Medical Device Daily Washington Editor

WASHINGTON – The increased scrutiny of FDA advisory committees has the agency jumping to appease its many critics, and the agency held a conference call Monday to announce a set of guidelines to govern the appointment of advisory committee members. However, the voting process was also revised to address some concerns about how votes might be influenced.

Randall Lutter, PhD, the agency's associate commissioner for policy and planning, said on the call "we're announcing a package of improvements designed to enhance decision-making capability." Among the minor improvements is a faster posting of briefing materials he said would allow Internet viewers to find those materials "in two clicks, as opposed to the eight clicks you used to need." The advisory committee portion of the FDA site now has its own page, with only one click needed to find the calendar for advisory committee meetings.

The new voting procedure essentially calls for all panelists to vote simultaneously on approvability, conditions of approvability and so on. This is not an uncommon practice at present and FDA does not propose an electronic voting regime, but some of the agency's critics have cited sequential voting as an area of concern due to the potential for bias induced by more assertive members of a panel.

The guidances also include a set of rules to determine under what conditions an advisory committee should meet. According to Lutter, the guidance in question poses three questions, but the second requirement hints at what many have suspected about such meetings. This requirement states that a meeting will take place if the matter at hand is "so controversial that it would be highly beneficial to obtain the advice of an advisory committee."

Much of the impetus behind this move is that some advisory committees – perhaps most conspicuously the circulatory systems advisory committee – have been called upon numerous times, making life for panel members complicated.

Jill Warner, a policy analyst at the Office of Policy and Planning, said during the conference call, "the guidance on waiver ... incorporates changes from public comments." She noted that FDA is "putting a cap of $50,000 on personal financial interest," but candidates whose interests fall under that number must still be vetted.

Whether the new standards will create recruitment headaches is difficult to say, but Warner said "we certainly see recruitment ... as an important goal and have stepped up recruitment to a significant degree." She said FDA has contacted 280 professional organizations for nominations to the various committees and has posted announcements in the Federal Register to further boost recruitment. "We've received 350 CVs [curricula vitae] at this point" as a result, she said.

As for how to deal with situations in which the panel might not have enough members present to constitute a voting quorum, Michael Orthwerth, PhD, director of the advisory committee oversight and management staff at FDA, said that a quorum is achieved with the presence of one person more than half the standard membership, but "we can augment with special government employee members," so it's not an issue.

New HDE guidance out for comment

The FDA Amendments Act of 2007 (FDAAA) changed the way FDA deals with pediatric devices, and the agency has published a proposed guidance for humanitarian device exemptions (HDE) in response to the law.

Some of the requirements of FDAAA for pediatric populations apply even to devices not intended for those under the age of 18 (or 21, which is often used as a standard at the Center for Devices and Radiological Health). According to FDA, the pediatric provisions of FDAAA mandate that any firms seeking an HDE must describe any pediatric populations who suffer from the condition, including an estimate of the number of such patients.

FDA says that it does not require a separate HDE application for any devices intended for both adult and pediatric populations, but sponsors will have to provide clinical data in support of both sets of patients. However, such data for pediatric populations must include information on "the probable risks and benefits of currently available devices or alternative forms of treatment."

The draft restates the long-standing position that the maximum number of patients with an indicated condition is still 4,000 diagnoses per year. The annual distribution number (ADN) of an exempted device – which is the total number of HDE devices permitted to be used by patients in a given year – is calculated by "the number of individuals (pediatric and adult patients) affected by the disease or condition and likely to use the device each year multiplied by the number of devices reasonably necessary to treat each individual."

However, the ADN is also said to be capped at 4,000 per year, which indicates that the ADN, not the total number of cases, is the functional ceiling of the number of devices that can be used in a given year. This provision becomes more pertinent given that FDA will henceforth require that companies provide FDA with "immediate notification when the number shipped or sold in a year exceeds the ADN whereas the current regulations require periodic reports" specified in the exemption. Companies are not permitted to profit from sales that exceed the ADN.

FDA also reminds industry that companies may profit from HDE devices used in pediatric patients only when those devices were cleared for such use after Sept. 27, 2007. Sponsors cannot use an HDE supplement to bootstrap an existing HDE device into profitability. For the most part, this applies to off-label uses of a device as well. Even when a firm does not profit from the device, charges of more than $250 for the device must be accompanied by documentation that the price of the device reflects the costs that went into its distribution, manufacture, and research and development.

FDA says that HDE data can be used toward a PMA without an investigational device exemption, but the requirements for institutional review board clearance and informed consent apply.