Update on the advances and challenges in bioequivalence testing methods for complex topical generic products

Abstract

Most of the government regulatory agencies, including the United States Food and Drug Administration and the European Medicine Agency, demand that the generic complex topical products prove pharmaceutical and bioequivalence. The evaluation of bioequivalence for complex topical dermatological formulations is a challenging task that requires careful consideration of several factors. Although comparative clinical studies are still considered the gold standard approach for establishing bioequivalence in most formulations, these studies can be costly and insensitive to detect formulation differences. Therefore, significant efforts have been made to develop and validate alternative approaches that demonstrate bioequivalence and expedite the availability of high-quality generic topical dermatological products. This article reviews the current methods for determining the bioequivalence of topical formulations in humans, with particular emphasis on recent advances in these methodologies. Most of the alternative methods are sensitive and reproducible, with the capability to ease the financial burden of comparative clinical studies within a short delivery time. The limitations associated with each technique are reviewed in detail.

Generic orphan drug substitution: a critical analysis of global practices and Saudi Arabia’s perspective

“…Although comparative clinical studies are still considered the gold standard approach for establishing bioequivalence in most formulations, these studies can be costly and insensitive to detect formulation differences. Thus, demonstrating bioequivalence of complex drugs often requires alternative in vitro and in vivo methods, advanced analytical technologies, quantitative methods, and modeling and data analytics methodologies to establish scientific standards that would ensure therapeutic equivalence in patients ( Zhang et al, 2023 ; Alomari and Alhussaini, 2024 ). Further refinement and standardization of these novel methodologies for regulatory purposes and product-specific guidances are needed to support the development and approval of safe and effective complex generic drugs ( FDA, 2024 ).…”