Survey of Data Package and Sample Size of Comparative Clinical Studies for Biosimilar Developments from PMDA Assessments

The Japanese biosimilar guideline requires that the sponsors conduct clinical studies such as comparative pharmacokinetic (PK), pharmacodynamic (PD), or efficacy studies. In each biosimilar development, the sponsors consider the clinical data package, and thus clinical data packages vary among biosimilar developments.

The aim of this study was to elucidate the clinical data packages for the biosimilars approved in Japan. The details of clinical data packages and sample size for the regulatory approvals of biosimilars in Japan was reported.

We surveyed the clinical data packages and sample size based on the Pharmaceuticals and Medical Devices Agency (PMDA) website review reports between 2009 and 2023.

Twenty-four biosimilars have been approved based on the comparative PK and efficacy studies, 10 biosimilars have been approved based on the comparative PK/PD study, and one biosimilar has been approved based on the comparative efficacy study. Regarding the sample size, comparative PK studies were conducted in healthy volunteers or patients for up to 300 cases, although the majority enrolled only 1–100 cases (68.1%, 32/47). Comparative PD studies enrolling 1–30, 31–60, and 61–90 cases totaled 4, 7, and 4 cases, respectively. Finally, comparative efficacy studies enrolling 1–300, 301–600, and 601–900 totaled 6, 10, and 11 cases, respectively. In particular, the oncology and rheumatology areas were the first and second disease areas recruiting 601–900 patients.

Large numbers of patients were enrolled to conduct a comparative efficacy study. Efficient biosimilar development should be considered on the basis of the accumulation of scientific understanding of comparable features of biosimilars and their development.