Leaders at FDA share highlights and updates for drugs and biologics at RAPS Convergence
Top officials from FDA’s Centers for drugs and biologics—including Center for Biologics Evaluation and Research (CBER) Director Peter Marks—provided high-level updates at RAPS Convergence 2023 this week. The briefing covered recent operational changes, recent accomplishments, and near-future projects.
At RAPS Convergence, senior leaders at the FDA spoke directly to regulatory professionals
- Speaker from the Center for Drug Evaluation and Research (CDER): KEVIN BUGIN, the Deputy Director of Operations in CDER’s Office of New Drugs (OND).
- Speakers from the Center for Biologics Evaluation and Research (CBER): Center Director PETER MARKS and Director of the Office of Regulatory Operations, CHRIS JONECKIS.
- The topic: Representatives from both centers discussed their recent activities and accomplishments and provided previews of upcoming initiatives and ongoing developments.
Both CDER and CBER have recently implemented operational tune-ups
- In line with recent pushes to modernize advisory committees, both centers have adjusted internal processes. The FDA’s scientific advisory committees are generally intended to provide independent expertise and technical assistance via a range of insights on statistics and methodologies, clinician experience, and patient experience. The convening of an advisory committee can occur at the FDA’s discretion, pursuant to a statutory requirement, or at the sponsor’s request. Tuning up advisory committees has been a priority of FDA Robert Califf since early 2023, when he called for reconsideration of the volume and agenda for these meetings. As part of this initiative, CDER has launched a team that offers support to review teams in preparation for advisory committee meetings, “similar to what industry might have on their end.” CBER has revised the process for developing advisory committee briefing materials, which Joneckis says has facilitated efficiency.
- Both centers are also in different stages of implementing integrated reviews. Through its New Drugs Regulatory Program modernization effort, CDER has “doubled down” on an integrated review template. It features a new collaborative authoring tool, described as “a new workflow management solution which allows us to modularize the collaborative review to allow multiple parties to work on separate sections in parallel, and then integrate those back together.” CDER expects all FY 2024 new molecular entity reviews to go through this streamlined template, with some exceptions for oncology products. CBER has similarly developed an integrated clinical review template, which it expects to pilot internally in the next year. The center notes that this catches up to the integrated nature of biologics review that has existed for “quite some time.”
- In-person interactions have returned but are not the preference of all applicants. CDER’s Bugin explained that not every eligible sponsor partook in an in-person meeting at FDA’s White Oak campus, which was expected. “I think we will always have hybrid meetings going forward unless there’s some dramatic shift in things, processes or technology, et cetera,” he said. CBER has received and granted requests for hybrid meetings, which it plans to expand by implementing new technology in its conference rooms. On a related note, Joneckis addressed CBER’s use of written response only (WRO) replies to meeting requests. In the context of increased workload without increases in staff, CBER had to increase the use of WRO in recent years. That said, the center has developed standard procedures for triaging these requests, with Joneckis emphasizing that “our intention is to hold the meeting whenever we can.”
- CBER is working with sponsors to reduce the number of clinical holds. Joneckis explained that an increase in clinical holds has occurred over the past few years due to a variety of reasons, such as the increased complexity of products and clinical trials or incomplete applications. CBER conducted an internal analysis that found that “people aren’t taking advantage of these meetings or they’re ignoring the advice that we’re providing them.” The center has worked to improve communications and processes to address this issue. While clinical holds reached levels as high as 30-33% in the past few fiscal years, the hold rate in FY 2023 is around 13%.
- Regarding artificial intelligence (AI), an important topic at RAPS Convergence, the two centers discussed external and internal use cases. Joneckis said that CBER has “some limited uses that we have seen in external submissions, mostly in the bioinformatics area,” but not as many as CDER. CBER is also using AI in its internal processes, “mostly for machine learning applications for searching and assimilating information in various areas.”
The speakers highlighted recent accomplishments and future directions
- CDER representative Bugin highlighted some high-profile drug approvals. He touted the approval of Opill, the first nonprescription contraception drug. Interestingly, AgencyIQ notes that this approval was not smooth, with the joint meeting of the Nonprescription Drugs Advisory Committee (NDAC) and Obstetrics, Reproductive and Urologic Drugs Advisory Committee (ORUDAC) fraught with strong FDA reviewer data quality concerns [ Read AgencyIQ’s analysis of that meeting here.]. CDER also highlighted the approval of nirsevimab, a monoclonal antibody for the prevention of RSV lower respiratory tract (LRT) disease in neonates, infants, and toddlers [ Read AgencyIQ’s analysis of the Antimicrobial Drugs Advisory Committee (AMDAC) meeting here.].
- Bugin also described a “productive year” for CDER in regards to approval volume and meeting commitments. With the caveat that “the dust is still settling” on FY 2023, Bugin described the center’s increase in novel approvals compared to last year. AgencyIQ recently conducted an in-depth analysis of this exact topic, identifying a recovery in approval numbers as the agency resumes a new normal following the pandemic, as well as some interesting trends for biologics and accelerated approvals that warrant consideration [ See the full analysis here.]. CDER is also on track to complete the 58 first-year requirements under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA), which included updated programs or processes, web updates, guidance documents, public meetings or workshops, and more.
- CDER continues to think about clinical trial innovation, and stakeholders will be able to weigh in soon. According to Bugin, “Later this month, we’re hoping to open up a document with various questions around barriers and facilitators to the implementation of clinical trial innovation,” he said.
- CBER Director Marks highlighted some of his Center’s accomplishments, including work to update the Covid-19 vaccines to reflect circulating strains, and the updated blood donor policy that takes an individualized approach [ Read AgencyIQ analysis of the guidance and implementation here.].
- Marks also offered thoughts on the “critical juncture” for gene therapies. With 15 gene therapies now approved in the U.S., Marks reiterated his oft-discussed stance that international regulatory convergence pilots akin to Project Orbis for oncology would be productive to move the needle in this area. He also noted that advanced manufacturing for certain gene therapies is a current focus of the center.
- Both Marks and Bugin highlighted the newly launched pilot program for rare disease communications, called the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) Pilot Program. The goal of the program, according to the announcement, is to “further accelerate the pace of development of novel drug and biological products that are intended to address an unmet medical need as a treatment for a rare disease.” [ Read full AgencyIQ analysis of the announcement here.] According to Bugin, the program offers “opportunities to consult with the FDA on very specific issues pertaining to the development of those products” and “will be very milestone driven… allowing us to focus on particular drug development milestones and how we can help the sponsor and in programs get from each one of those stages or milestones to the next.” Joneckis also emphasized its pilot status, explaining that “…this is not the final resting place for where we intend things to sit in terms of where we might expedite giving feedback.” The goal is “to be able to show our stakeholders including the industry that provides us user fees and our Congress that this program actually can produce.”
Featuring previous research by Alec Gaffney.