Regulation for the Bioequivalence Evaluation of Generic Topical Dermatological Drug Products in Japan.

Background and objective: In Japan, the "Guideline for Bioequivalence (BE) Studies of Generic Products for Topical Use" was issued in 2003 to present the basic principles for BE evaluation methods for generic topical dermatological drug products. However, a detailed analysis of trends in BE evaluation methods in Japan has not yet been reported. In addition, a detailed comparison of the BE evaluation methods used at the Pharmaceuticals and Medical Devices Agency (PMDA), the US Food and Drug Administration (US FDA), and the European Medicines Agency (EMA) has also not been performed.

Methods: We surveyed BE evaluation methods for generic topical dermatological drug products in Japan based on the PMDA website from 2000 to 2023. We also compiled the latest guideline information for the PMDA, US FDA, and EMA.

Results: Before the guideline was issued from 2000 to 2003, most generic topical dermatological drug products were evaluated using pharmacological tests in animals. After the guideline was issued in 2003, dermato-pharmacokinetic studies have become the main method for BE evaluation other than antiseptics in Japan. The greatest difference between the US FDA and EMA versus current Japanese regulations was the introduction of a biowaiver approach based on Q1/Q2 and Q3 similarities and in vitro test equivalence.

Conclusion: This finding confirmed that the publication of the guideline significantly influenced the BE evaluation methods for topical dermatological drug products in Japan. Furthermore, Japan may consider a biowaiver approach based on Q1/Q2 and Q3 similarity and in vitro test equivalence.