Bioequivalence In Topical Generics: Regulatory Considerations Around Bioequivalence In Topical Generic Drug Product Development

By Charles Evans, VP of pharmaceutical development, Marc Brown, co-founder, and Jon Lenn, chief technology officer, MedPharm

Demonstrating bioequivalence for generic topical drugs is a complex process, with regulatory bodies like the FDA and EMA constantly evolving their guidance. Originally, proving therapeutic equivalence required extensive and costly clinical studies, which were often cumbersome due to the physiological complexities of dermal absorption. To simplify this, regulators have increasingly focused on in vitro methods, primarily in vitro release testing (IVRT) and in vitro skin permeation testing (IVPT), as attractive alternatives to clinical trials. While there is general agreement between the FDA and EMA on qualitative and quantitative requirements, a growing emphasis is being placed on matching the physical structure and metamorphosis of the reference product. This requires extensive characterization and highlights the need for further work and guidance, as current in vitro methods may not be sufficient to statistically interpret subtle differences that appear after application. These evolving standards underscore the importance of seeking product-specific guidance from regulators.