Sometime today, according to a pre-publication in the Federal Register, the FDA will post twenty-six new bioequivalence guidance documents and announce the revision of seventeen more.  Since February 2018, the FDA has issued sixty-one new guidances and revised forty.

The OGD has indeed been busy but while the industry loves to see the new guidances, it cringes at many of the revisions.  Why?  Because a revised guidance may signal a need to repeat bioequivalence testing, and that can cost a firm in terms of time to approval and expense in conducting a new study.  In addition, sometimes when a bioequivalence guidance is revised, there already may be approved generics on the market for the product that used an old study design recommendation for initial approval.  This can pose a real quandary for application holders.  First, they don’t know whether they must redo a study to support continued marketing, and, secondly, what happens if the new study fails?

We have posted about this issue previously (here, here, here , and here just to cite a few.

OGD reviews its issued bioequivalence guidances based on new information it receives from innovators, from other studies it may review, or literature it reviews.  The questions raised in my mind are:

  • Is the revised study guidance doable? Can it result in a passing study?
  • If the new study also shows equivalence, how relevant was the information that caused the OGD to revise the existing guidance?
  • Is there a clinical relevance in the difference in results that could or should invalidate the original study results?
  • When does the OGD decide whether a new study is necessary for an already marketed product?
  • When does a product have to come off the market (the methylphenidate examples)?

This discussion needs to occur so firms can be prepared and have appropriate direction from the Agency.  Otherwise, everyone is just guessing!