It is always interesting to see how the Agency works when one action could trigger another action. In the Federal Register pre-publication page (here) this morning, the “Food and Drug Administration (FDA) [announced that it] is withdrawing approval of new drug application (NDA) 019832 for SULFAMYLON® (Mafenide Acetate, USP) Powder for 5% Topical Solution, held by Mylan Institutional, Inc., a Viatris company (Mylan). Mylan has voluntarily requested withdrawal of this application and has waived its opportunity for a hearing.” This application, NDA 019832, for SULFAMYLON® (Mafenide Acetate, USP) Powder for 5% for Topical Solution, received accelerated approval June 5, 1998.
As with all accelerated approvals, there is a requirement that the sponsor complete a study further supporting the safety and efficacy of the product for its intended use, as accelerated approvals are based on surrogate endpoints. The FDA notified the NDA sponsor that the required study has not yet been submitted to the FDA and the sponsor notified FDA that they wished to voluntarily withdraw the NDA, stating (according to the above-cited FR notice) that “conducting such a study is not feasible”.
Ok, thus ends the accelerated approval for the NDA for this product, as it is slated to be withdrawn; however, there are two additional ANDAs still approved based on the reference listed NDA that received the accelerated approval. These two ANDA are still listed as active in the Orange Book. How will the FDA deal with these two ANDAs that were approved now that the RLD is withdrawn? The two ANDA products approved (one on February 12, 2013, and the other on July 31, 2017) are topical powder products for solution, which are listed as having a therapeutic equivalence code of “AT”, meaning that no in vivo bioequivalence studies were required for approval but that the products are designated as therapeutically equivalent, and that designation is based solely on in vitro measures. Since the original NDA sponsor has failed to meet the post-marketing study requirement to “verify and describe its clinical benefit, where there is uncertainty as to the relation of the surrogate endpoint to clinical benefit, or of the observed clinical benefit to ultimate outcome”, the question of how and when the FDA will deal with the other two ANDA approved products is raised.
This dilemma, where there are generics approved based on reference to an NDA of an accelerated approved product, is one that the Agency will have to work through more frequently as other accelerated approval products are withdrawn for failure to submit the required confirmatory study or where the confirmatory study fails to support the clinical benefit of the product. We are still waiting for the final decision on another product (Makena) and the generics that are approved based on that accelerated approval.