FDA Releases Draft Guidance on Determining Exclusivity Periods for Biological Products

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By Bronwyn Mixter  

Aug. 4 — The Food and Drug Administration Aug. 4 released a draft guidance to assist sponsors and other interested parties in providing information that will help the agency determine the exclusivity period for biologics approved under Section 351(a) of the Public Health Service Act (PHS Act).

A notice announcing the draft guidance will be published in the Aug. 5 Federal Register.

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) amended the PHS Act and other statutes to create an abbreviated approval pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA-licensed biologic reference product. Section 351(k)(7) of the PHS Act describes reference product exclusivity, during which a 351(k) sponsor isn't permitted to submit and the FDA isn't permitted to license a 351(k) application that references a reference product, the agency said.

Under this section, approval of a 351(k) application may not take effect until 12 years after the date of first licensure of the reference product, the FDA said. A 351(k) application for a biosimilar or interchangeable biological product cannot be submitted for review until four years after the date on which the reference product was first licensed.

The FDA said 351(k) applicants may provide information to the agency to assist with its analysis of the date of first licensure for a biological product.

The agency said in the draft guidance that it is reviewing options for making information publicly available regarding reference product exclusivity and dates of first licensure. The FDA said that once a method is determined, it plans to communicate this information on its website.

FDA's Recommendations

In the draft guidance, the FDA recommended that sponsors provide the following information to help with evaluating the date of first licensure:

  •  A list of all licensed biological products that are structurally related to the biological product that is the subject of the application being considered. This list should include products that share some of the same principal molecular structural features of the product being considered, but generally can be limited to products that affect the same molecular target. Where specific molecular targets haven't been defined, this list should include products that share the narrowest target that can be characterized. This may be a pathway, cell type, tissue or organ system. If this assessment results in the conclusion that no product that has the same molecular target or shares some of the same principal molecular structural features has been licensed, a sponsor should provide an adequate justification to support the assertion that there are no previously licensed products relevant for purposes of determining the date of first licensure.
  •  Of those licensed biological products identified above, a list of those for which the sponsor or one of its affiliates, including any licensors, predecessors in interest or related entities, are the current or previous license holder (this is known as item 2).
  •  A description of the structural differences between the proposed product and any products identified in item 2 above. For protein products, this should include changes in amino acid sequence, differences due to post-translational events, infidelity of translation or transcription, differences in glycosylation patterns or tertiary structure and differences in biological activities.
  •  Evidence of the change in safety, purity and/or potency between the proposed product and any products identified in item 2 above. This should include a description of how the structural differences identified in item 3 above relate to changes in safety, purity and/or potency.
  • The agency said that any other information and data that would assist in making a determination regarding the date of first licensure also should be included.  

    The FDA said it estimates that it will receive a total of approximately 10 requests annually for determining the date of first licensure. The agency also said the average burden per response will be 150 hours, for a total estimated reporting burden of 1,500 hours.

    The agency asked that comments on the draft guidance, identified by Docket No. FDA-2013-D-1165, be submitted by Oct. 6.

    A spokeswoman for the Biotechnology Industry Organization (BIO) told Bloomberg BNA Aug. 4 that BIO is reviewing the draft guidance.

    To contact the reporter on this story: Bronwyn Mixter in Washington at bmixter@bna.com

    To contact the editor responsible for this story: Lee Barnes at lbarnes@bna.com

    The draft guidance is at http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM407844.pdf and the Federal Register notice is at http://op.bna.com/hl.nsf/r?Open=bdmr-9mnlbs.