The draft guidance—three documents to be exact—includes Scientific Considerations in Demonstrating Biosimilarity to a Reference Product; Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product; and Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009. FDA seems to have gone out of its way to anticipate and respond to key concerns in the documents, the first being whether animal and clinical data from a non-US licensed comparator drug can be used to demonstrate biosimilarity. The answer is yes, according to the Scientific draft guidance, although justification and adequate bridging data to a US-licensed reference product will be required in these cases.
Another answer provided is which studies a sponsor needs to perform and submit as part of its 351(k) application—the route to be taken for biosimilar approval. The BPCI Act set the stage for these requirements, and the draft Scientific guidance states that companies must include "analytical studies that demonstrate that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components; animal studies (including the assessment of toxicity); and a clinical study or studies (including the assessment of immunogenicity and pharmacokinetics or pharmacodynamics) that are sufficient to demonstrate safety, purity, and potency in one or more appropriate conditions of use for which the reference product is licensed and intended to be used and for which licensure is sought for the biological product."The guidance documents provide sought-after definitions for "protein" and "chemically synthesized polypeptides." These definitions are crucial because the pathway legislation added "protein" to the definition of a biological product for the first time and industry has been wondering how FDA would consider these products. Also noted are pediatric assessments, which the draft guidance states are required for a biosimilar product that is not deemed "interchangeable." Pediatric study plans should therefore be part of IND applications.
Overall, FDA is focusing on a step-wise approach for biosimilars manufacturers and a "totality-of-the-evidence" approach for regulatory assessment. Essentially, the manufacturer needs to look at each step of biosimilarity demonstration, starting with extensive structural and functional characterization of both the proposed product and the reference product. For FDA's part, the agency will be reviewing the "totality of data and information submitted in the application...."
Looking ahead, Sherman noted during the press briefing that FDA still plans to address naming and tracking standards for biosimilars as well as additional exclusivity issues, which are addressed briefly in the Q&A draft guidance. Also on the docket for the future: standards for "interchangeability." Public comments on the draft guidance will be used to shape the final guidance—hopefully sooner rather than later. The European Union has been ahead of the US in the biosimilar game for years, with some 14 approved products under its regional belt. It will be interesting to watch how the global market reacts to FDA's long-anticipated movement forward in this area.
Angie Drakulich is the editorial director of BioPharm International.