The U.S. Food and Drug Administration (FDA) recently released the fourth in a series of draft guidance documents on the approval pathway for biologicals that are biosimilar to or interchangeable with a reference biological product.  This latest guidance focuses on the mechanics of requesting, preparing for, scheduling, conducting and documenting a formal meeting with the FDA in connection with a sponsor’s biosimilar development program.  Because of the importance of obtaining application-related guidance from the FDA in this new program, and in the absence of regulations, companies involved in the development of biosimilars should take note of the conditions and process set forth by the FDA for these meetings.

The U.S. Food and Drug Administration (FDA) recently released draft guidance entitled “Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants.” The draft guidance is the latest in a series of draft guidance documents in which the agency describes how it intends to implement the biosimilar approval pathway created by the Biologics Price Competition and Innovation Act of 2009 (BPCI Act).  A biological product is “biosimilar” to an FDA-licensed biological (i.e., the reference product) if it is highly similar to the reference product notwithstanding minor differences in clinically inactive components, and there are no clinically meaningful differences between the products in terms of safety, purity and potency.  See BPCI Act § 7002(b)(3).  This particular document, issued in connection with the Biosimilar User Fee Act of 2012 (enacted as part of the Food and Drug Administration Safety and Innovation Act (FDASIA), Pub. L. No. 112-144, § 401 et seq.), focuses on the procedural requirements for formal meetings with the FDA regarding the development of biosimilars.  Because of the importance of obtaining application-related guidance from the FDA in this new program, and in the absence of regulations, companies involved in the development of biosimilars should take note of the conditions and process set forth by the FDA for these meetings.  

Highlights of the draft guidance include the following:

  • The agency will participate in five types of formal meetings with biosimilar sponsors and applicants.  The main characteristics of each type of meeting are summarized in the following table.
  • Sponsors and applicants must pay an annual, per-product fee to participate in the BPD meeting program (at least insofar as they would like to participate in a meeting other than an Initial Advisory meeting).  Sponsors and applicants must pay an annual per-product fee to participate in a Type 1, 2, 3 or 4 meeting.  There are three types of fees:
    • Initial fee—The initial fee is due on the date that a sponsor or applicant submits an investigational new drug application (IND) for an investigation that the FDA determines is intended to support an application for a biosimilar, or within five calendar days of the agency’s decision to grant a Type 1–4 meeting, whichever occurs first.  The amount of the initial fee is 10 percent of the fee rate established under the Prescription Drug User Fee Act (PDUFA) for a human drug application requiring clinical data ($195,880 in FY 2013).
    • Annual fee—Beginning in the fiscal year after which the sponsor or applicant pays the initial fee, an annual fee will be assessed until the sponsor or applicant submits a marketing application that is accepted for filing or discontinues participation in the BPD program.  The amount of the annual fee is 10 percent of the fee rate established under PDUFA for a human drug application requiring clinical data ($195,880 in FY 2013).
    • Reactivation fee—If the sponsor or applicant discontinues participation in the program but later wishes to re-engage the agency on the development of the product, the reactivation fee is due on the date that the sponsor or applicant submits an IND for an investigation that the FDA determines is intended to support an application for a biosimilar, or within five calendar days after the FDA grants the sponsor’s request for a Type 1–4 meeting, whichever occurs first.  The amount of the reactivation fee is 20 percent of the fee rate established under PDUFA for a human drug application requiring clinical data ($391,760 in FY 2013).

      Failure to pay the initial or reactivation fee within five calendar days after a meeting request is officially granted will result in cancellation of the meeting.  Similarly, if a sponsor is in arrears with regard to payment of the annual fee, the FDA will deny the sponsor’s request for a meeting and/or cancel any scheduled meetings for that product.

  • Sponsors and applicants that wish to meet with the FDA should submit a meeting request and a meeting package.  The meeting request should include adequate information for the FDA to assess the potential utility of the meeting and to identify FDA staff necessary to discuss proposed agenda items, while the meeting package should provide information relevant to the discussion topics and enable the agency to prepare adequately for the meeting.  As illustrated in the following table, the requirements for these documents are very similar. Click here to view table.

If a meeting package is not submitted with the meeting request, the meeting request will be considered incomplete and the FDA will generally deny the meeting request.

If a meeting request is granted, the agency will notify the sponsor or applicant in writing of the decision and schedule the meeting by determining the meeting type, date, length, time, place and format (e.g., face-to-face, teleconference).  Note: The agency may determine that a different meeting type is more appropriate than the type requested and grant a meeting of a different type.  If a meeting request is denied, the sponsor or applicant will be notified and the notification will include an explanation as to the reason for the denial.

In addition to the items described above, the draft guidance addresses issues related to rescheduling meetings, cancelling meetings, pre-meeting communications between the sponsor or applicant and the agency, procedures for the conduct of meetings, documentation of meetings (i.e., minutes) and resolution of disputes regarding minutes.

Interested parties should submit comments on the draft guidance by May 31, 2013.

Implications

In releasing this draft guidance, the FDA has taken another step toward providing sponsors and applicants with a comprehensive overview of its vision for the implementation of the biosimilar approval pathway.  It is apparent from earlier guidance issued by the agency that these meetings will be critical to the review and approval process for biosimilars—more so than is typical in the review process for small molecule drugs.  As such, potential sponsors and applicants should participate in these meetings in a stepwise manner, and should use such meetings as avenues for substantive discussions and to define the pathway to securing approval.  Potential sponsors and applicants now have written guidance regarding the information the agency indicates it needs to provide meaningful feedback on a biosimilar development program.

However, it remains clear that the agency continues to have serious concerns about the viability of the biosimilar pathway.  Consistent with its position in last year’s draft guidance, the agency suggests in this latest guidance that, for at least some reference biologicals, it may not be possible for an applicant to establish biosimilarity or interchangeability. 

Finally, although this is the fourth draft guidance that the agency has released with respect to the biosimilar approval pathway, a number of important issues remain unaddressed, including whether biosimilar products will have the same non-proprietary name as reference biologics.  Meetings between the agency and applicants will form an essential part of an iterative process which will help define the pathway.  Reference manufacturers and biosimilar sponsors and applicants alike should also continue to monitor communications from the FDA for further guidance on this and other issues.