On April 1, 2015 the Food and Drug Administration (FDA) released a draft guidance document discussing procedures for Medical Device Advisory Committee meetings, excluding the Medical Devices Dispute Resolution Panel (DRP). The draft guidance generally confirms existing FDA practices, but provides some additional detail regarding the timeline for exchange of briefing materials and the agenda for Panel meetings, including voting procedures.
The draft guidance, Procedures for Meetings of the Medical Devices Advisory Committee, is intended to provide more comprehensive information on the procedures associated with such a meeting than that which was included in previous guidance.
It provides more clarity regarding when the agency will consider taking a particular premarket submission in front of a Panel, specifically if: “the submission is of significant public interest, the submission is highly controversial, or there is a special type of expertise provided by the panel that could assist the Agency in its decision-making.” The guidance presents scenarios where this may be the case:
- where the device is a novel technology expected to have an important impact on clinical practice;
- where the study results raise questions about the risk-benefit ratio of the device (high rates of adverse events, failed primary endpoint, etc.); or
- where data quality or integrity issues are raised.
Interestingly, the guidance specifically states that the Center for Devices and Radiological Health (CDRH) intends to consider Panel review for multiple types of submissions, including premarket notifications
(510(k)s), de novo requests (de novo) and humanitarian device exemptions (HDEs). In such cases, the Panel’s recommendations will be considered as part of CDRH’s decision whether to allow marketing of the device. Historically, there have been very few Panel meetings relating to premarket notifications and only for ones with substantial clinical data which were also controversial. This may signal FDA’s intent to bring more device applications to Panel, especially with de novo requests sometimes being based on premarket approval (PMA)-like clinical data.
In addition, the draft guidance provides suggested detailed timelines for interactions related to the Panel briefing materials:
Click here to view table.
While the guidance reiterates FDA policy that the Panel Pack and presentation should be limited to information included in the submission, it also provides that new data and significant new analyses will generally not be reviewed by CDRH if received less than 12 weeks prior to the Panel (unless CDRH agrees to inclusion). FDA’s position on this point is a very important one for companies to keep in mind when preparing for Panel meetings.
The guidance also provides specific recommendations regarding the agenda for Advisory Panel meetings. It outlines CDRH’s current policy of allowing the Sponsor 60 minutes for its presentation at a Panel meeting to review a premarket submission, and up to 90 minutes if requested or if CDRH also plans to present for 90 minutes. For regulatory issues meetings (general issues Panel meetings and reclassification Panels), this same amount of time should be allotted but may be split among the affected industry representatives. The guidance states that there should be approximately one hour for general Panel deliberations, during which the Panel may ask questions of CDRH or the Sponsor. It states that “both CDRH and the affected person(s) should be provided an equal opportunity to respond to questions from panel members.” After this period, the Panel should discuss the FDA questions, generally uninterrupted.
Finally, the guidance outlines CDRH’s current electronic voting procedures, which were implemented several years ago. Electronic voting appears to have changed the dynamics of the voting process at Panel meetings, and provides less opportunity for Panel members who are more expert in the topic area to convey their thoughts to less experienced Panel members during the vote. In addition, instead of asking the Panel to vote on whether the application should be approved, as was the case several years ago, Panels are now asked to vote on the safety, effectiveness, and risk/benefit of the device under consideration. This may have been intended to provide FDA with more discretion in handling the Panel recommendation; however, the risk/benefit vote is widely considered a proxy for approvability.
There has sometimes been confusion at Panel meetings in recent years regarding whether a Panel could vote on a slightly different Indications for Use than the one described in the Panel materials, as the Panel may believe that a different indication might better describe how the device might be used or might be better supported by the data. This can be particularly confusing for Panel members if FDA asks the Panel to comment on the proposed Indications for Use in the discussion questions prior to the vote. However, the guidance specifies that the vote should be taken on the Indications for Use described in the Executive Summary of CDRH’s Panel Pack, which is based upon the premarket submission. The guidance explains that if an unfavorable vote is received, different Indications for Use may be considered at the discretion of the Panel Chair. In preparing for Panel, if there is any question regarding whether the proposed Indications for Use are fully supported by the data, companies may wish to work with FDA to ensure that the Indications for Use statement presented for Panel vote is fully supported.
The new draft guidance is silent in several key areas. First, it does not address the important topic of when during the device submission review process a Panel meeting will be considered. The guidance also does not discuss the role of Advisory Panels in considering the increasingly important question of post-approval studies (PAS). The great majority of original PMAs which go through the Panel process require hypothesis-driven PAS which are often as or more burdensome than pivotal studies supporting device approval. While there is no specific voting question on PAS studies, FDA routinely asks for Panel input and recommendations as to the nature of such a study when considering a PMA. In addition, as noted in FDA’s June 2009 guidance on PAS, FDA may also seek the advice of Advisory Panels when considering the progress of post-approval studies (Procedures for Handling Post-Approval Studies Imposed by PMA Order); this potential function of Panels is not addressed in the guidance. Finally, the guidance is also silent on the nature of the discussion questions presented for Panel consideration. Often, these questions pertain to indications for use, study design, safety, effectiveness, statistical issues, labeling, and the PAS.
The public comment period for the draft guidance will remain open until June 1, 2015, 90 days from publication in the Federal Register. Electronic comments should be submitted to http://www.regulations.gov referencing Docket No. FDA-2015-D-0838. When final, the draft guidance will supersede the Guidance on Amended Procedures for Advisory Panel Meetings (July 22, 2000) and the Panel Review of Premarket Approval Applications #P91-2 blue book memorandum (May 3, 1991).
Advisory Panel meetings are exceedingly important meetings in the approval of many novel medical devices. These meetings are often critical to the viability of the Sponsor of the medical device. The draft guidance underscores the importance of extensive and intensive preparation for these meetings. However, it presents the procedures primarily from FDA’s perspective. Hogan Lovells welcomes questions from industry regarding this draft guidance, or the industry perspective on preparing for Panel meetings.