Use of excised human skin to assess the bioequivalence of topical products

Background: Establishing the bioequivalence of topical drug products is a costly and time-consuming process since, with few exceptions, clinical efficacy trials are required.

Objective: To develop a surrogate for clinical bioequivalence testing through evaluation of the kinetics of drug absorption in vitro through excised human skin.

Methods: The percutaneous absorption of seven approved generic topical drug products was compared with their corresponding reference products during preclinical development using the Franz diffusion cell. Thereafter, following the conduct of bioequivalence trials and regulatory approval of these products in the United States, clinical data became available to which the in vitro data were compared.

Results: In six of the seven cases the in vitro test:reference ratio for total absorption was close to one and indicated that the products were equivalent, in agreement with the clinical data. Results from the seventh case, in which the test:reference ratio was only 0.63, indicated that the in vitro model actually had greater sensitivity than the clinical method to detect small differences between products.

Conclusion: These data demonstrate the relevance and predictive power of the in vitro human skin model and strongly support its use as a surrogate for in vivo bioequivalence studies.