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Looking back on regulatory challenges created by COVID in 2020.
The imperative to prevent, treat, and cure the deadly COVID-19 virus altered clinical research and drug development priorities and regulatory oversight this past year as the research community devised new strategies for testing compounds with potential to mitigate the virus’ lethal affects. FDA issued guidance and advice on how sponsors could obtain necessary data through modified research programs, while federal agencies provided billions in financial support to accelerate drug and vaccine development and production.
At the same time, FDA faced challenges to its independence and credibility from often divergent demands from the White House. A central topic was how much clinical data FDA would require to approve Emergency Use Authorization (EUA) of experimental COVID therapies and vaccines. FDA’s fairly new commissioner, Stephen Hahn, a respected oncologist, but with little government experience, became entangled in these issues, raising fears about growing public “vaccine hesitancy” if companies and regulators took shortcuts to speed the development of COVID vaccines.
The debate came to a head in October as vaccine experts from leading medical institutions agreed with FDA staff on the need for sufficient safety and efficacy data prior to authorizing any COVID vaccine for administration to millions of individuals. Manufacturers backed FDA’s demand for two months of safety data following vaccination and at least 50% efficacy in a randomized controlled trial. A main question was the ethics and practical challenges of continuing controlled studies after finding one vaccine safe and effective.
The demand for greater access to information on research initiatives exposed the public to a wide range of usually confidential R&D and analytical information. In August, leading vaccine manufacturers began releasing detailed research protocols for Phase III studies, including enrollment goals for treatment and control arms, dosages, and number of COVID cases in each group needed for interim analysis and data safety monitoring board review.
While shifting many FDA staffers to COVID product development and review activities, FDA offices also worked overtime to meet schedules for vetting and approving new drugs and medical products to treat many other medical conditions. At the same time, pandemic restrictions raised challenges in conducting new and ongoing clinical trials, generating wider acceptance of decentralized trials, remote monitoring, streamlined enrollment processes, and updated standards for early termination and unblinding of trials. FDA also advanced policies for ensuring greater diversity in clinical trials, more effective use of real-world evidence in enrollment and data assessment, and use of master protocols and common control arms.
The pandemic slowed, but did not derail FDA initiatives designed to improve the regulatory process. The Center for Drug Evaluation and Research finalized the overhaul of its Office of New Drugs to have more review offices and divisions and a team-based, “integrated review” for assessing NDAs. Generic drugs and biosimilars continued to draw attention as important for managing drug shortages and for ensuring consumer access to affordable medicines.
The public debate on vaccine R&D also highlighted the critical role of FDA’s Center for Biologics Evaluation and Research (CBER) and its director Peter Marks, which issued guidance in June clarifying requirements for developing and testing new COVID preventives. In addition, CBER’s Office of Tissues and Advanced Therapies continued to cope with a surge in proposals for developing new cellular and gene therapies, many raising challenging and unique medical and technical issues.
FDA has approved more than 40 innovative medicines this past year and worked hard to meet user fee timeframes for prescription drugs, generics, and biosimilars–vital programs that face revision and renewal in the coming year. At the same time, officials note that researchers designed and launched more than a thousand clinical trials for COVID treatments, but most, unfortunately, appear too small and inadequately structured to yield any useful information. With COVID-19 again surging across the nation and the world as this historic year draws to a close, the only certainty is that both obstacles and opportunities will continue to challenge biopharmaceutical companies, regulatory authorities, and the research community in the months ahead.
Jill Wechsler is Applied Clinical Trials' Washington Correspondent