FDA Planning to Hold Public Hearings on Biosimilar Approval Pathway

By Donald Zuhn --

Last week, the congressional daily The Hill reported on a draft notice from the Food and Drug Administration (FDA) that was being circulated among healthcare lobbyists on Capitol Hill.  The notice, which the agency has yet to publish in the Federal Register, concerns public hearings and a request for comments on the approval pathway for biosimilar biological products that was created last March when President Obama signed the Patient Protection and Affordable Care Act (PPACA) into law.

According to the draft notice, the FDA is planning to hold public hearings on Tuesday, November 2 and Wednesday, November 3 from 8:30 am to 4:30 pm at the White Oak Campus in Silver Spring, MD to obtain input from interested stakeholders on specific issues and challenges associated with the agency's implementation of the Biologics Price Competition and Innovation Act of 2009 (BPCIA), the portion of the PPACA that creates an abbreviated approval pathway for biosimilar and interchangeable biological products.  In the draft notice, the FDA indicates that it will take the information obtained from the public hearings into account when developing guidances and rulemaking for implementing the BPCIA.

Among the issues on which the FDA will be seeking comments are:

• Scientific and technical factors related to a determination of biosimilarity or interchangeability;
• The type of information that may be used to support a determination of biosimilarity or interchangeability;
• Development of a framework for optimal pharmacovigilance for biosimilar and interchangeable biological products;
• Scope of the revised definition of a "biological product";
• Priorities for guidance development;
• Scientific and technical factors related to reference product exclusivity;
• Scientific and technical factors that may inform the agency’s interpretation of "product class" as it relates to available regulatory pathways for certain protein products during the 10-year transition period following enactment of the BPCIA; and
• The establishment of a user fee program for biosimilar and interchangeable biological products.

With respect to the issue of biosimilarity, the draft notice provides four questions for which the FDA will be seeking comment:

1.  What scientific and technical factors should the agency consider in determining whether the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components?

2.  What scientific and technical factors should the agency consider in determining the appropriate analytical, animal, and clinical study or studies to assess the nature and impact of actual or potential structural differences between the proposed biosimilar product and the reference product?

3.  What range of structural differences between a proposed biosimilar product and the reference product is consistent with the standard "highly similar" and may be acceptable in a 351(k) application if the applicant can demonstrate the absence of any clinically meaningful differences between the proposed biosimilar product and the reference product?

4.  Under what circumstances should the agency consider finding that animal studies or a clinical study or studies are "unnecessary" for submission of a 351(k) application?

On the issue of interchangeability, the draft notice provides two questions for which the FDA will be seeking comment:

1.  What factors should the agency consider in determining whether a proposed interchangeable biological product can be "expected to produce the same clinical result as the reference product in any given patient?"

2.  What factors should the agency consider in evaluating the potential risk related to alternating or switching between use of the proposed interchangeable biological product and the reference product or among interchangeable biological products?

With respect to the definition of a biological product, the draft notice provides two questions for which the FDA will be seeking comment:

1.  What scientific and technical factors should FDA consider in developing a regulatory definition for the category of "protein" (as distinguished from peptide or polypeptide)?

2.  What scientific and technical factors should FDA consider in developing a regulatory definition for the category of "any chemically synthesized polypeptide"?

While the draft notice acknowledges that the issuance or nonissuance of FDA guidance on the approval pathway does not preclude submission, agency review, or agency action on 351(k) applications, the FDA will be seeking input regarding priorities for issuing guidance documents.  Among the specific questions posed in the draft notice are:

1.  What types of guidance documents for industry should be a priority for the agency during the early period of implementation?

2.  What scientific and technical factors should the agency consider in determining if the existing science and experience are sufficient to allow approval for a product or product class under section 351(k) of the Public Health Service Act (PHSA; which was amended by the BPCIA)?

On the issue of exclusivity, the draft notice provides two questions for which the FDA will be seeking comment:

1.  In light of the potential transfer of BLAs from one corporate entity to another and the complexities of corporate and business relationships, what factors should the agency consider in determining the types of related entities that may be ineligible for a period of 12-year exclusivity for a subsequent BLA?

2.  What factors should the agency consider in determining whether a modification to the structure of the licensed reference biological product results in a change in safety, purity, or potency, such that a subsequent BLA may be eligible for a second 12-year period of marketing exclusivity?

The draft notice also presents questions for comment regarding the issues of patient safety and pharmacovigilance, the use of supportive data and information, transition provisions, and user fees.

A live webcast of the hearings will be made available at http://www.fda.gov/Drugs/NewsEvents/ucm221688.htm.  Patent Docs will provide additional information regarding the hearings and request for comments, including details regarding registration and submission of comments, when the notice has been published in the Federal Register.

Comments

[EG]

Don,

Thanks for summarizing the FDA notice on the biosimilars approval pathway. Developing this pathway will be a handful to deal with.