As COVID-19 continues to affect the agency, several advisory committee meetings have been postponed or cancelled. As AgencyIQ’s analysis indicates, while the impact on a small number of products could be large, advisory committees are not used as often as they once were, mitigating the broader impacts of the cancellations.
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Executive IQ Brief
- How things work now: Advisory Committee Meetings are used by the Agency to solicit feedback from subject matter experts, typically when evaluating a new product for potential approval. In addition to experts, the committees include stakeholders from industry, consumer and patient groups. While the recommendations made by the advisory committees aren’t binding, the FDA follows them in about 78% of cases. However, only 25% of news drugs approved since 2011 used an advisory committee meeting, and that percentage has dropped significantly in recent years.
- What’s New: The Food and Drug Administration has postponed three Advisory Committee meetings and cancelled one. While only two of the notices regarding the postponements mention COVID-19 specifically, the cancellations could prove disruptive to the review of some products.
- Impact: It remains possible, even likely, that future advisory committee meetings will be affected by postponements or cancellations. Other companies with advisory committee meetings scheduled for May might experience a cancellation, though it’s unclear whether the FDA would delay approval of a product under those circumstances, or simply make a determination without the expertise of those experts.
When reviewing medical products for potential approval, the FDA will sometimes solicit advice from external experts by holding an Advisory Committee meeting. This typically occurs when the FDA is considering the approval of a new molecular entity (NME) or when the FDA has questions about the safety or efficacy of a drug.
These meetings are generally held prior to approval at the request of the FDA, but may also be held after a product has been approved if the FDA has concerns about the continued safety or efficacy of a product.
FDA Advisory Committees generally consist of about nine members, most of whom are scientific experts. However, they also include other stakeholder representatives for patients and industry. Advisory Committee meetings also include a public hearing portion where members of the public can make a statement to the committee.
Each committee covers different subject matter, and is tasked to help the FDA make decisions about whether to approve a product, recommend policy changes or address special topics. The committee may also invite other subject matter experts to join the meeting if additional expertise is needed to answer questions about safety or efficacy of a product.
At the end of a meeting, the committee will formally vote on whether to recommend approval of the product in question, and generally vote on several other questions related to the product as well (is it safe, is it safe for use at a specific dose, etc).
Regardless of the outcome of the Advisory Committee’s vote, the FDA has the final authority to make a decision, and it does not always follow the recommendations of advisory committees.
While Advisory Committees provide recommendations and insight to the agency for approval decisions, it is the discretion of the relevant review division’s Director to decide to involve an advisory committee.
NME approvals have been cited as a common instance in which the FDA will utilize an advisory committee. However, in an AgencyIQ analysis of NME approvals from CDER between 2011 and 2019, only 88 of 357 had an Advisory Committee Meeting.
The data further show that the number and proportion of Advisory Committee meetings among approvals are decreasing over time.
As previously noted, the FDA is not obligated to follow the advice or recommendations of its Advisory Committees. According to research published in The Milbank Quarterly, the FDA took actions others than those that were recommended in 22% of cases, of which 75% were more restrictive than what the committees had recommended.
Though Advisory Committees bring needed expertise to the regulatory review process, they are not always indicative of how the FDA will act.
Due to the recent outbreak of COVID-19, the FDA has postponed three Advisory Committee meetings set to take place in March and April.
The Agency explained that it is “canceling or postponing all non-essential meetings through the month of April. We will reassess on an ongoing basis for future months… where possible the agency will leverage technology to host meetings allowing for remote participation.”
The specific meetings that have been postponed include a meeting of the Nonprescription Drugs Advisory Committee, the Blood Products Advisory Committee, and the Circulatory Systems Devices Panel of the Medical Devices Advisory Committee.
Only one product was set to be discussed across these three postponed meetings in the Medical Devices Advisory Committee meeting. This meeting was set to discuss a Premarket Approval (PMA) for the TransMedics Organ Care System which is a “portable ex-vivo organ perfusion and monitoring system indicated for the resuscitation, preservation, and assessment of donor hearts” with various characteristics “for transplantation into a potential recipient in a near-physiologic, normothermic, and beating state.”
The other two meetings were not product-specific. The Blood Product meeting was set to discuss recommendations and strategies to reduce the risk of Zika virus (ZIKV) transmission by blood and blood components. In particular the goal was to “discuss whether universal testing of blood donations for ZIKV is an appropriate strategy considering the decline of ZIKV cases in the U.S. and worldwide.”
Similarly, the Nonprescription Drug Meeting would include a discussion of input FDA collected regarding “the current use of over-the-counter antiseptics in the food handler setting and the recommended testing criteria to establish the safety and effectiveness of these products.”
While the announcement in the postponed meetings notes that all non-essential meetings through April will be cancelled or postponed, there are four more Advisory Committee meetings scheduled for the end of the month which have not yet been canceled or postponed. These include the:
- Pulmonary-Allergy Drugs Advisory Committee Meeting on April 21,
- Orthopaedic and Rehabilitation Devices Panel of the Medical Devices Advisory Committee Meeting on April 23-24,
- Medical Imaging Drugs Advisory Committee Meeting on April 23, and
- Pediatric Advisory Committee Meeting on April 29.
The Pulmonary-Allergy Drugs meeting is set to discuss a supplemental NDA application (sNDA) to approve a proposed labeling claim for GlazoSmithKline’s trelegy ellipta. The Orthopaedic and Rehabilitation Panel will discuss the classification of facet screws systems and reclassification of noninvasive bone growth stimulators.
The Medical Imaging Drugs group agenda includes discussion of a New Drug Application (NDA) from Avid Radiopharmaceuticals for their flortaucipir F18 intravenous injection, a radioactive diagnostic agent “for positron emission tomography imaging of the brain to estimate the density and distribution of aggregated tau neurofibrillary tangles of Alzheimer’s disease.”
An agenda for the pediatric meeting has not yet been posted.
While communication from the Agency on the status of these later-April meetings is unclear, it is possible that the Agency is considering remote meetings for those which have longer lead times. The Cellular Tissue and Gene Therapies Advisory Committee scheduled for May 8th already notes the meeting will take place via teleconference.
Conversely, the May 15th meeting of the Allergenic Products Advisory Committee Meeting has been cancelled. The committee was set to discuss DBV Technologies’ Peanut Allergen Extract for treatment of peanut allergies in children.
While the announcement of this cancellation came the same day as the others, COVID-19 is not listed as the reason for cancellation. Instead it notes the change was made “to allow time for the FDA to review outstanding issues.”
As it stands, only one product approval discussion has been postponed due to COVID-19 meeting changes. While others on the horizon could certainly be impacted, it seems the Agency may make a decision to host these meetings over teleconference, when possible.
Currently, the postponement or cancellation of these meetings will primarily impact medical device companies, with most of the meetings impacted coming out of the Center for Devices and Radiological Health. However, looking forward, the impact will begin to split more evenly as we approach discussions of an NDA (Avid Pharmaceuticals) and other CDER related meetings.
The impact of a postponed Advisory Committee meeting for a company seeking product approval can be huge. The FDA review process can take anywhere between 6-12 months (depending in part on the use of an expedited pathway), making any delay a loss of precious time.
Any industry member with an upcoming Advisory Committee meeting should proactively communicate with the Agency about the possibility of contingency planning or future dates for postponed meetings.
The meetings listed as being postponed have yet to be given a future date, or even a timeframe, for rescheduling, putting products like the TransMedics Organ Care System in a state of flux. This could indicate the Agency believes the pandemic could continue to impact the Agency for many more months to come.
As AgencyIQ has discussed in the past, COVID-19 has the potential to interfere with many of the FDA’s key operations. These postponements signal the beginning of FDA reprioritizing its work under emergency conditions. Its focus may shift from scheduling and planning meetings, to developing new guidance related to COVID-19.
Advisory Committees are often useful to approvals in areas where there is a lack of precedent or expertise within FDA. So, while these postponements may impact a limited number of products, it will have a disproportionate impact on products that are more complex or novel moving forward. Still, as the FDA has indicated, these committees are helpful, but not necessarily essential to its understanding of a product and its risks.