An Evaluation of Foreign Clinical Data in the Approval Reviews of Antimicrobial Medicines in Japan: Considering Ethnic and Regional Differences in Data Extrapolations in Accordance With Regulatory Circumstances

The approval requirements in new regions that do not require domestic clinical data and the clinical data evaluation of multi-regional clinical trials (MRCTs) and foreign clinical trials (FCTs) in the Japanese approval review processes for antimicrobial medicines were explored. Foreign clinical data has been used to evaluate the efficacy of more than 60% (45/70) of approved antimicrobial drugs in Japan. Two FCT extrapolations based on bridging strategies were used for antimicrobial medicine approvals in the early 2000s after the issuance of International Council for Harmonization-Efficacy Guideline 5 (ICH-E5), but 40 approvals extrapolated efficacy evaluations from outside of Japan without bridging studies. Participation in MRCTs has increased since the 2010s, following Japan's notification "Basic Principles on Global Clinical Trials" for global clinical trials in 2007. From the commencement of the use of FCT extrapolations, comparisons of pharmacokinetic data have been used to examine regional differences. As experience with inter-regional data interpretation increases, similarities in the drug susceptibilities of infectious agents (pharmacodynamic data) and the medical environment (extrinsic factors) are being examined. In one approval in Japan, a different dose was set compared with that approved overseas because of differences in pharmacokinetics. We demonstrated that MRCTs and FCTs of antimicrobial medicines have been accepted as confirmatory trials in Japan without the need for bridging studies, which has been enabled by examining regional differences using pharmacokinetic data and additional comparisons of pharmacodynamic data and extrinsic factors.