A citizen petition filed by Mylan on December 5, 2017 asks the FDA not to approve any ANDA for a generic version of Advair Diskus that relies on data from multiple-batch PK bioequivalence studies “unless, after conducting an appropriately rigorous review under the established standards for establishing BE, generally, and for this product specifically, FDA concludes that such a study design is valid and will ensure patients receive a robust and reliable therapeutically equivalent product.”
Mylan’s own ANDA for a generic Advair received a complete response letter from the FDA in March 2017, shortly after the FDA responded to a citizen petition from Sandoz which challenged the PK BE study recommendations in the draft guidance for fluticasone propionate/salmeterol xinafoate DPIs on the grounds that it fails to take Advair Diskus 100/50 batch-to-batch variability into consideration.
The Mylan citizen petition specifically calls out Sandoz for being unable to establish BE for the 100/50 strength using the methods laid out in the guidance and for suggesting a multiple-batch approach for that strength. The petition claims that “it is possible, with an adequate understanding of the RLD and a well-designed proposed generic, to demonstrate BE using straightforward and established single-batch BE studies designed in accordance with FDA’s guidance, experience, and precedent.”
Mylan cites “a recent abstract and podium presentation exploring a multiple-batch PK BE study with a very large number of test and reference product batches as a way of demonstrating PK BE between a proposed generic and the Advair Diskus (Elise Burmeister Getz of Sandoz gave such a talk at RDD Europe 2017), saying “We are concerned that applicants may be attempting to rely on novel, unprecedented PK BE study designs to support bioequivalence of a proposed product to the RLD because they have not adequately performed the necessary development work to understand the RLD product and the proposed generic and, as a result, are unable to demonstrate PK BE using accepted methods as provided by the Guidance.”
Read the Mylan citizen petition.
