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U.S. Department of Health and Human Services

Drugs

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Questions and Answers: Issuance of Three Draft Guidance Documents on Biosimilar Product Development

What action is FDA announcing?

FDA is announcing the issuance of three draft guidance documents on biosimilar product development.  These documents provide FDA’s current thinking on approaches to demonstrating that a proposed biological product is biosimilar to an FDA-licensed biological product (the “reference product”) for the purposes of obtaining licensure by submitting a marketing application through the abbreviated licensure pathway under section 351(k) of the Public Health Service Act (PHS Act).  The abbreviated licensure pathway was established by the Biologics Price Competition and Innovation Act of 2009 (BPCI Act).

The draft guidance documents are:

What is the BPCI Act?

The Patient Protection and Affordable Care Act signed into law by President Obama on March 23, 2010, amended PHS Act to create an abbreviated approval pathway for biological products that are demonstrated to be highly similar (biosimilar) to or interchangeable with an FDA-licensed biological product. This provision is called the Biologics Price Competition and Innovation Act of 2009, or BPCI Act.

The BPCI Act establishes an abbreviated licensure pathway for biological products that are demonstrated to be biosimilar to, or interchangeable with, an FDA-licensed biological product.

What is the purpose of the BPCI Act?

The BPCI Act establishes an abbreviated licensure pathway for biological products under the PHS Act. A marketing application for a biological product that is demonstrated to be “biosimilar” to an FDA-licensed biological product (the “reference product”)  may rely on certain existing scientific knowledge about the safety, purity, and potency of the reference product. The BPCI Act encourages competition leading to increased access to biological products for patients. 

What is a biological product?

Biological products are therapies used to treat diseases and health conditions. They include a wide variety of products including vaccines, blood and blood components, gene therapies, tissues, and proteins. Unlike most prescription drugs made through chemical processes, biological products generally are made from human and/or animal materials. 

What is a biosimilar?

A biological product may be demonstrated to be “biosimilar” to an already-licensed FDA biological product (the “reference product”) if data show that the product is highly similar to the reference product notwithstanding minor differences in clinically inactive components and there are no clinically meaningful differences between the biological product and the reference product in terms of safety, purity and potency of the product.

What does it mean for a biological product to be “interchangeable”?

An “interchangeable” biological product is biosimilar to the reference product, and can be expected to produce the same clinical result as the reference product in any given patient.  In addition, for a biological product that is administered more than once to an individual (as many biological products are), the risk in terms of safety or diminished efficacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product without such alternation or switch.   

Why were these draft guidance documents the first documents issued by FDA?

Through the November 2-3, 2010 public hearing regarding implementation of the BPCI Act, FDA received public comments on the types of guidance documents for industry that should be a priority for FDA during the early period of implementation.  Many comments suggested FDA begin with general, overarching guidance documents describing the general principles for biosimilar product development.  The development and issuance of these guidance documents is consistent with that suggested approach.

What are some of the key scientific considerations related to biosimilar product development expressed in these draft guidance documents?

Key scientific considerations expressed in these draft guidance documents include the following approaches.

  • FDA intends to use a risk-based totality-of-the-evidence approach to evaluate all available data and information submitted in support of a determination of biosimilarity of the proposed product.  The type and amount of analyses and testing that will be sufficient to demonstrate biosimilarity will be determined on a product-specific basis.
  • FDA recommends sponsors use a stepwise approach in developing evidence to support a demonstration of biosimilarity, ensuring that development at each step evaluate the extent to which there is residual uncertainty regarding a demonstration of biosimilarity between the proposed and reference product, and identify next steps to address that uncertainty.
  • Advances in analytical sciences and manufacturing technology, including integration of Quality by Design approaches, may facilitate a “fingerprint”-like analysis of therapeutic protein products, and thus may provide appropriate bases for a more selective and targeted approach to subsequent animal and/or clinical studies for the demonstration of biosimilarity.
  • FDA will best be able to provide meaningful input on the extent and scope of animal and clinical studies needed for a biosimilar development program once FDA has considered the comparative data from structural and functional analyses.

Are these draft guidance documents consistent with requirements for biosimilar product development approved in other countries?

Any proposed biosimilar product that seeks to be marketed in the United States needs to meet the requirements set forth in the BPCI Act, and these draft guidance documents reflect FDA’s current thinking about how to meet such requirements for licensure.

How does one comment on the draft guidance documents?

Each draft guidance document is assigned a separate docket for written comments from stakeholders and interested persons. The Federal Register notices containing the appropriate docket number, as well as directions for submitting comments to each docket, will be published shortly.

Whom do sponsors contact with questions regarding their biosimilar development program?

If the reference product for a proposed biosimilar product is regulated by the Center for Drug Evaluation and Research (CDER), contact the Biosimilars Program Staff in CDER’s Office of New Drugs at 301-796-0700.

If the reference product for a proposed biosimilar product is regulated by the Center for Biologics Evaluation and Research (CBER), contact the Office of Communication, Outreach and Development (OCOD) at 800-835-4709 or 301-827-1800 or by email to ocod@fda.hhs.gov