FDA Authorizes First COVID-19 Vaccine in the US, Begins Distribution

An original version of this article was published to sister publication Contagion.

On Friday evening, the US Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) to BNT162b2, as the first vaccine for the prevention of coronavirus 2019 (COVID-19) in the US.

The authorization, granted to Pfizer and BioNTech, began a new stage of clinical response to a global pandemic which has afflicted more than 15 million Americans and killed 300,000 more in only 10 months.

This landmark decision also punctuated an unprecedented endeavor among pharmaceutical collaborators, clinicians, and federal agencies: the conception, creation, assessment, and regulation of a messenger RNA (mRNA) vaccine for a deadly, highly transmissible virus—again, in only 10 months.

As one virologist told Contagion® this week, this EUA could mark “the beginning of the end” of the COVID-19 pandemic.

The Authorization

The FDA and Pfizer announced that emergency authorization was granted to BNT162b2 for the prevention of COVID-19 in persons aged 16 years and older in the US.

The EUA was granted based on data from an ongoing, real-world, multinational phase 2/3 assessment of the mRNA vaccine versus placebo in the indicated age group. The data, shared by the FDA prior to the Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting for BNT162b2 on Thursday and submitted with the EUA application in November, showed a 95% overall vaccine efficacy among treated participants without previous SARS-CoV-2 infection prior to 7 days after their second dose of the vaccine.

At the time of their EUA submission, Pfizer had reported just 8 COVID-19 cases among the 18,198 eligible participants given the vaccine, versus 162 among those given placebo.

The FDA’s authorization was also supported by the endorsement of the expert VRBPAC panel which, after a lengthy series of public sessions scrutinizing the clinical efficacy and safety of BNT162b2, voted 17-4 with 1 abstention to support its benefit-risk profile in preventing COVID-19.

In a peer-reviewed article of the trial data published on The New England Journal of Medicine Thursday, investigators stressed the findings carry significance beyond overall performance of the vaccine.

"The results demonstrate that COVID-19 can be prevented by immunization, provide proof of concept that RNA-based vaccines are a promising new approach for protecting humans against infectious diseases, and demonstrate the speed with which an RNA-based vaccine can be developed with a sufficient investment of resources," they wrote.

As they noted, BNT162b2 was initiated on January 10 of this year, at the time of the China government's release of the SARS-CoV-2 sequence.

"This rigorous demonstration of safety and efficacy less than 11 months later provides a practical demonstration that RNA-based vaccines, which require only viral genetic sequence information to initiate development, are a major new tool to combat pandemics and other infectious disease outbreaks," they wrote.

The Vaccine

BNT162b2 is a nucleoside-modified mRNA vaccine which encodes SARS-CoV-2 full-length spike protein glycoprotein. Of the 4 initially assessed COVID-19 vaccines from Pfizer, it was designated for greater assessment in late July, at a two-dose regimen of 30 mcg. Just prior to that designation, the FDA granted Fast Track Designation to the candidate.

The mRNA vaccine platform is novel in regulated use, but has been under investigation for nearly 2 decades. As William Schaffner, MD, professor of Prevention Medicine at the Vanderbilt University Medical Center told Contagion, the expedited progression of COVID-19 mRNA vaccines including BNT162b2 and Moderna’s mRNA-1273 are preceded by 10-15 years’ worth of clinical assessment.

As Schaffner explains in the video below, the two-dose vaccine serves as a delivery of “genetic instructions” that leads to the creation of antibody response to the spike protein glycoprotein. The first and second vaccine doses have been administered 21 days apart in clinical assessment, though Schaffner stressed developed immunity would not be comprised by a “late” second dose.

“It takes about 2-3 weeks for the immune system to get primed up, then it’s ready to go,” he explained.

As per Pfizer’s available phase 2/3 data, solicited adverse events in the 7 days following vaccination were fairly common among trial participants. Common solicited local reactions included injection site pain, swelling, and redness. Common solicited systemic events included fever, fatigue, headache, chills, vomiting, diarrhea, and new or worsened muscle joint pain.

In response to the symptoms possibly giving would-be patients pause, Schaffner stressed the impossibility of getting COVID-19 from the vaccine.

The Distribution Plan

Pfizer currently projects to produce 50 million vaccine doses globally by the end of this year, then up to 1.3 billion doses by the end of 2021. The company also reached an agreement with the US Department of Health and Human Services (DHHS) to meet the US Operation Warp Speed program goal of 300 million COVID-19 vaccine doses by next year.

Through the agreement, the federal government will receive 100 million BNT162b2 doses upon EUA approval, for a cost of $1.95 billion and an option to acquire another 500 million doses.

Last week, the 15-member Advisory Committee on Immunization Practices (ACIP) voted 13-1 to prioritize frontline healthcare providers and long-term care residents—the latter being deemed most at risk of COVID-19 severity—for the first available doses of an impending vaccine.

The unique properties of BNT162b2 and the current need for expedited distribution of doses during the greatest outbreak of new US COVID-19 cases yet pose a unique challenge to Pfizer. The company stated they will ship vaccines in temperature-controlled thermal packages that can maintain a temperature of -70 degrees Celsius through dry ice.

As some experts have explained to Contagion, appropriately storing and administering such vaccines could make the difference in their efficacy.

What’s Next

While the authorization of BNT162b2 allows for the indicated administration of the vaccine among persons in the US, assessment and monitoring pertinent to its EUA allowance will be ongoing.

As Angela Rasmussen, PhD, of the Georgetown Center for Global Health Science and Security, told Contagion, there is currently little to no understanding of how investigated COVID-19 vaccines influence viral loads and community transmission risk—outcomes that can only be observed in larger vaccinated populations over longer period of times.

That means a continuation of COVID-19 spread-mitigation strategies, regardless of one’s own vaccination status.

“Even if you are in the first group to get the vaccine, even if the vaccine becomes available widely beyond the first groups that are going to get it, we still need to be wearing masks, social distancing, thinking about ventilation, and avoiding large gatherings for some time to come,” Rasmussen said.

Rasmussen further stressed caution to the US public going forward—emphasizing that, while the currently available BNT162b2 safety data is certainly warranting of its EUA indication, there is likely to be newly reported adverse events associated with the vaccine once it begins to be distributed to the greater population.

Given these uncertainties circling the vaccine, as well as the rate of vaccine hesitancy or opposition in the general population, Rasmussen anticipates a resumption of normalcy—a management of COVID-19 transmission without social distancing mandates—to come in late 2021.

In the meantime, there will be more COVID-19 vaccines considered for emergency authorization. Moderna’s mRNA-1273 vaccine will undergo its own VRBPAC public hearing on Thursday, December 17, after reporting efficacy rates and a safety profile similar to that known of Pfizer’s.

2020, the same year marked by burden brought on the COVID-19 pandemic, may very well close with multiple vaccines becoming available to the US public. Experts now stress people should consider these options seriously when the opportunity for vaccination reaches them.

“Take a look at this data, listen to science and physicians, listen to people who are explaining what the data actually says,” Rasmussen advised. “So far, that data says these vaccines are safe and highly efficacious, and you should consider taking them when they’re available.”