3 Key Concepts In the Development and Approval of Biosimilars

Pictured: A 3D rendering of Factor VII, one of the proteins that causes blood to clot in the coagulation cascade.

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) creates an abbreviated licensure pathway for biological products shown to be biosimilar to or interchangeable with an FDA-licensed reference product.  This allows for a shorter and less costly drug development program.  Because of this benefit, many companies have used this method to bring drugs to market.  In fact, as of December 1, 2017, 60 programs were enrolled in the FDA’s Biosimilar Product Development (BPD) Program.   

In order to qualify as a biosimilar, the product must demonstrate the following:

  • Is biosimilar to an FDA approved reference product
  • Utilizes the same mechanism(s) of action for the proposed condition(s) of use -- but only to the extent the mechanism(s) are known for the reference product
  • Condition(s) of use proposed in labeling have been previously approved for the reference product
  • Has the same route of administration, dosage form, and strength as the reference product
  • Is manufactured, processed, packed, or held in a facility that meets standards designed to assure that the biological product continues to be safe, pure, and potent.

FDA step-wise biologic develpement plan.pngBelow, we have outlined 3 key concepts to help you develop a stepwise evidence development plan to demonstrate that your biosimiliar is highly similar to the reference product and there are no clinically meaningful differences between the two in terms of safety, purity, and potency.  This stepwise approach will help you generate analytical and clinical data that will be needed when applying for FDA approval. 


Key Concept #1:  Generating Analytical Similarity Data

  • Obtain extensive structural and functional characterization of biosimilar compared to reference produce.
  • Develop a manufacturing process for the proposed biosimilar with minimal or no difference in product quality characteristics compared to the reference product.
  • Identify and evaluate the potential impact of differences observed and what study(ies) will address the residual uncertainty.

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Key Concept #2:  The Role of Clinical Studies

  • The nature and scope of clinical studies will depend on the extent of residual uncertainty about the biosimilarity of the two products after conducting structural and functional characterization and, where relevant, animal studies.
  • FDA expects clinical PK, and PD if relevant, comparison between the proposed biosimilar product and the reference product.
  • There should include atleast 1 clinical study that includes a comparison of the immunogenicity of the proposed and reference product generally will be expected.
  • A comparative clinical study should be designed to investigate whether there are clinically meaningful differences in safety and efficacy between the biosimilar and the reference product.


Key Concept #3:  Data Extrapolation

  • The potential exists for a biosimilar product to be approved for one or more conditions of use for which the reference product is licensed based on extrapolation
  • Sufficient scientific justification for to qualify as a biosimilar includes:
  1. MoA in each condition of use
  2. PK and biodistribution in different patient populations
  3. Immunogenicity in different patient populations
  4. Differences in expected toxicities in each condition of use and patient population

For additional information, a list of the FDA’s biosimiliar guidance’s can be found here.

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