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Pharmaceutical companies, Pfizer and Moderna, have announced promising interim results for candidate vaccines, raising hopes in the United States. And abroad The end of the epidemic may be imminent. However, if and when vaccines are licensed by the Food and Drug Administration, distributing them poses an enormous challenge.
One big reason? One of the first runners in the vaccine race – made by Pfizer – needs to be kept very cold: below 70 ° C, which is colder than Winter in Antarctica. Moderna said her vaccine needs to be frozen as well, but … Only at -20 ° C below zeroMore like a regular freezer.
Since there will be limited vaccine doses initially, immunization administrators across the country will need plans to distribute any and all available vaccine doses. For months, they have been Confused about special challenges Introduced by the Pfizer vaccine, which requires these extremely cold conditions.
“I think it can be done,” says Debra Christensen, a 30-year-old veteran in vaccine innovation and supply chains at PATH, an international nonprofit that focuses on public health. “The Ebola vaccine, for example, has been used successfully in a few African countries and also requires very cold storage.”
She says that distributing vaccines in these circumstances “is possible, but it will certainly be more expensive and more difficult.” Pfizer has tried to assuage concerns about the challenges these cold temperatures represent. They have their own packaging designed to keep doses extremely cold with dry ice, so that they can be stored for a few weeks without specialized freezers (the package has been informally called a “pizza box”).
Moderna vaccine, “It can be distributed in a more standard fashion – health workers are familiar with it, facilities are accustomed to – it’s more natural,” Christensen explains.
Here is some basic information on why keeping these vaccines very cold – and how they differ.
Why deep freeze? Think M & Ms
To understand why these vaccines need to be frozen, it is helpful to understand a little bit how they work.
Both Moderna and Pfizer vaccines use novel approaches to open the body’s immune defenses. The method uses messenger RNA, or mRNA, to transform a patient’s cells into factories that produce a protein for the coronavirus.
This protein initiates the immune response as if there was a real infection with the Coronavirus (to be clear, since it is only one viral protein, there is no way a vaccine can infect or make a person sick with COVID-19) after that, if someone who has been immunized is exposed to a virus Corona later, the body’s immune system will be able to fight it more easily and they will be more likely to avoid dangerous diseases.
It is a very new vaccine technology, and mRNA vaccines have not been approved by the Food and Drug Administration.
Vaccines made with mRNA can be made much faster than older vaccines, explains Margaret Liu, the vaccine researcher who chairs the Board of Directors. International Vaccine Association And a specialist in genetic vaccines. The problem, Liu says, is that mRNA “gets damaged really easily, because there are so many, many enzymes that will break it down.”
Here’s an analogy: Think of pollen as a chocolate bar that melts easily. Just as there are ways to prevent chocolate from dissolving into a viscous substance, there are things that drug makers have done to protect their COVID-19 vaccines.
The first step, Liu says, was to modify the nucleosides of mRNA – the “building blocks” of the RNA vaccine. “They used modified versions because they are more stable,” she says. This would be the same as changing the recipe for the chocolate so that it is not completely melted.
The next step was to use lipid nanoparticles, which, Liu explains, “is kind of like putting chocolate inside a candy wrapper – you have M&M, so the chocolate doesn’t melt.”
But even with stable building blocks and a lipid coating, mRNA can easily degrade, which is why the vaccine is frozen.
“Everything happens slower as I lower the temperature,” Liu says. “So your chemical reactions – the enzymes that break down RNA – will happen more slowly.” It’s the same idea as freezing food to prevent it from spoiling.
Because the specific formulations are classified, Liu says, it is not entirely clear why the temperature requirements of these two mRNAs differ.
“It’s just about what their data is,” she says of Moderna’s vaccine. “If their data shows that it’s more stable at a certain temperature, that’s it.”
A “stress test” to find out these temperatures
It is possible that the Pfizer vaccine will eventually prove stable in somewhat warmer conditions – or for longer periods outside the freezer.
To know the vaccine temperature requirements, drugmakers conduct extensive and time-consuming studies on thermal stability.
Liu explains that this research includes keeping the vaccine “at other temperatures to see how stressed the system”. It says you’ll start out in extremely cold temperatures, then try normal freezer temperature, then fridge temperature, and finally room temperature.
You can also place the pollen in fluctuating temperatures, to mimic what would happen if [a vaccine shipment] I was left on the dock and something went wrong. “
Then drugmakers have to analyze the vaccine samples that went through all of this and run tests (usually in mice) to see if the vaccine still works the way it is supposed to.
All of this is measured in real time. Christensen explains: “If the vaccine has a two-year shelf life at refrigerator temperatures, the manufacturer actually needs to put the vaccine at that cooling temperature for two years and see if the product is still effective in the end.” “Given the urgent need for these COVID-19 vaccines, manufacturers will likely start launching them with shorter shelf lives, and then expand the shelf life as more data is collected.”
Pfizer spokeswoman Jerica Bates told NPR that “there are studies underway on this front,” but she did not answer whether any imminent changes in temperature requirements might come as a result of those studies.
“I doubt it [Pfizer] You will be able to stay out of extremely cold conditions during the initial transportation and storage, “says Christensen,” but if they can demonstrate that the vaccine can be kept at cooled temperatures for some time after being removed from frozen storage, this helps facilitate distribution and administration in remote areas and groups. Specific people. “
Temperature requirements require different distribution plans
For now, Pfizer says its vaccine should be kept at minus 70 degrees Celsius, and it can last in a specialist freezer for up to six months. Professional shippers can carry up to five trays of “pizza boxes” from the vials, refreshed with dry ice every five days for up to 15 days to keep the vaccine in place frozen temperature.
Even that poses challenges, though – the Pfizer world The advisory board told the CDC in August It is not supposed to open more than twice a day, and it should be closed within 1 minute of opening it. Once the pollen is thawed, it can be cooled for five days.
Moderna says its candidate vaccine is stable at normal freezer temperature – below 20 ° C – for up to six months, and after thawing, it can last in the refrigerator for 30 days. It can also be kept at room temperature for up to 12 hours. This is beneficial for healthcare workers in the field, Christensen explains, “because the vaccine now does not need to go in and out of the refrigerator every time it is given.”
Looking at the demand, if both Pfizer and Moderna vaccines were licensed around the same time, the states would figure out how to use them in different settings.
Kristen Finlay, director of vaccination for Vermont Distribution plan for that stateHe says it makes sense to consider distributing the Pfizer vaccine to large population centers, not just because of its temperature, but because the lowest quantity you can order is 975 doses (usually more like 100 doses or less).
“[If] You have a large university where you will be able to reach more people, and it makes sense that you might consider distributing extreme cold there, “she says. Moderna will work better,” in areas where it might be difficult to use such a large demand or it might not. They have [cold] Storage. “
CDC, the federal agency responsible for vaccine distribution and decisions Groups that receive first shotsTry to dissuade health departments and hospitals from going out and buying expensive refrigerators to accommodate the Pfizer vaccine. But according A recent report in StatIn the past, richer hospitals are buying specialized freezers, raising concerns that hospitals with fewer resources or in rural areas will be left behind.
Moderna’s announcement may alleviate these concerns, although doses of Pfizer vaccine are also badly needed, that does not mean that very cold storage is no longer a problem.
“I think the best news is that there may be two effective vaccines because that means we can reach more people,” Finlay says. “We still need to show it is safe and effective and we need to build trust with the public – so there are still ways to go, but that’s good news.”
Despite the excitement and hope that Pfizer and Moderna have licensed COVID-19 vaccines, “This is not really a race,” Liu says. “Just with the numbers, we might need multiple and multiple vaccinations.”
And in the end, she says, “the second or fifty-two may actually be a better vaccine.”