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New FDA Guidance "CMC Post-Approval Manufacturing Changes to be Documented in Annual Reports"

FDA has published new guidance that describes chemistry, manufacturing, and controls (CMC) post-approval manufacturing changes that should be documented in an annual report.

This guidance consists of two lists published as Appendices. The first list, Appendix A, was developed using a risk-based evaluation to provide additional current recommendations to companies regarding some post-approval manufacturing changes for NDAs and ANDAs that may be considered to have a minimal potential to have an adverse effect on product quality, and, therefore, may be classified as a change to be documented in the next annual report (i.e., notification of a change after implementation) rather than in a supplement. The changes listed in Appendix A are categorised according to the type of manufacturing change.

Appendix B provides examples of minor changes to be documented in an annual report that were previously published in FDA’s Scale-up and Post-approval Changes (SUPAC) guidance and other post-approval change CMC guidance.

To document changes in an annual report, companies must include a full description of the CMC changes that were made that the applicant believes did not require a supplemental application. This description should include:

• A list of each change and the date each change was implemented; and
• Relevant summary of data from studies and tests performed to assess the effects of each change on product quality, including (where applicable) a list of cross-references to change control and change validation protocols and standard operating procedures (SOPs) that were used to assess or demonstrate the effect of the change.