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Japan’s Early Consideration on Handling of Japanese Data for Biosimilar Comparability

2025.10.17

• Biologics
• Biosimilar Comparability
• Clinical Data Requirements
• Data Localization
• Global Harmonization
• Japanese Regulatory Framework
• PMDA
• Regulatory Science

Introduction to Regulatory Perspective

According to the PMDA’s provisional translation released on September 19, 2025, Japan clarified its regulatory stance on the necessity of Japanese clinical data for biosimilar approvals. Traditionally, the development of biosimilars in Japan has required clinical trials involving Japanese subjects, either to demonstrate pharmacokinetic (PK) equivalence or efficacy equivalence in the Japanese population. However, following the 2024 revision of the Q&A on the biosimilar guideline, it is now acceptable to extrapolate non-Japanese clinical trial data to the Japanese population when ethnic factors are considered unlikely to affect outcomes. This new document complements the administrative notice and provides further details on PMDA’s regulatory perspective.

Principles on Handling Japanese Data

If approval applications rely solely on foreign clinical trial data, applicants must demonstrate that ethnic factors do not influence the trial results. PMDA highlights three key aspects:

1. Impact of Ethnic Factors – Applicants must assess both intrinsic (genetic, physiological, pathological, drug-related) and extrinsic (medical practice environment, standard of care, concomitant therapies) ethnic factors using existing data and literature.

• Subgroup Analysis of Reference Products – Evidence from subgroup analyses or post-marketing data of the original biopharmaceutical must confirm no significant differences in PK, efficacy, or safety between Japanese and non-Japanese subjects.

• Quality Attributes – Any differences in quality attributes between the biosimilar and its reference must be evaluated for potential ethnic impact, including PK, efficacy, safety, and immunogenicity.

Use of International Guidelines

PMDA references several international guidelines to support this evaluation:

• ICH E5(R1): Ethnic Factors in the Acceptability of Foreign Clinical Data (1998)
• ICH E17: General Principles for Planning and Design of Multi-Regional Clinical Trials (2017)
• Japan’s Q&A on Phase 1 Studies in Japanese prior to MRCT initiation (2023)

Framework for Ethnic Sensitivity Assessment

The document includes a reference table to categorize drugs as sensitive or not sensitive to ethnic factors. Parameters include PK linearity, therapeutic dose range, metabolism pathways, genetic polymorphisms, bioavailability, potential for drug-drug interaction, impact of BMI/body weight, and comparability in medical practice across regions.

Conclusion

Japan would no longer require mandatory Japanese-subject clinical trials for biosimilar approval, depending on the robustness of the justification for using non-Japanese clinical data. Sponsors must scientifically demonstrate the absence of ethnic impacts by considering intrinsic and extrinsic factors, subgroup analyses, and quality comparability. PMDA strongly recommends early consultation to ensure appropriate application of these principles.

References:

000277274.pdf