Friday, December 18, 2020

Capping a nearly year-long effort, the U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) of Moderna’s mRNA vaccine against SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19), after the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) voted yesterday 20-0, with 1 abstention, that the benefits of the vaccine outweigh its risks.

This comes less than 1 week after the FDA granted emergency use authorization to a similar vaccine made by Pfizer and BioNTech.

During yesterday’s deliberations, the advisory committee discussed plans to unblind participants in existing clinical studies, and considered whether scientific integrity requires placebo control of continuing studies. One possible solution that was discussed is a blinded crossover design. An additional research question is how to study whether vaccines protect against asymptomatic transmission. The committee member who abstained from the final vote said that expanded access would be better than emergency use authorization. Generally, the FDA adheres to the recommendations of its advisory committees, with only rare exceptions.

The Pfizer/BioNTech and Moderna mRNA vaccines are the first two of their kind: they contain ribonucleic acid (RNA) encased in lipid nanoparticles. The nanoparticles deliver the RNA to cells in the body of the person receiving the vaccine. Ribosomes, which are parts of all cells, then translate the RNA into spike protein which then produces an immune response.

The emergency use authorization of a second vaccine comes as a welcome addition to the first, since no one single company can make enough vaccine for every person in the world (5–8 billion doses will be necessary for herd immunity depending on whether the vaccines prevent asymptomatic transmission or not). Also, the Moderna vaccine must be stored at -20°C (-4°F) which, while very cold, is easier to attain than the -70°C (-94°F) ±10°C required for storage of the Pfizer/BioNTech vaccine which requires vast quantities of dry ice and special, ultra-low-temperature freezers.

In the United States, the first shipment of each vaccine (for example, 3 million doses of the Pfizer-BioNTech vaccine) will be reserved for health-care workers and nursing homes. Pfizer expects to manufacture 20 million doses of their vaccine in time to be administered this year, and 100 million by March. After nursing-home residents and health-care workers, the next people in line to receive the vaccines will be those over 65 years of age and those with significant co-morbidities and risk factors, and some essential workers. The general public in the United States can expect to have vaccines available in their doctors’ offices or pharmacies later in the spring of 2021.

The vaccine is designed to be taken twice; the second dose of the Moderna vaccine should be administered 4 weeks after the first. The second dose of the Pfizer/BioNTech vaccine should be administered 3 weeks after the first, and people should take the same brand twice.

The legal authority for emergency-use authorization is in section 564 of the Federal Food, Drug, and Cosmetic Act. An EUA is less than a full approval, and represents a determination by the FDA that

• The disease must be serious or life-threatening.
• The vaccine may be effective to prevent, diagnose, or treat the disease.
• The known and potential benefits of the vaccine outweigh the known and potential risks of the vaccine.
• No adequate, fully-approved, alternative product is available to prevent the disease.

The vaccine development process normally takes 5–20 years, but scientists developed the new vaccines in record time by building on their experience with SARS and by performing many of the development, manufacturing, and testing steps in parallel.

COVID-19 is a respiratory and hematologic disease caused by SARS-CoV-2, a positive-sense single-stranded RNA virus believed to have originated in bats. The virus typically causes a cold-like or flu-like illness, but illness severity ranges widely from no symptoms at all to death, and it is very contagious. Although many cases are asymptomatic (50% of all transmission is from asymptomatic and pre-symptomatic persons), the disease has killed over 1.5 million people (294,874 of whom are in the United States) in only a year.

Donald Trump had directed the FDA commissioner to issue the EUA for the first (Pfizer/BioNTech) vaccine by the end of the day on Friday, December 11. Researchers continue to test 63 different vaccines against the coronavirus on humans.

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• “FDA Takes Additional Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for Second COVID-19 Vaccine” — Food and Drug Administration, December 18, 2020
• “Vaccines and Related Biological Products Advisory Committee December 17, 2020 Meeting Announcement” —  December 16, 2020
• “Moderna announces longer shelf life for its COVID-19 vaccine” — Moderna, December 16, 2020
• “FDA Takes Key Action in Fight Against COVID-19 By Issuing Emergency Use Authorization for First COVID-19 Vaccine” — Food and Drug Administration, December 11, 2020
• “Covid-19 Vaccine Tracker” — The New York Times, December 11, 2020
• “Who will get the coronavirus vaccine first?” — The New York Times, December 11, 2020
• “Covid-19 Live Updates: F.D.A. Expected to Issue Pfizer Vaccine Authorization on Friday Evening” — The New York Times, December 11, 2020
• Reis Thebault, Meryl Kornfield, Carolyn Y. Johnson, Laurie McGinley, Paulina Firozi, Kim Bellware, Erin Cunningham, Hamza Shaban, Miriam Berger. “U.S. sets death record again as FDA advisers recommend Pfizer-BioNTech vaccine” — The Washington Post, December 10, 2020
• Josh Dawsey and Laurie McGinley. “White House orders FDA chief to authorize Pfizer-BioNTech vaccine Friday or submit his resignation” — The Washington Post, December 11, 2020
• Fernando P. Polack, M.D., Stephen J. Thomas, M.D., Nicholas Kitchin, M.D., Judith Absalon, M.D., Alejandra Gurtman, M.D., Stephen Lockhart, D.M., John L. Perez, M.D., Gonzalo Pérez Marc, M.D., Edson D. Moreira, M.D., Cristiano Zerbini, M.D., Ruth Bailey, B.Sc., Kena A. Swanson, Ph.D., et al., for the C4591001 Clinical Trial Group. “Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine” — New England Journal of Medicine, December 10, 2020
• “Public hearing of the Vaccines and Related Biological Products Advisory Committee” —  December 10, 2020
• “Covid 19 Vaccine U.S. Distribution Fact Sheet” — Pfizer, November 20, 2020
• “COVID-19, SARS-CoV-2 and the Pandemic (Lecture 1)” — MIT, September 3, 2020
• “COVID-19, SARS-CoV-2 and the Pandemic (Lecture 8: Vaccines)” — MIT, September 3, 2020
• “Coronavirus Resource Center” — Johns Hopkins University, December 11, 2020
• “Morbidity and Mortality Weekly Report” — Centers for Disease Control, December 11, 2020