India's drug regulatory authority has released draft guidelines that could significantly reshape the biosimilar approval landscape in the country, emphasizing advanced analytical methods and reducing reliance on animal studies.
The Central Drugs Standard Control Organisation (CDSCO) has published draft revised Guidelines on Similar Biologics for marketing authorization in India for 2025, seeking stakeholder feedback within a 30-day consultation period. The revision aims to update the current 2016 guidelines to reflect recent international standards and scientific advancements.
Key Changes in the Regulatory Framework
The draft guidelines represent a significant shift in India's approach to biosimilar approval, with a stronger emphasis on analytical characterization and in vitro studies rather than extensive animal testing. This aligns with global regulatory trends, particularly the World Health Organization's TRS 1043: Guidelines for Evaluation of Biosimilars.
"Since major countries are moving for a waiver of non-clinical studies for similar biologics, the current revision principally focuses on strengthened orthogonal analytical tools and in vitro studies to establish similarity between the similar biologic product and the reference biological product," states the CDSCO notice.
The revision was developed by a committee comprising technical experts, representatives from the National Institute of Biologicals (NIB), Department of Biotechnology (DBT), and industry stakeholders involved in biosimilar manufacturing.
Advanced Analytical Methods and Reduced Animal Testing
Among the most notable changes is the introduction of next-generation analytical methodologies for establishing similarity between biosimilars and reference products. The guidelines also provide detailed information on reference standards development and include an expanded list of in vitro studies.
The draft emphasizes the implementation of the 3Rs principles—"Replace, Reduce, Refine"—to minimize animal use in testing, providing new guidance on determining when in vivo animal studies are necessary. This represents a significant step toward more ethical and potentially more efficient testing protocols.
Dr. Ravi Mathur, a biotechnology expert who was not involved in drafting the guidelines but has reviewed them, commented, "The shift toward advanced analytical characterization reflects the growing confidence in these technologies to detect even subtle differences between biosimilars and reference products. This could potentially reduce development costs while maintaining rigorous safety standards."
Statistical Considerations and Approval Pathways
The revised guidelines also address statistical considerations more comprehensively, providing clarity on establishing similarity ranges and calculating appropriate sample sizes for clinical studies. This statistical rigor aims to ensure that biosimilarity assessments are scientifically sound and reproducible.
Additionally, the draft outlines a revised pathway for biosimilar approval in India, updating sections on quality, non-clinical, and clinical evaluation to align with current international practices while providing greater clarity and flexibility.
Regulatory Context and Definitions
According to the New Drugs and Clinical Trials (NDCT) Rules 2019, a "Similar Biologic" is defined as a biological product similar in quality, safety, and efficacy to a reference biological product approved in India or any innovator product approved in International Council of Harmonisation (ICH) member countries.
The CDSCO notice clarifies that the terms "similar biologics" and "biosimilar" refer to the same concept and can be used interchangeably, aligning Indian terminology with global regulatory language used by agencies such as the US FDA, European Medicines Agency (EMA), and WHO.
Stakeholder Consultation Process
The CDSCO has invited all stakeholders to submit comments and suggestions within 30 days to biological@cdsco.nic.in using a prescribed format provided in the annex to the notice.
"The Draft Guidelines is now being placed in the public domain for inviting comments/suggestions from concerned stakeholders. This window of opportunity will close within 30 days of publishing the draft guidelines on the CDSCO website, and, once finalized, there will be minimal scope for change in this document," the notice states.
Industry analysts suggest that these revised guidelines could potentially accelerate biosimilar development in India, which is already a significant player in the global biosimilars market. The emphasis on analytical characterization over animal studies may reduce development timelines and costs, potentially increasing access to biologic therapies.
The final guidelines, once implemented, will replace the 2016 version and are expected to provide a more streamlined and scientifically robust pathway for biosimilar approval in India while maintaining alignment with evolving international standards.
