CVM GFI #126 BACPAC I-Intermediates in Drug Substance Synthesis Bulk Actives Postapproval Changes: Chemistry, Manufacturing, and Controls Documentation
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.
This guidance describes chemistry, manufacturing, and controls information and documentation in support of each change and provides recommendations on reporting categories. The guidance applies to synthetic drug substances and the synthetic steps involved in the preparation of semisynthetic drug substances. It is limited to structurally well-characterized drug substances for which impurities can be monitored at the levels recommended. The guidance covers: (1) site, scale, and equipment changes involving the synthetic steps up to and including the step that produces the final intermediate, (2) specification changes for raw materials, starting materials, and intermediates, except the final intermediate, and (3) manufacturing process changes involving the synthetic steps up to and including the final intermediate.
Submit comments on this guidance document electronically via docket ID: FDA-2013-S-0610 - Specific Electronic Submissions Intended For FDA's Dockets Management Staff (i.e., Citizen Petitions, Draft Proposed Guidance Documents, Variances, and other administrative record submissions)
If unable to submit comments online, please mail written comments to:
Division of Dockets Management (HFA- 305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852
All comments should be identified with the title of the guidance.