Modernization and Strengthening of Bioequivalence Guidelines in Japan

Until now, human bioequivalence (BE) studies were conducted based on the revised ‘Guideline for Bioequivalence Studies of Generic Products’ issued in 2012 by the Ministry of Health, Labour and Welfare (MHLW) in Japan. However, revisions of BE guidelines were required to account for the globalization of pharmaceutical development, new technology, and scientific rationales over the last 8 years. Therefore, the MHLW published the revised ‘Guideline for Bioequivalence Studies of Generic Products’ in 2020. In this article, we introduce the main revised contents, such as the addition of a fed-state BE study, reconsideration of the pilot study and add-on study, acceptance of foreign subjects in a BE study, and clarification of the requirement of a reference product. Furthermore, we compare the BE evaluations of generic oral solid dosage forms with those of the Pharmaceuticals and Medical Devices Agency (PMDA), the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA).