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Guidance for Industry
Drug Substance Chemistry, Manufacturing,
and Controls Information
Submit comments on this guidance at any time. Submit written comments to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852. Comments may also be submitted electronically on the Internet at v. All written comments should be identified with the Docket No. FDA-2003-D-0243 (formerly 2003D-0571).
For further information regarding this document, contact Alem Ghiorghis, Center for Veterinary Medicine (HFV-143), Food and Drug Administration, 7500 Standish Place, Rockville, MD 20855, (240) 276-8266, E-mail: alem.ghiorghis@v.
Additional copies of this guidance document may be requested from the Communications Staff (HFV-12), Center for Veterinary Medicine, Food and Drug Administration, 7519 Standish Place, Rockville, M
D 20855, and may be viewed on the Internet at either
v/AnimalVeterinary/default.htm or v.
traceyU.S. Department of Health and Human Services
Food and Drug Administration
业余爱好英文Center for Veterinary Medicine (CVM)
August 6, 2010
TABLE OF CONTENTS1
I.INTRODUCTION (1)
II.BACKGROUND (3)
A.The Common Technical Document — Quality (CTD-Q) Format (3)
B.Content of an Application (4)
C.Additional Guidance (4)
D.References to Other Applications or Master Files (MFs) (4) pet
1.Other Applications (4)
2.Master Files (MFs) (4)
III.GENERAL INFORMATION (S.1) (6)非主流英文
A.Nomenclature (S.1.1) (7)初中定语从句讲解
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B.Structure (S.1.2) (7)
C.General Properties (S.1.3) (7)
IV.MANUFACTURE (S.2) (8)
A.Manufacturers (S.2.1) (8)
B.Description of Manufacturing Process and Process Controls (S.2.2) (9)
1.Flow Diagram (9)
2.Description of the Manufacturing Process and Process Controls (10)
3.Reprocessing, Reworking, Recycling, Regeneration, and Other Operations (13)
C.Control of Materials (S.2.3) (16)
1. Starting Materials (16)
2.Reagents, Solvents, and Auxiliary Materials (17)
3.Diluents (18)
D.Controls of Critical Steps and Intermediates (S.2.4) (18)
E.Process Validation and/or Evaluation (S.2.5) (20)
F.Manufacturing Process Development (S.2.6) (21)
V.CHARACTERIZATION (S.3) (21)
A.Elucidation of Structure and Other Characteristics (S.3.1) (21)
1.Elucidation of Structure (21)
2.Physicochemical Characterization (22)
3.Biological and Other Relevant Characteristics (23)
B.Impurities (S.3.2) (23)
VI.CONTROL OF DRUG SUBSTANCE (S.4) (25)
1 Alphanumeric designations in parenthes that follow headings show where information should be placed in applications that are submitted in Common Technical Document (CTD) format.
A.Specification (S.4.1) (25)
B.Analytical Procedures (S.4.2) (30)
C.Validation of Analytical Procedures (S.4.3) (31)
D.Batch Analys (S.4.4) (31)
1.Batch Analysis Reports (31)
2.Collated Batch Analys Data (32)
E.Justification of Specification (S.4.5) (32)
VII.REFERENCE STANDARDS OR MATERIALS (S.5) (35)
VIII.CONTAINER CLOSURE SYSTEM (S.6) (35)
IX.STABILITY (S.7) (35)
A.Stability Summary and Conclusions (S.7.1) (35)
B.Postapproval Stability Protocol and Stability Commitment (S.7.2) (35)
C.Stability Data (S.7.3) (36)
1.Primary Stability Studies (36)
2.Supporting Stability Studies (36)
3.Stress Studies (37)
X.APPENDICES (A) (37)
A.Facilities and Equipment (A.1) (37)
B.Adventitious Agents Safety Evaluation (A.2) (38)
1.Nonviral Adventitious Agents (39)
2.Viral Adventitious Agents (39)
XI.REGIONAL INFORMATION (R) (40)
A.Executed Production Records (R.1.S) (40)
B.Comparability Protocols (R.2.S) (40)
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C.Methods Validation Package (R.3.S) (40)
XII.LITERATURE REFERENCES (3.3) (41)
ATTACHMENT 1: (42)
STARTING MATERIALS FOR SYNTHETIC DRUG SUBSTANCES (42)
ATTACHMENT 2: (50)
STARTING MATERIALS OF PLANT OR ANIMAL ORIGIN (50)
GLOSSARY (53)
Guidance for Industry2
Drug Substance
Chemistry, Manufacturing, and Controls Information
This guidance reprents the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can u an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA
staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance.
I. INTRODUCTIONgoto
Information on the chemistry, manufacturing, and controls (CMC) for the drug substance must be submitted to support the approval of original new animal drug applications (NADAs) and abbreviated new animal drug applications (ANADAs).3 This guidance provides recommendations on the CMC information for drug substances that should be submitted to support the applications. The guidance is structured to facilitate the preparation of applications submitted in Common Technical Document (CTD) format.
This guidance address the information to be submitted for drug substances to ensure continued drug substance and drug product quality (i.e., the identity, strength, quality, purity, and potency). This guidance provides recommendations on the information that should be included for the following topics:
•Nomenclature, structure, and general drug substance properties
•Manufacture
•Characterization
•Control of drug substance
•Reference standards or materials
•Container closure system
•Stability
The recommendations provided in this guidance apply to the following types of drug substances: 2 This guidance has been prepared by the Office of New Animal Drug Evaluation in the Center for Veterinary Medicine at the Food and Drug Administration.
3 See 21 CFR 514.1(b).
北理工珠海分校•Drug substances manufactured by chemical synthesis
•Highly purified and well-characterized drug substances derived from plants or animals 4•Semisynthetic drug substances manufactured by the chemical modification of a highly purified and lady是什么意思
well-characterized intermediate derived from plants or animals •The synthetic portion of the manufacturing process for misynthetic drug substances manufactured by the chemical modification of an intermediate produced by conventional fermentation.
The guidance does not provide specific recommendations relating to the following: •Monoclonal antibodies
•Peptides
•Oligonucleotides
•Radiopharmaceuticals
•Medical gas
•Drug substances that are not well characterized (e.g., botanicals, some proteins) derived from plants or animals
•Drug substances derived using transgenic technology
•Drug substances derived directly from or manufacturing operations involving fermentation (conventional fermentation or using rDNA technology) or tissue or cell
culture.
More detailed guidance on the content of an application may be available in parate guidance documents (e ction II.C). Applicants with drug substances not specifically covered by this (Drug Substance guidance) or another guidance can apply the content recommendations in this guidance, as scientifically appropriate, and/or can contact the appropriate review teams for guidance.
FDA’s guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The u of the word should in Agency guidances means that something is suggested or recommended, but not required.
4 For purpos of this guidance, d rug substances derived from plants or animals does not include materials produced by plant cell fermentation, animal cell or tissue culture, or through u of transgenic technology (e.g., biotechnology-derived protein drug products).
