SummaryThe US Food and Drug Administration's (FDA) Advisory Committee (AdComm) process remains a source of significant uncertainty for medical product manufacturers, despite FDA's guidelines in the Code of Federal Regulations (CFR)1 and in guidance.2 While the AdComm process is generally the same across Centers,3 each AdComm is unique and subject to the expertise and opinions of individual panel members, opinions voiced during the public comment period, and challenges exclusive to each new product or indication.
With this in mind, Avalere’s Regulatory Strategy and FDA Policy Team has analyzed recent trends in FDA’s approach to the AdComm process in the first three years of the most recent authorization of the user fee programs under the FDA Safety and Innovation Act (FDASIA), enacted on October 1, 2012.*
The Agency currently has 34 standing AdComms across its Centers and Divisions,4 including a new Patient Engagement AdComm for devices. While FDA is not required to follow the advice of its AdComms when making approval decisions, it generally does. Previous research has found that of the 214 AdComms convened to discuss product approvals between 2008 and 2012, panelists voted to approve a product 74 percent of the time, and FDA ultimately approved the corresponding product 79 percent of the time.5 The number of AdComms over time is also variable; Figure 1 demonstrates a spike in Fiscal Year (FY) 2014 Center for Devices and Radiological Health (CDHR) AdComms, as well as a steady decline in the number of Center for Drug Evaluation and Research (CDER) AdComms over the last three fiscal years.
Some AdComms appear to be more challenging than others based on voting record data. The Cardiovascular and Renal Drugs AdComm under CDER has met on product approval 10 times (out of 11 meetings) since FDASIA, voting in favor of a product only 50 percent of the time; FDA has ultimately followed each of that Committee’s recommendations. The Oncologic Drugs AdComm, which met seven times to discuss approval of 11 products, voted in favor of approval less than one third of the time (FDA, however, ultimately approved about 64 percent of those products).
In contrast, our data show that product-specific AdComm votes under CDRH show high positive recommendation rates, with five CDRH AdComms voting in favor of approval 100 percent of the time. Other commonly-convened AdComms under CDER demonstrate positive product recommendations about four out of five times.
FDA has committed significant resources to the Advisory Committee process due to both statutory requirement and internally generated policy goals, indicating the Agency’s commitment to this format of expert recommendation. Given this commitment and the high degree to which the Agency agrees with its AdComm’s recommendations, sponsors should and do emphasize the importance of these meetings accordingly.
Given the number of new drugs coming to market, it should come as no surprise that CDER is the Center at the Agency that utilized the most number of AdComms to weigh in on the benefit/risk analysis and approvability of applications under its review.
The AdComm process continues to evolve as the Agency advances its understanding of regulatory science, and its priorities shift. For example, the Agency recently announced that the Patient Engagement AdComm will provide scientific and policy advice to FDA on how to incorporate the patient perspective into clinical trials, product labeling, and risk-benefit determinations. This follows the Agency’s patient experience focus as seen in other efforts, such as its Patient Focused Drug Development program. FDA may choose to add additional committees as new challenges arise, including those related to personalized medicine, real-world evidence, and medical software.
Although a product sponsor may not always be able to determine whether their product will be assigned an AdComm, a careful study of these recent trends in AdComm behavior can provide strategic advantages to a product’s development program should they be assigned one by the FDA.
*The programs include the fifth authorization of the Prescription Drug User Fee Amendments (PDUFA V), third authorization of the Medical Device User Fee Amendments (MDUFA III), first authorization of the Biosimilars User Fee Amendments (BsUFA I), and first authorization of the Generic Drug User Fee Amendments (GDUFA I). This review focuses on originator drugs, biologics, biosimilars, and devices, as these are the subject of the majority of AdComms.
1. US CFR Title 21. Available at: http://avale.re/2vxC3Vq
2. US FDA. “Guidance for the Public and FDA Staff on Convening Advisory Committee Meetings.” August 2008. Available at: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM125651.pdf
3. US FDA. “Guidance for Industry Advisory Committees: Implementing Section 120 of the Food and Drug Administration Modernization Act of 1997.” October 1998. Available at: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm079765.pdf
4. US FDA. “Committees & Meeting Materials.” February 2015. Available at: http://www.fda.gov/AdvisoryCommittees/CommitteesMeetingMaterials/default.htm
5. Ciociola et al. “The Food and Drug Administration Advisory Committees and Panels: How They Are Applied to the Drug Regulatory Process.” Am J Gast. (2014). 109:1508-1512. Available at: http://www.nature.com/ajg/journal/v109/n10/full/ajg201485a.html
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