Advances in statistical methodologies for assessing bioequivalence of topical dermatological products

For the determination of bioequivalence (BE) of generic topical dermatological drug products, In Vitro assessment of dermal pharmacokinetics is a critical aspect. The In Vitro Permeation Test (IVPT) is frequently used to evaluate the skin's drug absorption, using Ex Vivo human skin in conjunction with diffusion cells. The establishment of statistical methodology for BE assessment of IVPT data began in 2016 with the release of the FDA guidance for Acyclovir Cream 5%. Since then, there have been significant research activities that led to several advances and extensions of the original methodology. Such research includes extending the method to the case of unbalanced data, an adaptive design, and adopting a model-based approach for assessing BE in IVPT study data. While IVPT is recognized as a highly sensitive and discriminating method, there is a scarcity of the literature addressing the statistical methodology associated with it. This effort seeks to showcase the activities undertaken over the past decade, culminating in an efficient and rigorous process for the regulatory approval of topical generic products. The aim is to chronicle these activities as a journey from the inception of a statistical approach for assessing BE in IVPT data to the various advances promoted by regulatory challenges.