Drug Post-Approval Change Guidance Comments

Pfizer says an FDA draft guidance is less clear and helpful than a previous guidance on the same topic. In addition, the comment letter says, there are assumptions and general comments throughout the guidance that likely will be rendered incorrect by case-by-case science and program understanding. “Thus,” it says, “the guidance as drafted will prevent fundamental program knowledge, and PQS/change management experience from having the optimum impact on specific change management approaches. This is not well-aligned with optimal science and risk-based regulation.”

Janssen says the document is difficult to follow and requires jumping from section to section. It recommends a flow of discussing types of changes, risks associated with the changes, content and documentation requirements for each type of change, and filing category for each type of change.

The Association for Accessible Medicines commends FDA for issuing the draft and says it will be most helpful with clarification of certain areas. “Namely,” it says, “it would be helpful if the reporting categories were explicitly enumerated in the draft guidance, rather than referring to previously issued guidance…. Further, proposed changes not specifically listed in the draft guidance should default to a catch-all reporting category. Additionally, we ask FDA to consider incorporating International Council on Harmonization Q12 into the draft guidance.”

GlaxoSmithKline’s comment says the draft is intended to fulfill a GDUFA 2 commitment but is written to provide recommendations to holders of approved NDAs as well as ANDAs. Clarification around the scope is needed, it says. It also raises concerns that as written the guidance could present barriers to implementation of ICH Q12.

AbbVie says there are several topics on which further information is needed, including the relationship between the draft and other FDA guidances on post-approval changes, clarification of new terms and concepts, option to submit either the certificate of analysis or batch analyses data, requirement to include consecutive batches of pre-modification material, recommended documentation for the drug product in an approved application versus recommended documentation for the drug substance in a master file or approved application, and post-approval changes and process understanding.

Finally, Merck suggests the guidance be aligned more closely with ICH Q11 and draft ICH Q12 guidelines by accounting for application of scientific first principles and the knowledge gained during development and lifecycle management to inform the risk associated with the change and subsequent reporting requirements.

All stakeholders also submitted specific line-by-line comments.