Scientific Considerations in Demonstrating Biosimilarity to a Reference Product

Scientific Considerations in Demonstrating Biosimilarity to a Reference Product is the final version of a draft guidance for industry originally released in 2012. It provides an overview of FDA’s approach to determining biosimilarity and discusses important scientific considerations for demonstrating that a proposed therapeutic protein product is biosimilar to a reference product. The document reaffirms that FDA will use a risk-based “totality of the evidence” approach to reviewing applications for biosimilar products. It also supports a stepwise approach in developing evidence to support a demonstration of biosimilarity, which can include a comparison of the proposed product and the reference product with respect to structure, function, animal toxicity, human pharmacokinetics and pharmacodynamics, clinical immunogenicity, and clinical safety and effectiveness.

Additional topics discussed include:

  • General scientific principles in conducting comparative structural analyses, functional assays, animal testing, human studies, clinical immunogenicity assessments, and comparative clinical studies.
  • Considerations of the complexities of therapeutic protein products when designing a biosimilar development program, including manufacturing process considerations.
  • Use of data derived from studies comparing a proposed biosimilar product with a non-US-licensed comparator product.
  • Postmarketing safety monitoring considerations.

The full document is available on the FDA website.