Earlier this month, a group of twenty-seven scientists, clinicians, and patient advocates submitted a formal "Citizen Petition" with the United States Food and Drug Administration (FDA), requesting the agency to halt any consideration of a "full approval" of COVID19 vaccines. The message from the experts is, "slow down and get the science right—there is no legitimate reason to hurry to grant a license to a coronavirus vaccine." In a BMJ letter, the group urged:
"We believe the existing evidence base—both pre- and post-authorization—is simply not mature enough at this point to adequately judge whether clinical benefits outweigh the risks in all populations."
Currently not approved by the FDA, the COVID-19 vaccines are available under emergency use authorizations (EUA). The petitioners argue the spike protein-inducing vaccines lack the standard rigorous regulatory research necessary for approval to ensure the safety and effectiveness of the vaccines—issues that can only be addressed by further critical and meticulous studies.
The scholars—who maintain their petition does not debate the benefits or risks of the vaccines—argue additional focus must be centered on the many remaining unknowns and open questions about the safety and effectiveness of COVID-19 vaccines that can only be addressed by deeper analysis.
As outlined in Title 21 of the Code of Federal Regulations (21 CFR Part 10), the FDA citizen petition process provides the opportunity to request the agency execute changes to health policy. The regulation states that at any time, any "interested person" can request the FDA "issue, amend or revoke a regulation or order," or "take or refrain from taking any other form of administrative action."
If the FDA grants a pause to study COVID-19 vaccines properly, serious consideration to approval will not occur until 2022. Noting that time is of the essence, the petition lists several significant requests:
- The FDA requires manufacturers to submit data from completed Phase III trials—not interim results. Trials by vaccine manufacturers were designed to follow participants for two years. They should be completed before they are evaluated for full approval, even if they are now unblinded and lack placebo groups. These Phase III trials are not simply efficacy studies; they also are necessary and essential safety studies (as the study titles say), and all collected data remains invaluable.
- The FDA demands a more thorough assessment of spike proteins produced in-situ by the body following vaccination—including studies on their full biodistribution, pharmacokinetics, and tissue-specific toxicities.
- The FDA demands manufacturers complete proper biodistribution studies that would be expected of any new drug and request additional studies to better understand the implications of mRNA translation in distant tissues.
- In consideration of plans for future COVID-19 booster shots, we call on data demonstrating a thorough investigation of all serious adverse events reported to pharmacovigilance systems, carried out by independent, impartial individuals, and for safety data from individuals receiving more than two vaccine doses.
- The FDA requires necessary studies in specific populations, including those previously infected with SARS-CoV-2, pediatric subjects, and those with immunological or other underlying medical complexities.
- Given the nature of the novel vaccine platforms, our petition asks for experts in gene therapy to be included among the external committee advising the FDA.
The petition points out there is no need to rush COVID-19 vaccine approval to "help stop the pandemic" because the vaccines are already readily available to those who want them under EUA, which can "remain in place even after the expiry of the SARS-CoV-2 public health emergency declaration, as is the case for various Zika products." Nevertheless, with both Pfizer and Moderna submitting formal applications in the past month for "full approval," time is of the essence in taking steps to study these unprecedented vaccines properly.
Explaining that only time and better evidence will yield answers, the petitioners remark that "for each covid-19 vaccine, the benefits may ultimately outweigh the harms. Or not. Or we may end up in a more nuanced position, finding that benefits outweigh harms for some populations, but not others". We must allow the scientific process the time required "to gather and assess the evidence to be confident in the decisions we ultimately have to make."
In fact, the petitioners assert the "inherent unintended consequences of a rushed approval may contribute to growing mistrust of the U.S. public health and regulatory institutions." Then, commenting on "the elephant in the room," they offer their professional insight, advising:
Publicly raising any element of hesitation about covid-19 vaccines will be seen by some as irresponsible, stoking unfounded fears in the public's mind and contributing to the "vaccine hesitancy" problem trumpeted every day. But the alternatives—privately raising concerns or simply remaining silent—are arguably more detrimental to public trust in the long run. Staying silent is not the responsible option. And the implications of only privately raising concerns to regulatory bodies are murky—most would probably not be acted upon, and if they were, it would promulgate the baggage of insufficient accountability and transparency in decision making."
Led by Linda Wastila, Professor and Parke-Davis Endowed Chair of Geriatric Pharmacotherapy at the University of Maryland Baltimore School of Pharmacy, the petitioners believe the Citizen Petition offers the most responsible approach for them to "voice our concerns in our own words, in a professional and transparent manner, through a formal mechanism that can promote accountability in regulatory decision making."
The petition author and co-authors include:
- Linda Wastila, BSPharm, MSPH, Ph.D. and professor at University of Maryland School of Pharmacy
- Peter Doshi, Ph.D., associate professor at University of Maryland School of Pharmacy
- Patrick Whelan, MD, Ph.D. associate clinical professor of pediatrics David Geffen School of Medicine at UCLA
- Hamid A. Merchant, BPharm, MPharm, Ph.D., RPh, CQP, PGCertHE, FHEA, SRPharmS and subject leader department of pharmacy at University of Huddersfield
- Donald W. Light, Ph.D. and professor of comparative health policy and psychiatry at Rowan University School of Osteopathic Medicine
- Florence T. Bourgeois MD and associate professor of pediatrics at Harvard Medical School
- Robert M. Kaplan, Ph.D. and distinguished research professor UCLA Fielding School of Public Health
- Peter A. McCullough, MD and professor at Texas A & M College of Medicine
- Anthony J Brookes, Ph.D. and professor of genetics University of Leicester
- David Healy, MD, FRCPsych and professor of psychiatry McMaster University Ontario, Canada
- Byram Bridle, viral immunologist and associate professor at University of Guelph, Ontario
- Kim Witczak, founder and CEO of Woodymatters and global drug safety advocate
- Christine Stabell Benn, MD, Ph.D. and professor of global health at University of Southern Denmark
- Matthew Herder, JSM, LLM, Director, Health Law Institute at Dalhousie University Nova Scotia, Canada
- Tom Jefferson, MD, MRCGP FFPHM, British epidemiologist who works with the Cochrane Collaboration, advisor to the Italian National Agency for Regional Health Services and is senior associate tutor at University of Oxford
- Peter Collignon, infectious disease physician, microbiologist at Canberra Hospital and professor at the Australian National University Medical School
- Peter C. Gøtzsche, Professor, DrMedSci, MD, MSc Director Institute for Scientific Freedom Copenhagen, Denmark
- Peter Aaby, MSc, DMSc, Head of Bandim Health Project, Guinea-Bissau University of Southern Denmark
- Ulrich Keil, MD, MPH, Ph.D., FRCP professor emeritus University of Münster, Germany
- Juan Erviti, PharmD, Ph.D. Unit of Innovation and Organization Navarre Health Service, Spain
- Iona Heath, CBE FRCGP and past president of the Royal College of General Practitioners London, UK
- Joseph A. Ladapo, MD, Ph.D. associate professor of Medicine David Geffen School of Medicine at UCLA
- Barbara Mintzes, BA, MSc, Ph.D., associate professor, School of Pharmacy at the University of Sydney, Australia
- Huseyin Naci, MHS, Ph.D. associate professor of Health Policy London School of Economics and Political Science
- Angela Spelsberg, MD, Comprehensive Cancer Center Aachen, Germany
- Erick Turner, MD, associate professor of psychiatry at Oregon Health & Science University
- Allyson M Pollock, MBChB, FRCPH, FRCP, FRCGP, clinical professor of Public Health Institute of Health and Society, Newcastle University and director of the Newcastle University Centre for Excellence in Regulatory Science.
*Last updated on August 3, 2021 to include updated link for commenting on the petition.