The epic global effort to develop a Covid-19 vaccine has been unmatched in its scale, speed, and scientific advances. Now a vaccine for the disease, developed by Pfizer and BioNTech, is on the verge of being rolled out in the US under an emergency use authorization by the Food and Drug Administration, raising hopes of an end to the pandemic.
But the vaccine’s potential to provide immunity to the broader population is now threatened by a massive logistical hurdle in actually getting it to people safely: keeping the vaccine doses cold.
Vaccines are fragile drugs that demand strict temperature controls lest they spoil. And they spoil a lot. According to the World Health Organization, about half of the vaccines distributed around the world go to waste, in large part because of a failure to properly control storage temperatures. That in turn undermines efforts to contain and eradicate disease.
“They lose effectiveness and their potency if they’re exposed to temperatures outside of the range that they’re supposed to be kept in,” said Michelle Seidel, UNICEF’s immunization supply chain specialist.
This vulnerability stands to be an even bigger problem for the campaign against Covid-19, where just about everyone in the world is vulnerable, so just about everyone will need the shot. Containing the disease will require billions of people to be immunized around the world — likely with two doses — and fast.
Pfizer and BioNTech have reported that their vaccine is 95 percent effective at preventing the disease in a preliminary analysis. A vaccine using a similar approach from Moderna also reported 95 percent efficacy and will be evaluated by the FDA for an emergency use authorization this month.
But these vaccines, which use strands of genetic material known as mRNA, also have stringent temperature requirements. Moderna’s vaccine requires long-term storage at minus 20 degrees Celsius (minus 4 degrees Fahrenheit) and is stable for 30 days between 2° to 8°C (36° to 46°F). Pfizer and BioNTech’s vaccine, however, requires some of the coldest temperatures of any vaccine under consideration: minus 70°C (minus 94°F) or lower.
Pfizer, BioNTech, and other companies whose vaccine candidates require very cold storage say they are already preparing for this challenge, investing in freezers, transportation, and temperature-tracking devices. But with so many moving parts, there’s a lot that can go wrong. With recent struggles in the United States to maintain adequate supply chains for Covid-19 tests, masks, and personal protective equipment, the concern is that the same mistakes could be repeated in a high-stakes vaccination effort.
While full approval of a Covid-19 vaccine may still be months away, the infrastructure for getting it to people has to be coordinated now.
The vaccine cold chain, explained
Getting a vaccine through clinical trials and approved by the FDA is a tedious, expensive, and time-consuming process. But it’s not the finish line for a Covid-19 immunization campaign. It’s just one of the first hurdles.
“There’s almost an assumption that once a vaccine is created and approved, then everyone is healthy and fine, but the operational component is pretty complex,” said Caesar Djavaherian, an ER physician and chief clinical innovation officer at Carbon Health. “We’ve never tried to administer vaccines to 100 million Americans in a short period of time.”
To prepare for that, Covid-19 vaccine production is already underway. The idea is that once a vaccine does get the green light, doses are ready to roll out right away. Operation Warp Speed, the $10 billion US government vaccine development effort, is aiming to have enough vaccines to immunize 20 million Americans in December, another 30 million in January, and another 50 million in February.
But at that point, vaccines have to go from factories to shipping facilities to trucks to hospitals, clinics, and pharmacies, and, eventually, into the arms of people — all while without budging from narrow, specific temperature ranges.
This series of handoffs under strict temperature controls is known as the cold chain. It’s this chain — between the manufacturer and the clinic — that represents one of the biggest challenges of the vaccine distribution effort, and each step could potentially become a weak link.
It’s particularly challenging because vaccines are only manufactured in a handful of facilities around the world, demanding a sprawling international network of transportation and storage sites in order to get immunizations to wherever they’re needed.
Many major hospitals may have the specialized cold storage facilities needed to stockpile vaccines, but smaller clinics and pharmacies don’t. And even some of the big hospitals may not have the specialized ultra-cold freezers needed to store a vaccine like the one developed by Pfizer and BioNTech, especially in large quantities.
That’s why vaccines are typically sent from factories to regional warehouses. These facilities often have sophisticated freezers for long-term storage, as well as a reliable electricity supply and backup generators. They aren’t set up to administer the vaccine to people, however, so the vials still have to be delivered to the final users.
But every time a vaccine moves, it introduces yet another risk. Bad weather can delay delivery flights. Freezers can fail on refrigerator trucks. Vaccine shipping containers can end up stuck on the tarmac. Coolers can leak. Even opening freezers repeatedly to move things in and out can harm vaccines stored inside. Every breach in temperature control degrades the vaccine, and every time the vaccine moves, the chances of this happening increase, so health officials need to plan carefully to ensure the absolute minimum amount of movement.
Once a clinic receives a vaccine shipment, health workers can thaw out the vials in a refrigerator as they prepare to give injections to patients. But once a vaccine is warmed up, it’s only viable for a few days. For clinics without their own cold storage facilities, the clock starts ticking as soon as they receive their doses. So getting everyone vaccinated requires a precisely coordinated series of complex events spanning the globe, and any break therein could derail an effort to control a deadly disease.
Why supply chains are even more complicated for the Covid-19 pandemic
All that said, health systems in the United States and around the world have been administering vaccines for decades, and there is plenty of experience and know-how for effectively bringing vaccines to people.
But again, the Covid-19 vaccination effort has to happen at an even larger scale than just about any other vaccination effort to date. And it can’t seize infrastructure from existing vaccines, since immunizations for illnesses like measles, influenza, polio, and meningitis are still needed at the same time.
That means many of the things needed to distribute a Covid-19 vaccine have to be added to what’s already on the market; freezers, refrigerated shipping containers, and remote temperature monitoring systems can’t simply be cannibalized from other vaccine supply chains.
The scale of a Covid-19 vaccination campaign could also create other bottlenecks. Vaccine vials require a specific type of glass that can tolerate low temperatures and remain sterile, and there may not be enough of this glass to go around right away. Even the self-sealing rubber stoppers on the vials could face a shortfall. Syringes, personal protective equipment, and trained personnel to administer vaccines are already facing a crunch from dealing with the ongoing pandemic.
Then there are complications that arise from the Covid-19 vaccines themselves. Covid-19 vaccine development has allowed researchers to showcase new technologies that have never been tried before at scale. In particular, multiple companies are developing vaccines based on the genetics of the SARS-CoV-2 virus, the virus that causes Covid-19, rather than the classical approach of using the structure or pieces of the virus itself.
The problem is that these fragments of DNA and RNA are delicate. They can degrade quickly on their own, even at refrigerated temperatures. That’s why freezing them is so important for keeping them intact.
But that’s hard to do for vaccines like Pfizer and BioNTech’s vaccine candidate, which requires storage at such extreme temperatures. Some experts are concerned these cold requirements could end up being a deal breaker for widely distributing these vaccines. “These mRNA vaccines, which are stored at minus 80°C, from a practical perspective are showstoppers right now,” said Vijay Samant, the former chief operating officer of Merck’s vaccine division.
Ultra-cold freezers that can reach the requisite temperatures cost between $10,000 and $15,000 each. That’s out of the budget for many clinics and hospitals. With these logistical and storage constraints, that may mean that people will have to travel to centralized locations like regional hospitals to get vaccinated, instead of to their local clinics and pharmacies.
But Pfizer and BioNTech said they have a solution.
“We have specially designed, temperature-controlled thermal shippers utilizing dry ice to maintain recommended temperature conditions for up to 10 days,” said Jerica Pitts, a spokesperson for Pfizer, in an email. “The intent is to utilize Pfizer-strategic transportation partners to ship by air to major hubs within a country/region and by ground transport to dosing locations.”
According to the Wall Street Journal, Pfizer’s vaccine shipping system can hold up to 5,000 doses of its vaccine at minus 70°C for those 10 days. The company is also spending more than $2 billion to create its own distribution network, aiming to ship these containers on a just-in-time basis to the places that need them, bypassing the need for warehouses.
However, this strategy could run into its own supply chain constraints. There may be shortages in critical components for Pfizer and BioNTech’s containers, like the dry ice required to keep those super-cold temperatures.
Many of the Covid-19 vaccine candidates, including the ones from Pfizer and Moderna, also require two doses, spaced several weeks apart. “It does mean double the capacity requirements, so yes, there is an additional complication,” Seidel said. Ensuring there is the right number of doses available at just the right time for everyone’s second dose will require even more storage capacity and precise tracking and timing of shipments.
The Covid-19 vaccination campaign has to be global
One stark lesson of the Covid-19 pandemic is that an outbreak anywhere in the world can ripple across the whole planet. So the effort to contain the disease has to reach every country, in every circumstance.
Some health systems do have experience with keeping finicky vaccines frigid, even in places with limited resources. The Ebola vaccine, for instance, had to be stored at minus 80°C in remote areas of Guinea and the Democratic Republic of the Congo.
But the looming question is whether limited resources can also be stretched to accommodate a Covid-19 vaccination effort. “We are leveraging our experience in Ebola-prone countries to develop guidance on that, but that is something where we do lack funding,” Seidel said.
And ensuring distribution is seamless and also fast is critical. Every day, thousands of people are dying from Covid-19, so there is intense pressure to get people vaccinated as quickly as possible. That would require a simultaneous effort, in the United States and around the world.
However, if governments and private companies make the investments now, the weaker links in the supply chain can be strengthened and ideally avoid the same mistakes made in the earlier stages of the Covid-19 pandemic that left many scrounging for vital masks, gloves, gowns, and tests. The true test of the vaccine supply chain will come when vaccine vials start heading to hospitals, which could commence within days.