What we heard at FDA’s listening session on Advisory Committee processes: The agency’s priorities vary wildly from the public’s

First, a very quick introduction to the FDA’s Advisory Committee system

• The Federal Advisory Committee Act (FACA): Enacted in 1972, this law established processes and procedures for the creation, functioning, and dissolution of advisory bodies that support the federal government. Under FACA, advisory committees are “entit[ies] that [are] used by an agency of the Federal Government to gain advice or recommendations” and is not made up “entirely” of full-time government employees. Currently, there are over 1,000 such federal advisory committees.
• The FDA itself has 32 advisory committees, covering the breadth of FDA regulated products. Drug and biological product advisory committees are organized into distinct committees by subject area. Some of these committees – the Vaccine and Related Biological Product Advisory Committee (VRBPAC) and the Oncologic Drugs Advisory Committee (ODAC), for example – are prolific, meeting several times per year at minimum. Some committees also have subcommittees. However, there is only one Medical Device Advisory Committee (MDAC), which is structured as 18 panels focused on different areas of device regulation (including therapeutic areas) and two subcommittees. The MDAC has undergone some changes in recent years, with an overall uptick in the number of meetings and updates to the internal structure of the Center for Devices and Radiological Health (CDRH).
• What exactly do they do? The FDA’s advisory committees have a “complex job,” the agency acknowledges. According to the FDA, reviewing new products (or new information about existing products) “often involves many areas of expertise, and sometimes FDA turns to outside experts for counsel.” The role of the advisory committees is to “provide independent expert advice to the Agency in its evaluation of these regulated products” and “help the agency move toward making sound decisions based upon reasonable application of sound scientific principles.” The FDA’s advisory committees thus allow the agency to get outside opinions or solicit expert advice on a variety of topics that come up in the course of its regulatory activities.
• In practice, the FDA convenes advisory committees (or panels) in two general circumstances: First, to discuss individual product applications. These can be convened at the request of the FDA – for example, if the review staff wants to request outside expertise on particularly tricky clinical or statistical questions in an application. The committee/panel can also be convened to discuss an individual application upon request from an application sponsor under the Federal Food, Drug and Cosmetic (FD&C) Act section 562, as part of their “adequate dispute resolution procedures to provide for appropriate review of scientific controversies between the FDA and member so regulated industry.” In implementing that authority, the FDA amended its operating regulations under 21 CFR 10.75 to specify that “a sponsor, applicant or manufacturer of a drug or device regulated [by the FDA]… may request review of a scientific advisory panel….”
• At the meetings, the FDA often presents questions for discussion, and may ask the committee to vote on one or more questions. The discussion questions will typically focus on distinct areas of the application, including questions about the sufficiency of certain data, bias mitigations, statistical approaches, or the study/intended use population. The voting questions are generally predictble: Is the product safe for intended use; is the product effective for intended use; and do the benefits of the product outweigh the risks? Notably, the committee votes are nonbinding, and final decision-making authority lies with the FDA. However, the committee discussion can inform the specifics of an authorization, such as specific wording in labeling, the way that a post-market follow-up study is designed or reported, or potential risk mitigation measures.
• Second, the FDA can convene its advisory committees or panels to talk about high-level issues. These involve discussions about general approaches or new and emerging technology or research methods areas. For example, the FDA recently convened the Molecular and Clinical Genetics Panel (MCGP) of the MDAC to discuss requirements for marketing applications for multi-cancer detection (MCD) screening tests, including appropriate comparators, endpoints, and research populations. [Read AgencyIQ’s analysis of the meeting here.] As another example, in May 2024 the agency convened the Pediatric Oncology Subcommittee of the ODAC to discuss how the 2017 FDA Reauthorization Act’s pediatric cancer research provisions in the Research to Accelerate Cures and Equity (RACE) for Children Act were working so far. [Read AgencyIQ’s analysis of that meeting here.]
• The non-voting meetings allow the FDA to receive feedback from advisors about potential regulatory approaches to inform development programs, review processes, and highlight the potential issues that FDA reviewers or additional advisory committees would have in the consideration of a future application.

Recently, internal and external voices have been calling for process improvements to the advisory committee system

• In early 2023, the agency’s executive leadership began to preview changes to the Advisory Committee system. In a series of blog posts covering the most critical topics to address in FDA Commissioner ROBERT CALIFF’s second year of leadership, a brief section previewed plans to “tune up our Advisory Committee system in a way that enables our experts to get the best advice possible.” While that blog post offered few details, Califf provided much more detail in an April 2023 Medpage Today interview with Editor-in-Chief Jeremy Faust: “First of all, let’s be clear, Advisory Committees are advisory,” said Califf. “They are not decision making. In fact, as we’re re-evaluating Advisory Committees, we want to have more Advisory Committees but less voting, because people get all worked up about the voting and the voting doesn’t matter. What the FDA wants to know is, what is the thinking behind the reasons someone might vote one way or another? We need knowledge that we may not have inside the FDA [emphasis added].” [ Read AgencyIQ’s analysis of prior FDA statements on advisory committee reforms here.]

• However, not everyone within FDA fully agrees. FDA’s Oncology Center of Excellence (OCE) Director RICHARD PAZDUR has expressed continued support for the voting meetings in an interview with AgencyIQ at the AACR conference in April 2024. “Many of the people that are arguing for not having this voting question have not been in the review divisions,” he said. “So we do need that clarity” of an up-or-down vote, he added. [ Read AgencyIQ’s interview with Pazdur here.]
• Notably, this is hardly the first time there have been calls to reform the Advisory Committee process. In a 1992 review from the Institute of Medicine (IOM), researchers found that “relatively few current policies [on the operation of FDA’s advisory committees] are documented,” additionally citing significant variation in practices and policies between FDA’s product centers and a lack of transparency about how meetings are scheduled, agendas are set, and materials are distributed.
• The agency has, since that time, issued several guidance documents on its Advisory Committee processes, including one in 2008 on the Preparation and Public Availability of Information Given to Advisory Committee Members (or “briefing materials”), a guidance on the Open Public Hearing portion of the Advisory Committee meetings in 2013, and guidance on participation in Advisory Committees in 2016. The last of these guidance documents, which remains in draft format, discusses the FDA’s screening criteria for advisory committee candidates, to include “potentially disqualifying interests or relationships,” such as financial interests or other things that could cause “appearance issues.”

On June 13, 2024, the FDA held a listening session on potential improvements to the Advisory Committee system

• The meeting, which saw scores of individual contributions from members of the public, regulated industry, patient advocacy organizations, and public health researchers, sought public input on perception of the committee process. Per the meeting announcement, the FDA wanted feedback on how it can improve committee composition to ensure representative diversity and include relevant expertise; streamline “administrative burdens” to increase willingness to serve on committees; and improve public understanding of what Advisory Committees are meant to do. The agency’s announcement billed the meeting as focused on ways to “optimize” the advisory committees.
• The toplines: The FDA got a significant amount of input on the way it runs advisory committees, and the role of the meetings (and advisors) in regulating life sciences and tobacco products. AgencyIQ pulled out three key themes from the meeting: How committee members are chosen and the composition of committees; where, exactly, patient/caregiver input goes in meetings; and the actual operation of advisory committee meetings. Notably, the key points and priorities raised during this listening session vary significantly from what FDA leadership had pulled out as its topline priorities.

Key theme number one: Expertise, membership and conflicts

• The composition of committees: “In general, advisory committees include a Chair, several members, plus a consumer, industry and sometimes a patient representative. Additional experts with special knowledge may be added for individual meetings as needed,” according to FDA. Committee members are nominated – by professional societies, industry, advocacy groups or individually – and if selected by the FDA, they may serve terms of up to four years. The agency regularly posts Requests for Nominations to its various advisory committees and panels in the Federal Register. In addition to clearing screening criteria related to financial relationships or appearance issues, Advisory Committee members must be “technically qualified experts in their field (e.g., clinical medicine, engineering, biological and physical sciences, biostatistics, and food sciences) and have experience interpreting complex data.” Per FACA (and particularly the most recent amendment from May 2024), advisory committees must be “fairly balanced in terms of the points of view represented and the functions performed.” The regulation, though, largely defers to agencies on the specifics of their Membership Balance Plans (MBP). Most FDA advisory committee members are appointed to the committee as Special Government Employees (SGEs), although regular government employees (RGEs, e.g., staff scientists from the National Institutes of Health) may also serve; the industry representative generally falls into neither category. Potential committee members are tasked with self-reporting potential conflicts of interest.
• Temporary members versus permanent members: “An advisory committee ordinarily consist of 9 fixed or “standing” members including the chairperson,” according to FDA – although committee membership varies by product center and individual committee or panel. The standing members are those nominated (as discussed above) and appointed by the FDA, based on their technical expertise, experience, and financial relationships. Conversely, some committees also use temporary members, who “may also be invited to participate in specific meetings.”
• What’s the difference? According to feedback at the FDA’s listening session – and AgencyIQ’s own experience with attending the Advisory Committee meetings – temporary members typically have more specialized expertise than the standing members. Per FDA’s resources, temporary members include “other scientists or medical personnel whose expertise may not be represented by the fixed voting membership.” Standing members are likely to be more generalists within their field, with expertise applicable to a broad set of questions for the committee’s focus areas, while temporary members may have deep expertise in specific areas relevant to the topic of a given meeting.
• At the FDA listening session, DOUGLAS KELLER, who represented himself as an individual and has previously spoken at FDA Advisory Committee meetings as a patient advocate, cited discrepancies in how different committees leverage temporary members in different situations. Some committees use more temporary members, and the overall number of committee members can vary too: “I’ve seen as many as 13 members and as few as five,” he said.
• The case for and against temporary members: Temporary members on an advisory committee can provide more direct expertise on specific products, given their expertise. As Keller pointed out, this can enhance efficiency in the meetings, with less time spent backgrounding the committee on the particulars of the condition of interest. On the other hand, though temporary members may have more disease-specific perspectives, they also often need more orienting into the regulatory space (more on that below). Further, and importantly, disease-specific experts are more likely to have conflicts of interest (COI), since their backgrounds are pertinent to the topic the committee is addressing. As Keller pointed out, there is no standardized system across the FDA, its committees, to set a baseline on the number or share of temporary members that make up a committee at any given meeting.
• Several stakeholders made the case that FDA might be sacrificing even deeper expertise for non-conflicted members. As STEVEN CARPEN (Breakthrough T1D, formerly JDRF International) put it: “We believe it is critical to closely scrutinize any real or potential conflicts of interest. However, the top leaders and experts in any field are often some of the best suited individuals to guide the development of these products. The result is they often engage with industry or with product developers. By limiting their ability to participate in advisory committee meetings, some of the most important voices are left out of the discussion, and therefore the value of the opinions and the advice that the advisory committees provide to FDA can be diminished.” In short: the more specialized the expertise, the more likely it is that the agency might be concerned about “appearance issues.” JAMIE SULLIVAN (Everylife Foundation) expressed similar views: “It’s necessary to reconsider how members’ conflicts of interest are determined. While it’s understandable that the agency upholds strict COI procedures in most cases, as many FDA leaders, including Commissioner Califf, have recognized, there is rarely an expert in a rare disease that does not spend time working on therapy development programs. There must be processes to allow these experts to contribute to the tough questions FDA reviewers are wrestling with, with reasonable guardrails in place to manage any potential conflicts.”
• It’s worth noting that the FDA does have “significant flexibility and discretion” to decide whether an individual with an appearance issue can participate on particular matters under 5 CFR 2635.502 (“section 502”), and as described in the agency’s 2016 draft guidance on COI and appearance issues. This means that the agency can still authorize conflicted individuals to participate in a meeting (or portion of a meeting) if they determine “that the interest of the Government in the member’s participation outweighs the concern that a reasonable person may question the integrity of the agency’s programs and operations.”
• Based on self-reported COI disclosures, the FDA can grant waivers to allow individuals to participate in meetings. For example, see this disclosure document and waiver for CYNTHIA CARLSSON, of the University of Wisconsin-Madison, to serve as a temporary member of the Peripheral and Central Nervous System Drugs Advisory Committee in June 2024. Using that meeting as an illustrative example , out of 11 voting members of the committee, only three were standing members, while eight were temporary voting members.
• The push for specialized expertise: Several speakers at the listening session focused on COI policy reforms that would make it easier for the FDA to consult with individuals with more specialized expertise. In particular, stakeholders from the Haystack Project called out efforts through the 2022 Helping Experts Accelerate Rare Treatments (HEART) Act proposal, which would have made it easier for the agency to bring in advisors on “experts on the science of small population studies.” As KARA BERASI (Haystack) noted, however, “the HEART Act was met with FDA opposition,” as the agency held its line on COI policies.
• Committee members generally lack regulatory expertise: While advisory committee members will receive training from the FDA on the basics of health product-related regulations (including the definitions of key terms and relevant criteria for authorization or approval), their backgrounds usually focus on clinical science, statistics or direct patient care. This can result in, as Keller put it, inefficient meetings, as committee members may get hung up on issues that the FDA has no authority over. The time spent on non-salient discussion can sometimes derail the meeting, limiting the utility of the discussion or the advice and even trust in the committee itself.
• Some examples: In a November 2023 ODAC meeting on two products granted accelerated approval with long-delayed confirmatory studies, the committee members demonstrated a lack of familiarity with the accelerated approval process altogether, resulting in a back-and-forth, with OCE head Pazdur having to take meeting time to explain the pathway and FDA’s relevant authorities to the committee. Similarly, a December 2023 MDAC panel meeting on the concept of multi-cancer detection (MCD) screening tests – a meeting on a topic, not a specific application – sought feedback on what clinical studies for these products should look like, how they should be designed and what comparators or follow-up should be used. During the meeting, panelists engaged in an extensive discussion of the value of mortality as an endpoint for these studies – while then-FDA diagnostics office Director TIM STENZEL tried to remind the panel that diagnostics regulators “do not assess mortality as an endpoint,” (for diagnostics studies, specifically) and regulators “aren’t legally allowed to go, for this type of submission, into clinical utility assessments.” He went on: “It would require a change in our authorities before we could use mortality as an endpoint for this type of submission” – making clear that the extensive, impassioned discussion of the panel, which focused its conversation on the use of mortality as an endpoint, was effectively moot for regulatory purposes.
• The key take-away: During the listening session, stakeholders, especially those from rare disease communities, urged the FDA to enhance the use of temporary members and to engage in COI reform to make it easier for more specialized experts, who are more likely to have COI concerns, to participate in advisory committees. However, these discussions highlighted an existing gap in Advisory Committee policy: the lack of consistency across the agency, its product centers, or even individual committees and panels about committee composition and numbers. Nearly all of the FDA’s drug product committees and medical device committees and panels currently have vacancies – ranging from 10 individual vacancies on MDAC dental products devices panel to at least one vacancy on 11 of the 18 human drug committees.

Theme number two: The role of patient input – and opportunities for improvement

• A key priority for many at the listening session was to enhance the role of patient input at the meetings. Under current practice, Advisory Committee meetings include an Open Public Hearing (OPH), when individuals including academics, public health researchers, clinical research participants, patients, and caregivers can provide their perspective on the topic or application at hand. The FDA maintains final guidance from 2013 on the Open Public Hearing portion of the advisory committee meetings, describing the process and statutory requirements for a “minimum of 60 minutes per meeting be dedicated to an OPH session.”
• That said, the utility of an OPH varies based on the meeting. In general, the process for the OPH involves individual stakeholders presenting their “information or views” in sequence. However, these presentations are time-limited and often disjointed – and it’s entirely up to the discretion of the committee members as to whether any of the information presented is further discussed at the meeting.
• At the listening session, multiple stakeholders called on the FDA to do more to formalize the role of patient input at the advisory committee meetings, beyond including a consumer or patient representative (non-voting member) on the committee or panel and the OPH. In particular, NATALIE TOLLI, Vice President of Regulatory Affairs at AbbVie, called on the FDA to “consider standing agenda items with respect to objective and subjective patient data [as a] relative topic of discussion” (see here for the written comments from AbbVie). Sullivan (Everylife Foundation) also highlighted this point, noting that “experts in social sciences, patient preference studies and interpreting the use of patient experience data are often absent from [advisory committee] discussions.” She made a very similar call to Tolli’s, saying that FDA should consider “identify[ing] a distinct time in the agenda to hear and discuss available patient experience data, including evidence collected by credible organizations such as patient advocacy organizations.”
• The FDA is grappling with this topic more broadly, as it seeks a framework to translate anecdotal patient experience data into regulatory-grade evidence, or even regulatory-grade context in support of an application. In 2023, the FDA released a request for information (RFI) on the methodological challenges that sponsors face in using patient experience data to inform the benefit-risk evaluation of a product, or to inform its labeling; under the current PDUFA commitments, the agency is required to host a workshop on this subject by the end of the year, and a second in 2025, and then issue guidance on the “use and submission of patient preference information to support regulatory decision making” by the end of federal fiscal year 2026. Similar policies are on the docket for medical devices; while the agency does have a 2016 final guidance on using patient preference information (PPI) in device submissions, implementation has been challenging for product sponsors, and a new draft guidance is expected later this year.
• Still, the way that PPI or patient experience data is considered at Advisory Committees is still on a case-by-case basis; the OPH typically involves hearing from individual patients or research participants, with no room in the formal agenda for further discussion by committee members. With FDA trending toward policies that are intended to help formalize patient-reported data and information into regulatory-grade evidence or information, it could also become a bigger part of Advisory Committee meetings going forward as more sponsors include these data as part of their applications. Some at the listening session see more standardization of the OPH, such as providing speakers with a list of questions to respond similar to those the committee receives, could be a place to start. Still, OPH testimony likely wouldn’t rise beyond anecdotal information for the purposes of FDA decision making.

The last theme: The process and organizational future of Advisory Committees

• Several commenters at the meeting were focused on the actual operations of the Advisory Committees. Commenters discussed their concerns with the way that meetings are run, organized, and operated.
• First: Meetings are typically run by the chairperson, who is a member of the committee or panel. As anyone who has attended an Advisory Committee may know, the organizational skills, experience, charisma, or general attitude of the Chair can make or break a meeting. Sullivan, from EveryLife, summed up her organization’s concerns, noting that the leader of the committee meeting is “a role currently filled by the chairperson, typically an expert scientist, not an expert in generating fair and meaningful conversation for informing regulatory decisions. Community members have witnessed outcome discussions dominated by one member’s perspective, or meetings that were derailed by less than accurate concerns.”
• Sullivan recommended the agency hire a professional meeting facilitator, which could help the committee meetings stay on topic, within scope and on time.
• Second: FDA is transitioning back to in-person Advisory Committee meetings, which was nearly unilaterally flagged as a concern at the listening session. While stakeholders speaking at the meeting acknowledged the value of face-to-face meetings, they also highlighted serious concerns about a full return to in-person advisory committee meetings, which went fully virtual during the Covid-19 pandemic.
• Of a key concern here: Equity and representation. Multiple individuals commented on their concerns about the return to in-person meetings, both in terms of public access to the advisory committee meetings (which are still live-streamed, even when held in-person on FDA’s White Oak campus) and in terms of how requiring in-person participation may limit participation to certain potential committee members. For example, meeting attendees voiced concern about committee members having to travel to FDA’s White Oak campus in the District of Columbia suburbs, potentially leaving their patients behind to do so. Additionally, potential committee members may face their own complex health challenges, including mobility or visual disabilities.
• Notably, these are the same kinds of concerns that FDA flags in its push for decentralized clinical trials, which seek to avoid a research environment where time and travel commitments inherently limits research opportunities to certain people. These principles apply equally to advisory committee participation, although instead of multiple trial sites that may be spread out across the country, the FDA would require advisory committee members to travel to its Maryland headquarters in order to be able to participate. This would skew participation opportunities for those who either live in the area or can travel, disincentivizing participation for people with children or dependent adults at home, those with disabilities, or those who work with challenging patient populations. For example, one speaker at the meeting highlighted the anecdotal experience of a psychiatrist who works with vulnerable populations who was unable to travel to FDA around the holidays.

What’s next? There’s a ton of room for improvement, but it’s a ton of work

• The FDA’s call for input focused on reducing administrative burden, but the feedback at the meeting focused on ways to actually enhance the operations and structure of the Advisory Committee system – which might result in an increase in workload for the agency and its advisors. The listening session aired serious concerns about the overall Advisory Committee system, while continuing to support the value of the meetings themselves.
• Concerns included common refrains for improving a myriad of basic Advisory Committee processes, including how committees are staffed, trained, oriented on their subject matter, given information and convened. All of this, notably, impacts the public trust in the Advisory Committee process.
• For the extremely important role that these meetings play, there’s limited guidance on how they work. One of the key takeaways from the listening session was the general agreement from non-FDA stakeholders that there are serious improvements to be made to the Advisory Committee processes. While the FDA is seeking to “optimize” the Advisory Committee process, what the public views as the top-line priorities and how the agency would address its own concerns seem significantly different. While the agency is focused on bringing committee meetings back in person and decreasing the reliance on votes, key concerns heard at the listening session were concerns about vacancies, staffing, the expertise of committee members themselves, and how gaps in knowledge – about the specific disease, statistical methods, or even regulatory pathways through which a product is being considered – are taking away from the utility of the meetings.
• It seems niche, but it’s not. The FDA and industry both place a great deal of stock in the advisory committee process. Meetings that get derailed by a chairperson’s poor time management, technical issues, or off-topic discussions can limit the overall usefulness of the meeting – and undermine the process itself. If the FDA is looking to make transformative, or even just significant, changes to the advisory committee process itself, addressing many of these baseline, foundational issues would be a place to start.
• There does appear to be some low-hanging fruit, such as better information from the FDA about the actual make-up of its advisory committees, how it considers temporary members and COI on a case-by-case basis, and what kind of training the committee members receive. Things like orienting clinical experts and statisticians on the regulatory minutiae of the questions they’re being asked to provide input on may be more difficult, but could seriously enhance the utility of the meetings, as could a better framework for facilitating the meetings themselves that’s not necessarily dependent on the whims of the chair. Finally, the FDA and the public seem to be a loggerheads about whether in-person or virtual meetings are best – or whether a hybrid option should be considered. Crucially, these decision will inform not just who can attend advisory committee meetings, but also who can serve as an advisor.

To contact the author of this item, please email Laura DiAngelo ( ldiangelo@agencyiq.com).To contact the editors of this item, please email Kari Oakes ( koakes@agencyiq.com) and Alexander Gaffney ( agaffney@agencyiq.com).

Key Documents and Dates

• Public Meeting: Optimizing FDA’s Use of and Processes for Advisory Committees