While the FDA does appear to listen rather intently to comments on its bioequivalence (BE) draft guidances, and will occasionally reopen comment periods, it is still the exception rather than the rule. Today a Federal Register (FR) notice (here) announced another sixty-day comment period during which such comments will be entertained.
The FR notice explains that the Agency, based on two citizen petitions that it denied on May 17, 2018 (here), has decided to reopen the comment period due to significant interest in the matter. As a bit of background, the “FDA published a draft product-specific guidance for sucralfate oral suspension in July 2014, withdrew the draft guidance in December 2015, and published a revised draft guidance in October 2017.” The original draft guidance recommended a bio study with clinical endpoints in addition to certain in vitro testing to support a determination of bioequivalence. The revised BE guidance recommends an in-vitro testing regimen if the test and reference products are formulated qualitatively and quantitatively (Q1 and Q2) the same.
The petitions referenced above were submitted to the FDA after the revised guidance was published, the first on December 18, 2017 and the second on March 28, 2018. Each petition raised specific issues that could impact the approval recommendations for BE testing as stated in the original and revised draft guidance document. Apparently, the FDA has had a number of inquiries concerning its suggested BE approval recommendations and, even though the FDA notes in its petition response that BE guidances are only recommendations and firms could satisfy approval requirements by alternate methods, we all know that the fastest route to approval is to follow the FDA’s recommendations. Now, the FDA is wanting to hear more from the petitioners, as well as any other interested party, before finalizing its guidance for this particular non-absorbed product for which its mechanism of action is topical at the site of the ulcer itself.
The FDA, over the last several years, has been trying to address the issue of non-systemically absorbed products where the drugs action is topical to make BE testing more relevant (remember that bio studies with clinical endpoints are the least sensitive, accurate, and reproducible methods to establish bioequivalence) and less onerous. This appears to be another example of the FDA listening to public input to try to achieve the most relevant BE testing measure that can ensure the test and reference products behave the same and permit a finding of therapeutic equivalence.
