The race to create safe and effective vaccines against the coronavirus is facing another complex challenge: how to safely deliver tens of millions of doses to all corners of the world while ensuring they remain in super cold storage until ready for use.
Just how cold? As in minus 103 Fahrenheit for the first vaccine expected to be given the green light. That’s nearly four times colder than your home freezer, colder even than Antarctica in winter.
For months, manufacturers, federal and state governments, and large health care systems have been quietly planning how to navigate this ultra “cold chain” that stretches from vaccine manufacturers to hospitals, nursing homes, doctors’ offices, and many far-flung clinics. But the announcement last week by Pfizer, which is conducting one of four late-stage clinical trials in the United States, that it plans to seek emergency-use authorization for its vaccine in late November brought the challenge into stark focus.
In a letter Sunday to the Trump administration, the nation’s governors expressed a long list of concerns, including questions about the supply of ultracold freezers and dry ice — already experiencing shortages amid nationwide vaccine trials.
“We need to answer these questions before the vaccine is available so that we are ready to go and no one is caught flat-footed when the time comes to vaccinate people,” the letter stated.
Pfizer says it has developed specially designed, temperature-controlled shipping packages, using dry ice, to keep its vials at roughly minus 103 below Fahrenheit for up to 10 days.
“These shippers are roughly the size of a suitcase and weigh approximately 70 pounds fully loaded,” Pfizer said in a statement. Federal distribution of cold-storage vaccines is anticipated to be in 1,000-dose shipments, according to state health department documents. Hence the storage concern for doses not used in 10 days.
The vaccine from Cambridge biotech Moderna will not have such rigorous ultracold-storage concerns, with a required temperature around minus 4 Fahrenheit, about the temperature of a home freezer. Moderna said it could seek emergency use authorization from federal regulators as early as December.
In a move that may suggest the US Centers for Disease Control and Prevention is concerned about the supply of ultracold freezers, the agency last month advised states not to purchase such equipment. It noted Pfizer is already planning to ship its vaccine in super-cold cases.
But the nation’s governors and others are now questioning that advice, displaying a national psyche still raw from the spring’s acute shortages and bidding wars over personal protective gear and ventilators.
“If there is a shortage of dry ice,” the letter said, “does this change the guidance to states to not purchase additional ultracold storage freezers?”
The Massachusetts health department said in a statement that it is “assessing the current ultracold storage capacity within our provider network,” but noted many large hospitals and even a few smaller primary care offices already have ultracold freezers.
The department also said “significant quantities of ultracold storage units and/or dry ice are not as critical as originally thought,” citing the CDC guidance about Pfizer shipping in cases that can stay super cold for 10 days.
Still, the state is hedging its bets. In a vaccine plan it submitted to federal regulators last week, the Baker administration said the health department’s Vaccine Unit is buying an ultracold storage unit.
“The Vaccine Unit has also reached out to a refrigeration vendor that could be contracted if needed for large capacity ultracold storage,” it said.
Massachusetts is hardly alone.
“We have seen an increase in requests and demands from every state, maybe not Alaska, but I think even in Alaska," said Alex Esmon, general manager for cold storage at Waltham-based Thermo Fisher Scientific, one of the world’s leading manufacturers of ultralow-temperature freezers.
Keeping the vaccine cold is crucial to success.
Vaccines from both Pfizer and Moderna would require patients to receive two shots, 21 or 28 days apart, respectively. And patients would have to stay with the same type of vaccine for both doses. Esmon said that dosing regime is prompting some providers to worry about a potential blip in the supply chain, so some hospitals and health departments are seeking ultracold freezers to store enough second doses to cover the patients who receive the first shot.
“People are playing through the what-if scenarios,” he said.
Stirling Ultracold in Ohio, which is working with Pfizer, has increased production of ultracold freezers by 40 percent in the past three months, said Dusty Tenney, the company’s chief executive. Stirling has also been getting calls from various states, particularly for smaller ultracold freezers — think college dorm-sized refrigerators and portable units the size of large beach coolers — that cost less than $10,000.
“Cities have great infrastructure but you get into towns and rural areas, and it’s a magnitude different,” Tenney said.
At Acme Dry Ice in Cambridge, they’re working seven days a week, shipping dry ice for vaccines in development, said owner Marc Savenor.
“We are busier than we have ever been,” Savenor said Monday. “We are going through our complete inventory every day, going through 50 to 100,000 pounds every day.”
Many ethanol plants, which also produce carbon dioxide, shut down earlier in the pandemic. That set off a domino effect producing a shortage of dry ice, which is created from carbon dioxide. While that shortage has eased, Savenor said, dry ice is still not plentiful.
All of this has doctors at smaller medical practices, which typically don’t have ultracold freezers, concerned.
"It’s fair to say the [Massachusetts Medical Society] has heard concerns from members who work in smaller practices about lack of storage and its effect on the ability to administer the vaccine in those settings,” said society spokesman Thomas Flanagan.
For the past month, the state’s largest health care system, Mass General Brigham, has been surveying its supply of ultracold freezers across its 12 hospitals, six urgent care centers, and five community health centers. With 78,000 employees and more than a million patients, the system will need tens of thousands of doses.
While its academic medical centers, with research labs, typically have super cold freezers, it’s another matter for its hospitals and care centers outside Boston.
“It’s a complex logistical feat,” said Dr. Paul Biddinger, Mass General Brigham’s medical director for emergency preparedness.
But Biddinger thinks they will have enough cold storage and perhaps extra to offer other places that don’t. Still, that’s just a first step.
“People think as soon as they get a vaccine they don’t have to wear a mask anymore,” Biddinger said.
The reality, he said, is that it will take many months of administering vaccines to start protecting the population, and some of the restrictions now in place will have to continue because removing them too quickly could produce another surge in infections.
“We are trying to figure out a way to communicate that without depressing people," Biddinger said. “People are understandably tired of all of this."