DOCSLIB.ORG

Guidance for Industry- Synthetic Peptides

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Guidance for Industry- Synthetic Peptides ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin Guidance for Industry U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) May 2021 Generics ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin Guidance for Industry Additional copies are available from: Office of Communications, Division of Drug Information Center for Drug Evaluation and Research Food and Drug Administration 10001 New Hampshire Ave., Hillandale Bldg., 4th Floor Silver Spring, MD 20993-0002 Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 Email: [email protected] http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) May 2021 Generics Contains Nonbinding Recommendations TABLE OF CONTENTS I. INTRODUCTION............................................................................................................. 1 II. BACKGROUND ............................................................................................................... 3 III. SCIENTIFIC CONSIDERATIONS FOR ANDAS FOR PROPOSED GENERIC SYNTHETIC PEPTIDES ................................................................................................ 5 A. Active Ingredient Sameness .......................................................................................................... 5 B. Impurities ....................................................................................................................................... 6 IV. SUBMISSION OF ANDAS FOR PROPOSED GENERIC SYNTHETIC PEPTIDES ......................................................................................................................... 9 V. REQUESTING ASSISTANCE FROM FDA ..................................................................... 10 APPENDIX 1 – RECOMMENDED EVALUATION OF PEPTIDE-RELATED IMPURITIES TO DETERMINE WHETHER SUBMISSION OF AN ANDA FOR A SYNTHETIC PEPTIDE THAT REFERENCES A PEPTIDE OF rDNA ORIGIN IS APPROPRIATE .......................................................................................................................... 12 Contains Nonbinding Recommendations ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin 1 Guidance for Industry This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title page. I. INTRODUCTION This guidance is intended to assist potential applicants in determining when an application for a synthetic peptide drug product (synthetic peptide) that refers to a previously approved peptide drug product of recombinant deoxyribonucleic acid (rDNA) origin (peptide of rDNA origin) should be submitted as an abbreviated new drug application (ANDA) under section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) rather than as a new drug application (NDA) under section 505(b) of the FD&C Act.2 Specifically, this guidance provides recommendations for evaluating whether an ANDA submission is appropriate for a synthetic peptide that references any of the following five previously approved peptide drug products of rDNA origin: glucagon, liraglutide, nesiritide, teriparatide, and teduglutide.3 Given the current state of technology for peptide synthesis and characterization, FDA believes it is now possible for an ANDA applicant to demonstrate that the active ingredient in a proposed 1 This guidance has been prepared by the Office of Generic Drugs (OGD) in the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration. 2 This guidance does not address ANDAs for peptides of rDNA origin. Based on the types of data permitted to be submitted in an ANDA (see section 505(j)(2)(A) of the FD&C Act) and current scientific considerations, FDA does not expect that an ANDA could include sufficient evidence (e.g., clinical investigations to assess potential immunogenicity) for approval of a proposed peptide of rDNA origin at this time. An applicant seeking approval of a proposed peptide of rDNA origin may file a 505(b)(2) application or a “stand-alone” NDA submitted under section 505(b)(1) of the FD&C Act. 3 This guidance does not address all studies and information that should be submitted in support of an ANDA for a synthetic peptide. Applicants should check on the availability of other guidances, including product-specific guidances, for such recommendations. Guidances relating to generic drugs can be found at https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs. Product-specific guidances for generic drug development can be found athttps://www.fda.gov/drugs/guidances-drugs/product- specific-guidances-generic-drug-development. Also, a potential applicant may request information on a specific element of generic drug development via controlled correspondence or, for complex products such as peptides, may submit a request for a Pre-ANDA meeting. 1 Contains Nonbinding Recommendations generic synthetic peptide drug product (proposed generic synthetic peptide) is the “same” as the active ingredient in a previously approved peptide of rDNA origin. For a synthetic peptide that is intended to be a “duplicate”4 of a previously approved peptide of rDNA origin, a determination of whether an application for the synthetic peptide should be submitted as an ANDA depends largely on its impurity profile as compared to the impurity profile for the peptide of rDNA origin. Differences in impurities, particularly peptide-related impurities, may affect the safety or effectiveness of a peptide drug product as compared to the RLD. Submission of an ANDA for a proposed generic synthetic peptide for which the reference listed drug (RLD) is a peptide of rDNA origin generally would be appropriate if, among other things, the applicant can: 1) show that, for each peptide-related impurity that is found in both the proposed generic synthetic peptide and the RLD, the level of such impurity in the proposed generic synthetic peptide is the same as or lower than that found in the RLD; 2) show that the proposed generic synthetic peptide does not contain any new specified peptide-related impurity that is more than 0.5 percent of the drug substance;5 3) characterize each new specified peptide- related impurity; and 4) justify for each new specified peptide-related impurity that is no more than 0.5 percent of the drug substance why the presence of such impurity would not be expected to affect the safety or effectiveness of the proposed generic synthetic peptide as compared to that of the RLD.6 This information will enable FDA to evaluate the purity of the proposed generic synthetic peptide and to confirm that it and the RLD of rDNA origin can be expected to have the same safety profile (including with respect to the risk of immunogenicity due to peptide-related impurities) when administered to patients under the conditions specified in the labeling. The contents of this document do not have the force and effect of law and are not meant to bind the public in any way, unless specifically incorporated into a contract. This document is intended only to provide clarity to the public regarding existing requirements under the law. FDA guidance documents, including this guidance, should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidance means that something is suggested or recommended, but not required. 4 The term “duplicate” generally refers to a drug product that has the same active ingredient(s), dosage form, strength, route of administration, and conditions of use as a listed drug. See the proposed rule entitled “Abbreviated New Drug Application Regulations” (54 FR 28872 at 28877, July 10, 1989). 5 A new specified peptide-related impurity refers to an impurity that is present in the proposed generic synthetic peptide, but not in the RLD. 6 For definitions of specified and unspecified impurities, see guidances for industry ANDAs: Impurities in Drug Substances and ANDAs: Impurities in Drug Products, and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidances Impurities in New Drug Substances (ICH Q3A(R2)) and Impurities in New Drug Products (ICH Q3B(R2)). The guidances referenced in this document are available athttps://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs . We update guidances periodically. To make sure you have the most recent version of a guidance, check the FDA Drugs guidance Web page athttps://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs. 2 Contains Nonbinding Recommendations II. BACKGROUND FDA considers any alpha amino acid polymer composed of 40 or fewer amino acids to be a peptide, not a protein. Glucagon, liraglutide, nesiritide, teriparatide, and teduglutide are peptides. A peptide is regulated as a drug under the FD&C Act unless the peptide otherwise meets the statutory definition
Load more

Recommended publications
  • Oligomeric A2 + B3 Approach to Branched Poly(Arylene Ether Sulfone)
    “One-Pot” Oligomeric A 2 + B 3 Approach to Branched Poly(arylene ether sulfone)s: Reactivity Ratio Controlled Polycondensation A thesis submitted in partial fulfillment of the requirements for the degree of Master of Science By ANDREA M. ELSEN B.S., Wright State University, 2007 2009 Wright State University WRIGHT STATE UNIVERSITY SCHOOL OF GRADUATE STUDIES June 19, 200 9 I HEREBY RECOMMEND THAT THE THESIS PREPARED UNDER MY SUPERVISION BY Andrea M. Elsen ENTITLED “One-Pot” Oligomeric A2 + B3 Approach to Branched Poly(arylene ether sulfone)s: Reactivity Ratio Controlled Polycondenstation BE ACCEPTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF Master of Science . _________________________ Eric Fossum, Ph.D. Thesis Director _________________________ Kenneth Turnbull, Ph.D. Department Chair Committee on Final Examination ____________________________ Eric Fossum, Ph.D. ____________________________ Kenneth Turnbull, Ph.D. ____________________________ William A. Feld, Ph.D. ____________________________ Joseph F. Thomas, Jr., Ph.D. Dean, School of Graduate Studies Abstract Elsen, Andrea M. M.S., Department of Chemistry, Wright State University, 2009. “One-Pot” Oligomeric A 2 + B 3 Approach to Branched Poly(arylene ether sulfone)s: Reactivity Ratio Controlled Polycondensation The synthesis of fully soluble branched poly(arylene ether)s via an oligomeric A 2 + B 3 system, in which the A 2 oligomers are generated in situ, is presented. This approach takes advantage of the significantly higher reactivity toward nucleophilic aromatic substitution reactions, NAS, of B 2, 4-Fluorophenyl sulfone, relative to B 3, tris (4-Fluorophenyl) phosphine oxide. The A 2 oligomers were synthesized by reaction of Bisphenol-A and B 2, in the presence of the B 3 unit, at temperatures between 100 and 160 °C, followed by an increase in the reaction temperature to 180 °C at which point the branching unit was incorporated.
    [Show full text]
  • And Ph-Dependent Oligomerization of the Thrombin-Derived C-Terminal Peptide TCP-25
    biomolecules Article Concentration- and pH-Dependent Oligomerization of the Thrombin-Derived C-Terminal Peptide TCP-25 Ganna Petruk 1,* , Jitka Petrlova 1, Firdaus Samsudin 2 , Rita Del Giudice 3 , Peter J. Bond 2,4 and Artur Schmidtchen 1,5,6 1 Division of Dermatology and Venereology, Department of Clinical Sciences, Lund University, 22241 Lund, Sweden; [email protected] (J.P.); [email protected] (A.S.) 2 Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore 138671, Singapore; [email protected] (F.S.); [email protected] (P.J.B.) 3 Research Centre for Biointerfaces, Department of Biomedical Sciences and Biofilms, Malmö University, 20506 Malmö, Sweden; [email protected] 4 Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore 5 Copenhagen Wound Healing Center, Bispebjerg Hospital, Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark 6 Dermatology, Skane University Hospital, 22185 Lund, Sweden * Correspondence: [email protected]; Tel.: +46-46-22-23-315 Received: 18 October 2020; Accepted: 9 November 2020; Published: 19 November 2020 Abstract: Peptide oligomerization dynamics affects peptide structure, activity, and pharmacodynamic properties. The thrombin C-terminal peptide, TCP-25 (GKYGFYTHVFRLKKWIQKVIDQFGE), is currently in preclinical development for improved wound healing and infection prevention. It exhibits turbidity when formulated at pH 7.4, particularly at concentrations of 0.3 mM or more. We used biochemical and biophysical approaches to explore whether the peptide self-associates and forms oligomers. The peptide showed a dose-dependent increase in turbidity as well as α-helical structure at pH 7.4, a phenomenon not observed at pH 5.0.
    [Show full text]
  • Review of Current Real-World Experience with Teriparatide As Treatment of Osteoporosis in Different Patient Groups
    Journal of Clinical Medicine Review Review of Current Real-World Experience with Teriparatide as Treatment of Osteoporosis in Different Patient Groups Barbara Hauser 1,2,* , Nerea Alonso 2 and Philip L Riches 1,2 1 Rheumatic Disease Unit, Western General Hospital, NHS Lothian, Edinburgh EH4 2XU, UK; [email protected] 2 Rheumatology and Bone Disease Unit, Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK; [email protected] * Correspondence: [email protected] Abstract: Teriparatide has proven effective in reducing both vertebral and non-vertebral fractures in clinical trials of post-menopausal and glucocorticoid-induced osteoporosis. Widespread adoption of Teriparatide over the last two decades means that there is now substantial experience of its use in routine clinical practice, which is summarized in this paper. Extensive real-world experience of Teriparatide in post-menopausal osteoporosis confirms the fracture and bone density benefits seen in clinical trials, with similar outcomes identified also in male and glucocorticoid-induced osteoporosis. Conversely, very limited experience has been reported in pre-menopausal osteoporosis or in the use of Teriparatide in combination with other therapies. Surveillance studies have identified no safety signals relating to the possible association of Teriparatide with osteosarcoma. We also review the evidence for predicting response to Teriparatide in order to inform the debate on where best to use Teriparatide in an increasingly crowded therapeutic landscape. Citation: Hauser, B.; Alonso, N.; Riches, P.L. Review of Current Keywords: Teriparatide; anabolic treatment; osteoporosis; fracture Real-World Experience with Teriparatide as Treatment of Osteoporosis in Different Patient Groups.
    [Show full text]
  • The Activation of the Glucagon-Like Peptide-1 (GLP-1) Receptor by Peptide and Non-Peptide Ligands
    The Activation of the Glucagon-Like Peptide-1 (GLP-1) Receptor by Peptide and Non-Peptide Ligands Clare Louise Wishart Submitted in accordance with the requirements for the degree of Doctor of Philosophy of Science University of Leeds School of Biomedical Sciences Faculty of Biological Sciences September 2013 I Intellectual Property and Publication Statements The candidate confirms that the work submitted is her own and that appropriate credit has been given where reference has been made to the work of others. This copy has been supplied on the understanding that it is copyright material and that no quotation from the thesis may be published without proper acknowledgement. The right of Clare Louise Wishart to be identified as Author of this work has been asserted by her in accordance with the Copyright, Designs and Patents Act 1988. © 2013 The University of Leeds and Clare Louise Wishart. II Acknowledgments Firstly I would like to offer my sincerest thanks and gratitude to my supervisor, Dr. Dan Donnelly, who has been nothing but encouraging and engaging from day one. I have thoroughly enjoyed every moment of working alongside him and learning from his guidance and wisdom. My thanks go to my academic assessor Professor Paul Milner whom I have known for several years, and during my time at the University of Leeds he has offered me invaluable advice and inspiration. Additionally I would like to thank my academic project advisor Dr. Michael Harrison for his friendship, help and advice. I would like to thank Dr. Rosalind Mann and Dr. Elsayed Nasr for welcoming me into the lab as a new PhD student and sharing their experimental techniques with me, these techniques have helped me no end in my time as a research student.
    [Show full text]
  • Structural Mechanisms of Oligomer and Amyloid Fibril Formation by the Prion Protein Cite This: Chem
    ChemComm View Article Online FEATURE ARTICLE View Journal | View Issue Structural mechanisms of oligomer and amyloid fibril formation by the prion protein Cite this: Chem. Commun., 2018, 54,6230 Ishita Sengupta a and Jayant B. Udgaonkar *b Misfolding and aggregation of the prion protein is responsible for multiple neurodegenerative diseases. Works from several laboratories on folding of both the WT and multiple pathogenic mutant variants of the prion protein have identified several structurally dissimilar intermediates, which might be potential precursors to misfolding and aggregation. The misfolded aggregates themselves are morphologically distinct, critically dependent on the solution conditions under which they are prepared, but always b-sheet rich. Despite the lack of an atomic resolution structure of the infectious pathogenic agent in prion diseases, several low resolution models have identified the b-sheet rich core of the aggregates formed in vitro, to lie in the a2–a3 subdomain of the prion protein, albeit with local stabilities that vary Received 17th April 2018, with the type of aggregate. This feature article describes recent advances in the investigation of in vitro Accepted 14th May 2018 prion protein aggregation using multiple spectroscopic probes, with particular focus on (1) identifying DOI: 10.1039/c8cc03053g aggregation-prone conformations of the monomeric protein, (2) conditions which trigger misfolding and oligomerization, (3) the mechanism of misfolding and aggregation, and (4) the structure of the misfolded rsc.li/chemcomm intermediates and final aggregates. 1. Introduction The prion protein can exist in two distinct structural isoforms: a National Centre for Biological Sciences, Tata Institute of Fundamental Research, PrPC and PrPSc.
    [Show full text]
  • On the Mechanism of Oligomer Formation in Condensations of Alkyl Cyanoacetates with Formaldehyde
    Polymer Journal, Vol. 13, No. 10, pp 975-978 (1981) NOTE On the Mechanism of Oligomer Formation in Condensations of Alkyl Cyanoacetates with Formaldehyde J. M. ROONEY Loctite (Ireland) Limited, Whitestown Industrial Estate, Ta//aght, Co. Dublin. Ireland. (Received December II, 1980) KEY WORDS Alkyl Cyanoacetates I Formaldehyde / Condensation Anionic Polymerization I Cyanoacrylate I Chain Transfer I Industrial synthetic routes to the production of Since the apparent activation energy of the over­ alkyl cyanoacrylate monomers frequently involve all process was found to be similar to that of the base-catalyzed condensations of alkyl cyanoacetates condensation of diethyl dicyanoglutarate with for­ with formaldehyde to form low molecular weight maldehyde, the addition of diethyl dicyanoglutarate polymers. 1 Early studies attributed polymer for­ to formaldehyde is assumed to be the rate­ mation to a stepwise condensation2 of the form,3.4 determining step. CN CN I I CH2 + HCHO _..... CHCH20H I I COOR COOR CN CN CN CN I I I I CHCH2 0H + CH2 -----. CH-CH2-CH + H2 0 I I I I COOR COOR COOR COOR CN CN CN CN I I I I CH-CH2-CH + HCHO -----. CH-CH2-C-CH20H I I I I COOR COOR COOR COOR CN CN CN I I I CH-CH2-C-CH20H + CH2 etc. I I I COOR COOR COOR Subsequently, a kinetic study of the reaction of philic displacement of the hydroxyl group by cya­ formaldehyde with methyl cyanoacetate5 yielded noacetate anion. Instead, it is postulated that evidence that methyl cyanoacrylate monomer is an essential step in water evolution is the formation of intermediate in oligomer formation.
    [Show full text]
  • A Comparative Survey of the RF-Amide Peptide Superfamily
    EDITORIAL published: 10 August 2015 doi: 10.3389/fendo.2015.00120 Editorial: A comparative survey of the RF-amide peptide superfamily Karine Rousseau 1*, Sylvie Dufour 1 and Hubert Vaudry 2 1 Laboratory of Biology of Aquatic Organisms and Ecosystems (BOREA), Muséum National d’Histoire Naturelle, CNRS 7208, IRD 207, Université Pierre and Marie Curie, UCBN, Paris, France, 2 Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, INSERM U982, International Associated Laboratory Samuel de Champlain, Institute for Research and Innovation in Biomedicine (IRIB), University of Rouen, Mont-Saint-Aignan, France Keywords: RF-amide peptides, receptors, evolution, functions, deuterostomes, protostomes The first member of the RF-amide peptide superfamily to be characterized, in 1977, was the cardioexcitatory peptide, FMRFamide, isolated from the ganglia of the clam Macrocallista nimbosa (1). Since then, a large number of such peptides, designated after their C-terminal arginine (R) and amidated phenylalanine (F) residues, have been identified in representative species of all major phyla. The discovery, 12 years ago, that the RF-amide peptide kisspeptin, acting via GPR54, was essential for the onset of puberty and reproduction, has been a major breakthrough in reproductive physiology (2–4). It has also put in front of the spotlights RF-amide peptides and has invigo- rated research on this superfamily of regulatory neuropeptides. The present Research Topic aims at illustrating major advances achieved, through comparative studies in (mammalian and non- mammalian) vertebrates and invertebrates, in the knowledge of RF-amide peptides in terms of evolutionary history and physiological significance. Since 2006, by means of phylogenetic analyses, the superfamily of RFamide peptides has been divided into five families/groups in vertebrates (5, 6): kisspeptin, 26RFa/QRFP, GnIH (including LPXRFa and RFRP), NPFF, and PrRP.
    [Show full text]
  • Gattex Teduglutide Rdna Origin
    Subject: Gattex (teduglutide [rDNA origin]) Original Effective Date: 5/30/2014 Policy Number: MCP-176 Revision Date(s): Review Date(s): 12/16/15; 9/15/2016; 6/22/2017 DISCLAIMER This Medical Policy is intended to facilitate the Utilization Management process. It expresses Molina's determination as to whether certain services or supplies are medically necessary, experimental, investigational, or cosmetic for purposes of determining appropriateness of payment. The conclusion that a particular service or supply is medically necessary does not constitute a representation or warranty that this service or supply is covered (i.e., will be paid for by Molina) for a particular member. The member's benefit plan determines coverage. Each benefit plan defines which services are covered, which are excluded, and which are subject to dollar caps or other limits. Members and their providers will need to consult the member's benefit plan to determine if there are any exclusion(s) or other benefit limitations applicable to this service or supply. If there is a discrepancy between this policy and a member's plan of benefits, the benefits plan will govern. In addition, coverage may be mandated by applicable legal requirements of a State, the Federal government or CMS for Medicare and Medicaid members. CMS's Coverage Database can be found on the CMS website. The coverage directive(s) and criteria from an existing National Coverage Determination (NCD) or Local Coverage Determination (LCD) will supersede the contents of this Molina medical coverage policy (MCP) document and provide the directive for all Medicare members. FDA INDICATIONS � ∑ Short bowel syndrome: For the treatment of adult patients with short bowel syndrome who are dependent on parenteral support.
    [Show full text]
  • Polymer Exemption Guidance Manual POLYMER EXEMPTION GUIDANCE MANUAL
    United States Office of Pollution EPA 744-B-97-001 Environmental Protection Prevention and Toxics June 1997 Agency (7406) Polymer Exemption Guidance Manual POLYMER EXEMPTION GUIDANCE MANUAL 5/22/97 A technical manual to accompany, but not supersede the "Premanufacture Notification Exemptions; Revisions of Exemptions for Polymers; Final Rule" found at 40 CFR Part 723, (60) FR 16316-16336, published Wednesday, March 29, 1995 Environmental Protection Agency Office of Pollution Prevention and Toxics 401 M St., SW., Washington, DC 20460-0001 Copies of this document are available through the TSCA Assistance Information Service at (202) 554-1404 or by faxing requests to (202) 554-5603. TABLE OF CONTENTS LIST OF EQUATIONS............................ ii LIST OF FIGURES............................. ii LIST OF TABLES ............................. ii 1. INTRODUCTION ............................ 1 2. HISTORY............................... 2 3. DEFINITIONS............................. 3 4. ELIGIBILITY REQUIREMENTS ...................... 4 4.1. MEETING THE DEFINITION OF A POLYMER AT 40 CFR §723.250(b)... 5 4.2. SUBSTANCES EXCLUDED FROM THE EXEMPTION AT 40 CFR §723.250(d) . 7 4.2.1. EXCLUSIONS FOR CATIONIC AND POTENTIALLY CATIONIC POLYMERS ....................... 8 4.2.1.1. CATIONIC POLYMERS NOT EXCLUDED FROM EXEMPTION 8 4.2.2. EXCLUSIONS FOR ELEMENTAL CRITERIA........... 9 4.2.3. EXCLUSIONS FOR DEGRADABLE OR UNSTABLE POLYMERS .... 9 4.2.4. EXCLUSIONS BY REACTANTS................ 9 4.2.5. EXCLUSIONS FOR WATER-ABSORBING POLYMERS........ 10 4.3. CATEGORIES WHICH ARE NO LONGER EXCLUDED FROM EXEMPTION .... 10 4.4. MEETING EXEMPTION CRITERIA AT 40 CFR §723.250(e) ....... 10 4.4.1. THE (e)(1) EXEMPTION CRITERIA............. 10 4.4.1.1. LOW-CONCERN FUNCTIONAL GROUPS AND THE (e)(1) EXEMPTION.................
    [Show full text]
  • Peptide Synthesis: Chemical Or Enzymatic
    Electronic Journal of Biotechnology ISSN: 0717-3458 Vol.10 No.2, Issue of April 15, 2007 © 2007 by Pontificia Universidad Católica de Valparaíso -- Chile Received June 6, 2006 / Accepted November 28, 2006 DOI: 10.2225/vol10-issue2-fulltext-13 REVIEW ARTICLE Peptide synthesis: chemical or enzymatic Fanny Guzmán Instituto de Biología Pontificia Universidad Católica de Valparaíso Avenida Brasil 2950 Valparaíso, Chile Fax: 56 32 212746 E-mail: [email protected] Sonia Barberis Facultad de Química, Bioquímica y Farmacia Universidad Nacional de San Luis Ejército de los Andes 950 (5700) San Luis, Argentina E-mail: [email protected] Andrés Illanes* Escuela de Ingeniería Bioquímica Pontificia Universidad Católica de Valparaíso Avenida Brasil 2147 Fax: 56 32 2273803 E-mail: [email protected] Financial support: This work was done within the framework of Project CYTED IV.22 Industrial Application of Proteolytic Enzymes from Higher Plants. Keywords: enzymatic synthesis, peptides, proteases, solid-phase synthesis. Abbreviations: CD: circular dichroism CLEC: cross linked enzyme crystals DDC: double dimer constructs ESI: electrospray ionization HOBT: hydroxybenzotriazole HPLC: high performance liquid hromatography KCS: kinetically controlled synthesis MALDI: matrix-assisted laser desorption ionization MAP: multiple antigen peptide system MS: mass spectrometry NMR: nuclear magnetic resonance SPS: solution phase synthesis SPPS: solid-phase peptide synthesis t-Boc: tert-butoxycarbonyl TCS: thermodynamically controlled synthesis TFA: trifluoroacetic acid Peptides are molecules of paramount importance in the medium, biocatalyst and substrate engineering, and fields of health care and nutrition. Several technologies recent advances and challenges in the field are analyzed. for their production are now available, among which Even though chemical synthesis is the most mature chemical and enzymatic synthesis are especially technology for peptide synthesis, lack of specificity and relevant.
    [Show full text]
  • Novel Therapies in Osteoporosis: PTH-Related Peptide Analogs and Inhibitors of Sclerostin
    62 2 Journal of Molecular T D Rachner et al. Novel anabolic osteoporosis 62:2 R145–R154 Endocrinology treatments REVIEW Novel therapies in osteoporosis: PTH-related peptide analogs and inhibitors of sclerostin Tilman D Rachner1,2,3, Lorenz C Hofbauer1,2,3,4, Andy Göbel1,3 and Elena Tsourdi1,2,3 1Department of Medicine III, Technische Universität Dresden Medical Center, Dresden, Germany 2Center for Healthy Aging, Technische Universität Dresden Medical Center, Dresden, Germany 3German Cancer Consortium (DKTK), partner site Dresden and German Cancer Research Center (DKFZ), Dresden, Germany 4Center for Regenerative Therapies Dresden, Technische Universität Dresden, Dresden, Germany Correspondence should be addressed to T D Rachner: [email protected] Abstract Bone-forming approaches to treat patients with severe osteoporosis are effective, but Key Words treatment options are limited, and there is an unmet clinical need for additional drugs. f PTH This review discusses two novel and advanced anabolic therapeutic concepts that f PTH-related protein have successfully completed phase 3 trials. Romosozumab is a monoclonal antibody f abaloparatide that targets the Wnt inhibitor sclerostin. Two phase 3 trials (FRAME and ARCH) of f sclerostin romosozumab for the treatment of postmenopausal osteoporosis have been completed. f sclerostin antibody Both trials successfully reached their primary endpoint by reducing vertebral fractures by f romosozumab 75% compared to placebo (FRAME trial) and 48% compared to alendronate (ARCH trial), respectively. Abaloparatide is a PTH-related protein (PTHrP) analog that has displayed bone anabolic activity. In the phase 3 ACTIVE trial, abaloparatide was compared to placebo and teriparatide for 18 months in postmenopausal women who had already experienced an osteoporotic fracture.
    [Show full text]
  • NMR Spectroscopy for Protein Higher Order Structure Similarity Assessment in Formulated Drug Products
    molecules Article NMR Spectroscopy for Protein Higher Order Structure Similarity Assessment in Formulated Drug Products Deyun Wang 1, You Zhuo 2, Mike Karfunkle 3, Sharadrao M. Patil 2, Cameron J. Smith 4, David A. Keire 5 and Kang Chen 2,* 1 Northeast Medical Products Laboratory, Office of Regulatory Science, Office of Regulatory Affairs, U.S. Food and Drug Administration, Jamaica, NY 11433, USA; [email protected] 2 Division of Complex Drug Analysis, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA; [email protected] (Y.Z.); [email protected] (S.M.P.) 3 Division of Pharmaceutical Analysis, Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, St. Louis, MO 63110, USA; [email protected] 4 Division of Liquid Based Products I, Office of Lifecycle Drug Products, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD 20993, USA; [email protected] 5 Office of Testing and Research, Office of Pharmaceutical Quality, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, St. Louis, MO 63110, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-240-402-5550 Abstract: Peptide and protein drug molecules fold into higher order structures (HOS) in formulation and these folded structures are often critical for drug efficacy and safety. Generic or biosimilar drug Citation: Wang, D.; Zhuo, Y.; products (DPs) need to show similar HOS to the reference product.
    [Show full text]