The Food and Drug Administration published several enhanced policies and procedures for the management of its advisory committees, which include numerous improvements, such as stricter limits on financial conflicts of interest for committee members, revised voting procedures, and refinements to the processes for disclosing information pertaining to advisory committee members and the general public. These policies and procedures are contained in four final guidance documents and one guidance document that was reissued in draft form. Most of the changes in the final guidance documents are effective immediately, and all of the changes are expected to be fully implemented within 120 days.
The draft guidance, Guidance for the Public and FDA Staff on Convening Advisory Committee Meetings, proposes new criteria to clarify when the FDA should refer a matter to an advisory committee. By law there are circumstances when the FDA must refer a matter to an advisory committee. However, in most instances, the FDA has the discretion to determine if a matter should be reviewed by an advisory committee, and the FDA would use the following factors to make this determination:
- Is the matter at issue of such significant public interest that it would be highly beneficial to obtain the advice of an advisory committee as part of the agency’s regulatory decision-making process?
- Is the matter at issue so controversial that it would be highly beneficial to obtain the advice of an advisory committee as part of the agency’s regulatory decision-making process?
- Is there a special type of expertise that an advisory committee could provide that is needed for the agency to fully consider a matter?
Comments to this draft guidance must be submitted by Oct. 6, 2008, to be considered by the agency during this review cycle.
Guidance for Industry Advisory Committee Meetings – Preparation and Public Availability of Information Given to Advisory Committee Members, which was released in August 2008 with an effective date of Aug. 5, 2008, addresses the public availability of briefing materials and the background information provided to advisory committee members in advance of a meeting. In April 2007, AABB commented on the draft guidance stating that releasing documents 48 hours prior to the scheduled meeting does not provide enough time to adequately review, analyze and convene experts to discuss an appropriate position. AABB strongly encouraged the FDA to give a minimum of four weeks advance notification of meetings and agenda topics. However, the final guidance did not change, and FDA intends to post a publicly available version of the briefing materials on its Web site no later than two full business days before the scheduled advisory committee meeting.
This guidance document also provides details on preparing and submitting documents to FDA for inclusion in the briefing materials and recommends a timetable that sponsors should follow when submitting such documents. The timetable starts 55 business days from the date of the meeting, with a notification that will be sent to the affected sponsors stating the intent to discuss an issue that is directly related to them. The guidance explains how the documents will be reviewed to determine what can be released to the advisory committee and public. The review process has been established to protect proprietary information while at the same time providing adequate information to committee members for discussion and decision making.
Since the decisions of an advisory committee can influence FDA’s actions, it is critical that committee members do not have a significant conflict of interest regarding the information that will be discussed. The process for determining advisory committee participation is outlined in two of the guidance documents — Guidance for the Public, FDA Advisory Committee Members, and FDA Staff: Public Availability of Advisory Committee Members' Financial Interest Information and Waivers, which was effective on Aug. 5, 2008, and Guidance for the Public, FDA Advisory Committee Members, and FDA Staff on Procedures for Determining Conflict of Interest and Eligibility for Participation in FDA Advisory Committees, which will be effective on Dec. 3, 2008.
These guidance documents address FDA's processes for evaluating and disclosing information about potential conflicts of interest and waivers. Prior to each meeting, advisory committee members are screened by FDA staff to determine whether they have a potential financial conflict of interest, such as grants, stock holdings and contracts with a company that would be affected by the committee’s recommendations. FDA has adopted stricter criteria for the granting of a waiver in an effort to achieve the goal set forth in the Food and Drug Administration Amendments Act of 2007 (FDAAA) of reducing the number of waivers granted by focusing on efforts to recruit advisory committee members with few potential conflicts of interest. FDA outlined the four major mechanisms for success:
- FDA has instituted a cap of $50,000 as the maximum personal financial interest (self and immediate family member) an adviser may have in all companies that may be affected by a particular meeting. If an adviser’s personal financial interest is greater than $50,000, participation in that meeting will not be permitted. If the personal financial interest is less than $50,000, a waiver may be granted but only if it is determined that there is an essential need for the adviser’s particular expertise. In addition to financial interests, each adviser is subject to a stricter conflict-of-interest standard.
- FDA does not intend to issue a waiver in circumstances where the agency has determined the conflict of interest to be significant.
- FDA will apply a more stringent test to all waivers, which must meet the “essential expertise” standard.
- FDA will limit the number of waivers granted each year in accordance with FDAAA.
- Focus efforts on recruitment of advisory committee members with fewer potential conflicts of interest.
- Cap the numbers of waivers that the agency may grant in a given year.
- Reduce the rate of waivers the agency issues each year (total number of waivers issued per total number of members attending advisory committee meeting) to meet the following goals:
- Beginning in fiscal year 2008, the reduction is targeted to be 5 percent.
- By 2012, the agency may issue waivers at a maximum rate of 75 percent of the rate issued in 2007.
Waivers, which include a description of the adviser’s personal financial interest and the rationale why the expertise was essential, will be posted on the FDA Web site at least 15 days in advance of the meeting.
The purpose of the final guidance document — Guidance for FDA Advisory Committee Members and FDA Staff: Voting Procedures for Advisory Committee Meetings, which was effective on Aug. 5, 2008 — is to avoid the perception of any manipulation of votes. To help maximize the integrity, consistency and utility of advisory committee voting results, the following recommendations on the voting process are recommended:
- Briefing materials provided to advisory committee members as background materials before an advisory committee meeting should be thorough and, to the extent possible, include the questions that will be voted upon by the committee.
- Prior to voting, the committee should engage in a robust discussion about the matter.
- The question presented for a vote should have minimal qualifiers, not be leading and should avoid the use of double or triple negatives.
- The question put to the committee for vote should not be the subject of further discussion or clarification while the vote is in progress.
- Voting should be done simultaneously. Previously, advisory committees sometimes voted sequentially, with the committee chair calling on individual members and asking them to announce their votes aloud. Simultaneous voting avoids “voting momentum” in which some voters may be influenced, even subconsciously, by the votes of those who precede them. The agency also recommends that the results of votes be announced immediately in the meeting, and FDA intends to post on its Web site a list indicating how each member voted. Any posted list will be part of the permanent record of the meeting.
- If the chair wishes to put forth a question that was not asked by the FDA, he or she should first check with the FDA officials present to be sure that the question is appropriate for the meeting.