Approaching Clarity on Biosimilarity

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  • 02/10/2012

FDA issued three draft guidance documents on biosimilar product development. These documents provide FDA’s current thinking on approaches to demonstrate that a proposed biological product is biosimilar to an FDA-approved biological product (the “reference product”) using the abbreviated pathway under section 351(k) of the Public Health Service Act (PHS Act).

The draft guidance documents are:

Scientific Considerations in Demonstrating Biosimilarity to a Reference Product

Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product

Biosimilars:  Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009

FDA is accepting public comment on these draft guidance documents. Instructions on how to submit comments will be announced in an upcoming Federal Register notice.

Some higlights:

FDA intends to use a risk-based totality-of-the-evidence approach to evaluate all available data and information submitted in support of the 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 will be able to provide meaningful advice on the scope and extent of necessary animal and human testing after a thorough review of data from structural and functional analyses.  Additional animal and clinical studies should be tailored to address residual uncertainty regarding the biosimilarity between the two products to ensure such testing is appropriately targeted.

This draft guidance provides an overview of analytical factors that may be relevant to assessing whether a proposed therapeutic protein product and a reference product are highly similar, as required for a determination of biosimilarity under the BPCI Act.

The guidances discuss general scientific principles, including the importance of extensive analytical, physicochemical and biological characterization.

The type, nature, and extent of any differences between the proposed biosimilar product and the reference product, and the potential effect of any differences on the safety, purity, and potency of the proposed product should be clearly described and discussed by the sponsor in the 351(k) application. 

The agency recognizes that 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 to support a demonstration of biosimilarity.

And a solid definition of what it means for a biological product to be “interchangeable”?

The agency defines  “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.  

No surprises.  But it's good to see it on paper.  So let it be written, so let it be done.


Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

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