FDA publishes new Guidance on Post-Approval Changes

The US Food and Drug Administration (FDA) has published a new guidance on post-approval changes named as "CMC Post approval Manufacturing Changes To Be Documented in Annual Reports". The intention behind this document is to elucidate which changes need to be reported in annual reports by sponsors of new and generic drug products.

The FDA demands that changes to an approved new drug application (NDA) or abbreviated new drug application (ANDA) should be reported. The three ways to report these are:

•  in advance (Prior Approval Supplement)
•  at the time of the change or right before (Changes Being Effected-0 Day or CBE-30)
•  on an annual basis (Annual Report).

The changes which are reported on an annual basis have very little or no potential to affect safety, efficacy and quality of the product. In the new guidance, FDA emphasizes that changes with little risk to the product must be reported in annual reports not in supplements. The authority has compiled a new list of changes in the guidance (Appendix A and B), to support the decision making. The companies can refer to these guidelines to verify if their post-approval manufacturing changes would be appropriate to report in an annual report:

•  Appendix A "lists examples of CMC post approval manufacturing changes previously submitted under manufacturing supplements that we have determined generally to be of low risk to product quality".
•  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) guidances and other post approval change CMC guidances (see Section V. Resources for a list of those guidances)".