COVID vaccine candidate from Pfizer must be stored at minus 112, prompting a rush on dry ice
Minus 112 is so cold rubber shatters, metals can become brittle and exposed skin freezes almost instantly. It’s also the temperature required to store what’s expected to be the first COVID-19 vaccine.
With last week's news that the vaccine candidate from Pfizer and its collaborator BioNTech was more than 90% effective and could be approved within a month, the reality of moving and storing the life-saving vials came into sharp focus.
Dry ice orders are spiking and the backlog to buy some $15,000 medical-grade ultracold freezers is up to six weeks.
“Sales are up 250% from the first quarter,” said Dusty Tenney, CEO of Stirling Ultracold, an Athens, Ohio, company that makes laboratory-grade ultracold freezers.
Monday's announcement that Moderna's COVID-19 vaccine was 94.5% effective, is stable at regular refrigerator temperatures for 30 days and is able to be held at room temperature for up to 12 hours took the edge off the urgency.
But the United States will need all the vaccines it can get. Development of Moderna's vaccine is slightly behind Pfizer, and its manufacturing capacity is not as robust, making the Pfizer-required cold chain an issue local health departments will be grappling with for months.
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In Akron, fifth-generation ice man Harry Gehm is getting calls from across the region.
“The Ohio health department called for 15,000 pounds of dry ice a week,” he said from the offices of Gehm & Sons, founded in the 1880s. “The hospitals and Giant Eagle (a grocery and pharmacy chain) have been calling to make sure I have the capacity.”
States have known for months the Pfizer vaccine required an extreme cold chain distribution, and have been working to create the infrastructure necessary to deliver and store it. Now they've got to finalize their plans.
Of the four COVID-19 vaccines currently in Phase 3 clinical trials in the United States, Pfizer's is both the furthest along and the only one that requires such a low temperature.
Pfizer expects to produce up to 50 million vaccine doses by the end of the year, and up to 1.3 billion doses in 2021. If the vaccine is approved, the doses available this year will be allocated proportionally across countries that have supply agreements, the company said. Each person will need two doses, given 21 days apart.
As part of an agreement signed this summer with the U.S. government , Pfizer will deliver 100 million doses following the vaccine’s successful manufacture and approval, with the option to acquire an additional 500 million doses.
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The Pfizer candidate vaccine is composed of messenger RNA that tells the body to produce a protein from the SARS-CoV-2 virus that causes COVID-19. That protein tells the immune system to make antibodies against the virus, protecting it from infection.
The proteins are encased in tiny fat globules and very fragile. “It just sort of disintegrates,” said Dr. Paul Offit, director of the Vaccine Education Center at Children's Hospital of Philadelphia and a professor of vaccinology at the Perelman School of Medicine at the University of Pennsylvania.
To keep the molecule stable, the vaccine must be stored at ultracold temperatures, between minus 112 and minus 76. Generally, the guidance is minus 94 and below. At those temperatures, it is stable for up to six months.
Once the vaccine arrives at a hospital or clinic, it can be held at regular refrigerator temperatures of between 35 to 46 degrees for up to five days before it must be discarded.
That’s no mean feat. At minus 22, sap in trees freezes. At minus 58, some steel alloys become brittle. At minus 76, car batteries freeze. At minus 97, tires can shatter, said Tonya Kuhl, chair of the chemical engineering department at the University of California, Davis. Keeping anything that cold requires specialized equipment – or lots and lots of dry ice.
"In the science world, it’s not that cold," Kuhl said. "But in the regular world, it certainly is. That temperature is really important in storage to keep things stable.”Ultra-cold needs special equipment
Medical-grade ultracold freezers are not cheap. An upright model the size of a large home refrigerator can run about $25,000. An under-counter freezer the size of a dorm fridge is about $10,000. And a model on wheels about the size of a beach cooler runs $7,000.
Pharmacies, clinics, hospitals and doctors' offices have been snapping them up as fast as they can build them. Stirling Ultracold has increased hours on its factory floor and is working six days a week to meet demand. Even so, they’re back-ordered for at least a month, Tenney said.
Opening such a freezer is not like rummaging around in the fridge for a snack. Once the door is open, a wave of fog swirls out as the cold hits the moisture in the room air. Gloves and long sleeves must be worn to keep from getting freezer burns from the unit itself or the items inside.
The good news, say administrators, is that many hospitals and academic medical centers already had ultracold freezers because they’re used to store blood products, lab diagnostic materials and biological samples.
“More than 50% of our members already had them on hand,” said Azra Behlim, senior director of pharmacy sourcing at Vizient, a purchasing and support network for non-profit health systems. Vizient works with more than 60% of all hospitals in the United States.
Even so, some are buying the freezers “just to make things easier” when the vaccine starts shipping, she said.
But with the expectation that more vaccines will soon become available that can be stored at regular refrigerator temperatures, other medical systems are holding off.
“They’re wondering if they should jump through all these logistical hoops” when it might not be necessary, Behlim said. The first vaccines will be going to frontline health care workers, most of whom can be readily supplied at large hospitals that already have ultracold infrastructure.Dry ice is key for Pfizer vaccine delivery
Dry ice looms large in the Pfizer vaccine delivery system. The Pfizer vaccine is being shipped in specially designed, insulated containers about the size of a carry-on suitcase.
The vaccine is stored in flat, pizza box-sized compartments, each able to hold 195 vials. There are five doses per vial, so each tray holds 975 doses. The thermal container boxes, which are reusable, can hold up to five of the trays for a grand total of 4,875 doses per fully-loaded container, weighing about 70 pounds.
These "shippers," as Pfizer calls them, have space at the top for a bag of dry ice. The dry ice can keep the vaccine at the necessary temperature for 10 days if unopened, or five days as long as it’s opened no more than twice a day for very short periods of time, said Bob Swanson, the Immunization Program Director at the Michigan Department of Community Health.
Dry ice, as opposed to water-based “wet ice,” is the solid form of carbon dioxide when it’s cooled to minus 78.5 degrees.
The shipping containers require about 25 pounds of dry ice to be refilled. Gehm, the ice man, says he’s getting calls from small hospitals across Ohio that want to order 25 pounds a week.
“I can make 3,000 pounds an hour, so we’re good there,” he said.
Most dry ice in the United States is made in the Midwest near large ethanol gas plants, which produce carbon dioxide as a byproduct, said Gehm.
The carbon dioxide is transported in tankers and forced into a sealed chamber where it’s put under pressure to cool it.
“It runs about 2.3 pounds of liquid to make one pound of dry ice,” Gehm said. A 3-foot cube of dry ice weighs about 1,500 pounds.
Not everyone lives within easy transport distance of a dry ice manufacturer, however. North Dakota has so few, the state Department of Health is considering buying a small maker to produce its own, said state Immunization Program Manager Molly Howell.
If a medical center can be assured of getting dry ice, an expensive ultracold freezer may not be necessary because the packages are designed to be re-iced with dry ice.
“Really, you have up to 15 days,” said Swanson, with Michigan's health department. Once the vaccine container arrives at the site, it will be refilled with dry ice within 24 hours, he said.
“As long as you don’t open the container more than twice a day, you can refresh it with more dry ice five days out and then 10 days out. So it creates a 15-day window,” he said.
When it’s time to use the vaccine, it’s thawed to refrigerator temperature, which is between 35 and 46 degrees. It’s then mixed with a saline solution shipped separately.
Once that’s done, the five-dose vial can be stored for up to six hours in a refrigerator. If all the vaccine isn’t used by then, it would need to be discarded.
It’s the possibility of having to discard vaccine that keeps doctors up at night. After more than $10 billion in taxpayer money spent to create COVID-19 vaccines and in the midst of a frightening surge in cases, they don’t want any to go to waste.
“There's going to be a lot of tripping and falling,” said vaccine expert Offit. “We're going to learn a lot over the next few months about how we probably could have done this differently.”
This article originally appeared on USA TODAY: COVID vaccine candidate from Pfizer must be stored at minus 112, prompting a rush on dry ice