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.1
The abbreviated development program demonstrates biosimilarity through analytical, nonclinical, and clinical research and studies, and additional studies as needed to address any residual uncertainties.
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.
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.
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.