In two separate Federal Register (FR) Notices on the FR prepublication page (here and here), the FDA proposed to withdraw approval of two ANDAs based on lack of confidence in the bioequivalence data contained in the applications.  The concern relates to a problem at a bioequivalence testing laboratory.  The Notices state:

“In May 2010 and December 2010, FDA conducted comprehensive inspections of bioequivalence studies conducted by Cetero Research at the Houston, TX site.  The inspections were part of FDA’s Bioresearch Monitoring Program, which includes inspections to evaluate the conduct of research, to confirm that data intended for submission to FDA are reliable as a basis for FDA approval and regulatory decisions, and to verify compliance with the bioavailability and bioequivalence requirements in section 505 of the FD&C Act and 21 CFR part 320.  The findings of these inspections of bioequivalence studies conducted by Cetero Research raised significant concerns about the validity of the reported results of analytical studies conducted between April 1, 2005, and June 15, 2010, in support of drug applications.”

The two Notices outline the history of the issues with each of the products and the actions that the FDA has taken, which includes multiple letters and notices to the firms and ultimately downgrading the therapeutic equivalence codes because the firms failed to provide the required additional data to support the bioequivalence of the applications.  The process for both firms started with the first FDA letter issued in 2011.  It has taken the FDA eight-plus years to get to this point.  And now the firms have one more bite at an apple that is, by now, rotten.

The FR notices are interesting and provide an inside look at the way the Agency approaches these types of issues.