January 11, 2021Erica Tennenhouse, PhD
This time last year, working on a vaccine for COVID-19 would have been considered a low-priority undertaking. But by the end of March 2020, vaccines were being developed and pushed through clinical trials at record speeds.
The Food and Drug Administration (FDA) issued the first emergency-use authorization (EUA) for a vaccine—the Pfizer-BioNTech COVID-19 vaccine—in December 2020. Shortly after, Moderna’s COVID-19 vaccine also received FDA EUA.
Now that the US approved the distribution of its first vaccines, health facilities face another hurdle: The Pfizer-BioNTech vaccine must be stored at -70°C, which is much colder than typical freezers, making distribution a major logistical challenge—especially when considering how to transport doses to the farthest reaches of rural America.
“It’s really the first rodeo for the US and that’s why there’s so much ambiguity; we’ve never had to do this kind of mass distribution of a vaccine where we’re rolling out 300 million plus doses to the American population,” says Matthew Tallman, head of North American sales for B Medical Systems.
Keeping it Cold
The ultracold storage requirement of the Pfizer-BioNTech vaccine is related to its novel makeup. In contrast to traditional vaccines, which contain inactivated virus or viral protein components, the Pfizer-BioNTech vaccine consists of a short snippet of synthetic messenger RNA (mRNA). mRNA is a notoriously unstable molecule, under constant threat of being destroyed by chemicals in its environment. But damage can be avoided by storing mRNA at extremely low temperatures. For that reason, the vaccine must be kept at -70°C until it’s ready to be used.
Once doses of the Pfizer-BioNTech vaccine roll off the production line, they are air shipped and then ground-transported directly to regional health facilities. From there, some doses get transported again to local administration sites. Pfizer has designed a disposable transport box for the journey that can hold up to 5,000 doses. Packed with dry ice, the box will keep the vaccines at -70°C for 15 days, provided the dry ice is replenished every five days and the box is opened for only a minute at a time no more than twice a day. At the 15-day mark, the vials must be transferred to either an ultracold freezer, where they can be stored for up to six months, or a 2–8°C refrigerator for use within five days. Once thawed, the vials cannot be re-frozen.
Dry ice may be the best option to keep the vaccines cold while in transit, but it has its challenges. It sublimates over time and loses its cold temperature much faster than standard ice, which is why there are strict limits on how long the Pfizer transport box can be open each day, says Raja Rao, director of Cold Chain Strategy & Markets at B Medical Systems, who previously led the cold chain program at the Bill and Melinda Gates Foundation.
According to Pfizer, the box can also be used as temporary storage of the vaccine if it arrives at a destination without an ultracold freezer, but the need to replenish the dry ice in the box every five days means facilities must have a means to store dry ice onsite—and that, ironically, requires an ultracold freezer.
Unsurprisingly, urban health facilities are lining up to purchase ultracold freezers to store both dry ice and their vaccine doses. But with a high price tag and substantial footprint, an ultracold freezer is an item that few rural hospitals can afford, and those that can are likely to struggle to accommodate one in their facility’s limited space.
So, for many facilities, it will be a race against time to use up their vaccine doses. And while urban health centers are surrounded by dense populations of eager vaccine recipients, those in rural communities, where fewer people live farther apart, may struggle to use up the 1,000-5,000 doses packed into each Pfizer transport box before they go bad.
Those far-flung rural populations require a more active vaccine distribution strategy, according to Rao. “I envision the last mile of this as a transport box with dry ice being used to take the doses around to various administration sites.” Some of the doses would end up in pharmacy and doctor’s office refrigerators, where they could be administered to patients within five days. Others, he says, would be driven around to various outdoor locations in the communities, like parking lots, where people could wait to receive “drive-through vaccinations”.
But the requirement that the Pfizer transport box stay shut as much as possible, and the short window that the vaccines can be stored inside before they begin to thaw, severely limits how many administration sites an outreach worker can visit within a rural community, and thus the volume of people that can get immunized.
A key technological solution for the outreach scenario is a long-range vaccine carrier that keeps doses cold for longer than the Pfizer transport boxes, and one that can be open more frequently. B Medical’s RCW25 cooler, for instance, gives vaccines almost double the life that the Pfizer box does, says Rao, meaning doses can travel longer distances. He adds that the cooler can also be opened more often to retrieve doses due to its efficient design.
There is a unique set of challenges inherent to vaccinating rural communities, and the ultracold storage needs of the Pfizer-BioNTech COVID-19 vaccine only compound those challenges. The solutions must center on keeping those vaccines within their required temperature range for the duration of transport to ensure that the doses people in rural settings receive are safe and effective, says Rao.
Tallman notes that there has been a huge amount of research, investment, and planning involved in distributing the vaccine to the point at which it can be placed in an ultracold freezer.
“There needs to be just as much attention to detail in the last mile of delivery to rural or remote areas,” he says. “Otherwise all of these efforts are for naught because the vaccine efficacy will be compromised, and we could potentially find this pandemic continuing in the wrong direction instead of turning the corner back to normalcy.”