FDA 101: Regulating Biological Products

    MedlinePlus

    ... and immediately suspend licenses where there exists a danger to public health allows the agency to prepare ... You Given Blood Lately? More in Consumer Updates Animal & Veterinary Children's Health Cosmetics Dietary Supplements Drugs Food ...

  14. 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

  15. 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.

  16. 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......

  17. 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.

  18. 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.

  19. 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. )...

  20. 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. )...

  1. 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.

  2. 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...

  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...

  4. 77 FR 3780 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... 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..., Parasitic and Allergenic Products, Office of Vaccines Research and Review, Center for Biologics...

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. [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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... condition and has been designated as an orphan drug under section 526 of the Federal Food, Drug and Cosmetic..., 2000. (2) Cancer therapy drugs and biologicals. A drug or biological that is used in cancer...

  2. 42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... condition and has been designated as an orphan drug under section 526 of the Federal Food, Drug and Cosmetic..., 2000. (2) Cancer therapy drugs and biologicals. A drug or biological that is used in cancer...

  3. 42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... condition and has been designated as an orphan drug under section 526 of the Federal Food, Drug and Cosmetic..., 2000. (2) Cancer therapy drugs and biologicals. A drug or biological that is used in cancer...

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. [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.

  10. 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.

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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.

  17. 21 CFR 333.350 - Labeling of acne 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 acne drug products. 333.350 Section... Acne Drug Products § 333.350 Labeling of acne drug products. (a) Statement of identity. The labeling of the product contains the established name of the drug, if any, and identifies the product as an...

  18. 21 CFR 333.350 - Labeling of acne 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 acne drug products. 333.350 Section... Acne Drug Products § 333.350 Labeling of acne drug products. (a) Statement of identity. The labeling of the product contains the established name of the drug, if any, and identifies the product as an...

  19. 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

  20. 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.

  1. 78 FR 20663 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ... 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... DNA Viruses, Division of Viral Products, Office of Vaccines Research and Review, Center for...

  2. 76 FR 3639 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-20

    ... 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 2011-2012 influenza season....

  3. 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...

  4. 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,...

  5. 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...

  6. 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....

  7. 77 FR 42319 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-18

    ... 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... lines derived from human tumors for vaccine manufacture. FDA intends to make background...

  8. 76 FR 55397 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-07

    ... 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... the Laboratory of Method Development, Division of Viral Products, Office of Vaccines Research...

  9. 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...

  10. 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...

  11. 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......

  12. 42 CFR 419.64 - Transitional pass-through payments: Drugs and biologicals.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... orphan drug under section 526 of the Federal Food, Drug and Cosmetic Act if payment for the drug or biological as an outpatient hospital service was being made on August 1, 2000. (2) Cancer therapy drugs and biologicals. A drug or biological that is used in cancer therapy, including, but not limited to,...

  13. 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....

  14. 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...

  15. 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...

  16. 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...

  17. 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.

  18. 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

  19. 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.

  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. Systems biology solutions for biochemical production challenges.

    PubMed

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

    2017-03-16

    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.

  2. 21 CFR 341.78 - Labeling of expectorant 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 expectorant drug products. 341.78 Section 341.78 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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 (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE...

  7. [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.

  8. 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.

  9. 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

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

    MedlinePlus

    ... premature birth 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 ...

  11. 75 FR 59729 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-28

    ... 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... for protective antigen-based anthrax vaccines for a post-exposure prophylaxis indication using...

  12. 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.

  13. 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.

  14. 21 CFR 314.108 - New drug product exclusivity.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false New drug product exclusivity. 314.108 Section 314.108 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications...

  15. 21 CFR 314.108 - New drug product exclusivity.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false New drug product exclusivity. 314.108 Section 314.108 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications...

  16. 21 CFR 314.108 - New drug product exclusivity.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false New drug product exclusivity. 314.108 Section 314.108 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications...

  17. 21 CFR 314.108 - New drug product exclusivity.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false New drug product exclusivity. 314.108 Section 314.108 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG FDA Action on Applications...

  18. 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

  19. 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.

  20. 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...

  1. 9 CFR 103.1 - Preparation of experimental biological products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., 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...

  2. 42 CFR 409.25 - Drugs, biologicals, supplies, appliances, and equipment.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Drugs, biologicals, supplies, appliances, and... Drugs, biologicals, supplies, appliances, and equipment. (a) Drugs and biologicals. Except as specified... can obtain a continuing supply. (c) Supplies, appliances, and equipment. Except as specified...

  3. 42 CFR 409.25 - Drugs, biologicals, supplies, appliances, and equipment.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Drugs, biologicals, supplies, appliances, and... Drugs, biologicals, supplies, appliances, and equipment. (a) Drugs and biologicals. Except as specified... can obtain a continuing supply. (c) Supplies, appliances, and equipment. Except as specified...

  4. 42 CFR 409.25 - Drugs, biologicals, supplies, appliances, and equipment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Drugs, biologicals, supplies, appliances, and... Drugs, biologicals, supplies, appliances, and equipment. (a) Drugs and biologicals. Except as specified... can obtain a continuing supply. (c) Supplies, appliances, and equipment. Except as specified...

  5. 42 CFR 409.25 - Drugs, biologicals, supplies, appliances, and equipment.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Drugs, biologicals, supplies, appliances, and... Drugs, biologicals, supplies, appliances, and equipment. (a) Drugs and biologicals. Except as specified... can obtain a continuing supply. (c) Supplies, appliances, and equipment. Except as specified...

  6. 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

  7. 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.

  8. 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

  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. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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...

  17. 21 CFR 355.50 - Labeling of anticaries 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 anticaries drug products. 355.50 Section 355.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... identity if the product also has a cosmetic use, as defined in section 201(i) of the Federal Food,...

  18. 21 CFR 355.50 - Labeling of anticaries 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 anticaries drug products. 355.50 Section 355.50 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... identity if the product also has a cosmetic use, as defined in section 201(i) of the Federal Food,...

  19. 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...

  20. 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...

  1. 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...

  2. 21 CFR 211.208 - Drug product salvaging.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 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...

  3. 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...

  4. 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...

  5. 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...

  6. 21 CFR 211.208 - Drug product salvaging.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 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...

  7. 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...

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 21 CFR 335.50 - Labeling of antidiarrheal 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 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...

  17. 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

  18. 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.

  19. 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

  20. [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.

  1. 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...

  2. 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.

  3. 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.

  4. 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…

  5. 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...

  6. 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.

  7. 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.

  8. [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.

  9. 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

  10. 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

  11. 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.

  12. 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

  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.

  14. 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

  15. 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.

  16. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 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...

  17. 9 CFR 112.6 - Packaging biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 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...

  18. 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...

  19. 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...

  20. 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...

  1. 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...

  2. 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...

  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...

  4. 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...

  5. 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...

  6. 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 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 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 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...

  8. 9 CFR 113.3 - Sampling 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 Sampling of biological products. 113.3 Section 113.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD...

  9. 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)...

  10. 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)...

  11. 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

  12. 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...

  13. 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.

  14. "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.

  15. 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

  16. 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...

  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. 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

  19. 9 CFR 103.3 - Shipment of experimental biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... animals, Provided, that, the Administrator determines that the conditions under which the experiment is to... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Shipment of experimental biological products. 103.3 Section 103.3 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION...

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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...

  7. 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.

  8. 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.

  9. 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 approval of duplicate versions of drug products under an ANDA procedure. ANDA applicants must... drug that was previously approved. ANDA applicants do not have to repeat the extensive clinical testing... the drug's NDA or ANDA for reasons of safety or effectiveness or if FDA determines that the...

  10. Production of hydrogen using an anaerobic biological process

    SciTech Connect

    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.

  11. 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

  12. 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.

  13. 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.

  14. [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.

  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. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 21 CFR 358.350 - Labeling of ingrown toenail relief 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 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 USE Ingrown Toenail Relief Drug Products...

  1. 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.

  2. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 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... biological products shall be selected. (2) Comparable samples shall be used by Animal and Plant...

  3. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 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... biological products shall be selected. (2) Comparable samples shall be used by Animal and Plant...

  4. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 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... biological products shall be selected. (2) Comparable samples shall be used by Animal and Plant...

  5. 9 CFR 113.3 - Sampling of biological products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 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... biological products shall be selected. (2) Comparable samples shall be used by Animal and Plant...

  6. 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.

  7. 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...

  8. 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.

  9. 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.

  10. 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...

  11. 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...

  12. 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...

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. 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....

  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. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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.

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

    PubMed Central

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

    2014-01-01

    Introduction: 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. Areas covered: 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. Expert opinion: 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. PMID:25016923

  13. 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.

  14. 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.

  15. 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,...

  16. 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,...

  17. 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.

  18. 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…

  19. 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

  20. 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...

  1. 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.

  2. 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.

  3. 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.

  4. 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....

  5. 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....

  6. 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....

  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. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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...

  16. 21 CFR 310.509 - Parenteral drug products in plastic containers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 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...

  17. 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...

  18. 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...

  19. 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...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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...

  6. 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...

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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.

  12. 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

    ... fenfluramine hydrochloride. Flosequinan: All drug products containing flosequinan. Gelatin: All intravenous drug products containing gelatin. Glycerol, iodinated: All drug products containing iodinated...

  13. 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

    ... fenfluramine hydrochloride. Flosequinan: All drug products containing flosequinan. Gelatin: All intravenous drug products containing gelatin. Glycerol, iodinated: All drug products containing iodinated...

  14. 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

    ... fenfluramine hydrochloride. Flosequinan: All drug products containing flosequinan. Gelatin: All intravenous drug products containing gelatin. Glycerol, iodinated: All drug products containing iodinated...

  15. 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

  16. 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.

  17. 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 ADMINISTRATION, DEPARTMENT OF JUSTICE RECORDS AND REPORTS OF LISTED CHEMICALS AND CERTAIN MACHINES §...

  18. 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 §...

  19. 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 ADMINISTRATION, DEPARTMENT OF JUSTICE RECORDS AND REPORTS OF LISTED CHEMICALS AND CERTAIN MACHINES §...

  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....

  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...

  2. 21 CFR 333.150 - Labeling of first aid antibiotic 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 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...

  3. 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...

  4. 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...

  5. 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...

  6. 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...

  7. 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

  8. 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.

  9. 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.

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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...

  15. 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

  16. 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.)

  17. 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

  18. 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...

  19. 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

  20. 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.

  1. Modelling chemistry and biology after implantation of a drug-eluting stent. Part I: Drug transport.

    PubMed

    Vo, Tuoi; Lee, William; Peddle, Adam; Meere, Martin

    2017-04-01

    Drug-eluting stents have been used widely to prevent restenosis of arteries following percutaneous balloon angioplasty. Mathematical modelling plays an important role in optimising the design of these stents to maximise their efficiency. When designing a drug-eluting stent system, we expect to have a sufficient amount of drug being released into the artery wall for a sufficient period to prevent restenosis. In this paper, a simple model is considered to provide an elementary description of drug release into artery tissue from an implanted stent. From the model, we identified a parameter regime to optimise the system when preparing the polymer coating. The model provides some useful order of magnitude estimates for the key quantities of interest. From the model, we can identify the time scales over which the drug traverses the artery wall and empties from the polymer coating, as well as obtain approximate formulae for the total amount of drug in the artery tissue and the fraction of drug that has released from the polymer. The model was evaluated by comparing to in-vivo experimental data and good agreement was found.

  2. 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

  3. 21 CFR 338.50 - Labeling of nighttime sleep-aid 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 nighttime sleep-aid drug products. 338... SERVICES (CONTINUED) DRUGS FOR HUMAN USE NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 338.50 Labeling of nighttime sleep-aid drug products. (a) Statement of identity. The labeling...

  4. 21 CFR 338.50 - Labeling of nighttime sleep-aid 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 nighttime sleep-aid drug products. 338... SERVICES (CONTINUED) DRUGS FOR HUMAN USE NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 338.50 Labeling of nighttime sleep-aid drug products. (a) Statement of identity. The labeling...

  5. 21 CFR 338.50 - Labeling of nighttime sleep-aid 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 nighttime sleep-aid drug products. 338... SERVICES (CONTINUED) DRUGS FOR HUMAN USE NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 338.50 Labeling of nighttime sleep-aid drug products. (a) Statement of identity. The labeling...

  6. 21 CFR 338.50 - Labeling of nighttime sleep-aid 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 nighttime sleep-aid drug products. 338... SERVICES (CONTINUED) DRUGS FOR HUMAN USE NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 338.50 Labeling of nighttime sleep-aid drug products. (a) Statement of identity. The labeling...

  7. 21 CFR 338.50 - Labeling of nighttime sleep-aid 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 nighttime sleep-aid drug products. 338... SERVICES (CONTINUED) DRUGS FOR HUMAN USE NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 338.50 Labeling of nighttime sleep-aid drug products. (a) Statement of identity. The labeling...

  8. 21 CFR 348.50 - Labeling of external analgesic 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 external analgesic drug products. 348... SERVICES (CONTINUED) DRUGS FOR HUMAN USE EXTERNAL ANALGESIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE Labeling § 348.50 Labeling of external analgesic drug products. (a) Statement of identity. The labeling...

  9. Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

    PubMed

    San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

    2014-12-01

    Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA.

  10. Large-Scale Predictive Drug Safety: From Structural Alerts to Biological Mechanisms.

    PubMed

    Garcia-Serna, Ricard; Vidal, David; Remez, Nikita; Mestres, Jordi

    2015-10-19

    The recent explosion of data linking drugs, proteins, and pathways with safety events has promoted the development of integrative systems approaches to large-scale predictive drug safety. The added value of such approaches is that, beyond the traditional identification of potentially labile chemical fragments for selected toxicity end points, they have the potential to provide mechanistic insights for a much larger and diverse set of safety events in a statistically sound nonsupervised manner, based on the similarity to drug classes, the interaction with secondary targets, and the interference with biological pathways. The combined identification of chemical and biological hazards enhances our ability to assess the safety risk of bioactive small molecules with higher confidence than that using structural alerts only. We are still a very long way from reliably predicting drug safety, but advances toward gaining a better understanding of the mechanisms leading to adverse outcomes represent a step forward in this direction.

  11. Drug-Encoded Biomarkers for Monitoring Biological Therapies

    PubMed Central

    Bedenk, Kristina; Zhang, Qian; Frentzen, Alexa; Cappello, Joseph; Fischer, Utz; Szalay, Aladar A.

    2015-01-01

    Blood tests are necessary, easy-to-perform and low-cost alternatives for monitoring of oncolytic virotherapy and other biological therapies in translational research. Here we assessed three candidate proteins with the potential to be used as biomarkers in biological fluids: two glucuronidases from E. coli (GusA) and Staphylococcus sp. RLH1 (GusPlus), and the luciferase from Gaussia princeps (GLuc). The three genes encoding these proteins were inserted individually into vaccinia virus GLV-1h68 genome under the control of an identical promoter. The three resulting recombinant viruses were used to infect tumor cells in cultures and human tumor xenografts in nude mice. In contrast to the actively secreted GLuc, the cytoplasmic glucuronidases GusA and GusPlus were released into the supernatants only as a result of virus-mediated oncolysis. GusPlus resulted in the most sensitive detection of enzyme activity under controlled assay conditions in samples containing as little as 1 pg/ml of GusPlus, followed by GusA (25 pg/ml) and GLuc (≥375 pg/ml). Unexpectedly, even though GusA had a lower specific activity compared to GusPlus, the substrate conversion in the serum of tumor-bearing mice injected with the GusA-encoding virus strains was substantially higher than that of GusPlus. This was attributed to a 3.2 fold and 16.2 fold longer half-life of GusA in the blood stream compared to GusPlus and GLuc respectively, thus a more sensitive monitor of virus replication than the other two enzymes. Due to the good correlation between enzymatic activity of expressed marker gene and virus titer, we conclude that the amount of the biomarker protein in the body fluid semiquantitatively represents the amount of virus in the infected tumors which was confirmed by low light imaging. We found GusA to be the most reliable biomarker for monitoring oncolytic virotherapy among the three tested markers. PMID:26348361

  12. 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

  13. Structural biology and drug discovery for protein-protein interactions.

    PubMed

    Jubb, Harry; Higueruelo, Alicia P; Winter, Anja; Blundell, Tom L

    2012-05-01

    Although targeting protein-protein interfaces of regulatory multiprotein complexes has become a significant focus in drug discovery, it continues to pose major challenges. Most interfaces would be classed as 'undruggable' by conventional analyses, as they tend to be large, flat and featureless. Over the past decade, encouragement has come from the discovery of hotspots that contribute much of the free energy of interaction, and this has led to the development of tethering methods that target small molecules to these sites, often inducing adaptive changes. Equally important has been the recognition that many protein-protein interactions involve a continuous epitope of one partner and a well-defined groove or series of specific small pockets. These observations have stimulated the development of stapled α-helical peptides and other proteomimetic approaches. They have also led to the realisation that fragments might gain low-affinity 'footholds' on some protein-protein interfaces, and that these fragments might be elaborated to useful modulators of the interactions.

  14. 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.

  15. Analysis of Investigational Drugs in Biological Fluids Method Development and Routine Assay

    DTIC Science & Technology

    1988-04-12

    The purpose of work under this contract is to develop and routinely use analytical methods for the determination of the concentration in biological specimens of investigational drugs in support of pharmacokinetic and bioavailability studies undertaken for the purpose of new drug development for the US military establishment. Accepted scientific procedures including normal and reversed phase high-performance liquid chromatographic methods, post column derivatization, and protein precipitation and

  16. Recreational drug discovery: natural products as lead structures for the synthesis of smart drugs.

    PubMed

    Appendino, Giovanni; Minassi, Alberto; Taglialatela-Scafati, Orazio

    2014-07-01

    Covering: up to December 2013. Over the past decade, there has been a growing transition in recreational drugs from natural materials (marijuana, hashish, opium), natural products (morphine, cocaine), or their simple derivatives (heroin), to synthetic agents more potent than their natural prototypes, which are sometimes less harmful in the short term, or that combine properties from different classes of recreational prototypes. These agents have been named smart drugs, and have become popular both for personal consumption and for collective intoxication at rave parties. The reasons for this transition are varied, but are mainly regulatory and commercial. New analogues of known illegal intoxicants are invisible to most forensic detection techniques, while the alleged natural status and the lack of avert acute toxicity make them appealing to a wide range of users. On the other hand, the advent of the internet has made possible the quick dispersal of information among users and the on-line purchase of these agents and/or the precursors for their synthesis. Unlike their natural products chemotypes (ephedrine, mescaline, cathinone, psilocybin, THC), most new drugs of abuse are largely unfamiliar to the organic chemistry community as well as to health care providers. To raise awareness of the growing plague of smart drugs we have surveyed, in a medicinal chemistry fashion, their development from natural products leads, their current methods of production, and the role that clandestine home laboratories and underground chemists have played in the surge of popularity of these drugs.

  17. 21 CFR 358.550 - Labeling of corn and callus remover 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 corn and callus remover drug products... USE Corn and Callus Remover Drug Products § 358.550 Labeling of corn and callus remover drug products... any, and identifies the product as a “corn and callus remover.” (b) Indications. The labeling of...

  18. 21 CFR 358.550 - Labeling of corn and callus remover 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 corn and callus remover drug products... USE Corn and Callus Remover Drug Products § 358.550 Labeling of corn and callus remover drug products... any, and identifies the product as a “corn and callus remover.” (b) Indications. The labeling of...

  19. 21 CFR 358.550 - Labeling of corn and callus remover 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 corn and callus remover drug products... USE Corn and Callus Remover Drug Products § 358.550 Labeling of corn and callus remover drug products... any, and identifies the product as a “corn and callus remover.” (b) Indications. The labeling of...

  20. 21 CFR 358.550 - Labeling of corn and callus remover 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 corn and callus remover drug products... USE Corn and Callus Remover Drug Products § 358.550 Labeling of corn and callus remover drug products... any, and identifies the product as a “corn and callus remover.” (b) Indications. The labeling of...

  1. 21 CFR 358.550 - Labeling of corn and callus remover 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 corn and callus remover drug products... USE Corn and Callus Remover Drug Products § 358.550 Labeling of corn and callus remover drug products... any, and identifies the product as a “corn and callus remover.” (b) Indications. The labeling of...

  2. 21 CFR 344.52 - Labeling of ear drying aid 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 ear drying aid drug products. 344.52... Labeling of ear drying aid drug products. (a) Statement of identity. The labeling of the product contains the established name of the drug, if any, and identifies the product as an “ear drying aid.”...

  3. 21 CFR 344.52 - Labeling of ear drying aid 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 ear drying aid drug products. 344.52... Labeling of ear drying aid drug products. (a) Statement of identity. The labeling of the product contains the established name of the drug, if any, and identifies the product as an “ear drying aid.”...

  4. 21 CFR 344.52 - Labeling of ear drying aid 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 ear drying aid drug products. 344.52... Labeling of ear drying aid drug products. (a) Statement of identity. The labeling of the product contains the established name of the drug, if any, and identifies the product as an “ear drying aid.”...

  5. The Acquisition of Drugs and Biologics for Chemical and Biological Warfare Defense. Department of Defense Interactions with the Food and Drug Administration

    DTIC Science & Technology

    2003-01-01

    ing processes, clinical studies, and pharmacovigilance procedures. The audit group performs final product quality control, maintains the inventory...of released products, and periodically tests stability. The pharmacovigilance department is responsible for collecting information about adverse drug...employs about 3,000 people: About 1,500 are in quality control; 150 in technical services; 1,000 in quality assurance; and 50 in audit. Pharmacovigilance

  6. Formate Formation and Formate Conversion in Biological Fuels Production

    PubMed Central

    Crable, Bryan R.; Plugge, Caroline M.; McInerney, Michael J.; Stams, Alfons J. M.

    2011-01-01

    Biomethanation is a mature technology for fuel production. Fourth generation biofuels research will focus on sequestering CO2 and providing carbon-neutral or carbon-negative strategies to cope with dwindling fossil fuel supplies and environmental impact. Formate is an important intermediate in the methanogenic breakdown of complex organic material and serves as an important precursor for biological fuels production in the form of methane, hydrogen, and potentially methanol. Formate is produced by either CoA-dependent cleavage of pyruvate or enzymatic reduction of CO2 in an NADH- or ferredoxin-dependent manner. Formate is consumed through oxidation to CO2 and H2 or can be further reduced via the Wood-Ljungdahl pathway for carbon fixation or industrially for the production of methanol. Here, we review the enzymes involved in the interconversion of formate and discuss potential applications for biofuels production. PMID:21687599

  7. 78 FR 38349 - Draft Guidance for Industry on Expedited Programs for Serious Conditions-Drugs and Biologics...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-26

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Expedited Programs for Serious Conditions--Drugs and Biologics; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the availability of a...

  8. [New drugs for horses and production animals in 2013].

    PubMed

    Emmerich, I U

    2014-01-01

    In 2013, only one newly developed active pharmaceutical ingredient for horses and food-producing animals was released on the German market for veterinary drug products. The ionophore monensin from the group of polyether antibiotics is now available as an orally administered continuous release intraruminal device for cattle (Kexxtone®). Furthermore, two established veterinary active pharmaceutical ingredients are available for additional species: The antibiotic amoxicillin (Suramox®) is also authorized for ducks and turkeys and the dissociative anesthetic ketamine is now authorized for sheep, goats and dairy cattle. Additionally, one veterinary drug with a new pharmaceutical form as well as one product with a new strength have been launched on the market for veterinary drugs for horses and food producing animals.

  9. 21 CFR 357.150 - Labeling of anthelmintic drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... taking this drug. If any of these conditions persist consult a doctor.” (2) “If you are pregnant or have liver disease, do not take this product unless directed by a doctor.” (d) Directions. The labeling of... Do not use unless directed by a doctor. 25 to 37 pounds 125 milligrams. 38 to 62 pounds...

  10. 21 CFR 357.150 - Labeling of anthelmintic drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... taking this drug. If any of these conditions persist consult a doctor.” (2) “If you are pregnant or have liver disease, do not take this product unless directed by a doctor.” (d) Directions. The labeling of... Do not use unless directed by a doctor. 25 to 37 pounds 125 milligrams. 38 to 62 pounds...

  11. 21 CFR 357.150 - Labeling of anthelmintic drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... taking this drug. If any of these conditions persist consult a doctor.” (2) “If you are pregnant or have liver disease, do not take this product unless directed by a doctor.” (d) Directions. The labeling of... Do not use unless directed by a doctor. 25 to 37 pounds 125 milligrams. 38 to 62 pounds...

  12. 21 CFR 357.150 - Labeling of anthelmintic drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... taking this drug. If any of these conditions persist consult a doctor.” (2) “If you are pregnant or have liver disease, do not take this product unless directed by a doctor.” (d) Directions. The labeling of... Do not use unless directed by a doctor. 25 to 37 pounds 125 milligrams. 38 to 62 pounds...

  13. 21 CFR 357.150 - Labeling of anthelmintic drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... taking this drug. If any of these conditions persist consult a doctor.” (2) “If you are pregnant or have liver disease, do not take this product unless directed by a doctor.” (d) Directions. The labeling of... Do not use unless directed by a doctor. 25 to 37 pounds 125 milligrams. 38 to 62 pounds...

  14. A New Golden Age of Natural Products Drug Discovery

    PubMed Central

    Shen, Ben

    2016-01-01

    The 2015 Nobel Prize in Physiology or Medicine has been awarded to William C. Campbell and Satoshi Omura, and Youyou Tu for the discovery of avermectins and artemisinin, respectively, therapies that revolutionized the treatment of devastating parasite diseases. With the recent technological advances, a New Golden Age of natural products drug discovery is dawning. PMID:26638061

  15. 21 CFR 341.76 - Labeling of bronchodilator drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... are now taking a prescription monoamine oxidase inhibitor (MAOI) (certain drugs for depression... product, but seek medical assistance immediately if symptoms are not relieved within 1 hour or become... loss of appetite. If these symptoms persist or become worse, consult your doctor.” (6) For...

  16. Radiation and ethylene oxide terminal sterilization experiences with drug eluting stent products.

    PubMed

    Lambert, Byron J; Mendelson, Todd A; Craven, Michael D

    2011-12-01

    Radiation and ethylene oxide terminal sterilization are the two most frequently used processes in the medical device industry to render product within the final sterile barrier package free from viable microorganisms. They are efficacious, safe, and efficient approaches to the manufacture of sterile product. Terminal sterilization is routinely applied to a wide variety of commodity healthcare products (drapes, gowns, etc.) and implantable medical devices (bare metal stents, heart valves, vessel closure devices, etc.) along with products used during implantation procedures (catheters, guidewires, etc.). Terminal sterilization is also routinely used for processing combination products where devices, drugs, and/or biologics are combined on a single product. High patient safety, robust standards, routine process controls, and low-cost manufacturing are appealing aspects of terminal sterilization. As the field of combination products continues to expand and evolve, opportunity exists to expand the application of terminal sterilization to new combination products. Material compatibility challenges must be overcome to realize these opportunities. This article introduces the reader to terminal sterilization concepts, technologies, and the related standards that span different industries (pharmaceutical, medical device, biopharmaceuticals, etc.) and provides guidance on the application of these technologies. Guidance and examples of the application of terminal sterilization are discussed using experiences with drug eluting stents and bioresorbable vascular restoration devices. The examples provide insight into selecting the sterilization method, developing the process around it, and finally qualifying/validating the product in preparation for regulatory approval and commercialization. Future activities, including new sterilization technologies, are briefly discussed.

  17. Evolution of approaches to viral safety issues for biological products.

    PubMed

    Lubiniecki, Anthony S

    2011-01-01

    CONFERENCE PROCEEDING Proceedings of the PDA/FDA Adventitious Viruses in Biologics: Detection and Mitigation Strategies Workshop in Bethesda, MD, USA; December 1-3, 2010 Guest Editors: Arifa Khan (Bethesda, MD), Patricia Hughes (Bethesda, MD) and Michael Wiebe (San Francisco, CA) Approaches to viral safety issues for biological products have evolved during the past 50+ years. The first cell culture products (viral vaccines) relied largely on the use of in vitro and in vivo virus screening assays that were based upon infectivity of adventitious viral agents. The use of Cohn fractionation and pasteurization by manufacturers of plasma derivatives introduced the concepts that purification and treatment with physical and chemical agents could greatly reduce the risk of viral contamination of human albumin and immunoglobulin products. But the limitations of such approaches became clear for thermolabile products that were removed early in fractionation such as antihemophilic factors, which transmitted hepatitis viruses and HIV-1 to some product recipients. These successes and limitations were taken into account by the early developers of recombinant DNA (rDNA)-derived cell culture products and by regulatory agencies, leading to the utilization of cloning technology to reduce/eliminate contamination due to human viruses and purification technologies to physically remove and inactivate adventitious and endogenous viruses, along with cell banking and cell bank characterization for adventitious and endogenous viruses, viral screening of biological raw materials, and testing of cell culture harvests, to ensure virus safety. Later development and incorporation of nanofiltration technology in the manufacturing process provided additional assurance of viral clearance for safety of biotechnology products. These measures have proven very effective at preventing iatrogenic infection of recipients of biotechnology products; however, viral contamination of production cell cultures has

  18. "New drug" designations for new therapeutic entities: new active substance, new chemical entity, new biological entity, new molecular entity.

    PubMed

    Branch, Sarah K; Agranat, Israel

    2014-11-13

    This Perspective addresses ambiguities in designations of "new drugs" intended as new therapeutic entities (NTEs). Designation of an NTE as a new drug is significant, as it may confer regulatory exclusivity, an important incentive for development of novel compounds. Such designations differ between jurisdictions according to their drug laws and drug regulations. Chemical, biological, and innovative drugs are addressed in turn. The terms new chemical entity (NCE), new molecular entity (NME), new active substance (NAS), and new biological entity (NBE) as applied in worldwide jurisdictions are clarified. Differences between them are explored through case studies showing why new drugs have different periods of exclusivity in different jurisdictions or none at all. Finally, this Perspective recommends that in future, for the purpose of new drug compilations, NME is used for a new chemical drug, NBE for a new biological drug, and the combined designation NTE should refer to either an NME or an NBE.

  19. Postmarket Drug Safety Information for Patients and Providers

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Drugs Home Drugs Drug Safety and Availability Postmarket Drug Safety Information for Patients and Providers Postmarket Drug Safety Information for Patients and Providers Share Tweet ...

  20. Intensification of tropical Pacific biological productivity due to volcanic eruptions

    NASA Astrophysics Data System (ADS)

    Chikamoto, Megumi O.; Timmermann, Axel; Yoshimori, Masakazu; Lehner, Flavio; Laurian, Audine; Abe-Ouchi, Ayako; Mouchet, Anne; Joos, Fortunat; Raible, Christoph C.; Cobb, Kim M.

    2016-02-01

    Major volcanic eruptions generate widespread ocean cooling, which reduces upper ocean stratification. This effect has the potential to increase nutrient delivery into the euphotic zone and boost biological productivity. Using externally forced last millennium simulations of three climate/Earth System models (Model for Interdisciplinary Research On Climate (MIROC), Community Earth System Model (CESM), and LOch-Vecode-Ecbilt-CLio-agIsm Model (LOVECLIM)), we test the hypothesis that large volcanic eruptions intensify nutrient-driven export production. It is found that strong volcanic radiative forcing enhances the likelihood of eastern Pacific El Niño-like warming in CESM and LOVECLIM. This leads to an initial reduction of nutrients and export production in the eastern equatorial Pacific. However, this initial response reverses after about 3 years in association with La Niña cooling. The resulting delayed enhancement of biological production resembles the multiyear response in MIROC. The model simulations show that volcanic impacts on tropical Pacific dynamics and biogeochemistry persist for several years, thus providing a new source for potential multiyear ecosystem predictability.

  1. 76 FR 11330 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-02

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 510, 520, and 558 Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug Applications; Phenylbutazone; Pyrantel; Tylosin AGENCY: Food and Drug Administration, HHS. ACTION: Final rule. SUMMARY: The Food and...

  2. 75 FR 24394 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 556 and 558 Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug Application; Buquinolate; Coumaphos AGENCY: Food and... amending the animal drug regulations by removing those portions that reflect approval of two new...

  3. Standard Preparations, Limits of Potency, and Dating Period Limitations for Biological Products. Direct final rule.

    PubMed

    2016-05-04

    The Food and Drug Administration (FDA or Agency or we) is amending the general biological products standards relating to dating periods and also removing certain standards relating to standard preparations and limits of potency. FDA is taking this action to update outdated requirements, and accommodate new and evolving technology and testing capabilities, without diminishing public health protections. This action is part of FDA's retrospective review of its regulations in response to an Executive order. FDA is issuing these amendments directly as a final rule because the Agency believes they are noncontroversial and FDA anticipates no significant adverse comments.

  4. Estimating product bioequivalence for highly variable veterinary drugs.

    PubMed

    Claxton, R; Cook, J; Endrenyi, L; Lucas, A; Martinez, M N; Sutton, S C

    2012-04-01

    The occurrence of drugs and drug formulations associated with large intrasubject pharmacokinetic (PK) variability has been well described in humans and is likewise encountered in veterinary medicine. The scaled average bioequivalence (SABE) approach adopted by CDER of the FDA for the determination of bioequivalence (BE) of highly variable drugs (HVD) needs to be considered when applied to veterinary dosage forms. However, because of some of the unique challenges that are encountered within the framework of veterinary medicine, variations of CDER's approach are presented. The present manuscript discusses HVD and highly variable veterinary drugs (HVVD) from the perspective of possible alternative approaches to support the assessment of product BE in veterinary medicine. Limitations in the use of 3- and 4-way crossover study designs are enumerated. In addition to a need for a statistical analysis of HVVD when using a parallel study design, the use of the secondary criteria (test-to-reference ratio), definition of σ(0) , and average BE with expanding limits are raised. A number of the details need to be finalized, from the selection of a regulatory constant to the determination of 'highly variable' in a veterinary drug product. Academicians, industrial scientists, and regulators should continue this discussion and resolve these details.

  5. 77 FR 22327 - Draft Guidance for Industry on New Animal Drugs and New Animal Drug Combination Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ... Animal Drug Combination Products Administered in or on Medicated Feed or Drinking Water of Food-Producing... Drinking Water of Food- Producing Animals: Recommendations for Drug Sponsors for Voluntarily Aligning... and New Animal Drug Combination Products Administered in or on Medicated Feed or Drinking Water...

  6. 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

    ... compendial drug products that contain a salt. Under the new policy, drug names and strengths for new compendial drug products will be based on the active moiety. The name and strength of the active ingredient... monograph title, and the strength will be expressed in terms of the active moiety. The policy allows...

  7. 21 CFR 355.55 - Principal display panel of all fluoride rinse drug products.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Principal display panel of all fluoride rinse drug products. 355.55 Section 355.55 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 355.55 Principal display panel of all fluoride rinse drug products. In addition to the statement...

  8. 21 CFR 355.55 - Principal display panel of all fluoride rinse drug products.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Principal display panel of all fluoride rinse drug products. 355.55 Section 355.55 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 355.55 Principal display panel of all fluoride rinse drug products. In addition to the statement...

  9. 21 CFR 355.55 - Principal display panel of all fluoride rinse drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Principal display panel of all fluoride rinse drug products. 355.55 Section 355.55 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 355.55 Principal display panel of all fluoride rinse drug products. In addition to the statement...

  10. 21 CFR 355.55 - Principal display panel of all fluoride rinse drug products.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Principal display panel of all fluoride rinse drug products. 355.55 Section 355.55 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 355.55 Principal display panel of all fluoride rinse drug products. In addition to the statement...

  11. 21 CFR 355.55 - Principal display panel of all fluoride rinse drug products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Principal display panel of all fluoride rinse drug products. 355.55 Section 355.55 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 355.55 Principal display panel of all fluoride rinse drug products. In addition to the statement...

  12. 21 CFR 357.810 - Active ingredients for 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 Active ingredients for deodorant drug products for internal use. 357.810 Section 357.810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant...

  13. 21 CFR 357.810 - Active ingredients for 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 Active ingredients for deodorant drug products for internal use. 357.810 Section 357.810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant...

  14. 21 CFR 357.810 - Active ingredients for 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 Active ingredients for deodorant drug products for internal use. 357.810 Section 357.810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant...

  15. 21 CFR 357.810 - Active ingredients for deodorant drug products for internal use.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Active ingredients for deodorant drug products for internal use. 357.810 Section 357.810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant...

  16. 21 CFR 357.810 - Active ingredients for deodorant drug products for internal use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Active ingredients for deodorant drug products for internal use. 357.810 Section 357.810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant...

  17. 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...

  18. [Drug development from natural fermentation products: establishing a manufacturing process which maximizes the potential of microorganisms].

    PubMed

    Nagao, Koji; Ueda, Satoshi; Kanda, Munekazu; Oohata, Nobutaka; Yamashita, Michio; Hino, Motohiro

    2010-11-01

    Natural fermentation products have long been studied as attractive targets for drug discovery due to their amazing diverse, complex chemical structures and biological activities. As such, a number of revolutionary drugs developed from natural fermentation products have contributed to global human health. To commercialize a drug derived from natural fermentation products, an effective chemical entity must be identified and thoroughly researched, and an effective manufacturing process to prepare a commercial supply must be developed. To construct such a manufacturing process for tacrolimus and micafungin, the following studies were conducted: first, we focused on controlling the production of the tacrolimus-related compound FR900525, a fermentation by-product of tacrolimus which was critical for quality assurance of the drug substance. FR900525 production was reduced by using a mutant strain which produced more pipecolic acid, the biosynthesis material of tacrolimus, than the original strain. Then, to optimize the fermentation process of FR901379, an intermediate of micafungin, a fed-batch culture was adopted to increase FR901379 productivity. Additionally, FULLZONE(TM) impeller was installed into the scaled-up fermenter, reducing the agitation-induced damage to the mycelium. As a result, the mycelial form changed from filamentous to pellet-shaped, and the air uptake rate during fermentation was drastically improved. Finally, we conducted screening for FR901379 acylase-producing microorganisms, as FR901379 acylase is necessary to manufacture micafungin. We were able to easily discover FR901379 acylase-producing microorganisms in soil samples using our novel, convenient screening method, which involves comparing the difference in antibiotic activity between FR901379 and its deacylated product.

  19. First-principles modeling of biological systems and structure-based drug-design.

    PubMed

    Sgrignani, Jacopo; Magistrato, Alessandra

    2013-03-01

    Molecular modeling techniques play a relevant role in drug design providing detailed information at atomistic level on the structural, dynamical, mechanistic and electronic properties of biological systems involved in diseases' onset, integrating and supporting commonly used experimental approaches. These information are often not accessible to the experimental techniques taken singularly, but are of crucial importance for drug design. Due to the enormous increase of the computer power in the last decades, quantum mechanical (QM) or first-principles-based methods have become often used to address biological issues of pharmaceutical relevance, providing relevant information for drug design. Due to their complexity and their size, biological systems are often investigated by means of a mixed quantum-classical (QM/MM) approach, which treats at an accurate QM level a limited chemically relevant portion of the system and at the molecular mechanics (MM) level the remaining of the biomolecule and its environment. This method provides a good compromise between computational cost and accuracy, allowing to characterize the properties of the biological system and the (free) energy landscape of the process in study with the accuracy of a QM description. In this review, after a brief introduction of QM and QM/MM methods, we will discuss few representative examples, taken from our work, of the application of these methods in the study of metallo-enzymes of pharmaceutical interest, of metal-containing anticancer drugs targeting the DNA as well as of neurodegenerative diseases. The information obtained from these studies may provide the basis for a rationale structure-based drug design of new and more efficient inhibitors or drugs.

  20. Solid Phase Microextraction and Related Techniques for Drugs in Biological Samples

    PubMed Central

    Moein, Mohammad Mahdi; Said, Rana; Bassyouni, Fatma

    2014-01-01

    In drug discovery and development, the quantification of drugs in biological samples is an important task for the determination of the physiological performance of the investigated drugs. After sampling, the next step in the analytical process is sample preparation. Because of the low concentration levels of drug in plasma and the variety of the metabolites, the selected extraction technique should be virtually exhaustive. Recent developments of sample handling techniques are directed, from one side, toward automatization and online coupling of sample preparation units. The primary objective of this review is to present the recent developments in microextraction sample preparation methods for analysis of drugs in biological fluids. Microextraction techniques allow for less consumption of solvent, reagents, and packing materials, and small sample volumes can be used. In this review the use of solid phase microextraction (SPME), microextraction in packed sorbent (MEPS), and stir-bar sorbtive extraction (SBSE) in drug analysis will be discussed. In addition, the use of new sorbents such as monoliths and molecularly imprinted polymers will be presented. PMID:24688797

  1. COMPUTER-AIDED DRUG DISCOVERY AND DEVELOPMENT (CADDD): in silico-chemico-biological approach

    PubMed Central

    Kapetanovic, I.M.

    2008-01-01

    It is generally recognized that drug discovery and development are very time and resources consuming processes. There is an ever growing effort to apply computational power to the combined chemical and biological space in order to streamline drug discovery, design, development and optimization. In biomedical arena, computer-aided or in silico design is being utilized to expedite and facilitate hit identification, hit-to-lead selection, optimize the absorption, distribution, metabolism, excretion and toxicity profile and avoid safety issues. Commonly used computational approaches include ligand-based drug design (pharmacophore, a 3-D spatial arrangement of chemical features essential for biological activity), structure-based drug design (drug-target docking), and quantitative structure-activity and quantitative structure-property relationships. Regulatory agencies as well as pharmaceutical industry are actively involved in development of computational tools that will improve effectiveness and efficiency of drug discovery and development process, decrease use of animals, and increase predictability. It is expected that the power of CADDD will grow as the technology continues to evolve. PMID:17229415

  2. Molecular biology in studies of oceanic primary production

    SciTech Connect

    LaRoche, J.; Falkowski, P.G.; Geider, R.

    1992-07-01

    Remote sensing and the use of moored in situ instrumentation has greatly improved our ability to measure phytoplankton chlorophyll and photosynthesis on global scales with high temporal resolution. However, the interpretation of these measurements and their significance with respect to the biogeochemical cycling of carbon relies on their relationship with physiological and biochemical processes in phytoplankton. For example, the use of satellite images of surface chlorophyll to estimate primary production is often based on the functional relationship between photosynthesis and irradiance. A variety of environmental factors such as light, temperature, nutrient availability affect the photosynthesis/irradiance (P vs I) relationship in phytoplankton. We present three examples showing how molecular biology can be used to provide basic insight into the factors controlling primary productivity at three different levels of complexity: 1. Studies of light intensity regulation in unicellular alga show how molecular biology can help understand the processing of environmental cues leading to the regulation of photosynthetic gene expression. 2. Probing of the photosynthetic apparatus using molecular techniques can be used to test existing mechanistic models derived from the interpretation of physiological and biophysical measurements. 3. Exploratory work on the expression of specific proteins during nutrient-limited growth of phytoplankton may lead to the identification and production of molecular probes for field studies.

  3. Molecular biology in studies of oceanic primary production

    SciTech Connect

    LaRoche, J.; Falkowski, P.G. ); Geider, R. . Coll. of Marine Studies)

    1992-01-01

    Remote sensing and the use of moored in situ instrumentation has greatly improved our ability to measure phytoplankton chlorophyll and photosynthesis on global scales with high temporal resolution. However, the interpretation of these measurements and their significance with respect to the biogeochemical cycling of carbon relies on their relationship with physiological and biochemical processes in phytoplankton. For example, the use of satellite images of surface chlorophyll to estimate primary production is often based on the functional relationship between photosynthesis and irradiance. A variety of environmental factors such as light, temperature, nutrient availability affect the photosynthesis/irradiance (P vs I) relationship in phytoplankton. We present three examples showing how molecular biology can be used to provide basic insight into the factors controlling primary productivity at three different levels of complexity: 1. Studies of light intensity regulation in unicellular alga show how molecular biology can help understand the processing of environmental cues leading to the regulation of photosynthetic gene expression. 2. Probing of the photosynthetic apparatus using molecular techniques can be used to test existing mechanistic models derived from the interpretation of physiological and biophysical measurements. 3. Exploratory work on the expression of specific proteins during nutrient-limited growth of phytoplankton may lead to the identification and production of molecular probes for field studies.

  4. Tunable and reversible drug control of protein production via a self-excising degron

    PubMed Central

    Chung, Hokyung K.; Jacobs, Conor L.; Huo, Yunwen; Yang, Jin; Krumm, Stefanie A.; Plemper, Richard K.; Tsien, Roger Y.; Lin, Michael Z.

    2015-01-01

    An effective method for direct chemical control over the production of specific proteins would be widely useful. We describe Small Molecule-Assisted Shutoff (SMASh), a technique in which proteins are fused to a degron that removes itself in the absence of drug, leaving untagged protein. Clinically tested HCV protease inhibitors can then block degron removal, inducing rapid degradation of subsequently synthesized protein copies. SMASh allows reversible and dose-dependent shutoff of various proteins in multiple mammalian cell types and in yeast. We also used SMASh to confer drug responsiveness onto a RNA virus for which no licensed inhibitors exist. As SMASh does not require permanent fusion of a large domain, it should be useful when control over protein production with minimal structural modification is desired. Furthermore, as SMASh only involves a single genetic modification and does not rely on modulating protein-protein interactions, it should be easy to generalize to multiple biological contexts. PMID:26214256

  5. 21 CFR 310.518 - Drug products containing iron or iron salts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Drug products containing iron or iron salts. 310... Drug products containing iron or iron salts. Drug products containing elemental iron or iron salts as...) that contains iron or iron salts for use as an iron source shall bear the following statement:...

  6. 21 CFR 310.518 - Drug products containing iron or iron salts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Drug products containing iron or iron salts. 310... Drug products containing iron or iron salts. Drug products containing elemental iron or iron salts as...) that contains iron or iron salts for use as an iron source shall bear the following statement:...

  7. 21 CFR 310.518 - Drug products containing iron or iron salts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Drug products containing iron or iron salts. 310... Drug products containing iron or iron salts. Drug products containing elemental iron or iron salts as...) that contains iron or iron salts for use as an iron source shall bear the following statement:...

  8. 21 CFR 310.518 - Drug products containing iron or iron salts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Drug products containing iron or iron salts. 310... Drug products containing iron or iron salts. Drug products containing elemental iron or iron salts as...) that contains iron or iron salts for use as an iron source shall bear the following statement:...

  9. 21 CFR 357.850 - Labeling of deodorant drug products for internal use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... incontinence.” (c) Warnings. The labeling of the product contains the following warnings under the heading... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Labeling of deodorant drug products for internal... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE MISCELLANEOUS INTERNAL DRUG PRODUCTS FOR...

  10. 21 CFR 357.850 - Labeling of deodorant drug products for internal use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... incontinence.” (c) Warnings. The labeling of the product contains the following warnings under the heading... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Labeling of deodorant drug products for internal... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE MISCELLANEOUS INTERNAL DRUG PRODUCTS FOR...

  11. 21 CFR 357.850 - Labeling of deodorant drug products for internal use.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... incontinence.” (c) Warnings. The labeling of the product contains the following warnings under the heading... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Labeling of deodorant drug products for internal... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE MISCELLANEOUS INTERNAL DRUG PRODUCTS FOR...

  12. 21 CFR 357.850 - Labeling of deodorant drug products for internal use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... incontinence.” (c) Warnings. The labeling of the product contains the following warnings under the heading... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Labeling of deodorant drug products for internal... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE MISCELLANEOUS INTERNAL DRUG PRODUCTS FOR...

  13. 21 CFR 357.850 - Labeling of deodorant drug products for internal use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... incontinence.” (c) Warnings. The labeling of the product contains the following warnings under the heading... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Labeling of deodorant drug products for internal... HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE MISCELLANEOUS INTERNAL DRUG PRODUCTS FOR...

  14. Isoleukotrienes are biologically active free radical products of lipid peroxidation.

    PubMed

    Harrison, K A; Murphy, R C

    1995-07-21

    The free radical oxidation of arachidonic acid esterified to glycerophospholipids is known to generate complex metabolites, termed isoprostanes, that share structural features of prostaglandins derived from prostaglandin H2 synthase. Furthermore, certain isoprostanes have been found to exert biological activity through endogenous receptors on cell surfaces. Using mass spectrometry and ancillary techniques, the free radical oxidation of 1-hexadecanoyl-2-arachidonoyl-glycerophosphocholine was studied in the search for products of arachidonic acid isomeric to the leukotrienes that are derived from 5-lipoxygenase-catalyzed metabolism of arachidonic acid. Several conjugated triene metabolites were chromatographically separated from known 5-lipoxygenase products and structures characterized as 5,12-dihydroxy-6,8,10,14-eicosatetraenoic acid esterified to the glycerophosphocholine backbone. We have termed these products as B4-isoleukotrienes. Following saponification some, but not all, B4-isoleukotrienes were found to exert biological activity in elevating intracellular calcium in Indo-1-loaded human polymorphonuclear leukocytes. This activity could be blocked by a leukotriene B4 receptor antagonist. An EC50 of approximately 30 nM was determined for one unique B4-isoleukotriene with a relative retention index of 2.54. We have shown that free radical processes can lead to the formation of biologically active isoleukotrienes in glycerophosphocholine liposomes, and we propose that B4-isoleukotrienes may also be formed in membrane glycerophospholipids as a result of lipid peroxidation during tissue injury. Such B4-isoleukotrienes could then mediate events of tissue damage through activation of leukotriene B4 receptors on target cells.

  15. Discharge of pharmaceutical products (PPs) through a conventional biological sewage treatment plant: MECs vs PECs?

    PubMed

    Coetsier, C M; Spinelli, S; Lin, L; Roig, B; Touraud, E

    2009-07-01

    Pharmaceuticals for human use are consumed in significant quantities and their occurrence in aquatic systems has been reported by a number of authors. In the context of environmental risk assessment, there is an increasing interest in evaluating the discharge of pharmaceutical products to surface waters through sewage treatment plants (STP). This case study was carried out on a conventional biological treatment plant (Alès, France) and focused on a set of eleven drugs representing the main therapeutic classes. Measured environmental concentrations (MECs) range from the low ng L(-1) to 1.5 microg L(-1) in effluent and up to few hundred ng L(-1) in receiving surface waters. There is a good agreement between MEC and predicted environmental concentration (PEC) values for seven of the eleven investigated drugs in STP effluent. There is not such a good match between PEC and MEC values in surface waters, and this highlights the limits of this approach, at the local scale.

  16. Liposomal Drug Products: A Quality by Design Approach

    NASA Astrophysics Data System (ADS)

    Xu, Xiaoming

    Quality by Design (QbD) principles has been applied to the development of two liposomal formulations, containing a hydrophilic small molecule therapeutic (Tenofovir) and a protein therapeutic (superoxide dismutase). The goal of the research is to provide critical information on 1) how to reduce the preparation variability in liposome formulations, and 2) how to increase drug encapsulation inside liposomes to reduce manufacturing cost. Most notably, an improved liposome preparation method was developed which increased the encapsulation efficiency of hydrophilic molecules. In particular, this method allows for very high encapsulation efficiency. For example, encapsulation efficiencies of up to 50% have been achieved, whereas previously only 20% or less have been reported. Another significant outcome from this research is a first principle mathematical model to predict the encapsulation efficiency of hydrophilic drugs in unilamellar liposomes. This mathematical model will be useful in: formulation development to rapidly achieve optimized formulations; comparison of drug encapsulation efficiencies of liposomes prepared using different methods; and assisting in the development of suitable process analytical technologies to achieve real-time monitoring and control of drug encapsulation during manufacturing. A novel two-stage reverse dialysis in vitro release testing method has also been developed for passively targeted liposomes, which uses the first stage to mimic the circulation of liposomes in the body and the second stage to imitate the drug release process at the target. The developed in vitro release testing method can be used to distinguish formulations with varied compositions for quality control testing purposes. This developed method may pave the way to the development of more biorelevant quality control testing methods for liposomal drug products in the future. The QbD case studies performed in this research are examples of how this approach can be used to

  17. Comparing Drug-Disease Associations in Clinical Practice Guideline Recommendations and Drug Product Label Indications.

    PubMed

    Leung, Tiffany I; Dumontier, Michel

    2015-01-01

    Clinical practice guidelines (CPGs) and structured product labels (SPLs) are both intended to promote evidence-based medical practices and guide clinicians' prescribing decisions. However, it is unclear how well CPG recommendations about pharmacologic therapies for certain diseases match SPL indications for recommended drugs. In this study, we use publicly available data and text mining methods to examine drug-disease associations in CPG recommendations and SPL treatment indications for 15 common chronic conditions. Preliminary results suggest that there is a mismatch between guideline-recommended pharmacologic therapies and SPL indications. Conflicting or inconsistent recommendations and indications may complicate clinical decision making and implementation or measurement of best practices.

  18. [Studies on market of drug delivery system product and drug delivery system of compound Chinese medicine].

    PubMed

    Feng, Yi; Xu, De-Sheng; Hong, Yan-Long; Zhang, Ning; Ma, Yue-Ming

    2006-10-01

    Based on the progress in the world market of drug delivery system (DDS) product and the research profile of DDS of compound Chinese Medicine, The article puts forward a new method of studies on DDS of compound Chinese Medicine. It is expected that the theory of compatibility of compound Chinese Medicine can be shown and its role can be exerted to the largest extent with the application of pharmaceutics technology to change the mode of drug delivery of activated components of compound Chinese Medicine.

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

    PubMed

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

    2017-02-03

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

  20. Random laser in biological tissues impregnated with a fluorescent anticancer drug

    NASA Astrophysics Data System (ADS)

    Lahoz, F.; Martín, I. R.; Urgellés, M.; Marrero-Alonso, J.; Marín, R.; Saavedra, C. J.; Boto, A.; Díaz, M.

    2015-04-01

    We have demonstrated that chemically modified anticancer drugs can provide random laser (RL) when infiltrated in a biological tissue. A fluorescent biomarker has been covalently bound to tamoxifen, which is one of the most frequently used drugs for breast cancer therapy. The light emitted by the drug-dye composite is scattered in tissue, which acts as a gain medium. Both non-coherent and coherent RL regimes have been observed. Moreover, the analysis of power Fourier transforms of coherent RL spectra indicates that the tissues show a dominant random laser cavity length of about 18 µm, similar to the average size of single cells. These results show that RL could be obtained from other drugs, if properly marked with a fluorescent tag, which could be appealing for new forms of combined opto-chemical therapies.

  1. MALDI-MS drug analysis in biological samples: opportunities and challenges.

    PubMed

    Steuer, Andrea E; Poetzsch, Michael; Kraemer, Thomas

    2016-09-01

    Drug analysis represents a large field in different disciplines. Plasma is commonly considered to be the biosample of choice for that purpose. However, concentrations often do not represent the levels present within deeper compartments and therefore cannot sufficiently explain efficacy or toxicology of drugs. MALDI-MS in drug analysis is of great interest for high-throughput quantification and particularly spatially resolved tissue imaging. The current perspective article will deal with challenges and opportunities of MALDI-MS drug analysis in different biological samples. A particular focus will be on hair samples. Recent applications were included, reviewed for their instrumental setup and sample preparation and pros and cons as well as future perspectives are critically discussed.

  2. Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers

    PubMed Central

    2011-01-01

    Background In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system. Methods We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both in vitro in immune cells from mice and human, and in vivo in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after in vitro treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice in vivo treatment. Results None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS)-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α) release and M1, and M8 decreased IFN-γ production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. In vivo treatment lead to a decrease in reactive oxygen species (ROS), nitric oxide (NO) production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity. Conclusions Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised. PMID:22029602

  3. Drug development from natural products: exploiting synergistic effects.

    PubMed

    Ulrich-Merzenich, Gudrun; Panek, D; Zeitler, H; Vetter, H; Wagner, H

    2010-03-01

    Drug development in phytomedicine has been focused in the past on the discovery and analysis of new structures from natural products. The search aimed at the determination of the single "active principle" in plants, based on the assumption that a plant has one or a few ingredients which determine its therapeutic effects. But traditional systems of medicines like Ayurveda, traditional Chinese medicine or the European phytotherapy generally assume that a synergy of all ingredients of the plants will bring about the maximum of therapeutic efficacy. This approach has for long been impossible to investigate since adequate methods to standardize complex plant mixtures as well as to rationalize complex mode of actions were lacking. The introduction of high throughput technologies provides the opportunity to determine profiles of plants and to systematically explore the mode of action of combinatory drug regimes. The present review highlights the concept of synergy and gives examples of synergistic effects of plant constituents. It elaborates on how the high throughput technologies can be used in drug development from natural products with the aim of creating evidence-based plant medications in prevention and treatment of different diseases in the form of new single treatments or new combinatory drug regimes while exploiting synergy-effects.

  4. Community-Reviewed Biological Network Models for Toxicology and Drug Discovery Applications

    PubMed Central

    Namasivayam, Aishwarya Alex; Morales, Alejandro Ferreiro; Lacave, Ángela María Fajardo; Tallam, Aravind; Simovic, Borislav; Alfaro, David Garrido; Bobbili, Dheeraj Reddy; Martin, Florian; Androsova, Ganna; Shvydchenko, Irina; Park, Jennifer; Calvo, Jorge Val; Hoeng, Julia; Peitsch, Manuel C.; Racero, Manuel González Vélez; Biryukov, Maria; Talikka, Marja; Pérez, Modesto Berraquero; Rohatgi, Neha; Díaz-Díaz, Noberto; Mandarapu, Rajesh; Ruiz, Rubén Amián; Davidyan, Sergey; Narayanasamy, Shaman; Boué, Stéphanie; Guryanova, Svetlana; Arbas, Susana Martínez; Menon, Swapna; Xiang, Yang

    2016-01-01

    Biological network models offer a framework for understanding disease by describing the relationships between the mechanisms involved in the regulation of biological processes. Crowdsourcing can efficiently gather feedback from a wide audience with varying expertise. In the Network Verification Challenge, scientists verified and enhanced a set of 46 biological networks relevant to lung and chronic obstructive pulmonary disease. The networks were built using Biological Expression Language and contain detailed information for each node and edge, including supporting evidence from the literature. Network scoring of public transcriptomics data inferred perturbation of a subset of mechanisms and networks that matched the measured outcomes. These results, based on a computable network approach, can be used to identify novel mechanisms activated in disease, quantitatively compare different treatments and time points, and allow for assessment of data with low signal. These networks are periodically verified by the crowd to maintain an up-to-date suite of networks for toxicology and drug discovery applications. PMID:27429547

  5. Is there potential for therapeutic drug monitoring of biologic agents in rheumatoid arthritis?

    PubMed

    Bastida, Carla; Ruíz, Virginia; Pascal, Mariona; Yagüe, Jordi; Sanmartí, Raimon; Soy, Dolors

    2016-12-19

    The use of biologics has significantly changed the management of rheumatoid arthritis over the last decade, becoming the cornerstone treatment for many patients. The current therapeutic arsenal consists of just under 10 biologic agents, with four different mechanisms of action. Several studies have demonstrated a large interindividual pharmacokinetic variability, which translates to unpredictability in clinical response among individuals. The present review focuses on the pharmacokinetics and pharmacodynamics of biologic agents approved for rheumatoid arthritis. The literature relating to their concentration-effect relationship and the use of pharmacokinetic-pharmacodynamic modelling to optimize drug regimens is analysed. Due to the scarcity and complexity of these studies, the current dosing strategy is based on clinical indexes/aspects. In general, dose individualization for biologics should be implemented increasingly in clinical practice as there is a direct benefit for treated rheumatoid arthritis patients. Moreover, there is an indirect benefit in terms of cost-effectiveness.

  6. Natural products as a resource for biologically active compounds

    SciTech Connect

    Hanke, F.J.

    1986-01-01

    The goal of this study was to investigate various sources of biologically active natural products in an effort to identify the active pesticidal compounds involved. The study is divided into several parts. Chapter 1 contains a discussion of several new compounds from plant and animal sources. Chapter 2 introduces a new NMR technique. In section 2.1 a new technique for better utilizing the lanthanide relaxation agent Gd(fod)/sub 3/ is presented which allows the predictable removal of resonances without line broadening. Section 2.2 discusses a variation of this technique for use in an aqueous solvent by applying this technique towards identifying the binding sites of metals of biological interest. Section 2.3 presents an unambiguous /sup 13/C NMR assignment of melibiose. Chapter 3 deals with work relating to the molting hormone of most arthropods, 20-hydroxyecdysone. Section 3.1 discusses the use of two-dimensional NMR (2D NMR) to assign the /sup 1/H NMR spectrum of this biologically important compound. Section 3.2 presents a new application for Droplet countercurrent chromatography (DCCC). Chapter 4 presents a basic improvement to the commercial DCCC instrument that is currently being applied to future commercial instruments. Chapter 5 discusses a curious observation of the effects that two previously known compounds, nagilactone C and (-)-epicatechin, have on lettuce and rice and suggest a possible new role for the ubiquitous flavanol (-)-epicatechin in plants.

  7. Systems chemical biology and the Semantic Web: what they mean for the future of drug discovery research.

    PubMed

    Wild, David J; Ding, Ying; Sheth, Amit P; Harland, Lee; Gifford, Eric M; Lajiness, Michael S

    2012-05-01

    Systems chemical biology, the integration of chemistry, biology and computation to generate understanding about the way small molecules affect biological systems as a whole, as well as related fields such as chemogenomics, are central to emerging new paradigms of drug discovery such as drug repurposing and personalized medicine. Recent Semantic Web technologies such as RDF and SPARQL are technical enablers of systems chemical biology, facilitating the deployment of advanced algorithms for searching and mining large integrated datasets. In this paper, we aim to demonstrate how these technologies together can change the way that drug discovery is accomplished.

  8. Characterization of p38 MAPK isoforms for drug resistance study using systems biology approach

    PubMed Central

    Engler, David A.; Matsunami, Risë K.; Su, Jing; Zhang, Le; Chang, Chung-Che (Jeff); Zhou, Xiaobo

    2014-01-01

    Motivation: p38 mitogen-activated protein kinase activation plays an important role in resistance to chemotherapeutic cytotoxic drugs in treating multiple myeloma (MM). However, how the p38 mitogen-activated protein kinase signaling pathway is involved in drug resistance, in particular the roles that the various p38 isoforms play, remains largely unknown. Method: To explore the underlying mechanisms, we developed a novel systems biology approach by integrating liquid chromatography–mass spectrometry and reverse phase protein array data from human MM cell lines with computational pathway models in which the unknown parameters were inferred using a proposed novel algorithm called modularized factor graph. Results: New mechanisms predicted by our models suggest that combined activation of various p38 isoforms may result in drug resistance in MM via regulating the related pathways including extracellular signal-regulated kinase (ERK) pathway and NFкB pathway. ERK pathway regulating cell growth is synergistically regulated by p38δ isoform, whereas nuclear factor kappa B (NFкB) pathway regulating cell apoptosis is synergistically regulated by p38α isoform. This finding that p38δ isoform promotes the phosphorylation of ERK1/2 in MM cells treated with bortezomib was validated by western blotting. Based on the predicted mechanisms, we further screened drug combinations in silico and found that a promising drug combination targeting ERK1/2 and NFκB might reduce the effects of drug resistance in MM cells. This study provides a framework of a systems biology approach to studying drug resistance and drug combination selection. Availability and implementation: RPPA experimental Data and Matlab source codes of modularized factor graph for parameter estimation are freely available online at http://ctsb.is.wfubmc.edu/publications/modularized-factor-graph.php Contact: xizhou@wakehealth.edu or zhanglcq@swu.edu.cn Supplementary information: Supplementary data are available at

  9. Systems biological approaches towards understanding cellulase production by Trichoderma reesei.

    PubMed

    Kubicek, Christian P

    2013-01-20

    Recent progress and improvement in "-omics" technologies has made it possible to study the physiology of organisms by integrated and genome-wide approaches. This bears the advantage that the global response, rather than isolated pathways and circuits within an organism, can be investigated ("systems biology"). The sequencing of the genome of Trichoderma reesei (teleomorph Hypocrea jecorina), a fungus that serves as a major producer of biomass-degrading enzymes for the use of renewable lignocellulosic material towards production of biofuels and biorefineries, has offered the possibility to study this organism and its enzyme production on a genome wide scale. In this review, I will highlight the use of genomics, transcriptomics, proteomics and metabolomics towards an improved and novel understanding of the biochemical processes that involve in the massive overproduction of secreted proteins.

  10. Microbial biotransformation as a tool for drug development based on natural products from mevalonic acid pathway: A review

    PubMed Central

    Hegazy, Mohamed-Elamir F.; Mohamed, Tarik A.; ElShamy, Abdelsamed I.; Mohamed, Abou-El-Hamd H.; Mahalel, Usama A.; Reda, Eman H.; Shaheen, Alaa M.; Tawfik, Wafaa A.; Shahat, Abdelaaty A.; Shams, Khalid A.; Abdel-Azim, Nahla S.; Hammouda, Fayza M.

    2014-01-01

    Natural products are structurally and biologically interesting metabolites, but they have been isolated in minute amounts. The syntheses of such natural products help in obtaining them in bulk amounts. The recognition of microbial biotransformation as important manufacturing tool has increased in chemical and pharmaceutical industries. In recent years, microbial transformation is increasing significantly from limited interest into highly active area in green chemistry including preparation of pharmaceutical products. This is the first review published on the usage of microbial biocatalysts for some natural product classes and natural product drugs. PMID:25685541

  11. 37 CFR 1.779 - Calculation of patent term extension for a veterinary biological product.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... extension for a veterinary biological product. 1.779 Section 1.779 Patents, Trademarks, and Copyrights... Calculation of patent term extension for a veterinary biological product. (a) If a determination is made pursuant to § 1.750 that a patent for a veterinary biological product is eligible for extension, the...

  12. 21 CFR 601.26 - Reclassification procedures to determine that licensed biological products are safe, effective...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... licensed biological products are safe, effective, and not misbranded under prescribed, recommended, or... Reclassification procedures to determine that licensed biological products are safe, effective, and not misbranded... for the reclassification of all biological products that have been classified into Category IIIA....

  13. Biological standards: problems in large-scale production.

    PubMed

    Campbell, P J

    1976-10-01

    A biological standard usually consists of a batch of perhaps several thousand ampoules. In defining a batch of ampoules to be a standard, we are in essence making a number of fundamental claims: (1) That in terms of content, (mass and potency) each individual ampoule is identical to every other amoule in the batch. (2) That in the course of preparation of the standard, the contents of each ampoule have been treated in exactly the same way and held for the same length of time under the same conditions, (i.e. all the ampoules of the standard have been treated as one single batch, each stage of processing being carried out under constant conditions in one complete working session, however long). (3) That the stability or instability of the biological activity of the contents of each ampoule of the batch is identical to every other ampoule (i.e. that moisture, oxygen, light, raised temperature--all factors which cause deterioration of biological activity--have been exculuded to the same degree in each and every ampoule in the batch, so that each ampoule of the standard is equally stable or unstable). It is quite a difficult task to meet these criteria even in a small number of ampoules at the bench. It becomes a very demanding exercise to achieve the same results in 4,000 ampoules--the normal batch size at NIBSC. Details of the methods used at NIBSC for the production of large batches of ampoules of biological standards have already been published (Campbell, 1974). The author of the papers will take the opportunity to develop various aspects of the published detail.

  14. An overview of biological production of L-theanine.

    PubMed

    Mu, Wanmeng; Zhang, Tao; Jiang, Bo

    2015-01-01

    L-Theanine (γ-glutamylethylamide) is a unique non-protein amino acid that is naturally found in tea plants. It contributes to the umami taste and unique flavor to green tea infusion, and thus its content in tea leaves highly impacts the tea quality and price. In addition to the graceful taste, it has been proved to have many beneficial physiological effects, especially promoting relaxation and improving concentration and learning ability. Based on these promising advantages, L-theanine has been commercially developed as a valuable ingredient for use in food and beverages to improve and/or maintain human health. L-Theanine can be obtained by chemical synthesis or isolation from tea, while chemical synthesis of L-theanine is hard to be accepted by consumers and is not allowed to use in food industry, and isolation of L-theanine in high purity generally involves time-consuming, cost-ineffective, and complicated operational processes. Accordingly, the biological production of L-theanine has recently attracted much attention. Four kinds of bacterial enzymes, including L-glutamine synthetase, γ-glutamylmethylamide synthetase, γ-glutamyltranspeptidase, and L-glutaminase, have been characterized to have L-theanine-producing ability. Herein, an overview of recent studies on the biological production of L-theanine was presented.

  15. The pharmaceutical biochemistry group: where pharmaceutical chemistry meets biology and drug delivery.

    PubMed

    Kalia, Yogeshvar N; Perozzo, Remo; Scapozza, Leonardo

    2012-01-01

    Successful drug discovery and development of new therapeutics is a long, expensive multidisciplinary process needing innovation and the integration of smart cutting edge science and technology to overcome the challenges in taking a drug from the bench to the bedside. The research activities of the Pharmaceutical Biochemistry group span the drug discovery and development process, providing an interface that brings together pharmaceutical chemistry, biochemistry, structural biology, computational chemistry and biopharmaceutics. Formulation and drug delivery are brought into play at an earlier stage when facing the perennial challenge of transforming a potent molecule in vitro into a therapeutic agent in vivo. Concomitantly, drug delivery results can be understood at a molecular level. This broad range of interdisciplinary research activities and competences enables us to address key challenges in modern drug discovery and development, provides a powerful collaborative platform for other universities and the pharmaceutical industry and an excellent training platform for pharmacists and pharmaceutical scientists who will later be involved in drug discovery and development.

  16. Indicators of Club Management Practices and Biological Measurements of Patrons’ Drug and Alcohol Use

    PubMed Central

    Byrnes, Hilary F.; Miller, Brenda A.; Johnson, Mark B.; Voas, Robert B.

    2015-01-01

    Background Electronic Music Dance Events in nightclubs attract patrons with heavy alcohol/drug use. Public health concerns are raised from risks related to these behaviors. Practices associated with increased risk in these club settings need to be identified. Objectives The relationship between club management practices and biological measures of patrons’ alcohol/drug use is examined. Methods Observational data from 25 events across 6 urban clubs were integrated with survey data (N=738 patrons, 42.8% female) from patrons exiting these events, 2010–2012. Five indicators of club management practices were examined using mixed model regressions: club security, bar crowding, safety signs, serving intoxicated patrons, and isolation. Results Analyses revealed that serving intoxicated patrons and safety signs were related to less substance use. Specifically, serving intoxicated patrons was related to heavy alcohol and drug use at exit, while safety signs were marginally related to less exit drug use. Conclusions/Importance Findings indicate observable measures in nightclubs provide important indicators for alcohol/drug use, suggesting practices to target. Study strengths include the use of biological measures of substance use on a relatively large scale. Limitations and future directions are discussed. PMID:24832721

  17. Searching for disease-modifying drugs in AD: can we combine neuropsychological tools with biological markers?

    PubMed

    Caraci, Filippo; Castellano, Sabrina; Salomone, Salvatore; Drago, Filippo; Bosco, Paolo; Di Nuovo, Santo

    2014-02-01

    Drug discovery efforts in Alzheimer's disease (AD) have been directed in the last ten years to develop "disease-modifying drugs" able to exert neuroprotective effects in an early phase of AD pathogenesis. Unfortunately several candidate disease-modifying drugs have failed in Phase III clinical trials conducted in mild to moderate AD for different methodological difficulties, such as the time course of treatment in relation to development of disease as well as the appropriate use of validated biological and neuropsychological markers. Mild cognitive impairment (MCI) has been considered a precursor of AD. Much effort is now directed to identify the most appropriate and sensitive markers which can predict the progression from MCI to AD, such as neuroimaging markers (e.g. hippocampal atrophy and amyloid positron emission tomography imaging), cerebrospinal fluid markers (i.e. association of elevated tau with low levels of amyloid β -peptide(1-42) and neuropsychological markers (i.e. episodic memory deficits and executive dysfunction). Recent studies demonstrate that the combination of these different biomarkers significantly increases the chance to predict the conversion into AD within 24 months. These biomarkers will be essential in the future to analyze clinical efficacy of disease-modifying drugs in MCI patients at high risk to develop AD. In the present review we analyze recent evidence on the combination of neuropsychological and biological markers in AD as a new tool to track disease progression in early AD as well as the response to disease-modifying drugs.

  18. Public databases of plant natural products for computational drug discovery.

    PubMed

    Tung, Chun-Wei

    2014-01-01

    Plant natural products have been intensively investigated during the past decades with a considerable amount of generated data. Databases are subsequently developed to facilitate the management and analysis of accumulated information including plant species, chemical compounds, structures and bioactivities. With the support of databases, the screening of novel bioactivities for plant natural products can benefit from advanced computational methods to accelerate the progress of drug discovery. This overview describes the contents of publicly available databases useful for computational research of plant natural products. Based on the databases, quantitative structure-activity relationship models and protein-ligand docking methods can be developed and applied to analyze and screen bioactive compounds. More public and structured databases with unique contents, search functions and links to major databases are needed for efficiently exploring the chemical space of plant natural products.

  19. Mimicking Biological Delivery Through Feedback-Controlled Drug Release Systems Based on Molecular Imprinting

    PubMed Central

    Kryscio, David R.; Peppas, Nicholas A.

    2015-01-01

    Intelligent drug delivery systems (DDS) are able to rapidly detect a biological event and respond appropriately by releasing a therapeutic agent; thus, they are advantageous over their conventional counterparts. Molecular imprinting is a promising area that generates a polymeric network which can selectively recognize a desired analyte. This field has been studied for a variety of applications over a long period of time, but only recently has it been investigated for biomedical and pharmaceutical applications. Recent work in the area of molecularly imprinted polymers in drug delivery highlights the potential of these recognitive networks as environmentally responsive DDS that can ultimately lead to feedback controlled recognitive release systems. PMID:26500352

  20. Recent advances in Entamoeba biology: RNA interference, drug discovery, and gut microbiome

    PubMed Central

    Singh, Upinder

    2016-01-01

    In recent years, substantial progress has been made in understanding the molecular and cell biology of the human parasite Entamoeba histolytica, an important pathogen with significant global impact. This review outlines some recent advances in the Entamoeba field in the last five years, focusing on areas that have not recently been discussed in detail: (i) molecular mechanisms regulating parasite gene expression, (ii) new efforts at drug discovery using high-throughput drug screens, and (iii) the effect of gut microbiota on amoebiasis. PMID:27853522

  1. Drug levels, immunogenicity and assessment of active sacroiliitis in patients with axial spondyloarthritis under biologic tapering strategy.

    PubMed

    Almirall, Miriam; Gimeno, Ramón; Salman-Monte, Tarek Carlos; Iniesta, Silvia; Lisbona, Maria Pilar; Maymó, Joan

    2016-04-01

    The aim of the study was to assess drug levels, immunogenicity and sacroiliitis on MRI in patients with axial spondyloarthritis under biologic tapering strategy. Consecutive patients with axial spondyloarthritis who remained in low disease activity more than 1 year after dose tapering of infliximab and adalimumab were included. Plasma drug concentrations of TNF inhibitors and anti-drug antibodies were determined, and MRI of sacroiliac joints was evaluated. Of twenty patients included, eighteen had therapeutic drug levels, no patient had anti-drug antibodies, and no patient had active sacroiliitis on MRI. These data could support the biologic tapering strategy and their maintenance over time.

  2. Biological evaluation of nanosilver incorporated cellulose pulp for hygiene products.

    PubMed

    Kavitha Sankar, P C; Ramakrishnan, Reshmi; Rosemary, M J

    2016-04-01

    Cellulose pulp has a visible market share in personal hygiene products such as sanitary napkins and baby diapers. However it offers good surface for growth of microorganisms. Huge amount of research is going on in developing hygiene products that do not initiate microbial growth. The objective of the present work is to produce antibacterial cellulose pulp by depositing silver nanopowder on the cellulose fiber. The silver nanoparticles used were of less than 100 nm in size and were characterised using transmission electron microscopy and X-ray powder diffraction studies. Antibacterial activity of the functionalized cellulose pulp was proved by JIS L 1902 method. The in-vitro cytotoxicity, in-vivo vaginal irritation and intracutaneous reactivity studies were done with silver nanopowder incorporated cellulose pulp for introducing a new value added product to the market. Cytotoxicity evaluation suggested that the silver nanoparticle incorporated cellulose pulp is non-cytotoxic. No irritation and skin sensitization were identified in animals tested with specific extracts prepared from the test material in the in-vivo experiments. The results indicated that the silver nanopowder incorporated cellulose pulp meets the requirements of the standard practices recommended for evaluating the biological reactivity and has good biocompatibility, hence can be classified as a safe hygiene product.

  3. CYANOS: A Data Management System for Natural Product Drug Discovery Efforts Using Cultured Microorganisms

    PubMed Central

    Chlipala, George E.; Krunic, Aleksej; Mo, Shunyan; Sturdy, Megan; Orjala, Jimmy

    2010-01-01

    A software package, termed “CYANOS”, has been developed to facilitate the data management and data mining for natural product drug discovery efforts. This system allows for the management of data associated with field collections, culture conditions, harvests, extractions, chemical separations, and biological evaluation. This software utilizes a MySQL database for data storage, which allows for reporting and data mining via third party tools. In addition, a web-based interface was constructed to allow for multi-user access from a variety of desktop platforms. The code for this system is freely available and has been released under the Illinois Open Source license. PMID:21162567

  4. Ecological Momentary Assessment of Illicit Drug Use Compared to Biological and Self-Reported Methods

    PubMed Central

    Genz, Andrew; Westergaard, Ryan P; Chang, Larry W; Bollinger, Robert C; Latkin, Carl; Kirk, Gregory D

    2016-01-01

    Background The use of mHealth methods for capturing illicit drug use and associated behaviors have become more widely used in research settings, yet there is little research as to how valid these methods are compared to known measures of capturing and quantifying drug use. Objective We examined the concordance of ecological momentary assessment (EMA) of drug use to previously validated biological and audio-computer assisted self-interview (ACASI) methods. Methods The Exposure Assessment in Current Time (EXACT) study utilized EMA methods to assess drug use in real-time in participants’ natural environments. Utilizing mobile devices, participants self-reported each time they used heroin or cocaine over a 4-week period. Each week, PharmChek sweat patch samples were collected for measurement of heroin and cocaine and participants answered an ACASI-based questionnaire to report behaviors and drug using events during the prior week. Reports of cocaine and heroin use captured through EMA were compared to weekly biological or self-report measures through percent agreement and concordance correlation coefficients to account for repeated measures. Correlates of discordance were obtained from logistic regression models. Results A total of 109 participants were a median of 48.5 years old, 90% African American, and 52% male. During 436 person-weeks of observation, we recorded 212 (49%) cocaine and 103 (24%) heroin sweat patches, 192 (44%) cocaine and 161 (37%) heroin ACASI surveys, and 163 (37%) cocaine and 145 (33%) heroin EMA reports. The percent agreement between EMA and sweat patch methods was 70% for cocaine use and 72% for heroin use, while the percent agreement between EMA and ACASI methods was 77% for cocaine use and 79% for heroin use. Misreporting of drug use by EMA compared to sweat patch and ACASI methods were different by illicit drug type. Conclusions Our work demonstrates moderate to good agreement of EMA to biological and standard self-report methods in

  5. Suitability of Gray Water for Hydroponic Crop Production Following Biological and Physical Chemical and Biological Subsystems

    NASA Technical Reports Server (NTRS)

    Bubenheim, David L.; Harper, Lynn D.; Wignarajah, Kanapathipillai; Greene, Catherine

    1994-01-01

    The water present in waste streams from a human habitat must be recycled in Controlled Ecological Life Support Systems (CELSS) to limit resupply needs and attain self-sufficiency. Plants play an important role in providing food, regenerating air, and producing purified water via transpiration. However, we have shown that the surfactants present in hygiene waste water have acute toxic effects on plant growth (Bubenheim et al. 1994; Greene et al., 1994). These phytotoxic affects can be mitigated by allowing the microbial population on the root surface to degrade the surfactant, however, a significant suppression (several days) in crop performance is experienced prior to reaching sub-toxic surfactant levels and plant recovery. An effective alternative is to stabilize the microbial population responsible for degradation of the surfactant on an aerobic bioreactor and process the waste water prior to utilization in the hydroponic solution (Wisniewski and Bubenheim, 1993). A sensitive bioassay indicates that the surfactant phytotoxicity is suppressed by more than 90% within 5 hours of introduction of the gray water to the bioreactor; processing for more than 12 hours degrades more than 99% of the phytotoxin. Vapor Compression Distillation (VCD) is a physical / chemical method for water purification which employees sequential distillation steps to separate water from solids and to volatilize contaminants. The solids from the waste water are concentrated in a brine and the pure product water (70 - 90% of the total waste water volume depending on operating conditions) retains non of the phytotoxic effects. Results of the bioassay were used to guide evaluations of the suitability of recovered gray water following biological and VCD processing for hydroponic lettuce production in controlled environments. Lettuce crops were grown for 28 days with 100% of the input water supplied with recovered water from the biological processor or VCD. When compared with the growth of plants

  6. Some recent approaches of biologically active substituted pyridazine and phthalazine drugs.

    PubMed

    Asif, M

    2012-01-01

    Nitrogen atom containing heterocyclic compounds, pyridazines, pyridazinones and phthalazines are important structural feature of many biologically active compounds and show diverse pharmacological properties. Pyridazines and phthalazines hold considerable interest relative to the preparation of organic intermediates and physiologically active compounds. On the basis of literature, pyridazines, pyridazinone and phthalazines further focus our attention because of their easy fictionalization at various ring positions, which makes them attractive synthetic compounds for designing and development of the novel pyridazines and phthalazines drugs in future.

  7. Biological hydrogen production by dark fermentation: challenges and prospects towards scaled-up production.

    PubMed

    RenNanqi; GuoWanqian; LiuBingfeng; CaoGuangli; DingJie

    2011-06-01

    Among different technologies of hydrogen production, bio-hydrogen production exhibits perhaps the greatest potential to replace fossil fuels. Based on recent research on dark fermentative hydrogen production, this article reviews the following aspects towards scaled-up application of this technology: bioreactor development and parameter optimization, process modeling and simulation, exploitation of cheaper raw materials and combining dark-fermentation with photo-fermentation. Bioreactors are necessary for dark-fermentation hydrogen production, so the design of reactor type and optimization of parameters are essential. Process modeling and simulation can help engineers design and optimize large-scale systems and operations. Use of cheaper raw materials will surely accelerate the pace of scaled-up production of biological hydrogen. And finally, combining dark-fermentation with photo-fermentation holds considerable promise, and has successfully achieved maximum overall hydrogen yield from a single substrate. Future development of bio-hydrogen production will also be discussed.

  8. 78 FR 75570 - Guidance for Industry on New Animal Drugs and New Animal Drug Combination Products Administered...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-12

    ... Drug Combination Products Administered in or on Medicated Feed or Drinking Water of Food-Producing... or Drinking Water of Food-Producing Animals: Recommendations for Drug Sponsors for Voluntarily... Medicated Feed or Drinking Water of Food- Producing Animals: Recommendations for Drug Sponsors...

  9. 77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-13

    ... HUMAN SERVICES Food and Drug Administration Single-Ingredient, Immediate-Release Drug Products... AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and Drug... such products in interstate commerce. The document was published with an incorrect Web link....

  10. The Redox Biology of Schistosome Parasites and Applications for Drug Development

    PubMed Central

    Huang, Hsin-Hung; Rigouin, Coraline; Williams, David L.

    2013-01-01

    Schistosomiasis caused by Schistosoma spp. is a serious public health concern, especially in sub-Saharan Africa. Praziquantel is the only drug currently administrated to treat this disease. However, praziquantel-resistant parasites have been identified in endemic areas and can be generated in the laboratory. Therefore, it is essential to find new therapeutics. Antioxidants are appealing drug targets. In order to survive in their hosts, schistosomes are challenged by reactive oxygen species from intrinsic and extrinsic sources. Schistosome antioxidant enzymes have been identified as essential proteins and novel drug targets and inhibition of the antioxidant response can lead to parasite death. Because the organization of the redox network in schistosomes is significantly different form that in humans, new drugs are being developed targeting schistosome antioxidants. In this paper the redox biology of schistosomes is discussed and their potential use as drug targets is reviewed. It is hoped that compounds targeting parasite antioxidant responses will become clinically relevant drugs in the near future. PMID:22607149

  11. [Action mechanism of drugs for preventing and treating coronary heart disease based on biological networks].

    PubMed

    Zhang, Yan-Ling; Huang, Ming-Feng; Qiao, Yan-Jiang

    2013-08-01

    Coronary heart disease (CHD) related genes and targets, as well as drug targets for preventing and treating CHD were taken as the study objects to build a CHD disease network and a drug action network preventing and treating CHD. Such topological characteristic parameters of the networks as degree distribution, characteristic path length, connectivity and heterogeneity were analyzed to verify the reliability of the networks. On that basis, the intersection calculation was conducted for both networks to analyze the drug action mechanism of their sub-networks. The disease network are composed of 15,221 nodes and 31,177 sides, while the drug action network preventing and treating CHD has 15,073 nodes and 32,376 sides. Both of their topological characteristic parameters showed scale-free small world structural characteristics. Two reaction pathways in the sub-networks-calcitonin gene-related peptide and IL-6 activated JAK/STAT were taken as examples to discuss the indirect action mechanism for preventing and treating CHD. The results showed that the biological network analysis method combining the disease network and the drug action network is helpful to further studies on the action mechanism of the drugs, and significant to the prevention and treatment of diseases.

  12. Is biological productivity enhanced at the New England shelfbreak front?

    NASA Astrophysics Data System (ADS)

    Zhang, Weifeng G.; McGillicuddy, Dennis J.; Gawarkiewicz, Glen G.

    2013-01-01

    A two-dimensional (cross-shelf) numerical model of the mean seasonal circulation offshore of southern New England predicts upwelling at the shelfbreak front. Expected ramifications of this upwelling include enhancement of nutrient supply, phytoplankton biomass, and productivity. However, seasonal climatologies of chlorophyll based on both in situ data and satellite observations show no mean enhancement at the front. We investigate this apparent discrepancy with a four-component planktonic ecosystem model coupled to the two-dimensional physical model. Nutrient fields are restored to climatological values at depth, and upper ocean values evolve freely according to physical and biological forcing. Vertical diffusivity is based on seasonally averaged surface and bottom mixed layer depths compiled from in situ observations. The model reproduces the general pattern of the observed cross-shelf and seasonal variations of the chlorophyll distribution. It predicts a local enhancement of phytoplankton productivity at the shelfbreak in spring and summer as a result of the persistently upwelled nutrient-rich slope water. In the model, zooplankton grazing prevents accumulation of phytoplankton biomass at the site of the upwelling. The predicted enhancement of primary productivity (but not phytoplankton biomass) at the shelfbreak constitutes a hypothesis that could be tested in the future with suitable measurements from regional long-term observatories, such as the Ocean Observatories Initiative Pioneer Array.

  13. Systems biology of recombinant protein production using Bacillus megaterium.

    PubMed

    Biedendieck, Rebekka; Borgmeier, Claudia; Bunk, Boyke; Stammen, Simon; Scherling, Christian; Meinhardt, Friedhelm; Wittmann, Christoph; Jahn, Dieter

    2011-01-01

    The Gram-negative bacterium Escherichia coli is the most widely used production host for recombinant proteins in both academia and industry. The Gram-positive bacterium Bacillus megaterium represents an increasingly used alternative for high yield intra- and extracellular protein synthesis. During the past two decades, multiple tools including gene expression plasmids and production strains have been developed. Introduction of free replicating and integrative plasmids into B. megaterium is possible via protoplasts transformation or transconjugation. Using His(6)- and StrepII affinity tags, the intra- or extracellular produced proteins can easily be purified in one-step procedures. Different gene expression systems based on the xylose controlled promoter P(xylA) and various phage RNA polymerase (T7, SP6, K1E) driven systems enable B. megaterium to produce up to 1.25g of recombinant protein per liter. Biomass concentrations of up to 80g/l can be achieved by high cell density cultivations in bioreactors. Gene knockouts and gene replacements in B. megaterium are possible via an optimized gene disruption system. For a safe application in industry, sporulation and protease-deficient as well as UV-sensitive mutants are available. With the help of the recently published B. megaterium genome sequence, it is possible to characterize bottle necks in the protein production process via systems biology approaches based on transcriptome, proteome, metabolome, and fluxome data. The bioinformatical platform (Megabac, http://www.megabac.tu-bs.de) integrates obtained theoretical and experimental data.

  14. Biological production of ethanol from coal. Final report

    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.

  15. Optimization of the Bacterial Cytochrome P450 BM3 System for the Production of Human Drug Metabolites

    PubMed Central

    Di Nardo, Giovanna; Gilardi, Gianfranco

    2012-01-01

    Drug metabolism in human liver is a process involving many different enzymes. Among them, a number of cytochromes P450 isoforms catalyze the oxidation of most of the drugs commercially available. Each P450 isoform acts on more than one drug, and one drug may be oxidized by more than one enzyme. As a result, multiple products may be obtained from the same drug, and as the metabolites can be biologically active and may cause adverse drug reactions (ADRs), the metabolic profile of a new drug has to be known before this can be commercialized. Therefore, the metabolites of a certain drug must be identified, synthesized and tested for toxicity. Their synthesis must be in sufficient quantities to be used for metabolic tests. This review focuses on the progresses done in the field of the optimization of a bacterial self-sufficient and efficient cytochrome P450, P450 BM3 from Bacillus megaterium, used for the production of metabolites of human enzymes. The progress made in the improvement of its catalytic performance towards drugs, the substitution of the costly NADPH cofactor and its immobilization and scale-up of the process for industrial application are reported. PMID:23443101

  16. 21 CFR 211.86 - Use of approved components, 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 Use of approved components, drug product containers, and closures. 211.86 Section 211.86 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  17. 21 CFR 211.89 - Rejected components, 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 Rejected components, drug product containers, and closures. 211.89 Section 211.89 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED...

  18. 21 CFR 211.87 - Retesting of approved components, 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 Retesting of approved components, drug product containers, and closures. 211.87 Section 211.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  19. 21 CFR 211.89 - Rejected components, 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 Rejected components, drug product containers, and closures. 211.89 Section 211.89 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED...

  20. 21 CFR 211.86 - Use of approved components, 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 Use of approved components, drug product containers, and closures. 211.86 Section 211.86 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  1. 21 CFR 212.110 - How must I maintain records of my production of PET drugs?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 4 2014-04-01 2014-04-01 false How must I maintain records of my production of PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  2. 21 CFR 211.82 - Receipt and storage of untested components, 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 Receipt and storage of untested components, drug product containers, and closures. 211.82 Section 211.82 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE...

  3. 21 CFR 211.89 - Rejected components, 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 Rejected components, drug product containers, and closures. 211.89 Section 211.89 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED...

  4. 21 CFR 211.82 - Receipt and storage of untested components, 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 Receipt and storage of untested components, drug product containers, and closures. 211.82 Section 211.82 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE...

  5. 21 CFR 211.86 - Use of approved components, 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 Use of approved components, drug product containers, and closures. 211.86 Section 211.86 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  6. 21 CFR 211.86 - Use of approved components, 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 Use of approved components, drug product containers, and closures. 211.86 Section 211.86 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  7. 21 CFR 212.110 - How must I maintain records of my production of PET drugs?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 4 2011-04-01 2011-04-01 false How must I maintain records of my production of PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  8. 21 CFR 211.87 - Retesting of approved components, 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 Retesting of approved components, drug product containers, and closures. 211.87 Section 211.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  9. 21 CFR 211.87 - Retesting of approved components, 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 Retesting of approved components, drug product containers, and closures. 211.87 Section 211.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  10. 21 CFR 211.87 - Retesting of approved components, 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 Retesting of approved components, drug product containers, and closures. 211.87 Section 211.87 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  11. 21 CFR 212.110 - How must I maintain records of my production of PET drugs?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false How must I maintain records of my production of PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  12. 21 CFR 211.82 - Receipt and storage of untested components, 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 Receipt and storage of untested components, drug product containers, and closures. 211.82 Section 211.82 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE...

  13. 21 CFR 211.89 - Rejected components, 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 Rejected components, drug product containers, and closures. 211.89 Section 211.89 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED...

  14. 21 CFR 211.82 - Receipt and storage of untested components, 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 Receipt and storage of untested components, drug product containers, and closures. 211.82 Section 211.82 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE...

  15. 21 CFR 211.110 - Sampling and testing of in-process materials and drug products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Sampling and testing of in-process materials and drug products. 211.110 Section 211.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  16. 21 CFR 212.110 - How must I maintain records of my production of PET drugs?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 4 2013-04-01 2013-04-01 false How must I maintain records of my production of PET drugs? 212.110 Section 212.110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS: GENERAL CURRENT GOOD MANUFACTURING PRACTICE FOR...

  17. 78 FR 72897 - Draft Guidance for Industry on Interim Product Reporting for Human Drug Compounding Outsourcing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-04

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Interim Product Reporting for Human Drug Compounding Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic... Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Drug Quality and Security Act...

  18. 21 CFR 1304.26 - Additional recordkeeping requirements applicable to drug products containing gamma-hydroxybutyric...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 9 2010-04-01 2010-04-01 false Additional recordkeeping requirements applicable to drug products containing gamma-hydroxybutyric acid. 1304.26 Section 1304.26 Food and Drugs DRUG... accordance with an application under section 505 of the Federal Food, Drug, and Cosmetic Act must...

  19. 21 CFR 310.518 - Drug products containing iron or iron salts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Drug products containing iron or iron salts. 310.518 Section 310.518 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... requirements: (a) Labeling. (1) The label of any drug in solid oral dosage form (e.g., tablets or...

  20. Drug Efficacy Monitoring in Pharmacotherapy of Multiple Sclerosis with Biological Agents.

    PubMed

    Caldano, M; Raoul, W; Rispens, T; Bertolotto, A

    2017-03-22

    Multiple Sclerosis (MS) is a heterogeneous disease. Although several EMA approved Disease Modifying Treatments including biopharmaceuticals are available, their efficacy is limited and a certain percentage of patients are always non-responsive. Drug Efficacy Monitoring is an important tool to identify these non-responsive patients early on. Currently, Detection of Anti-Drug Antibodies and quantification of Biological Activity are used as methods of efficacy monitoring for Interferon beta (IFNβ) and Natalizumab (NAT) therapies. For NAT and Alemtuzumab treatments, drug level quantification could be an essential component of the overall disease management. Thus, utilization and development of strategies to determine treatment response are vital aspects of MS management given the tremendous clinical and economic promise of this tool.