Description
Under section 506A of the Federal Food, Drug, and Cosmetic Act (the Act), the holder of an NADA or ANADA must notify FDA about each change in each condition established in an approved application beyond the variations already provided for in the application. The Act provides for four reporting categories: (1) Prior Approval Supplement, (2) Supplement – Changes Being Effected in 30 days, (3) Supplement – Changes Being Effected, and (4) Annual Report. The reporting category for a change is based on the potential for the change to have an adverse effect on the identity, strength, quality, purity, or potency of the drug product as these factors may relate to the safety or effectiveness of the drug product. This guidance provides recommendations on reporting categories for postapproval changes relating to intermediates in drug substance synthesis based on a determination by the Center for Veterinary Medicine (CVM) of the potential for a specified change to have an adverse effect on the drug product. It also provides recommendations on the information that should be provided to CVM to ensure continued drug substance quality and drug product quality and performance characteristics.
Scope & Applicability
Product Classes
4Drugs subject to section 512 of the FD&C Act
Product type excluded from the scope of this guidance
RTRT and CTD sections apply to drug substances
RTRT and CTD sections apply to drug products
Stakeholders
4Entity submitting development data and knowledge; Entity performing the work process for change
Facility supplying raw materials or ingredients; Facility providing raw materials to a manufacturer
Entity that owns and maintains a Drug Master File
Entity responsible for maintaining the DMF
Regulatory Context
Attributes
8The size of the batch or production run
The sum of all impurities observed.
Specific quantity of a drug intended to have uniform character and quality
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.
levels of existing and new impurities; Characteristic of drug substance that may change with starting material redesignation; A comparison of the impurity profile of pre- and post-modification material to establish equivalence; Evaluation of the impurity profile for intermediates or drug substance; Potential to adversely affect drug substance quality; A description of the identified and unidentified impurities present in a drug substance.; The description of identified and unidentified impuritie
Physical property considered critical for evaluation of equivalence
Characteristic relevant to nanotechnology NDIs
The amount of product held or processed at a specific step.; Used to calculate servings per batch
Identified Hazards
Hazards
2Potential that transformation was caused by an adventitious agent; A microorganism inadvertently introduced into the production of a biological product.; Detection of contaminants in cell substrates and vaccine components
New process impurities generated by manufacturing changes
Related CFR Sections (3)
- 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 →
- 21CFR210.3§ 210.3 Definitions.
(a) The definitions and interpretations contained in section 201 of the act shall be applicable to such terms when used in this part and in parts 211 , 225 , and 226 of this chapter .Read full regulation →
- 21CFR514.8§ 514.8 Supplements and other changes to an approved application.
(a) Definitions.Read full regulation →
See Also (8)
- 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)
- Environmental Assessment of Human Drug and Biologics Applications: Guidance for Industry (Status: Final)
- Drug Master Files for Bulk Antibiotic Drug Substances: Guidance for Industry (Status: Final)