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What Is A Cold Chain? And Why Do So Many Vaccines Need It?

An employee makes dry ice pellets at Capitol Carbonic, a dry ice factory in Baltimore in Nov. 2020. Dry ice helps keep COVID-19 vaccines cool during transport.
Saul Loeb
AFP via Getty Images
An employee makes dry ice pellets at Capitol Carbonic, a dry ice factory in Baltimore in Nov. 2020. Dry ice helps keep COVID-19 vaccines cool during transport.

Vaccines are like milk. Both make us stronger, but if stored at the wrong temperature, they spoil.

The reason? At least in the context of COVID-19, shots rely on messenger RNAs — particles, which in oversimplified terms, carry the key instructions for teaching your immune system to fight the coronavirus. mRNAs are fickle things, or as chemists would describe them, they're "unstable." They break down quickly unless adequately protected from those pesky enzymes which eat away at them.

Enter cold storage.

As countries race — and struggle— to deliver mass inoculations in far-reaching corners of the globe, the most formidable challenge for political leaders and public health authorities face is this: how do you transport tiny vaccine vials thousands of miles, keeping them at temperatures colder than an Arctic winter?

Of the three vaccines approved for rollout in many countries, the Pfizer vaccine wins for most high maintenance with storage requirements at -70 degrees Celsius (-94 degree Fahrenheit) — a bit chillier than record low temps at the South Pole. Pfizer announced Friday, however, that the vaccine can actually be kept at around typical home freezer temperatures (a balmy -25 to -15 degrees Celsius or -13 to 5 degrees Fahrenheit) for up to two weeks.

The Pfizer vaccine's new storage requirements are more in line with the Moderna and AstraZeneca vaccines. Moderna can be kept between -25 and -15 degrees Celsius (-13 and 5 degrees Fahrenheit) according to the Centers for Disease Control, while AstraZeneca can go a bit warmer at up to 2-8 degrees Celsius (36 to 46 degrees Fahrenheit).

Bottom line? These vaccines have to stay cold while they leapfrog across continents, hopping from storage site to shipping yard until they finally reach their target cities.

From there, they'll be distributed to regional clinics — some of which may be disconnected from national power grids and/or lack basic refrigeration facilities. They'll travel on trucks with unreliable air conditioning, snaking through hot and humid environments. How will companies ensure the doses stay cold the entire journey?

The answer lies in an orchestra of technologies called "cold chain." North Carolina State systems engineer and vaccine distribution researcher Dr. Julie Swann explains it's a catch-all term for the infrastructure used to transport temperature-sensitive products — like many vaccines — from the point of production to consumers. Fridges, temperature-monitoring technology, ice boxes and even dry ice are all part of the process.

It's not a new idea. Disseminating vaccines via cold chain has been an evolving method for vaccine transport dating back to the 1960s and 1970s. And it's been a perennial public health puzzle for just as long — especially in low-resource countries.

The first problem: it's not cheap. A sub-80 Celsius cooling box, the gold-standard for ultra cold chain storage costs anywhere from $10,000 to $20,000 apiece. It's not surprising then that the technology to preserve ultra-cold medical products is sparsely available in low-income countries.

"The only infrastructure [most low-income countries] do have occasionally exists in academic medical centers located in capital cities," says Prashant Yadav, a senior fellow at the Center for Global Development, whose research focuses on health care supply chains in developing countries. "Many developing countries have only one ultra cold-chain fridge [total]." Cold chain infrastructure is even hard to find in middle and high-income countries, Yadav says.

Yadav adds that while most low- to middle-income countries use routine vaccines that require standard refrigeration, it's taken nearly three decades for there to be reliable access to commercial refrigeration in health clinics and key delivery points across Africa, rural parts of India and island states in the Western Pacific.

At first glance, this may paint a disheartening picture for COVID-19 vaccine distribution. But experts urge hope, pointing to the 2014 Ebola outbreak, where ultra-cold vaccine distribution was relatively successful, "working against all odds," Yadav says.

"The Ebola vaccine relied on ultra-low temperature systems," Swann says. "And systems were put in place to get vaccines all the way to patients. It included a combination of some centralized storage in a distribution center combined with a special kind of thermos, called ArKTek."

Companies and investors are pouring money into innovating and enhancing cold chain infrastructure to get the COVID-19 vaccine around the world. UPS, for one, has constructed "freezer farms" — banks of ultra cold chain freezers — in Louisville, Ky. and the Netherlands, where it plans to store millions of vaccines at subzero temperatures. From there, the company plans to ship the shot worldwide.

Even companies that haven't been in the vaccine business before are investing in and improving upon technology they use to jump in the game. Ember, a company that specializes in temperature-controlled tea and coffee mugs, is working to adapt its temperature monitoring technology into a self-refrigerated shipping box for COVID vaccines.

From temperature-tracking stickers stuck onto vials to make sure they stay at the right temperature, to products resembling the ultra-cold mobile cold storage used during Ebola, the gamut of possible solutions runs wide, says Yadev.

Companies invested in supply are also pushing back on the initial requirements for how cold vaccines really need to be, as well as how long they can actually last. "On the supply side, drugmakers continue to do testing to see how far they can relax temperature requirements," Swann explains. And the gains have been considerable.

Experts say relaxations on the Pfizer's vaccine storage to typical freezer temperatures, for instance, could make a difference in distribution efficiency and getting the vaccine out faster. And the U.S. Food & Drug Administration is poised to approve Pfizer and BioNTech's bid to store COVID-19 vaccines at high temperatures than the ultra-cold.

The path forward to better worldwide distribution doesn't just rely on vaccine innovation, though. In the end, Yadav says it's "simple workarounds" that may end up being part of the answer — things basic picnic coolers or even clever ways of packaging to "get vaccines where they need to go."

Pranav Baskar is a freelance journalist who regularly answers coronavirus FAQs for NPR.

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Pranav Baskar