Current regulatory scenario and alternative surrogate methods to establish bioequivalence of topical generic products

Generic drug products are bioequivalent version of the innovator products and are available at significantly reduced costs mainly due to the reduced expenditure on the research, clinical trials and sometimes waiver of associated bioequivalent studies. However, bioequivalence concept till date was more relevant for solid oral dosage forms that fall under Biopharmaceutics Classification System (BCS). In case of topical products that elicit their action at the local site rather than systemically, clinical end point studies is the current regulatory norm to establish the bioequivalence. Assessing the therapeutic equivalence using these studies for such products is expensive, complex and requires several patients in order to achieve statistical significance. This article focuses on the possibility of utilizing various in vitro and minimally invasive in vivo methods as surrogate to the highly expensive clinical studies, a key concept the USFDA has been extensively working on. Changes in the paradigm of considering human clinical studies as the gold standard, Topical Drug Classification System (TCS), its drawbacks are also discussed. The regulatory status of incorporating in vitro methods to assess bioequivalence to ensure faster submission and approval processes, enabling availability of generic topical drug products has also been addressed here.