In today’s Federal Notice pre-publication page (here), the FDA is requesting information and comment from industry and the public on whether it’s time to update the series of Scale-Up and Post Approval Changes (SUPAC) guidance documents. The SUPAC documents were issued between 1995 and 1997 (with the exception of SUPAC Manufacturing Equipment Addendum, which was published in 2014), and they were designed to downregulate certain post-approval changes, depending on the relative risk of the proposed change. SUPAC has guided firms in proper classification of CMC (Chemistry and Manufacturing Control) changes into CBE (Changes Being Effected) supplements, CBE-30 submissions, PASs (Prior Approval Supplements), or annual reportable changes based on a risk-assessment algorithm contained in the guidance documents.

While the SUPAC guidances have served the industry well over the years, the FDA recognizes “that the effectiveness of the SUPAC guidances may be impacted by subsequent guidances (e.g., ICH Q9(R1) and ICH Q12), where particular recommendations in those guidances either supersede or potentially conflict with certain recommendations in the SUPAC guidances.”

The FDA is now looking to update the SUPAC documents to further recognize technological improvements and analytical advances since the first SUPAC guidances were developed. This FR Notice is the first step in the process of evaluating whether the SUPAC guidance should be updated to further improve firms’ ability to make changes to conditions of approval through a least burdensome approach while ensuring and maintaining drug product quality.

Here are the four general questions for which the FDA is seeking comment:

    1. How are the recommendations provided in the SUPAC guidances still helpful and meaningful to regulated industry?
    2. What challenges do you have when interpreting or applying the recommendations in the SUPAC guidances?
    3. How can the FDA provide clarity on the recommendations provided in the SUPAC guidances?
    4. Are there new topics that should be added to the SUPAC guidances?

 

There are multiple subparts associated with each of the above questions and we urge you to study the FR request and offer your suggestions as this is a significant opportunity for industry to effectuate potential downregulation of certain post-approval changes.