The Food and Drug Administration (FDA) has announced that a meeting will be held on November 2 and 3, 2010 in Washington, D.C. to obtain input on specific issues and challenges associated with the implementation of the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). The BPCI Act established an approval pathway for biological products that are demonstrated to be “highly similar” (biosimilar) to, or “interchangeable” with, an FDA-licensed biological product. In addition to hearing about general issues related to this new framework, the FDA is also seeking comments on the issues of biosimilarity, interchangeability, exclusivity, definition of a biological product, the use of comparative data, pharmacovigliance, guidance, and user fees.

A summary of the key issues on which the FDA is seeking input on are described below. After receiving input, the FDA will promulgate rules to implement the provisions of the BPCI Act. Therefore, companies that will be affected by the BPCI Act should strongly consider submitting comments adn attending the meeting to protect their interests. Pepper Hamilton LLP can assist companies to better understand how these issues will impact the BLA holders and biosimilar applicants and help prepare comments and proposals for submission to the FDA.

Biosimilarity

The FDA is seeking comments on the following issues related to determining biosimilarity:

  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?

Interchangeability

The FDA is seeking comments on the following issues related to determining interchangeability of a biosimilar product with a BLA reference product:

  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?

Definition of a Biological Product

The definition of the term “biological product” was modified by the BPCI Act. In view of the changes, the FDA announced that the agency may establish a regulatory definition of “protein” and “any chemically synthesized polypeptide” to clarify the authority under which such products will be licensed and regulated to avoid the conflicting regulation of certain products under different authorities. Therefore, the FDA is seeking comments on the following questions:

  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”?

Exclusivity

The BPCI Act provides a 12-year period of marketing exclusivity fro an approved BLA product, which may be extended to 12 years and six months (via pediatric exclusivity), from the date of first licensure of the reference biological product. During this 12-year or 12 years adn six months of exclusivity, a biosimilar product cannot be appoved by the FDA. Currently, according to the FDA, the date of first licensure does not apply to a license for or approval of:

  • a supplement for the biological product that is the reference product
  • a subsequent application filed by the same sponsor or manufacturer of the biological product that is the reference product (or a related entity) for a change (not including a modification to the structure of the biological product) that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device, or strength, or
  • a subsequent application filed by the same sponsor or manufacturer of the biological product that is the reference product (or a related entity) for a modification to the structure of the biological product that does not result in a change in safety, purity, or potency.

Accordingly, the FDA is seeking input on the following questions relating to exclusivity:

  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?

In addition to the issues above, the FDA is also seeking input on the use of comparative data that uses a non-U.S. approved biologic drug, developing a framework for optimal pharmacovigilance, the structure of the user fees, and whether or not the FDA should publish guidance documents for applicants.

Pepper Hamilton LLP can help companies identify and discuss the issues and can assist companies in the preparation of comments to be submitted to the FDA for their consideration. Comments on any of these issues can be submitted electronically through http://www.regulations.gov/ or in writing to the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Room 1061, Rockville, MD 20852.

The meeting can be attended in person, and individuals who wish to present at the public hearing must register on or before October 11, 2010. The meeting be held between 8:30 a.m. and 4:30 p.m. on each day. The public hearing will be held at the FDA’s White Oak Campus, at 10903 New Hampshire Ave., Building 31, Room 1503, Silver Spring, MD 20993. The meeting can also be viewed via webcast.

More information about the meeting can be found at http://www.pepperlaw.com/pdfs/Docket No.FDA-2010-N-0477]_biosimilars.pdf.