Biosimilar Regulatory Pathways Simplified

Biosimilar products have emerged as a crucial aspect of the biopharmaceutical industry, offering cost-effective alternatives to originator biologics. The regulatory landscape for biosimilars has been rapidly evolving since the passage of the Biologics Price Competition and Innovation (BPCI) Act in 2009. This article aims to simplify the complex regulatory pathways for biosimilars, highlighting key concepts, requirements, and the role of regulatory agencies.

Key Concepts and Definitions

  • Biosimilar: A biological product that is highly similar to an existing approved biological medicine (biologic), with minor differences due to their complex nature and manufacturing methods.
  • Reference Product: An FDA-approved biological product against which a proposed biosimilar is evaluated.
  • Interchangeable Biosimilar: A biosimilar that meets additional requirements to ensure no change in efficacy or safety after multiple switches between the biosimilar and the reference product.

Regulatory Pathways

The FDA has established an abbreviated approval pathway for biosimilars under Section 351(k) of the Public Health Service Act. This pathway allows for the submission of less extensive data compared to a full Biologics License Application (BLA).

Stepwise Approach to Biosimilar Development

  1. Analytical Similarity Data: Extensive structural and functional characterization of the reference product and the proposed biosimilar to identify potential differences and their impact on product quality and performance.
  2. Animal Studies: Toxicology and pharmacology studies to address any remaining uncertainties about the safety and efficacy of the proposed biosimilar.
  3. Clinical Studies: Pharmacology studies to demonstrate that the proposed biosimilar moves through the body in the same way and provides the same effects as the reference product, along with immunogenicity assessments and other comparative clinical studies as needed.

FDA Guidance and Evaluation

  • Totality-of-the-Evidence Approach: FDA evaluates all the evidence submitted, considering the totality of the data to determine biosimilarity.
  • Risk-Based Approach: FDA recommends a risk-based approach to determine the scope and extent of studies required, considering the degree of residual uncertainty after each step.

Interchangeable Biosimilars

  • Additional Studies: Interchangeable biosimilars require additional studies to demonstrate that there is no change in efficacy or safety after multiple switches between the biosimilar and the reference product.
  • State-Specific Requirements: Most states permit the substitution of a reference product for an interchangeable biosimilar without the approval of the prescribing physician, with varying time frames for communication to the prescriber about such substitutions.

Global Harmonization

  • World Health Organization (WHO): The WHO has been active in fostering the harmonization of development guidelines for biosimilars globally, ensuring better access to safe and effective biosimilar products.


The regulatory pathways for biosimilars are complex and multifaceted. Understanding the key concepts, requirements, and the role of regulatory agencies is crucial for the successful development and approval of biosimilar products. By simplifying these pathways, we can facilitate the adoption of biosimilars and improve patient access to these cost-effective alternatives.

The ability to rely on FDA’s previous finding regarding the reference product to support approval of the biosimilar product allows for a potentially shorter and less costly drug development program. – Sue Lim, M.D., Director of the Scientific Staff, Therapeutic Biologics and Biosimilars Team/CDER/FDA


  1. LabCorp. (2014). Regulatory Considerations for the Development of Biosimilar Products. Retrieved from
  2. FDA. (2018). Overview of the Regulatory Framework and FDA’s Guidance for the Development and Approval of Biosimilar and Interchangeable Products in the US. Retrieved from
  3. AJMC. (2023). Understanding Interchangeable Biosimilars at the Federal and State Levels. Retrieved from
  4. LinkedIn. (2024). Regulatory Pathways for Biosimilars: A Comparative Analysis. Retrieved from
  5. FDA. (2022). Review and Approval – FDA. Retrieved from

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