FDA Advisory Panels
What exactly are you up against—and why?
The views and opinions in this article are those of the author and do not necessarily reflect those of the US FDA, the US Department of Health and Human Services, or the Public Health Service.
The investigational phase of your device development is finally over. You have submitted your premarket approval application (PMA) to the FDA (the Agency) and answered their questions. There is only one last hurdle to leap over before receiving approval to market—you must defend your device before an FDA advisory panel.
President Gerald Ford signed the Medical Device Amendments to the Federal Food, Drug, and Cosmetic Act (the Act) on May 28, 1976. The Act stipulates that an advisory panel will review all PMAs. These advisory panels are intended to contribute additional expertise to the review process, to allow public participation, and to provide the Agency with advice. The Agency, however, makes the final decisions regarding product approvals.
The rules have changed since the acceptance of the Act regarding the need for panel review for each PMA. According to the Safe Medical Devices Act of 1990, the Agency decides if panel review is needed based on whether the issues in question have been previously discussed by the panel.
Officially, each panel is composed of seven voting members, one nonvoting consumer representative, and one nonvoting industry representative. The panel chair is a nonvoting member, except in the event of a tie, in which the chair casts the deciding vote. Each panel also has a number of consultants brought in to provide the appropriate expertise for a particular meeting. In order to ensure a quorum of voting members, consultants may be deputized to vote.
The consultant portion of each panel is variable. For example, the Circulatory System Devices Panel has approximately 50 consultants. These individuals encompass various fields of expertise (eg, electrophysiology, radiology, surgery, pediatric surgery); such variety is a necessity given the diversity of devices reviewed by this panel. Depending on the type of item to be discussed and consultant availability, panel composition may have very little overlap from meeting to meeting.
PANEL MEMBER SELECTION
Applications for panel membership are accepted on a continuing basis. Applicants may be self-nominated, or can be nominated by a peer or professional organization. The application consists of a CV and bibliography, with a letter regarding the applicant’s willingness to serve, a description of his qualifications, and a statement regarding any potential conflicts of interest. Members should be experts in their field and have experience in medical practice, teaching, and/or relevant research. Consideration is given to balancing membership enrollment with respect to race, gender, and geographic location, as well as required expertise. Restrictions are also considered; for example, two people from one institution cannot serve on a panel together. A group at the Agency is involved in the selection of members; this team includes panel executive secretaries as well as individuals specializing in assessment of conflicts of interest.
Advisory committee members are appointed as special government employees who serve for about 4 years. They are paid a modest salary for the meetings they attend, and are reimbursed for travel and lodging expenses.
SCREENING FOR CONFLICTS OF INTEREST
The screening process for prospective panel members and consultants focuses greatly on the potential for conflicts of interest. Details regarding financial holdings, employment, research grants and contracts, patents held, and study participation help to determine whether an applicant has a conflict of interest. This general screening extends to the applicant’s institution.
When a member or consultant is being considered for participation in a particular panel meeting, more specific conflicts are considered. This screening extends to the person’s immediate family (eg, siblings, parents, spouse, and children), as well as his or her institution. Currently, this screening is extremely conservative, partially due to recent Senate hearings related to committee processes that have come out of the media focus on drug panels and the appearance of conflicts. This stringent screening translates into strict limitations regarding acceptable levels of conflicts of interest.
The Emoluments Clause is another interesting aspect of conflict screening. According to this clause, members and consultants cannot have accepted any non-US support whatsoever, including travel reimbursement. Any such support renders an applicant generally conflicted and therefore not a potential member or consultant. This exclusion is regardless of any other considerations, such as needed and recognized expertise.
PANEL MEETING PREPARATION
In preparation for a panel meeting PMA discussion, the FDA works with the PMA sponsor to prepare a ?panel package.? This package contains appropriate sections of the PMA (eg, the clinical summary, the summary of safety and effectiveness data, and labeling information), FDA review memos (or a summary), questions for panel consideration (eg, whether or not the data reasonably demonstrate the safety and effectiveness of the device), and any other information needed to prepare the panel for the discussion. This information is sent to the panel about 1 month prior to the meeting. The panel package is the only training provided regarding the device to be evaluated.
THE MEETING PROCESS
Meetings commonly open with formal disclosures and introductions, followed by an opportunity for public comment on general or specific issues. Next, the sponsor and the FDA make presentations that are generally limited to 1 hour each. Issues may be clarified upon request of the panel; the sponsor and the FDA are given equal time to respond. Deliberation begins with the sponsor sitting in front of the panel, prepared to address questions and concerns.
The designated lead panel reviewer usually begins the discussion; each member in turn then has the opportunity to add remarks. There is sometimes discussion among the panel members regarding these comments, and the sponsor may attempt to provide clarification to address concerns. Panel members often place emphasis on the labeling or instructions for use of the device, because these are the primary tools that the FDA must communicate to potential device users. The panel then considers each question posed by the FDA. At the end of the deliberations, any interested people are allowed to make comments specific to the PMA under consideration.
TIME TO VOTE
The panel may vote in one of three ways: to recommend that the PMA is approvable, approvable with conditions, or not approvable. Conditions of approval must be individually specified and voted on by the panel. One example of a condition would be to require a postapproval study in which follow-up out to 5 years would be reported to the FDA. Reasons for recommending that a PMA is not approvable are as numerous as the PMAs that are presented to the panel. A sponsor may have failed to collect the amount of clinical data originally planned (for example, the group may not have enrolled the number of patients specified in the protocol), or the sponsor may have submitted its PMA before the specified follow-up data were collected.
The final vote provides the FDA with the panel’s recommendation as to whether the device can be granted approval. The FDA generally agrees with the recommendations received. Agency staff members then go through the panel transcripts and document the ways in which any outstanding issues have been addressed, or the reasons why no additional action is needed.
If the panel recommends approval and all other requirements have been met, the labeling and summary of safety and effectiveness data are finalized and an approval order is issued. These final steps may take more than 1 month to complete, depending on the complexity of the conditions and the number of changes required to the summary and label.
If the panel recommends that a PMA is not approvable, a “not approvable” order is issued, specifying the rationale for the decision.
JUDGING THE SYSTEM
Panel review is required by law, and has been since the beginning of device regulation. The most common criticism of the review process is that it overemphasizes avoiding conflict of interest, possibly to the point of overshadowing the panel’s requirement for the appropriate expertise to discuss the device. Perhaps there is a need to supplement the training of the panel to compensate for this potential problem.
When it comes to judging whether the FDA panel review system is working, the value of the public forum is paramount. Panel meetings allow participation and availability of information to anyone who is interested. This advantage should be considered in light of the frustration many people have regarding the confidential nature of information submitted to the FDA. Panel meetings are critically important in conveying both issues and achievements to the public.
To learn more about FDA advisory panels, log on to http://www.fda.gov/cdrh/panel/index.html.
Dorothy B. Abel is a Regulatory Review Scientist with the US FDA Center for Devices and Radiological Health in Rockville, Maryland. Ms. Abel may be reached at (301) 443-8262, ext. 165; email@example.com.