The US FDA has released draft guidance on how post-approval manufacturing changes should be reported in annual reports.
Specifically, the guidance describes chemistry, manufacturing, and controls (CMC) postapproval manufacturing changes that we have determined will likely have a minimal potential to have an adverse effect on product quality and, therefore, should be documented by applicants in an annual report.
The number of CMC manufacturing supplements for NDAs (new drug applications) and ANDAs (abbreviated new drug applications) 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 CMC postapproval manufacturing supplements.
The changes listed in Appendix A are categorized according to the type of manufacturing change. These changes are either additions or revisions to the CMC changes recommended for documentation in an annual report that were previously published in multiple other guidance documents.
“We expect NDA and ANDA holders to evaluate the specific change that they are planning to make in the context of their particular circumstances to determine whether the proposed change would present a minimal potential to have an adverse effect on product quality,” the FDA says. When an evaluation shows that a change would have minimal potential impact, the change can be documented in the next year’s annual report.
The applicant also must include a full description of the CMC changes that were made that the applicant believes did not require a supplemental application.
Appendix A lists examples of CMC postapproval 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 Postapproval Changes (SUPAC) guidances and other postapproval change CMC guidances.
Executed batch records, SOPs (standard operating procedures), and data from studies and tests performed to assess the effects of each change should be kept on file and made available to the Agency on request.