Description
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). This guidance provides recommendations on the CMC information for drug substances that should be submitted to support these applications. The guidance is structured to facilitate the preparation of applications submitted in Common Technical Document (CTD) format.
Scope & Applicability
Product Classes
5application is submitted for a drug product involving two or more drug substances
additional recommendations for recombinant DNA-derived products
requires evaluation of purification processes; Requires additional information on facilities and equipment
requires specific information for intermediates; produced by modification of a chemical obtained from the biological source; Drug substance with structural elements from chemical synthesis and biological origin
Additional information should be included for naturally derived protein drug substances.; information on biological activity and purity should be provided
Stakeholders
8Entity responsible for submitting NDINs
Facility supplying raw materials or ingredients; Facility providing raw materials to a manufacturer
Entity submitting development data and knowledge; Entity performing the work process for change
Responsible for managing changes and qualifying vendors
if the MF holder provides written authorization
Name and address should be provided for each firm including contract manufacturers.
Name and address should be provided for testing laboratories involved in manufacturing.
Representative of a foreign owner who serves as the FSVP importer; Person in the US acting as a communications link or FSVP representative.; Designated representative for foreign owners; designated representative for foreign owners
Regulatory Context
Attributes
10A functional role of sodium in food
Equivalence of physical properties; Evaluation of physical properties for drug substance; Properties likely to influence drug product manufacturability; Attributes such as physical state, melting point, solubility, and density.
Conditions that can be adjusted to control the manufacturing process such as temperature, pressure, pH
biological identification of plant starting materials
identification and quantification of all compounds present with molecular weights ≤1500 Daltons
A property of a starting material that reduces documentation requirements.
separation of starting material from final intermediate
established based on data from stability studies
Drug substance stability data to define a retest period
The quantity of drug substance produced in a single cycle
Identified Hazards
Hazards
10Safety concern regarding viral contamination
nonviral adventitious agents
information should be placed in 3.2.A.2
Prions requiring specific inactivation processes
evaluation should primarily be guided by knowledge of the method of manufacture
identified and unidentified impurities observed in the drug substance
concern in raw agricultural commodities grown in contaminated soils; Applicability to heavy metals: approved suppliers control arsenic and lead
rely on your supplier to control pesticide residues in the raw vegetables
contamination with transmissible spongiform encephalopathy agents
Testing excluded from the simplified analytical change approach
Related CFR Sections (5)
- 21CFR514.1§ 514.1 Applications.
(a) Applications to be filed under section 512(b) of the act shall be submitted in the form and contain the information described in paragraph (b) of this section, as appropriate to support the particular submission. If any part of the application is in a foreign language, an accurate and complete ERead full regulation →
- 21CFR314.3§ 314.3 Definitions.
(a) The definitions and interpretations contained in section 201 of the Federal Food, Drug, and Cosmetic Act apply to those terms when used in this part and part 320 of this chapter .Read full regulation →
- 21CFR25.15§ 25.15 General procedures.
(a) All applications or petitions requesting agency action require the submission of an EA or a claim of categorical exclusion. A claim of categorical exclusion shall include a statement of compliance with the categorical exclusion criteria and shall state that to the applicant's knowledge, no extraRead full regulation →
- 21CFR211.194§ 211.194 Laboratory records.
(a) Laboratory records shall include complete data derived from all tests necessary to assure compliance with established specifications and standards, including examinations and assays, as follows:Read full regulation →
- 21CFR211.84§ 211.84 Testing and approval or rejection of components, drug product containers, and closures.
(a) Each lot of components, drug product containers, and closures shall be withheld from use until the lot has been sampled, tested, or examined, as appropriate, and released for use by the quality control unit.Read full regulation →
Related Warning Letters (10)
- 2025-12-23
CGMP/Active Pharmaceutical Ingredient (API)/Adulterated/Misbranded
Darmerica, LLC
- 2025-08-12
OTC/Unapproved New Drug/Misbranded
Supergoop!
- 2025-08-12
OTC/Unapproved New Drug/Misbranded
K & Care Organics
- 2025-08-12
OTC/Unapproved New Drug/Misbranded
Fallien Cosmeceuticals Ltd. dba Fallene Ltd.
- 2025-07-08
CGMP/Finished Pharmaceuticals/Adulterated
Libby Laboratories, Inc.
- 2025-05-27
Failure to List/Misbranded
Shenzhen Hengkaifeng Commerce and Trade Co., Ltd
- 2025-05-20
CGMP/Finished Pharmaceuticals/Adulterated
NWL Netherlands Services B.V.
- 2025-04-29
Electronic Drug Registration and Listing System (eDRLS)/Violations
Prodose, Inc. formerly known as Spirit Pharmaceuticals LLC
- 2025-04-15
Compounding Pharmacy/Adulterated Drug Products
Nubratori, Inc. dba Nubratori Rx
- 2025-03-25
CGMP/Finished Pharmaceutical/API/Adulterated
Yangzhou Sion Commodity Co., Ltd.
See Also (8)
- CVM GFI #82 Development of Supplemental Applications for Approved New Animal Drugs (Status: Final)
- CVM GFI #61 Special Considerations, Incentives, and Programs to Support the Approval of New Animal Drugs for Minor Uses and for Minor Species (Status: Final)
- Quantitative Labeling of Sodium, Potassium, and Phosphorus for Human Over-the-Counter and Prescription Drug Products (Status: Draft)
- Formas posológicas orales sólidas de liberación inmediata Cambios de escala y posteriores a la aprobación: documentación química, de fabricación y controles, de pruebas de disolución in vitro y bioequivalencia in vivo. (Status: Final)
- SUPAC-IR: Immediate-Release Solid Oral Dosage Forms: Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation (Status: Final)
- SUPAC-SS: Nonsterile Semisolid Dosage Forms; Scale-Up and Post-Approval Changes: Chemistry, Manufacturing and Controls; In Vitro Release Testing and In Vivo Bioequivalence Documentation: Guidance for Industry (Status: Final)
- Extended Release Oral Dosage Forms: Development, Evaluation, and Application of In Vitro/In Vivo Correlations (Status: Final)
- 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: Guidance for Industry (Status: Final)