FDA Releases Draft Guidance On Biosimilars
The U.S. Food and Drug Administration (FDA) has released its first new biosimilar guidance to help sponsors with the design and use of clinical pharmacology studies in order to determine a proposed biological product’s biosimilarity to its reference.
The document defines biosimilarity as a biological product being highly similar to its reference in spite of minor differences in clinically inactive components. However, biosimilars must demonstrate no clinically significant differences in terms of safety, purity, and efficacy.
Based on the guidance, the FDA may classify biosimilars into four categories through a comparative analytical characterization. These include:
Not similar: There may be certain differences in the analytical characterization results, in which case changes to manufacturing process of the proposed biosimilars are required before moving on to further development.
Similar: More data and additional analytical studies are needed to see if the products’ differences are within acceptable range.
Highly similar: The candidate biosimilar product has been determined to satisfactorily meet statutory standards for analytical similarity. Sponsors are given green light to pursue targeted studies to resolve residual uncertainty and demonstrate biosimilarity.
Highly similar with fingerprint-like similarity: Candidate biosimilar product meets statutory standard for analytical similarity, supported by results from integrated and multi-parameter approaches. Sponsors are given green light to pursue further studies and demonstrate biosimilarity.
Sponsors can use data from pharmacology studies with PD endpoints and pharmacometric analysis to test whether or not their candidate has clinically significant differences to its reference.
In addition, the agency outlined three concepts that will play an important role in the assessment of biosimilar candidates:
- Exposure and response assessment
- Evaluation of residual uncertainty
- Assumptions about analytical quality and similarity
The FDA made it clear that the latest biosimilar guidance, while designed to be more specific, is being distributed to the industry for comment purposes only. The agency maintained that its Biologics Price Competition and Innovation Act (BPCIA) administration remains a work in progress.