FDA Issues Final Formal Meetings Guidance; Includes Important Clarifications and Explanations

By David B. Clissold –  

FDA’s meeting guidance “Guidance for Industry: Formal Meetings With Sponsors and Applicants for PDUFA Products” was issued in final form in February 2000.  On May 19, 2009, FDA released Revision 1 to that guidance, now entitled “Guidance for Industry: Formal Meetings Between the FDA and Sponsors or Applicants” (“Revision” or “Guidance”).  The Revision retains the 3 classifications of meetings (Types A, B, and C) and the same scheduling goals (within 30, 60, and 75 days of FDA receipt of a meeting request, respectively).  However, the new Guidance provides some important clarifications and explanations of FDA’s policies and expectations.  For example, as in the 2000 meeting guidance, FDA explained that Type A meetings are designed “to help an otherwise stalled product development program proceed” and FDA provided the same three examples of such meetings (dispute resolution, clinical hold, and special protocol assessment).  Guidance at 2.  However, the Revision clarifies that Type A meetings to discuss a clinical hold are appropriate only after the applicant has submitted a complete response to the hold “but the FDA and the sponsor or applicant agree that the development is stalled and a new path forward should be discussed.”  Id.  In addition, if an applicant is considering submitting a request for a Type A meeting, FDA now advises contacting the review division “to discuss the appropriateness of the request” (Id. at 3) and a Type A meeting request must now include the rationale for the request (Id. at 4).

Meeting requests are generally to be submitted to the sponsor’s application (IND, NDA, or BLA) through the controlled document system.  If there is no application, then meeting requests may be mailed, faxed, or emailed but if faxed or emailed, should only be sent “during official business hours (8:00 a.m. to 4:30 p.m. EST/EDT) Monday through Friday (except Federal government holidays).”  Id. at 4.  For fax and email submissions, FDA urges the submitter to contact the appropriate review division first and arrange for confirmation of receipt of the request since “[p]rocessing and receipt may be delayed for requests where confirmation of receipt has not been pre-arranged.”  Id.  Questions in meeting requests should include “a brief explanation of the context and purpose” of each question.  Id.  The “affiliations” of the individuals attending with the sponsor or applicant should be included in the request.  The applicant or sponsor should now request the format of the meeting (face to face, teleconference, or videoconference).  FDA recognizes that the projected attendees can change and so advises companies to update the list when submitting the information package, and again shortly before the meeting.  Id. at 5.

The most extensive changes to the Revision explain the reasons that FDA may reschedule or cancel a meeting.  A decision to reschedule or cancel a meeting is at the discretion of the review division.  A rescheduled meeting should be arranged “as soon as possible after the original date” and no new meeting request should be submitted.  Id. at 6.  On the other hand, a cancelled meeting needs a new meeting request that is subject to the same time frames as a new request.  Rescheduling may occur if the sponsor or applicant experiences a minor delay in submitting the meeting package, the review team determines that the meeting package is inadequate but that the additional information can be submitted, the information submitted is too “voluminous,” essential attendees are unavailable due to an emergency, the sponsor or applicant submits additional questions or data after the meeting package is submitted, or because FDA attendees not originally anticipated or requested by the sponsor but deemed to be “critical” are not available.  Id. at 6-7.  FDA warns that it may cancel a meeting if the meeting package is late or “grossly inadequate.”  Id. at 6.  In addition, a sponsor or applicant may determine that FDA’s “premeeting responses to its questions are sufficient” and request that a meeting be cancelled.  Id. at 7.  In our experience, this is far and away the most common reason that meetings are cancelled.  FDA’s preliminary responses have proven to be an important communication that at the very least helps to focus the meeting, resulting in a more efficient use of both parties’ time and resources. Although it took some time for all of the review divisions to adopt the practice of sending premeeting responses to a sponsor’s questions, the practice is now practically universal and FDA is to be commended for this effort.  However, the Revision states only that FDA “may” communicate premeeting responses to the sponsor (Id. at 9), and contains a somewhat disturbing qualification to this practice.  If a sponsor requests that a meeting be cancelled because FDA’s premeeting responses are thought to be clear,

[t]he division will consider whether it agrees that the meeting should be cancelled.  Some meetings, particularly milestone meetings, can be valuable because of the broad discussion they generate and the opportunity for the division to ask about relevant matters (e.g., dose-finding, breadth of subject exposure, particular safety concerns), even if the premeeting communications seem sufficient to answer the sponsor’s or applicant’s questions.  If the division agrees that the meeting can be cancelled, the division will document the reason for cancellation and the premeeting communication will represent the final responses and the official record.

Id. at 7. One way to read this qualification is that while the sponsor’s questions must be “precise” and asked far in advance of any meeting, FDA can apparently reserve its blockbuster questions for the meeting itself.  If FDA doesn’t ask the questions before the meeting, the sponsor may not have the appropriate time or personnel available to respond to FDA during the meeting, thus generating another meeting request that is subject to another delay.  We understand that “broad discussion” during a meeting may generate additional questions for both parties, but if FDA has questions about “relevant matters,” it is not clear why such questions can not be asked in advance of the meeting.  Ideally, such questions would be communicated ad hoc throughout the development cycle (e.g., when “particular safety concerns” are first observed).  But even if FDA asked their questions in the context of FDA’s premeeting responses to the sponsor’s questions, that would be far better than if FDA held them until the meeting itself.  Our observation is that such issues usually are raised by FDA no later than the premeeting responses.  Moving away from such a practice would be disastrous for sponsors.

In assembling the meeting package, FDA advises sponsors to consult FDA and ICH guidances, and to consider them in planning and developing the meeting package:

If a product development plan deviates from current guidances, or from current practices, the deviation should be recognized and explained.  Known difficult design and evidence issues should be raised for discussion (e.g., use of a surrogate endpoint, reliance on a single study use of a noninferiority design, adaptive designs).

Id. at 8.  FDA discourages presentations by sponsors or applicants noting that they “generally are not needed because the information necessary for review and discussion should be part of the meeting package.”  Id. at 9.  If a sponsor or applicant nevertheless wants to make a presentation, it should be discussed ahead of time with FDA “to determine if a presentation is warranted."  Id.

The Revision draws on FDA’s experience in conducting meetings over the last several years.  FDA’s expectations are more clearly described and the consequences for not meeting those expectations are highlighted.  FDA’s minutes of a meeting are the “official record” of decisions following what may have been a series of conversations and negotiations with the agency.  Thus, companies need to be familiar with the policies and procedures that lead to the creation of those minutes.