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Two drugmakers, Pfizer and Moderna, have announced promising interim results for their vaccine candidates, raising hopes in the United States and abroad that the end of the pandemic can be seen. But if and when vaccines are approved by the Food and Drug Administration, their distribution is a daunting challenge.
One big reason? One of the leaders in the vaccine race – the one made by Pfizer – must be kept extremely cold: minus 70 degrees Celsius, which is colder than the winter in Antarctica. Moderna said that her vaccine should also be frozen, but only at minus 20 Celsius, more like a regular freezer.
As there will be limited doses of vaccines in the beginning, immunization managers across the country will need to have plans for allocating all available doses of vaccines. For months, they have puzzled the specific challenges posed by the Pfizer vaccine, which requires these ultra-cold conditions.
“I believe this can be done,” said Debra Christensen, a 30-year veteran of innovation and vaccine supply chains at PATH, an international nonprofit organization focused on public health. “The Ebola vaccine, for example, has been used successfully in several African countries and also required this ultra-cold chain storage.”
The spread of vaccines under these conditions “is possible, but it will definitely be much more expensive and difficult,” she said. Pfizer has tried to allay concerns about the challenges posed by these cold temperatures. He designed his own packaging to keep doses super cool with dry ice so that they could be stored for several weeks without specialized freezers (the packaging is informally called the “pizza box”).
The Moderna vaccine, Christensen explains, “it can be distributed in a more standard way – healthcare professionals are used to it, facilities are used to it – it’s more normal.”
Here are some preconditions for why these vaccines should be kept so cold – and how they differ.
Why deep freezing? Think M & Ms
To understand why these vaccines need to be frozen, it helps to understand a little about how they work.
Both Moderna and Pfizer vaccine candidates are using a new approach to unlocking the body’s immune defenses. The approach uses messenger RNA or mRNA to turn patient cells into factories that produce a particular coronavirus protein.
This protein triggers an immune response as if it had a real coronavirus infection (to be clear, since this is just a viral protein, there is no way the vaccine can actually infect anyone or get COVID-19). Then, if someone who has been immunized is later exposed to a coronavirus, their body’s immune system will be able to fight more easily and is more likely to avoid serious illness.
This is a vaccine technology that is so new that no mRNA vaccine has ever been approved by the Food and Drug Administration.
Vaccines made from mRNA can be made much faster than older vaccines, explains Margaret Liu, a vaccine researcher who chairs the board of the International Vaccine Society and specializes in genetic vaccines. The problem, Liu says, is that mRNA is “really easy to destroy, and that’s because there are many, many enzymes that will just break it down.”
Here’s an analogy: Think of the vaccine as a chocolate bar that melts easily. Just as there are ways to keep chocolate from melting, there are things that drug manufacturers have done to protect their vaccines against COVID-19.
The first step, Liu said, was to modify the mRNA nucleosides, the “building blocks” of the RNA vaccine. “They used modified versions because they are more stable,” she said. This would be like changing the chocolate recipe so that it is not so melted.
The next step was to use lipid nanoparticles, which, Liu explains, “is like putting your chocolate in a candy wrapper – you have M&M so the chocolate doesn’t melt.”
But even with stabilized building blocks and a lipid coating, mRNA can still easily break down, leaving the vaccine frozen.
“Everything happens more slowly as you lower the temperature,” says Liu. “So your chemical reactions – the enzymes that break down RNA – will happen more slowly.” It’s the same idea as freezing food so it doesn’t spoil.
Liu says that because the specific formulations are secret, it is not clear why exactly these two mRNA vaccines have different temperature requirements.
“It just comes down to what their data is,” she says of the Modern vaccine. “If their data shows it’s more stable at a certain temperature, that’s all.”
“Stress testing” to irritate these temperatures
The Pfizer vaccine may end up stable in slightly warmer conditions – or for longer outside the freezer.
To understand the temperature requirements of the vaccine, drug manufacturers are conducting extensive, time-consuming studies on thermal stability.
This study involves keeping the vaccine “at other temperatures to see how much you can load the system,” Liu explains. She says you will start with ultra-cold temperatures, then try a regular freezer temperature, then a refrigerator temperature, and finally a room temperature.
You can also put the vaccine at variable temperatures, “to mimic what would happen if [a vaccine shipment] I stayed at the cargo dock and something went wrong, “Liu said.
Drug manufacturers should then analyze the vaccine samples that have gone through all of this and perform tests (usually in mice) to see if the vaccine is still working as expected.
All this is measured in real time. “If the vaccine has a two-year shelf life at refrigerated temperatures, the manufacturer must actually put the vaccine at that refrigerated temperature for two years and see if it is still effective at the end of the product,” Christensen explains. “Given the urgent need for these COVID-19 vaccines, manufacturers are likely to start releasing them with a shorter shelf life and then extend the shelf life when they collect more data.”
Pfizer spokeswoman Jerica Pitts told NPR that “there are ongoing studies on this front”, but did not answer whether these studies could result in inevitable changes in temperature requirements.
“I doubt it [Pfizer] will be able to move away from extreme cold conditions during the initial transport and storage, “says Christensen. But if they can prove that the vaccine can be stored in refrigerated temperatures for some time after being removed from frozen storage, it helps facilitate administration in more remote areas and to certain groups of people. “
Temperature requirements require different distribution plans
Currently, Pfizer says its vaccine should be maintained at minus 70 degrees Celsius and can continue in a special freezer for up to six months. Specialized shippers can keep up to five trays of pizza boxes with bottles and refresh with dry ice every five days for up to 15 days to keep the vaccine right frozen temperature.
However, even this is challenging, a Pfizer scientist told the CDC’s Advisory Board in August that it should not open more than twice a day and should be closed within a minute of opening. Once thawed, the vaccine can be stored in the refrigerator for five days.
Moderna says the vaccine candidate is stable at normal freezer temperatures – minus 20 degrees Celsius – for up to six months and can last 30 days in the fridge after thawing. It can be stored at room temperature for up to 12 hours. This, Christensen explains, is good for on-site health workers, “because now the vaccine doesn’t have to come in and out of the fridge every time it’s given.”
Given the demand, if both Pfizer and Moderna vaccines are allowed at the same time, countries will figure out how to use both in different settings.
Christine Finley, an immunization manager in Vermont, finalizing the country’s distribution plan, says it makes sense to think about spreading the Pfizer vaccine to larger towns, not just because of its temperature, but because of the smallest amount. what you can order is 975 doses (usually this is rather 100 doses or less).
“[If] you have a great university where you can reach more people, it would make sense that you could consider spreading your ultra-cold there, “she says. Modern will work better, she says,” in areas where it may be more difficult to use such a large order or they may not [cold] storage. “
The CDC, the federal agency responsible for distributing vaccines and deciding which groups receive the first pictures, tried to discourage health departments and hospitals from going out and buying expensive freezers to accommodate the Pfizer vaccine. But according to a recent report in Stat, wealthier hospitals are buying specialized freezers, raising fears that hospitals with fewer resources or in rural areas will be abandoned.
Moderna’s announcement may allay these fears, although since doses of Pfizer vaccine will also be urgently needed, this does not mean that ultra-cold storage is no longer an issue.
“I think the best news is that there may be two vaccines that are effective because that means we can reach more people,” Finley said. “We still need to show that they are safe and effective, and we need to build public confidence – so there are still ways to go, but that’s good news.”
Despite the excitement and hopes of Pfizer and Moderna, which potentially have the first vaccines allowed against COVID-19, “this really isn’t a race,” Liu said. “Only in pure numbers, we probably need many, many vaccines.”
Finally, she says, “it may turn out that the second or 50th is actually a better vaccine.”