The FDA Releases New Draft Guidance for Demonstrating Biosimilarity

On May 13, the Food and Drug Administration released a new draft guidance on the data needed to establish that a proposed therapeutic biological product is biosimilar to an approved reference product. This new guidance gives sponsors a roadmap, detailing the procedures needed to demonstrate biosimilarity between a proposed drug candidate and a reference product, and highlighting the types of data needed to support such a demonstration.

The Biosimilars Act, formally known as the Biologics Price Competition and Innovation Act, established an abbreviated approval pathway for biological products demonstrated to be interchangeable with or “biosimilar” to FDA-approved reference products. “Biosimilarity,” according to § 351 of the Public Health Service Act, indicates that a biological product is “highly similar to the reference product notwithstanding minor differences in clinically inactive components and that there are ‘no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.’” Therefore, a sponsor seeking FDA approval via this abbreviated approval pathway must be able to demonstrate biosimilarity of its proposed drug candidate and an approved reference product, using data derived from analytical studies, animal studies, and clinical studies, including the assessment of immunogenicity, pharmacokinetics, and pharmacodynamics.

The new guidance highlights three areas of critical consideration that the FDA will evaluate in its assessment of biosimilar products:

  • Exposure and response assessment – The FDA asserts that this information “is important for the determination of safety, purity, and potency of any biological product, as well as for the determination of any potentially clinically meaningful difference between two products.” For this assessment, “exposure” refers to PK variables, e.g., drug dose, drug concentrations, etc., and “response” refers to PD information, e.g., pharmacological or toxicological effects.
  • Evaluation of residual uncertainty – The FDA will use a risk-based approach, considering the totality of data submitted. The data is to be collected in a stepwise manner with the need for additional studies determined by the degree of residual uncertainty remaining at each step.
  • Assumptions about analytical quality and similarity – The FDA expects sponsors to use “extensive and robust comparative structural and functional studies” to demonstrate biosimilarity. State-of-the-art analytical assays should be employed, and sponsors will be expected to “describe the capabilities and limitations of the methods used” in their studies.

Depending on the results of the comparative analytical characterizations, the FDA will grade the biosimilar candidates into one of four categories:

  • Not similar – Products under this category are not recommended for approval under the Biosimilars Act.
  • Similar – Products under this category need further information to determine if they are highly similar to the reference product, and additional data and study information will be necessary.
  • Highly similar – Products under this category meet the statutory standards for analytical similarity, and there is a high degree of confidence in the analytical similarity of the proposed product and the reference product. Further targeted and selective animal or clinical studies to resolve any residual uncertainty and to support a demonstration of biosimilarity would be appropriate.
  • Highly similar with fingerprint-like similarity – Products under this category meet the statutory standards for analytical similarity based on multiple, fingerprint-like analyses, and there is a very high level of confidence in the analytical similarity of the proposed product and the reference product. Further targeted and selective animal or clinical studies to resolve any residual uncertainty and to support a demonstration of biosimilarity would be appropriate.

This new draft guidance will enable sponsors to make a rough prediction on how much time and resources it may take to get approval for a biosimilar therapeutic product. In addition, it brings the pharmaceutical industry one step closer to the first approval under the Biosimilars Act.

Comments and suggestions regarding the draft guidance should be submitted to the FDA by August 12, 2014.

Samuel H. Megerditchian is Counsel in the Gibbons Intellectual Property Department.
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