FDA Releases 34 New and 33 Updated Bioequivalence Guidance Documents

FDA has been busy putting out new bioequivalence (BE) guidance documents and revising others.  Under the new provisions of GDUFA II, the Office of Generic Drugs (OGD) will set a goal of issuing 90 product-specific BE Guidances at least 2 years prior to the earliest lawful approval date (here) of an innovator product.

While this activity is good news for product developers, it can throw a real monkey wrench into the firms’ plans, especially when BE guidance is revised.  Here is the story line.  OGD often learns and forms opinions from the information it receives from applicants in the form of ANDA submissions, protocols for BE testing, controlled correspondence, and yes, even through petitions from innovators.  As the FDA learns from the information it receives, it issues product-specific draft BE guidance.  Many times after the guidance is issued, the innovator will chime in, or once BE studies are submitted using the existing guidance, the FDA review of the data may suggest that the studies are not sufficiently supportive of a BE finding.  In either case, if the innovator is persuasive in their scientific argument or the FDA recognizes that its original guidance is not sufficient, FDA may revise the guidance slightly or, in some cases, recommend a major revision to its recommendations based on its review.

Imagine a sponsor getting ready to submit its ANDA only to learn that the study it conducted is no longer recommended.  How about pending ANDAs?  Will the firm need to submit a new study based on the FDA’s revised BE recommendation?  What about firms that have approved products that were based on a previous FDA recommended BE design that the Agency revises post-approval?  Will the firm need to perform a study using the new recommendation?  If so, what happens to the FDA’s assigned therapeutic equivalence evaluation during the pendency of completion and review of the new study?

All of these are legitimate questions and require firms to stay on top of changes in recommendations made to BE guidance documents.  One thing that might help firms assess the revisions in that regard, is if the FDA would clearly articulate what revisions it makes to a BE recommendation either by redlining the changes in the document or by providing a change history to accompany the changed document.  Why? Because once a revised guidance is issued, the previous version can no longer be accessed making evaluating the specific changes very difficult.  Just a suggestion, FDA (if you are reading this blog)!