Introduction to PMDA’s Early Consideration on Comparative Efficacy Studies for Biosimilars
According to the Early Consideration document issued by the Pharmaceuticals and Medical Devices Agency (PMDA) on May 18, 2026, PMDA has expressed its recent views on the requirement of the comparative efficacy study in the development of biosimilars. The document is an amendment of the recently issued Q&A on biosimilar development and aims to improve transparency regarding the scientific and regulatory factors for the assessment of the necessity of comparative efficacy trials. As an Early Consideration, the document reflects PMDA’s current perspective based on available scientific evidence and regulatory experience and may evolve as new knowledge emerges.
Background: Evolving Global Discussion on the Role of Comparative Efficacy Studies
Traditionally, biosimilar development programs have included:
However, advances in analytical characterization technologies have significantly improved the ability to detect differences between biosimilars and reference products. PMDA notes that comparative efficacy studies are often less sensitive than analytical comparability assessments in identifying product differences. In addition, increasing regulatory experience worldwide has led to growing recognition that biosimilarity can sometimes be adequately demonstrated without conducting dedicated efficacy comparison trials.
Fundamental Regulatory Principle
PMDA emphasizes that the primary objective of biosimilar development is to demonstrate equivalence/similarity to the reference biologic through a scientifically justified totality-of-evidence approach.
The document states that comparative efficacy studies may be waived when:
Under such circumstances, biosimilarity may be adequately established without conducting a dedicated efficacy comparison trial.
Reliable Data Evidence in Quality is Playing a More Central Role
The guidance highlights the growing importance of analytical and quality data in biosimilar development.
For productive discussion on the necessity of comparative efficacy studies with PMDA in the PMDA formal consultation process, the applicants are expected to provide detailed justification, including the following:
Importantly, the applicants should provide justification for any identified differences that may affect the product profile in efficacy, safety, or immunogenicity.
Expectations for Clinical Development Packages
Although comparative efficacy studies may potentially be omitted, PMDA still expects robust clinical evidence to support biosimilarity.
The aplicants should provide:
In addition, the applicants should explain the scientific rationale supporting the proposed indications to be sought in the initial marketing authorization application.
Considerations for Rare Diseases
PMDA acknowledges that conducting comparative efficacy studies may be particularly challenging in rare disease settings due to limited patient populations.
Where sponsors seek to justify omission of efficacy studies based on feasibility considerations, they are expected to provide a detailed explanation regarding:
These factors may be considered as part of the overall scientific justification.
Alignment with International Regulatory Trends
The document reflects a broader international regulatory movement toward reducing unnecessary comparative efficacy studies for biosimilars.
PMDA specifically references:
This reflects a growing alignment between Japan and global regulators in their approaches to improving biosimilar development efficiency.
Conclusion
This Early Consideration represents an important step toward a more science-based and risk-proportionate biosimilar development framework in Japan. PMDA clearly acknowledges that advances in analytical science and accumulated regulatory experience may allow biosimilarity to be demonstrated without comparative efficacy studies in certain cases.
While decisions will continue to be made on a case-by-case basis through PMDA consultation procedures, the document provides greater regulatory clarity and aligns Japan more closely with evolving international approaches aimed at reducing unnecessary clinical burden while maintaining confidence in biosimilar quality, safety, and efficacy.
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