On Dec. 11, the U.S. Federal Drug Administration granted emergency use authorization (EUA) to a vaccine developed by Pfizer and German firm BioNTech to protect against the novel coronavirus, COVID-19, that was identified roughly one year ago in Wuhan, China.

The Press reached out to local hospital networks and long-term care facilities to learn more about these organizations’ plans for offering the Pfizer COVID-19 vaccine to their employees and residents. These healthcare organizations were initially reticent, but that all changed Dec. 19 when both networks raced to provide media with coverage of their “first shots.” See pages A3 and A4 for our coverage.

First-ever emergency vaccine approval

An EUA is a new form of drug authorization created by congress as a response to bioterrorism concerns in the wake of the Sept. 11, 2001, terrorist attacks. Unlike a biological license application (BLA) – the customary method of approving vaccines in the U.S. – an EUA does not certify that a vaccine is safe and effective. Rather, it states the FDA’s opinion that the currently known benefits of the product outweigh the currently known risks for all or a subset of the US population.

No vaccine has ever been authorized in the U.S. solely via an EUA. However, the anthrax vaccine BioThrax, manufactured by Emergent BioSolutions, which has a biological license for pre-exposure prophylaxis, does have an EUA for post-exposure prophylaxis in the event of a bioterrorism attack.

The Pfizer-BioNTech COVID-19 vaccine, BNT162b2, was not only developed and authorized in record time – 11 months, compared with several years for a typical vaccine – but it also uses brand-new mRNA technology. BNT162b2 is a lipid (fat) nanoparticle dispersion of modified ribonucleic acid (mRNA) that carries the code for the spike protein (S) on the outside of the COVID-19 virus. Without carrying the live or inactivated virus itself, this vaccine tells the body of the recipient to make antibodies against the S protein.

Because of its nearly unique design – biotech startup Moderna has been testing its own mRNA vaccine, scheduled for an FDA committee hearing Dec. 17 – the Pfizer vaccine has to be kept very cold (roughly 94 degrees Fahrenheit below zero), must be diluted according to a painstaking process, and has a side effect profile that has only been studied for a median time of two months in trial participants.

At the Dec. 10 Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting, a panel of 22 experts discussed the two months’ worth of data submitted by Pfizer with executives from the drug company, as well as FDA officials. Some of the committee members’ questions – like the duration of follow-up for the African-American volunteers in the study, and the number of study volunteers with food and/or drug allergies – went unanswered by Pfizer. Nevertheless, 17 of the 22 members voted “yes” to the question, “Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 vaccine outweigh its risks for use in individuals 16 years of age and older?”

First priority:

Healthcare workers

The Advisory Committee on Immunization Practices (ACIP), part of the Centers for Disease Control & Prevention (CDC), issued guidance Dec. 11 stating that the first group of Americans who should be eligible to receive any authorized or licensed coronavirus vaccine are health care personnel, defined as “all paid and unpaid persons serving in healthcare settings who have the potential for direct or indirect exposure to patients or infectious materials […]. These HCP may include, but are not limited to, emergency medical service personnel, nurses, nursing assistants, physicians, technicians, therapists, phlebotomists, pharmacists, students and trainees, contractual staff not employed by the health care facility, and persons […] not directly involved in patient care but potentially exposed to infectious agents that can be transmitted among from HCP and patients.” Dental healthcare personnel, autopsy personnel, and laboratory personnel are not included in the ACIP definition of HCP (https://www.cdc.gov/infectioncontrol/guidelines/healthcare-personnel/appendix/terminology.html).

Lehigh Valley Health Network (LVHN) was one of the Pfizer vaccine trial sites, with 75 employees or patients taking part in the third phase, under the direction of principal investigator (PI) Dr. Joseph Yozviak (https://news.lvhn.org/lvhn-employees-patients-and-community-members-participating-in-covid-19-clinical-trial/). LVHN had not responded to multiple requests for comment from the Press, so it was unclear when this article was written whether the hospital would require or even offer the vaccine to its staff. That all changed last Thursday.

There does, however, appear to be some confusion regarding what an EUA signifies. In LVHN-generated media (https://news.lvhn.org/covid-19-vaccines-the-clinical-trials-and-what-we-know-right-now/), Dr. Yozviak says, “I can assure you that the FDA will not issue an Emergency Use Authorization or approve the vaccine without data proving that this vaccine is safe and effective.” This stands in contrast to the definition of an EUA, as well as the explicit instructions of Dr. Marion Gruber, director of the FDA Office of Vaccines Research & Review. During the Dec. 10 VRBPAC meeting, Dr. Gruber told the committee members, “We are looking at whether the benefits outweigh the risks, not whether it’s safe and effective.”

The paucity of data supporting safety and efficacy underlies the decision of UPMC (as reported by PennLive: https://www.pennlive.com/news/2020/12/upmc-wont-require-employees-to-get-covid-19-vaccine.html) not to require its employees to take the Pfizer vaccine. UPMC does compel its employees to get an annual flu shot, but medical director Dr. Graham Snyder contrasts the hospital system’s “decades of [flu vaccination] experience” with the hastily developed and speedily approved Pfizer COVID-19 vaccine.

Neither St. Luke’s University Health Network nor Lehigh Valley Health Network responded to multiple requests for comment regarding their plans to offer the Pfizer vaccine to their employees. Both began vaccinating employees Dec. 17.

Second in line:

Nursing home

residents

The second priority group defined by ACIP are residents of long-term care facilities, and the federal government has created a program to expedite vaccination of these individuals.

As noted by Anita Patel, CDC Vaccine Task Force deputy, during the Dec. 11 meeting, the vast majority of long-term care facilities in the U.S. had already chosen by Nov. 15 to participate in this program. This program, run by the CDC (https://www.cdc.gov/vaccines/covid-19/long-term-care/pharmacy-partnerships.html), allows a drugstore company selected as a federal partner to manage the entire process of ordering, cold chain management, and administration of any authorized or licensed coronavirus vaccine to nursing home residents and any employees who have not been vaccinated through another program. National pharmacy partners include CVS and Walgreens; in some states, additional companies are part of the program.

Morningstar Senior Living, Inc., a not-for-profit organization based in Nazareth, has two campuses as well as operating Senior Solutions, a home care service. Its Moravian Hall Square campus in Northampton County has residences, assisted living accommodations, and a skilled nursing facility. This campus has consistently earned a spot on the US News & World Report “Best Nursing Homes” list.

According to Morningstar spokeswoman Liz Brundl, the skilled nursing facility at Moravian Hall Square is enrolled in the pharmacy partnership program; however, no start date has been set, nor has a specific vaccine been selected. (The Pfizer-BioNTech vaccine is the only one that has received an EUA as of press time; however, a similar mRNA vaccine developed by Moderna is under EUA review at FDA, and may have been authorized as soon as Dec. 18.)

Vaccines will be administered at Moravian Hall Square by CVS Pharmacy; CVS will also perform all reporting duties associated with the vaccine. According to CDC information on the program, a jurisdiction – in this case, the Pa. Department of Health – must provide two weeks’ notice in order to receive an allotment of vaccines for participating facilities.

Neither Alexandria Manor nor Country Meadows responded to multiple requests for comment regarding any plans they have to offer the vaccine to employees, or whether they are participating in the national pharmacy partnership program.

Not right

for everyone

Although the authorization letter sent to Pfizer by FDA does not require the drug company to provide adverse event information until Feb. 15 (15 days after the end of the first full calendar month following EUA), reports of anaphylaxis have already emerged.

According to Pfizer safety officer Dr. Patrick Caubel, three patients in the UK suffered immediate anaphylactic or related events. Two were on the first day of vaccinations, when 6,000 UK healthcare workers received shots. One had known food allergies to eggs, cheesecake, lemons, and limes; the second had drug allergies, although Dr. Caubel did not know which drugs. The third was a patient who developed skin redness and supraventricular tachycardia (abnormally fast heartbeat) just after receiving the vaccine.

In the U.S., a healthcare worker in Alaska suffered an anaphylactic reaction after receiving the Pfizer vaccine Dec. 15. She did not have any known allergies, was treated with epinephrine and steroids, and was still hospitalized in the intensive care unit Dec. 16, as reported by the New York Times and Metro UK.

Fact sheets mandated for distribution to all recipients of this emergency-authorized vaccine, as well as their caregivers, include statements that “The Pfizer-BioNTech COVID-19 vaccine may not protect everyone,” “The Pfizer-BioNTech COVID-19 vaccine is an unapproved vaccine,” and “The duration of protection against COVID-19 is currently unknown.” Recipients are notified that “It is your choice to receive or not receive the Pfizer-BioNTech COVID-19 vaccine,” and further instructed that “Should you decide not to receive it, it will not change your standard medical care.”

Fact sheets also include information on how to find out about the Countermeasures Injury Compensation Program (CICP), administered by the Health Resources & Services Administration (HRSA), part of the U.S. Dept. of Health and Human Services (HHS). Congressional legislation prohibits vaccine recipients from suing vaccine manufacturers for any alleged vaccine-related injury; individuals injured by a vaccine must request compensation from a non-tort system administered and funded by the federal government (www.hrsa.gov/cicp). HRSA is a payor of last resort, so any compensation it awards is reduced by the amount that an individual’s health or life insurance pays out.

At the Dec. 10 VRBPAC meeting, both committee members and commenters from the public, voiced concerns about EUA of this vaccine.

Committee member Dr. A. Oveta Fuller, associate professor of microbiology and immunology at the University of Michigan Medical School, voted “no” after describing what she saw as the problem: “So we’re putting a messenger RNA in a lipid in people who have never gotten either before? And with a very limited amount of risk assessment? We don’t know what’s going to happen long-term to these people. I think the uptake in the community is going to be fairly poor.”

Attorney Sheldon Toubman, who is also a VRBPAC member, voted “yes” and appeared to support authorizing the vaccine for healthcare workers and nursing home residents, but criticized the FDA’s specific voting question. “Can the EUA be limited to the groups that ACIP has already identified?” he asked, adding, “The data is limited in so many ways. It’s not compelling at all. If you grant an EUA broadly, it’s going to present problems.” Toubman also asked the Pfizer executives at the meeting to provide data beyond the Nov. 14 material the company had already submitted, but they declined, citing the time it takes to analyze data, and the lack of additional infections.

Committee member Dr. Pamela McInnes of the National Institutes of Health (NIH) questioned the drug company’s ability to advertise the product or compensate physicians and patients in the event of an EUA. Dr. Doran Fink of the FDA Office of Vaccines Research and Review clarified the regulations: “An EUA does not allow for commercial distribution of the vaccine via the usual marketing that would be available to a licensed vaccine […] In terms of transfer of money between vaccine recipients and providers, or between the U.S. government and the manufacturer, I can’t speak to that.”

Dr. Peter Doshi of the University of Maryland, who is an associate editor at the British Medical Journal (The BMJ), spoke during the public comment portion of the meeting to encourage the committee not to grant an EUA, but to provide access to the vaccine through the FDA expanded access pathway. Expanded access allows individuals who want to receive an unapproved product that may or may not help their serious medical condition, to request that product through the FDA.

Doshi specifically asked the committee to consider whether trial participants were able to guess, based in part on side effects they may have experienced, whether they were in the experimental group, making the study not truly blind to participants. He also asked what effect fever and pain relief medications might have had in masking symptoms, thus driving down testing for coronavirus, particularly in the vaccine group, leading to potentially higher-than-actual estimates of vaccine efficacy.

“In the real world,” Doshi said, “the mantra has been to ‘test, test, test.’ But this wasn’t the case in the trial. The study protocol says in the seven days after vaccination, do not test unless, in the investigator’s opinion, the clinical picture suggested COVID rather than vaccine side effects. This amounts to asking investigators to make guesses as to which intervention group patients were in.”

WHO spokeswoman Margaret Harris was reassuring. “People should not be too anxious,” she said. “There are a number of vaccine candidates coming online at the same time. One vaccine may not be right for particular individuals, but you may well find another vaccine is.”

According to The Wall Street Journal, the study enrolled more than 44,000 participants.