Biosimilar Approval Process

Biosimilar Approval Process

FDA approval process for biosimilars

A stepwise approach

A stepwise approach

To support biosimilarity to an existing FDA-approved reference product, the FDA has established a stepwise approach that supports a totality of evidence for approval, instead of a one-size-fits-all assessment for manufacturers.1

In this stepwise approach, data from each phase of development is evaluated to determine differences observed between the tested product and its reference product, and any potential impact of these differences.



Key concepts of FDA biosimilar development:

FDA biosimilar development

Key Concept 1: Abbreviated Development Program1*

The abbreviated development program demonstrates biosimilarity through analytical, nonclinical, and clinical research and studies, and additional studies as needed to address any residual uncertainties.

FDA biosimilar development

Stepwise Evidence Development

Key Concept 2: Stepwise Evidence Development1

Since no single study demonstrates biosimilarity, a stepwise approach has been outlined by the FDA to generate data and establish any areas of uncertainty between the developing biologic and its reference product.

  • After each phase of development, differences between the 2 products are observed
  • Next steps are established as to which study or studies will best address any uncertainties
Analytical Similarity Data

Key Concept 3: Analytical Similarity Data1

Characterization is established through extensive structural and functional study to fully understand the reference molecule and its critical quality attributes. Analytical data helps demonstrate that the proposed biosimilar product is highly similar to the reference product in terms of activity, PK/PD, safety, and immunogenicity.

Role of Clinical Studies

Key Concept 4: Role of Clinical Studies1

To consider a product for biosimilarity, the FDA expects data comparing differences between the product and its reference for PK (PD if relevant), immunogenicity, and if uncertainties remain, a comparative clinical study or studies.

*Section 351(k) of the Public Health Service Act defines an abbreviated licensure pathway as less than a full complement of product-specific preclinical and clinical data.1  

Reference: 1. US Food and Drug Administration. Christl L. Overview of the regulatory pathway and FDA’s guidance for the development and approval of biosimilar products in the US.