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Experts discuss the FDA’s COVID-19 emergency clearances and how to recalibrate the regulatory mechanism.
When COVID-19 entered the United States, individuals across the country took urgent adaptation measures. But they were not alone. Government agencies tasked with protecting the nation’s health have also stepped up to provide access to needed medical supplies.
Under the Federal Food, Drug and Cosmetic ActSecretary of the United States Department of Health and Human Services (HHS) declared the COVID-19 pandemic a public health emergency warranting emergency use authorizations (EUAs) of various products used to control the virus. In turn, the United States Food and Drug Administration (FDA) authorized the use of otherwise unapproved medical products for the testing, treatment and vaccination of COVID-19.
To issue an EUA, the FDA must Check that several criteria for each product have been met: (1) the product responds to a serious or life-threatening emergency, (2) the given product “may be effective” as a countermeasure to that emergency, (3) known effects, and the potential benefits outweigh the known and potential risks, and (4) there are no approved alternatives available.
However, the EUA way serves as a relatively new regulatory tool for the FDA. An EUA brings a product to market based on the best available evidence rather than waiting for all the evidence typically required for full FDA clearance. FDA Posted its first EUA in 2005 for the use of an anthrax vaccine—Absorbed– and since Posted EUA in response to five other infectious disease outbreaks.
Since the start of the COVID-19 pandemic, the FDA has Posted more than 600 EUAs for personal protective equipment, drugs, medical equipment, diagnostics and vaccines. Such unprecedented use of emergency permissions distinct the COVID-19 pandemic from past public health crises. For example, the FDA Posted only 22 EUAs during the H1N1 pandemic.
In addition to the FDA’s response, former HHS secretary Alex Azar invoked the Public Preparedness and Civil Protection Act in February 2020, granting private manufacturers, healthcare professionals, and others identified by the Secretary of HHS broad legal immunities for all COVID-19 countermeasures authorized through an EUA.
The proliferation of EUAs during the COVID-19 pandemic has capture the attention of experts, raising concerns about standardizing a process that bypasses the traditional approval mechanism. Accelerated access, some experts Argue, must be weighed against the FDA’s rigorous safety and efficacy standards. In addition, experts fear that the current EUA pathway remains susceptible to political influence because the legal standard for issuing an EUA leaves room for undue discretion.
In this week’s Saturday seminar, scholars explore the use of EUAs during the COVID-19 pandemic and how FDA officials might recalibrate the EUA mechanism for future public health emergencies.
- In a article published in the Journal of Food and Drug Law, Efthimios Parasidis, Micah L. Bermanand Patricia J. Zettler of The Ohio State University argue that the FDA has issued an unprecedented number of EUAs based on scarce evidence due to the pressurized pandemic context. Parasidis, Berman and Zettler to suggest ways to improve the EUA framework within the existing FDA statutory authority, including requiring manufacturers to perform more demanding clinical trials, conditioning EUAs on robust post-marketing observational studies, and issuing guidance identifying a risk-based framework for evaluating device EUAs. They too combat that the U.S. Congress should consider amending the Federal Food, Drug, and Cosmetic Act to incorporate a more robust standard for vaccine EUAs due to their unique clinical and ethical concerns.
- In a article published in the Journal of Law and Biosciences, Walter G Johnson and Gary E. Marchant of the Arizona State University Sandra Day O’Connor College of Law argue that the history of public health legislation is characterized by a “punctuated equilibrium”, long periods of stability followed by new crises that cause brief periods of rapid change. Johnson and Marchant Explain that nearly all major changes in the legislative authority of public health agencies, such as the FDA and EPA, stem from high-profile public tragedies or crises attributable, at least in part, to regulatory failures. Thus, as a major public health crisis, the COVID-19 pandemic has created a political window to reform diagnostics and vaccine regulation, Argue Johnson and Marchant. They to fearhowever, that by circumventing procedural standards, emergency policymaking will result in regulatory agendas that do not address longer-term interests and concerns.
- In a article in the Journal of Food and Drug Law, Yaniv Heled of Georgia State University College of Law, Ana Santos Rutschman of Saint-Louis University Faculty of Lawand Liza Vertinsky of Emory University School of Law say public health emergencies require regulators, including the FDA and the Centers for Disease Control and Prevention (CDC), to engage in evidence-based decision-making. Heled, Rutschman and Vertinsky Argue that “regulatory responsiveness,” a mode of regulation that deviates from evidence-based decision-making in response to external pressures, is problematic because it favors short-term problem solving over public health goals long-term. Although the existing legal framework failed to cope with regulatory responsiveness, insulate agencies from outside influences, establish decision-making procedures in advance for emergencies, and increase the level of scrutiny applied to agency decisions during emergencies could reduce negative impacts, according to Heled, Rutschman and Vertinsky.
- The rapid approval and revocation of FDA authorization of hydroxychloroquine to treat COVID-19 illustrates concerns about the EUA process, say Kyle Thomsonformer lawyer of American Medical Associationand Herschel Nachlis of Dartmouth College in a article in the Journal of the American Medical Association. Issues such as a lack of scientific evidence and pressure from advocacy groups without health expertise present complications for FDA regulators. Thomson and Nachlis combat that health-related advisory committees and accessible communication with the general public will enhance FDA’s efforts to protect public health while ensuring high standards and accountability.
- National regulators should review the use of EUAs during the COVID-19 pandemic to ensure adequate procurement, approvals and imports of essential medical products during future crises, Argue Almir Badnjevic of the University of Warwick and several co-authors. In a paper Posted in Biomedical Engineering Online, Badnjevic’s team praises the FDA-defined validation process for mechanical ventilator EUAs, which has allowed manufacturers to make minor changes to already approved products and control ventilator shortages. Likewise, the FDA published regulation of quality systems to ensure the safety of the production of personal protective equipment. However, the authors prevent EUAs are risky. In response, Badnjevic’s team recommended that regulatory agencies define minimum technical specifications and coordinate an international medical product inventory database to maintain consistent diagnostic standards.
- In a article Posted in Health Affairs, Aaron S. Kesselheim of Harvard Medical School and several co-authors assess FDA vaccine approval mechanisms, comparing the traditional approval process to the EUA process used during the COVID-19 pandemic. Kesselheim’s team review of recent vaccine trials found that the majority of these trials used immunogenicity – the tendency of a vaccine to elicit an immune response – to measure effectiveness, as opposed to the more traditional measure of disease incidence, such as the rate of new cases of a disease. But the immunogenicity is a less reliable metric when dealing with a new pathogen, according to Kesselheim’s team. Balancing accelerated availability and security considerations, Kesselheim and coauthors Argue that the FDA should continue to use the EUA pathway for vaccines during public health crises, but also implement post-approval systems to detect adverse events, such as the CDC Vaccine Safety Data Linkand vaccine injury compensation programs.
The Saturday Seminar is a weekly feature that aims to put into written form the type of content that would be conveyed in a live seminar involving regulatory experts. Every week, Regulatory Review publishes a brief overview of a selected regulatory topic, then distills recent research and academic writing on that topic.