Bioequivalence of topical generic products. Part 2. Paving the way to a tailored regulatory system.

Hitherto, for the approval of a topical generic drug product, the majority of the regulatory agencies require clinical endpoint studies to prove its therapeutic equivalence in relation to a reference product. Pharmacodynamic studies are also available to support bioequivalence, however, these are solely applicable for corticosteroids. The first strategy is considered the "gold standard", since it can be applied to all drug products. Nevertheless, the high variability intrinsic to topical drug delivery makes this analysis relatively insensitive, costly, time-consuming, besides requiring a large number of subjects. There are, however, alternative methods capable of providing a more rigorous analysis and requiring a lower cost. Amongst them, in vitro methods have sparked considerable attention, not only in the academic field, but also in the pharmaceutical industry and regulatory agencies. In this context, this review attempts to discuss the main regulatory constraints and the recent advances in the regulatory science of topical generic drugs bioequivalence assessment. Initiatives, such as the Strawman decision tree and the topical drug classification system are specially referred, since these highlight the importance of establishing a broader concept of pharmaceutical equivalence for topical generic drugs, similar to the one already set for orally administered conventional dosage forms, such as tablets and capsules. Finally, the FDA Product-Specific Guidances for Generic Drug Development released for topical products in recent years and particular European Public Assessment Reports are presented and discussed, to illustrate the change of paradigm which is occurring in this regulatory field.