Chemistry Manufacturing and Controls (CMC) Guidances for Industry (GFIs) and Questions and Answers (Q&As)
CVM CMC Guidances and Q&As
Other CMC Guidances
CMC Guidance Documents Applicable to Minor Use or Minor Species (MUMS) Animal Drugs, Biotech Animal Drugs, and Biotherapeutics
CMC Guidance Documents Applicable to Generic Animal Drug Products and Drug Substances
CVM CMC Guidances and Q&As
Administrative and General
- CVM GFI #106 The Use of Published Literature in Support of New Animal Drug Approvals
- CVM GFI #156 Comparability Protocols - Chemistry, Manufacturing, and Controls Information for New Animal Drugs
- CVM GFI #227 Chemistry, Manufacturing, and Controls (CMC) Technical Section Filing Strategies
- CVM GFI #234 Question-Based Review for the Chemistry, Manufacturing, and Controls Technical Section of Animal Drug Applications
- Chemistry, Manufacturing, and Controls (CMC) Information Submitted to Both CDER and CVM
- Submitting Establishment Information to the Animal Drug Manufacturing System (ADMS)
- CVM GFI #288 Chemistry, Manufacturing, and Controls in Support of Recombinant Protein Products for Veterinary Medicinal Use
- CVM GFI #292 Chemistry, Manufacturing, and Controls Considerations for Type A Medicated Articles
Master File and Drug Substance
- CVM GFI #57 Preparation and Submission of Veterinary Master Files
- CVM GFI #92 (VICH GL10(R)) Impurities In New Veterinary Drug Substances
- CVM GFI #126 BACPAC I: Intermediates in Drug Substance Synthesis Bulk Actives Postapproval Changes: Chemistry, Manufacturing, and Controls Documentation
- CVM GFI #169 Drug Substance Chemistry, Manufacturing, and Controls Information
- CVM GFI #216 Fermentation-Derived Intermediates, Drug Substances, and Related Drug Products for Veterinary Medicinal Use
- Common Questions Related to Type II Veterinary Master Files (VMFs)
- CVM GFI #286 (VICH GL60) - Good Manufacturing Practice for Active Pharmaceutical Ingredients Used in Veterinary Medicinal Products
Manufacturing
- CVM GFI #23 Medicated Free Choice Feeds - Manufacturing Control
- CVM GFI #253 Current Good Manufacturing Practice for Animal Cells, Tissues, and Cell- and Tissue-Based Products
- CVM GFI #254 Donor Eligibility for Animal Cells, Tissues, and Cell- and Tissue-Based Products
- CVM GFI #258 Use of Tracers in Animal Food, Type A Medicated Articles, and Medicated Feeds
- CVM GFI #285 - Manufacture of Batches in Support of Original NADAs, ANADAs, and CNADAs
- CVM GFI #290 (VICH GL61) – Pharmaceutical Development
- Manufacturing Considerations for Penicillin or Cephalosporin Animal Drugs
- Split Tablet Studies
Analytical Controls
- CVM GFI #63 (VICH GL1) Validation of Analytical Procedures: Definition and Terminology
- CVM GFI #64 (VICH GL2) Validation of Analytical Procedures: Methodology
- CVM GFI #135 Validation of Analytical Procedures for Type C Medicated Feeds
- CVM GFI #136 Protocols for the Conduct of Method Transfer Studies for Type C Medicated Feed Assay Methods
- CVM GFI #137 Analytical Methods Description for Type C Medicated Feeds
- CVM GFI #176 (VICH GL39) Specifications: Test Procedures and Acceptance Criteria for New Veterinary Drug Substances and New Medicinal Products: Chemical Substances
- CVM GFI #177 (VICH GL40) Specifications: Test Procedures and Acceptance Criteria for New Biotechnological/Biological Veterinary Medicinal Products
- CVM GFI #238 Modified Release Veterinary Parenteral Dosage Forms: Development, Evaluation, and Establishment of Specifications
- CVM GFI #264 Standardized Medicated Feed Assay Limits
- Compilation of FDA Guidance and Resources for in vitro Dissolution Testing of Immediate Release Solid Oral Dosage Forms
Impurities
- CVM GFI #92 (VICH GL10(R)) Impurities in New Veterinary Drug Substances
- CVM GFI #93 (VICH GL11(R)) Impurities in New Veterinary Medicinal Products
- CVM GFI #100 (VICH GL18 (R2)) Impurities: Residual Solvents in New Veterinary Medicinal Products, Active Substances and Excipients (Revision 2)
- CVM GFI #211 Residual Solvents in Animal Drug Products Questions and Answers
- CVM GFI #255 Elemental Impurities in Animal Drug Products Questions and Answers
Stability
- CVM GFI #5 Drug Stability Guidelines
- CVM GFI #73 (VICH GL3(R)) Stability Testing of New Veterinary Drug Substances and Medicinal Products
- CVM GFI #74 (VICH GL4) Stability Testing of New Veterinary Dosage Forms
- CVM GFI #75 (VICH GL5) Stability Testing: Photostability Testing of New Veterinary Drug Substances and Medicinal Products
- CVM GFI #91 (VICH GL8) Stability Testing for Medicated Premixes
- CVM GFI #99 (VICH GL17) Stability Testing of New Biotechnological/Biological Veterinary Medicinal Products
- CVM GFI #198 (VICH GL45) Bracketing and Matrixing Designs for Stability Testing of New Veterinary Drug Substances and Medicinal Products
- CVM GFI #219 (VICH GL51) Statistical Evaluation of Stability Data
- CVM GFI #242 In-Use Stability Studies and Associated Labeling Statements for Multiple-Dose Injectable Animal Drug Products
- CVM GFI #259 (VICH GL58) Stability Testing of New Veterinary Drug Substances and Medicinal Products in Climatic Zones III and IV
Post-approval Changes
- CVM GFI #83 Chemistry, Manufacturing, and Controls Changes to an Approved NADA or ANADA
- CVM GFI #126 BACPAC I: Intermediates in Drug Substance Synthesis Bulk Actives Postapproval Changes: Chemistry, Manufacturing, and Controls Documentation
- CVM GFI #271 Reporting and Mitigating Animal Drug Shortages
- CVM GFI #279 Demonstrating Bioequivalence for Type A Medicated Articles Containing Active Pharmaceutical Ingredient(s) Considered to be Poorly Soluble in Aqueous Media, That Exhibit Little to No Systemic Bioavailability, and Are Locally Acting
Other CMC Guidances
Other FDA guidances may also provide useful information for the submission of CMC information for animal drugs, including Cross-Center guidances, Center for Drug Evaluation and Research (CDER) guidances, and International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidances. Any other Cross-Center, CDER, or ICH guidance pertaining to CMC information may also be considered applicable to animal drugs. Drug sponsors should contact CVM’s Division of Manufacturing Technologies if they have any questions regarding the applicability of a guidance to animal drugs. For further information, contact AskCVM@fda.hhs.gov.
Administrative and General Guidances
- CDER/CBER/CVM GFI: Providing Regulatory Submissions in Electronic Format – Drug Establishment Registration and Drug Listing
- CDER/CVM/ORA GFI: PAT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance
- OC GFI: Considering Whether an FDA-Regulated Product Involves the Application of Nanotechnology
- CDER/CBER/CVM GFI: Contract Manufacturing Arrangements for Drugs: Quality Agreements
- CDER/CBER/CVM/ORA GFI: Quality Systems Approach to Pharmaceutical Current Good Manufacturing Practice Regulations
- CDER/CVM GFI: Pharmaceutical Components at Risk for Melamine Contamination
- CDRH/CDER/CBER/CVM GFI: Recommendations for Labeling Medical Products to Inform Users that the Product or Product Container is not Made with Natural Rubber Latex
- CDER GFI: Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation
- CDER/CVM GFI: Harmonizing Compendial Standards With Drug Application Approval Using the USP Pending Monograph Process Guidance for Industry
- CDER/CBER/CVM GFI: Resuming Normal Drug and Biologics Manufacturing Operations During the COVID-19 Public Health Emergency Guidance for Industry
- CDER/CBER/CVM GFI: Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities During the COVID-19 Public Health Emergency Guidance for Industry
- CDER/CBER/CVM GFI: Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol
- CDER/CBER/CVM GFI: Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities
Master File and Drug Substance Guidances
- CDER GFI Drug Master Files: Guidelines
- CDER GFI Drug Master Files for Bulk Antibiotic Drug Substances
- CDER GFI: Regulatory Classification of Pharmaceutical Co-Crystals
- CDER GFI: Development of New Stereoisomeric Drugs
- ICH GFI Q7: Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients
- ICH GFI Q7: Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients Questions and Answers
- ICH GFI Q11: Development and Manufacture of Drug Substances
- ICH GFI Q11: Development and Manufacture of Drug Substances (Chemical Entities and Biotechnological/Biological Entities) Questions and Answers
Manufacturing Guidances
- CDER/CVM GFI: Submission Documentation for Sterilization Process Validation in Applications for Human and Veterinary Drug Products
- CDER/CBER/CVM GFI: Process Validation: General Principles and Practices
- CDER/CBER/CVM GFI: Submission of Documentation in Applications for Parametric Release of Human and Veterinary Drug Products Terminally Sterilized by Moist Heat Processes
- CDER/CBER/ORA GFI: Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice
- CDER GFI: Quality Attribute Considerations for Chewable Tablets
- CDER GFI: Nasal Spray and Inhalation Solution, Suspension, and Spray Drug Products – Chemistry, Manufacturing, and Controls Documentation
- CDER GFI: Metered Dose Inhaler (MDI) and Dry Powder Inhaler (DPI) Products – Quality Considerations
- CDER GFI: Botanical Drug Development
- CDER GFI: Non-Penicillin Beta-Lactam Drugs: A cGMP Framework for Preventing Cross-Contamination
- CDER GFI: Microbiological Quality Considerations in Non-Sterile Drug Manufacturing
- ICH GFI Q8(R2): Pharmaceutical Development
- ICH GFI Q9: Quality Risk Management
- ICH GFI Q10: Pharmaceutical Quality System
- ICH GFI: Q8, Q9, and Q10 Questions and Answers (R4)
- CDER/CBER/CVM GFI: Changes to Disposable Manufacturing Materials: Questions and Answers
Analytical Control Guidances
- CDER/CVM GFI: Bioanalytical Method Validation
- CBER/CDER/CDRH/CVM GFI: Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products
- CDER/CBER/CVM/CDRH/ORA GFI: Pyrogen and Endotoxins Testing: Questions and Answers
- CDER GFI: Dissolution Testing of Immediate Release Solid Oral Dosage Forms
- CDER GFI: Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production
- CDER GFI: Inspection of Injectable Products for Visible Particulates Draft Guidance for Industry
Container Closure Guidances
- CDER/CBER GFI: Container Closure Systems for Packaging Human Drugs and Biologics
- CDER/CBER GFI: COVID-19 Container Closure System and Component Changes: Glass Vials and Stoppers Guidance for Industry
Impurities Guidances
Post-approval Changes Guidances
- CDER GFI: PAC-ATLS: Postapproval Changes – Analytical Testing Laboratory Sites
- CDER GFI: SUPAC-MR: Modified Release Solid Oral Dosage Forms: Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation
- CDER GFI: SUPAC-IR: Immediate Release Solid Oral Dosage Forms: Scale-Up and Postapproval Changes: Chemistry, Manufacturing, and Controls, In Vitro Dissolution Testing and In Vivo Bioequivalence Documentation
- CDER GFI: SUPAC-IR: Questions and Answers about SUPAC-IR Guidance
- CDER GFI: SUPAC-SS: Nonsterile Semisolid Dosage Forms: Scale-up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation
- CDER GFI: CMC Postapproval Manufacturing Changes to be Documented in Annual Reports
- ICH GFI Q12 Technical and Regulatory Considerations for Pharmaceutical Lifecycle Management Guidance for Industry
- ICH GFI Q12 Technical and Regulatory Considerations for Pharmaceutical Lifecycle Management Annex
- Physicochemical and Structural (Q3) Characterization of Topical Drug Products Submitted in ANDAs
CMC Guidance Documents Applicable to Minor Use or Minor Species (MUMS) Animal Drugs, Biotech Animal Drugs, and Biotherapeutics
Guidances are available that may also provide useful information for the submission of CMC information for Minor Use or Minor Species (MUMS) animal drugs, biotech animal drugs, and biotherapeutics. These other guidances include Cross-Cutting guidances, CBER guidances, and ICH guidances. Any other guidances pertaining to CMC information in addition to those listed below may also be applicable to such animal drugs. Drug sponsors considering an approach outlined in these CMC guidances should contact CVM’s Division of Manufacturing Technologies if they have any questions regarding the applicability of a guidance to MUMS, biotech, or biotherapeutic animal drugs. For further information, contact AskCVM@fda.hhs.gov.
Administrative/General/Manufacturing Guidances
- CBER/CDRH GFI: Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use
- CDER/CBER GFI: For the Submission of Chemistry, Manufacturing, and Controls Information for a Therapeutic Recombinant DNA-Derived Product or a Monoclonal Antibody Product for In Vivo Use
- CBER GFI: Guidance for Human Somatic Cell Therapy and Gene Therapy
- ICH GFI Q5D: Derivation and Characterization of Cell Substrates Used for Production of Biotechnological/Biological Products
- CBER GFI: Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use
- CBER GFI: Current Good Tissue Practice (CGTP) and Additional Requirements for Manufacturers of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps)
- CBER GFI: Chemistry, Manufacturing, and Control (CMC) Information for Human Gene Therapy Investigational New Drug Applications (INDs)
- CVM GFI #61 Special Considerations, Incentives, and Programs to Support the Approval of New Animal Drugs for Minor Uses and for Minor Species
Analytical Controls Guidances
- ICH GFI Q5B: Quality of Biotechnological Products: Analysis of the Expression Construct in Cells Used for Production of r-DNA Derived Protein Products
- CBER GFI: Potency Tests for Cellular and Gene Therapy Products
- ICH GFI Q5A(R1): Viral Safety Evaluation of Biotechnology Products Derived from Cell Lines of Human or Animal Origin
Stability Guidances
Post-approval Changes Guidances
- CDER/CBER GFI: Demonstration of Comparability of Human Biological Products, Including Therapeutic Biotechnology-derived Products
- ICH GFI Q5E: Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process
- CDER/CBER GFI: Chemistry, Manufacturing, and Controls Changes to an Approved Application: Certain Biological Products
- CDER/CBER GFI: Changes to an Approved Application for Specified Biotechnology and Specified Synthetic Biological Products
CMC Guidance Documents Applicable to Generic Animal Drug Products and Drug Substances
CVM has guidances (including VICH guidances) that cover many CMC topics that are applicable not only to new animal drug applications, but also to original and supplemental abbreviated new animal drug applications (ANADAs) and generic investigational new animal drug files (JINADs). Other FDA guidances (i.e., CDER CMC guidances) may also provide useful information for the submission of CMC information for generic animal drugs. Any other guidance pertaining to CMC information in addition to those listed below may also be applicable to generic animal drugs. Drug sponsors should contact CVM’s Division of Manufacturing Technologies if they have any questions regarding the applicability of a guidance to generic animal drugs. For further information, contact AskCVM@fda.hhs.gov.
Manufacturing Guidances
Analytical Controls Guidances
- CVM GFI #63 (VICH GL1) Validation of Analytical Procedures: Definition and Terminology
- CVM GFI #64 (VICH GL2) Validation of Analytical Procedures: Methodology
- CVM GFI #176 (VICH GL39) Specifications: Test Procedures and Acceptance Criteria for New Veterinary Drug Substances and New Medicinal Products: Chemical Substances
Impurities Guidances
- CVM GFI #92 (VICH GL10(R)) Impurities in New Veterinary Drug Substances
- CVM GFI #93 (VICH GL11(R)) Impurities in New Veterinary Medicinal Products
- CVM GFI #100 (VICH GL18) Impurities: Residual Solvents in New Veterinary Medicinal Products, Active Substances and Excipients
- CDER GFI: ANDAs: Impurities in Drug Products
- CDER GFI: ANDAs: Impurities in Drug Substances
Stability Guidances
- CVM GFI #73 (VICH GL3(R)) Stability Testing of New Veterinary Drug Substances and Medicinal Products
- CVM GFI #75 (VICH GL5) Stability Testing: Photostability Testing of New Veterinary Drug Substances and Medicinal Products
- CVM GFI #91 (VICH GL8) Stability Testing for Medicated Premixes
- CVM GFI #198 (VICH GL45) Bracketing and Matrixing Designs for Stability Testing of New Veterinary Drug Substances and Medicinal Products