The US Food and Drug Administration (FDA) has issued draft guidance, CMC Postapproval Manufacturing Changes for Specified Biological Products To Be Documented in Annual Reports, to recommend the types of manufacturing changes for approved biologics license applications (BLAs) that need to be documented in an annual report.
Specifically, the guidance describes chemistry, manufacturing, and controls (CMC) post-approval manufacturing changes that the FDA generally considers to have a minimal potential to have an adverse effect on product quality. Under FDA regulations, post-approval changes in the product, production process, quality controls, equipment, facilities, or responsible personnel that have a minimal potential to have an adverse effect on product quality must be documented by applicants in an annual report.
Examples of CMC post-approval manufacturing changes listed in the appendix of the draft guidance include: (1) components and composition; (2) manufacturing sites; (3) manufacturing process, batch size, and equipment; (4) specifications; and (5) container-closure systems.
The FDA noted in its draft guidance that the number of CMC manufacturing supplements for BLAs has continued to increase over the last several years. In connection with FDA’s Pharmaceutical Product Quality Initiative and its risk-based approach to CMC review, the agency evaluated the types of changes that have been submitted in postapproval manufacturing supplements and determined that certain changes being reported generally present minimal risk to the quality of the product. Thus, FDA determined that it would be appropriate to issue guidance to recommend that certain changes, listed in the appendix of the draft guidance, generally should be documented in an annual report.
The FDA recommends that the changes listed in the appendix generally should be submitted in an annual report. However, if a BLA holder is planning to make a change that is listed in the appendix, the BLA holder should evaluate the change in the context of the holder’s particular circumstances to determine whether the proposed change would present a minimal potential to have an adverse effect on product quality and therefore would be appropriately documented in an annual report. BLA holders may, based on their specific circumstances, determine that a change described in the appendix would appropriately be submitted as a supplement rather than in an annual report. If the FDA disagrees with the categorization, the FDA may notify the applicant of the correct category and request additional information.
Source: US Food and Drug Administration