Almost two years to the date after President Obama signed the Affordable Care Act, introducing a regulatory pathway for biosimilar
approval in the United States, FDA has released draft guidance for industry about how to get such a product into the marketplace.
Industry has been at a pivotal standstill since the Biologics Price Competition and Innovation Act (BPCI Act) was passed in
2010,but biologics developers and manufacturers seem ready to pounce. According to a press briefing given by FDA's Rachel
Sherman in early February, there have been 35 pre-investigational new drug (IND) meeting requests for proposed biosimilars
to 11 reference products, 21 pre-IND sponsor meetings held, and 9 INDs received. Sherman is the associate director for Medical
Policy within FDA's Center for Drug Evaluation and Research. With the doors to FDA's biosimilar review desk widened, those
numbers are likely to skyrocket.
The draft guidance—three documents to be exact—includes Scientific Considerations in Demonstrating Biosimilarity to a Reference Product; Quality Considerations in Demonstrating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according to the Scientific draft guidance, although justification and adequate bridging data to a US-licensed reference product will be required in
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
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.