Pfizer and BioNTech are asking the FDA to approve a change that would permit storage of their Covid-19 vaccine within a temperature range found in medical-grade freezers.

To be clear, this proposed change doesn’t eliminate the need for ultra-cold temperatures as the vaccine moves throughout the supply chain—temperatures that require specialized equipment. Those storage requirements are a barrier to its distribution because not all facilities have equipment that can achieve the required temperatures. What Pfizer and BioNTech are proposing is that when the vaccine reaches its destination, such as a hospital or pharmacy, it could be stored for up to two weeks at (relatively) warmer freezer temperatures.

The FDA granted emergency use authorization to the messenger RNA vaccine, named Comirnaty, last December. According to the product’s label, the vaccine must be stored in ultra-cold temperatures between minus 112 degrees and minus 76 degrees Fahrenheit (minus 80 degrees and minus 60 degrees Celsius). At those temperatures, the vaccine can last up to six months. Pfizer ships the vaccines in specially designed containers that can be refilled with dry ice every five days. Those containers can serve as temporary storage for up to 30 days.

The vaccine can be stored at refrigerator temperatures for up to five days. Pfizer and BioNTech are asking the FDA to approve an additional option to store the vaccine at minus 13 degrees to 5 degrees Fahrenheit (minus 25 degrees to minus 15 degrees Celsius) for two weeks. That range would put it closer to the storage requirements for the mRNA vaccine from Moderna. The temperature range Pfizer and BioNTech are proposing would be in addition to the five days at refrigerator temperatures that is currently permitted under the authorization.

“If approved, this new storage option would offer pharmacies and vaccination centers greater flexibility in how they manage their vaccine supply,” Pfizer CEO Albert Bourla said in a prepared statement.

Pfizer and BioNTech are proposing the additional temperature option based on new data about their vaccine’s stability. The data span from the earliest clinical trials up to batches currently in production.

Messenger RNA vaccines are a new technology that employ a snippet of genetic material from the novel coronavirus. This mRNA serve as a blueprint that a cell’s protein-making machinery use make the characteristic spike protein found on the surface of the novel coronavirus. That protein is what triggers an immune response and confers immunity.

Though mRNA vaccines are administered at room temperature, they must be kept at ultra-cold temperatures in the supply chain because mRNA is fragile. The extremely cold temperatures keep the components of the vaccine from breaking down. As mRNA companies study the storage data they have for vaccines, they are getting a better understanding of how long these vaccines can last at certain temperatures. Last November, Moderna released data that it said supported storage of its vaccine at refrigerator temperatures for up to 30 days.

Temperature requirements can be a barrier to the distribution of the vaccine to rural areas, which may not have facilities with appropriate freezers. In that regard, the Johnson & Johnson Covid-19 vaccine is seen as offering an advantage. In addition to requiring only a single shot (both authorized mRNA vaccines require two), the J&J vaccine can be stored at standard refrigerator temperatures. An FDA advisory committee is scheduled to hold a hearing about that vaccine on Feb. 26.

Photo by BioNTech

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A second vaccine for Covid-19 has won the blessing of U.S. regulators.

The U.S. Food and Drug Administration on Friday approved for emergency use a vaccine developed by Moderna, a biotech company based in Cambridge, Massachusetts.

The green light comes a week after similar approval was given to a vaccine from New York-based Pfizer and its German partner, BioNTech. That first vaccine is already being deployed on the front lines of a pandemic currently claiming more than 3,000 lives a day in the U.S. and stretching the country’s health care resources to a breaking point.

The approval of Moderna’s vaccine means it, too, will soon join the fight against Covid-19. The U.S. has committed to buying 200 million doses of the vaccine, which is administered in two shots, according to the company. Hospitals are expecting deliveries as soon as next week.

“With the availability of two vaccines now for the prevention of Covid-19, the FDA has taken another crucial step in the fight against this global pandemic that is causing vast numbers of hospitalizations and deaths in the United States each day,” FDA Commissioner Dr. Stephen M. Hahn said in a statement.

The initial shipment from Moderna is expected to total 5.9 million doses, more than double the initial 2.9 million doses of the Pfizer/BioNTech vaccine.

Further, the Moderna vaccine may pose less of a logistical challenge. Unlike the Pfizer/BioNTech product, it does not need to be stored at extremely low temperatures, enabling it to go more places. 

Moderna plans to make 20 million doses available by the end of December.

“We remain focused on scaling up manufacturing to help us protect as many people as we can from this terrible disease,” Moderna CEO Stephane Bancel said in a statement. He said the vaccine, while developed quickly, is based on a decade of research.

The Moderna and Pfizer/BioNTech vaccines are based on a similar platform: messenger RNA, which helps human cells create their own antibodies to the Covid-19 virus. Developed in record time, both vaccines are around 95% effective but generate some temporary side effects, including pain at the injection site, fever, joint pain and headaches. Both also require two doses.

More severe reactions are possible as the vaccines are given to a larger population. Two health care workers in Alaska reportedly developed allergic reactions to the Pfizer vaccine, with one requiring hospitalization. This was also observed in the U.K. 

The Pfizer/BioNTech vaccine is approved for use in people 16 and over, though members of an FDA advisory panel questioned whether there was enough evidence to support use in those under 18. The Moderna vaccine is approved for those 18 and over.

The age difference led to different outcomes for the vaccines when they came before an FDA advisory panel comprised of outside experts. Panelists were voting on whether the vaccines’ benefits outweighed the risks. The Pfizer/BioNTech vaccine was cleared on a 17 to four vote, with one abstention, while the Moderna vaccine was cleared unanimously, also with one abstention. The abstention reflected concern about the broad scope of the question up for approval

“I’m very uncomfortable with the language,” said Michael Kurilla, an infectious disease expert and director of the clinical innovation division at the National Center for Advancing Translation Sciences, a part of the National Institutes of Health.

“I think in the midst of a pandemic and with limited vaccine supply available, a blanket statement for individuals 18 years and older is just too broad,” Kurilla said at the end of the advisory panel meeting on Thursday. “I’m not convinced that for all of those age groups, the benefits do actually outweigh the risks and I would prefer to see it more targeted toward people at high risk of serious and life-threatening Covid disease.”

Another critical question facing the vaccine makers is what to do about people taking part in clinical trials, some of which are expected to last into 2022. The trials are comparing the results in those given the actual vaccine against those given a placebo. Participants are not supposed to know which one they received.

But on a website about their vaccine, Pfizer and BioNTech said they are allowing people who got a placebo in their trial to get the actual vaccine. The offer is limited initially to healthcare workers and nursing-home residents, two groups that have been prioritized for vaccination in the U.S. But it will eventually extend to others. There are nearly 44,000 participants in the Pfizer/BioNTech trial.

Moderna also has a plan for the so-called unblinding of its trial participants, of which there are more than 30,000.

The next vaccine candidates are expected to come before regulators early next year. One candidate is being developed by AstraZeneca and Oxford University. Another is from Johnson & Johnson, which said this week it expects to ask for emergency use authorization in February.

Photo: Michael Burrell, Getty Images

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Red seal and imprint "FDA APPROVED" on white surface. FDA - Food and Drug Administration is a federal agency of the United States Department of Health and Human Services.

Under public pressure from President Donald Trump, the U.S. Food and Drug Administration on Friday night approved the country’s first Covid-19 vaccine, paving the way for its distribution as early as the weekend.

The emergency approval follows the vaccine’s endorsement Thursday by an outside advisory panel to the FDA and comes as the Covid-19 pandemic continues to cut a deadly swath through the U.S.

The move, though, sets up another difficult chapter in the fight against Covid-19: distributing the vaccine to millions of Americans, starting with health care workers and nursing-home residents. The vaccine was developed in record time by New York-based drug maker Pfizer and a German partner, BioNTech

The initial shipment will include 2.9 million doses. Overall, Pfizer and BioNTech are expected to provide 100 million doses of the vaccine over the next few months, enough to immunize 50 million people. It’s still unclear how many doses will be available after that, with the companies and the government reportedly at odds over future deliveries

Given the challenges ahead, the FDA’s approval was cause for measured celebration.

“While a commercially available Covid-19 vaccine is an important milestone on the road to recovery, mass vaccination of the American people represents a monumental effort unlike any we’ve undertaken before,” Andy Brailo, chief customer officer of health care services company Premier Inc., said in a statement. “The distribution and administration of Covid-19 vaccines to the public will be the supply chain and population health challenge of the pandemic.”

It will also represent a public relations challenge, as events leading up to the FDA’s approval renewed fears that the process was being politicized, potentially sowing distrust

In a Friday morning tweet, President Trump publicly lobbied the FDA to act. “Stop playing games and start saving lives!!!” the president wrote. Then, the White House reportedly threatened FDA Commissioner Stephen Hahn to approve the vaccine on Friday or resign. The FDA reportedly had been planning to act Saturday.

Trump announced the approval with a video message on Twitter.

“Today our nation has achieved a medical miracle,” the president said. “We have delivered a safe and effective vaccine in just nine months. This is one of the greatest scientific accomplishments in history.”

In a statement of his own, Hahn played up the scientific rigor underlying the vaccine’s approval.

“Today’s action follows an open and transparent review process that included input from independent scientific and public health experts and a thorough evaluation by the agency’s career scientists to ensure this vaccine met FDA’s rigorous, scientific standards for safety, effectiveness, and manufacturing quality needed to support emergency use authorization,” he said in a statement. “The tireless work to develop a new vaccine to prevent this novel, serious, and life-threatening disease in an expedited timeframe after its emergence is a true testament to scientific innovation and public-private collaboration worldwide.”

But while the vaccine’s benefits have been judged to outweigh its risks, there are some things to be considered. 

Sheba Medical Center’s Dr. Noam Tau, the lead researcher of a recent study assessing the safety of all U.S.-approved vaccines over a twenty year period, believes that no vaccine trial is perfect, and Pfizer’s Phase 3 trials has issues and shortcomings — for instance, the vaccine wasn’t sufficiently tested on some minorities (such as African Americans and Native Americans); not tested on “special populations” (pregnant and lactating women, immunocompromised, patients of 75, children under 16 years old). Further, he added in an email that the endpoint was assessed for symptomatic Covid-19 infection, for which it is 95% efficacious. Efficacy for asymptomatic infections was not tested. These shortcomings should be kept in mind when deciding who should be vaccinated first and in deciding on which populations should be studied next.

Pfizer and BioNTech began a two-year clinical trial of the vaccine in July and announced interim results last month showing it was 90% effective. That was later revised upwards to 95%.

Not surprisingly, the FDA advisory panel questioned whether enough data had been collected on the vaccine’s impact on 16- and 17-year-olds and on pregnant women. Members also questioned whether the vaccine protected against asymptomatic infection, a main channel for spreading Covid-19.

The panel also noted allergic reactions in two British people who had received shots. Most reactions, though, are mild and similar to what happens with other vaccines.

The Pfizer/BioNTech vaccine relies on a relatively new technology known as messenger RNA, which essentially triggers an immune response to Covid-19 without having to inject any of the virus itself. It is given in a series of two shots, 21 days apart.

The distribution challenge begins with the extremely cold temperatures at which the vaccine must be kept: between -60 and -80 degrees Celsius. Questions also have arisen over the medical staff needed to administer vaccines, given the demands of caring for people already sick with Covid-19.

State and health systems have been bracing for the distribution effort, guided in part by recommendations from the U.S. Centers for Disease Control and Prevention.

“While we along with public health officials throughout the country spent countless hours preparing, this mission is fraught with significant challenges that go well beyond just transporting the vaccine from point a to point b,” Pennsylvania Health Secretary Dr. Rachel Levine testified Thursday during a Senate hearing on vaccine transport.

Funding, equity and coordination among the public and private sectors as among the challenges ahead, Levine said, “all confounded by the lack of a coordinated communication strategy to promote confidence in the safety and efficacy of Covid-19 vaccines.”

Next week, an FDA panel will evaluate data from Moderna’s mRNA Covid-19 vaccine. 

“We should remember — no one vaccine, and no one manufacturer will be enough for the US, and definitely not for the whole world’s supply of vaccines,” Dr. Tau said in an email. “This means that the approval of the EUA for Pfizer’s vaccine is not the beginning of the end, but merely an important step towards the end of the beginning of the pandemic. There is a long way to go yet before we are out of the woods, both locally in the US and globally.

Photo: Waldemarus, Getty Images

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