Survey on the Role of Comparative Efficacy Studies Required for Biosimilar Monoclonal Antibody Approval in Japan to Justify the Quality Attribute Differences Between Biosimilars and Their Reference Products Based on the Pharmaceuticals and Medical Devices Agency (PMDA) Assessments.

Abstract

Background and objective: Since the approval of the first biosimilar monoclonal antibody (mAb) in 2014, 18 biosimilar mAbs have been approved in Japan as of December 2023. These biosimilar mAbs are typically developed using data that exhibit comparability with their reference products (RPs) in terms of quality, pharmacokinetics, safety, and efficacy. Although comparative efficacy studies are not necessarily required under Japanese biosimilar Guidelines, such studies have been conducted for all 18 approved biosimilar mAbs. Meanwhile, there is growing global interest in reevaluating the absolute necessity of these studies. The objective of this original research article was to analyze the data packages of biosimilar mAbs using publicly available review reports from 2014 to 2023 to assess the role of comparative efficacy studies.

Methods: First, we identified quality attributes (QAs) that differed between each biosimilar mAb and its RP on the basis of publicly available review reports from the Pharmaceuticals and Medical Devices Agency (PMDA) website. Subsequently, we examined the evidence used to justify these differences.

Results: The results showed that 64% of QA differences were justified using data from other QAs. Conversely, only 6% of QA differences were justified through findings from comparative efficacy studies.

Conclusions: These findings indicate that comparative efficacy studies play a limited role in establishing comparability between biosimilars and their RPs. Therefore, sponsors may consider whether a comparative efficacy study is necessary to determine if differences in comparative quality studies are clinically meaningful, rather than automatically conducting such studies.