On the last day of at the Association for Accessible Medicines GRx-Biosims conference in Bethesda, members of the FDA joined industry for an informative and interactive discussion on post-approval supplements.  Dr. Paul Schwartz and his colleague Olugbenga Okubadejo expressed satisfaction with the current state of the post-approval supplement process, as well as the example of teamwork it has taken to get it there (both within the FDA and also in partnership with industry).  And, it seems, they are looking to keep up their teamwork and continue to look for opportunities to partner with industry to drive improvements.

The FDA received over 9,000 post-approval supplements in 2019 (up from around 7,500 in 2018) so they had a lot of examples to give of things that help the process and things that do not.  And, with that volume of work, it’s not surprising that they are working toward continuous improvement–they are busy!  The FDA presented on some “things to know” and common questions, and, during the industry portion of the session, openly answered a consolidated list of questions.  Here are a few of the discussion highlights:

  • Be aware of relevant FDA Guidances and use them to support change categorization. Guidances specifically noted were: NDA/ANDA Changes; Annual Report Changes; SUPAC (IR, MR and SS); PAC-ATLS; MAPP 5015.6 on Grouped Supplement; Tablet Scoring; and Comparability Protocols.
  • Use the cover letter to describe changes clearly (tables for multiple changes are highly encouraged), make sure 356h forms are complete, and provide the right Module 3 sections to support changes.
  • Use the most recent 356h form and manage the status of facilities listed on it accurately.
  • Grouped Supplements are a useful tool for reporting common changes, but they must be used for the same change, affecting all the products in the grouping. Product-specific changes must be submitted separately and should be referenced in the grouped supplement for visibility.
  • Withdrawal of a facility from an application should be submitted as a supplement and not in an annual report. Once the supplement is approved, that facility can be permanently removed from the 356h list of facilities.
  • As there is no formal mechanism for providing the acknowledgement, notice that the change category has been accepted may or may not be sent to the sponsor. The FDA suggested that sponsors follow up on Day 30 for any CBE-0 or CBE-30 submitted.
  • Submit questions not qualified as controlled correspondence or covered under guidance directly to CDER-OPQ-Inquiries@fda.hhs.gov; there is no timeline for response.
  • Contact genericdrugs@fda.hhs.gov to reach the RPMs that manage labeling, bioequivalence, ANDA Transfer of Ownership, and Withdrawal and Consolidation of ANDAs.

Dr. Schwartz reminded the group in Bethesda that it is the change itself, not the impact of the change or the supporting data provided, that should be used to determine and assign a submitted change category.  The FDA will be assessing the category assigned with this in mind (within thirty days) and, if the supplement category is upgraded, resubmission will be required, goal dates will change, and, if the change has been implemented, it can get messy.  So, get your change categories right, make your cover letters clear and your 356h forms complete, and give the FDA good scientific and risk-based justifications to make your supplements agreeable and approvable.