The rush to vaccinate vs. the cold chain last mile

If developing COVID-19 vaccines at record speeds seemed improbable, delivering them to almost eight billion people can still feel like an impossible task.

“It’s one of the most ambitious things we’ve ever had to face in our lives,” said Dr. Daniel Bausch, Director of Emerging Threats & Global Health Security at FIND, the global alliance for diagnostics. “From the moment a vaccine is ordered, to the moment is it shipped … to the moment it is delivered, we’ve seen that implementation has been quite challenged.”

One part of the challenge lies in the mammoth logistics. Another, in the indispensable human resources required. But even if those two challenges are met, maintaining the cold chain – the sequenced precise-temperature environments that keep vaccines safe in their journey from factory to arm – in places where ultra-cold refrigeration and electricity are scarce can be a monstrous task.

The two COVID-19 mRNA vaccines that have proven to be among the most effective must be stored in temperatures anywhere between -61 or -20 degrees Celsius. According to the U.S. FDA, frozen, undiluted vaccine vials of the Pfizer vaccine can be stored between -25 and -15 degrees Celsius for up to two weeks after they arrive at a vaccination site. After, they need to be stored below -61 degrees Celsius.) Standard commercial freezers cool at -18 Celsius, hardly cold enough to keep certain mRNA vaccines from spoiling.

Dr. Daniel Lieberman, Senior Director of Engineering at Global Health Labs, and his team in Seattle, Washington, were faced with a similar challenge in 2014, when the world was scrambling to beat an Ebola outbreak in Africa’s hot equatorial belt. The Ebola vaccine also ended up being developed at breakneck speed. But it would require an ultra-cold chain to be safely delivered.

“We had made a cold storage unit that could transport vaccines, like the polio vaccine, at two to eight degrees Celsius, a standard temperature found in most refrigerators. But -80 Celsius is a completely different playing field,” he said. “That’s four times colder than freezers in a typical home.”

Lieberman looked for inspiration in the Arktek, which he and his team previously created. The microwave-sized, barrel-shaped leak-proof container uses fiberglass, vacuum chambers, and ice packs to keep the cold in and heat out.

“Water ice packs were good ‘thermal batteries’ for polio vaccine, but for Ebola, we needed them to be much cooler,” he said. So, they played with different kinds of phase-change materials, or elements whose thermodynamic properties only freeze and melt at certain temperatures, and found one that worked.

In 2020, as the COVID-19 pandemic broke out, they looked to the Arktek and once again, adapted their thermal batteries. “Dry ice is an amazing refrigerant for cryogenic storage, and it makes a lot of sense to use it, especially in areas where cryogenic freezers or electricity may not be available,” Lieberman said. Carbon dioxide, which is needed to make dry ice, can often be found in such places.

Lieberman and team considered it a win, although one that he caveated. “The Arktek is just one possible solution,” he emphasized. “For everyone to have access to COVID-19 vaccines, many complimentary cold chain solutions are needed.”

In Rwanda, a complementary solution was exemplified in the rollout of the HPV vaccine. In 2011, the country became the first African nation to implement a national HPV vaccination program, after securing enough of Merck’s 9-valent recombinant doses to vaccinate 96 percent of its girls.

Dr. Agnes Binagwaho, Vice Chancellor of the University of Global Health Equity and Rwanda’s former Minister of Health, said it was a huge accomplishment.

“How do you explain that in Rwanda we managed to implement the HPV vaccine at 96 percent? We never went below 93 percent, and the rich countries barely get to 75 or 80? People don’t get vaccinated because they are obliged to be vaccinated. People get vaccinated because of the way we implement [vaccination],” she said. “Implementation is the big problem in everything. If [for COVID-19] we implemented all that we know, we would save millions of people.”

The cold chain, she said, is one such implementation problem that can be solved by planning and preparation. “It’s not a matter of money. The budget is just part of the evidence. [Just like] you teach people clinical services and what to do, you have to teach people how to deliver [vaccines] in the best way, according to context."

She said Rwanda faced similar challenges in rolling out its pneumococcal vaccine. “We did a financial study saying the risk to die was X, so if we invested Y, we’d win this much life, meaning you’d win Z GDP over time” she said, describing her argument to the minister of finance to secure funding for refrigeration.

“Knowing that to have the Pfizer vaccine you need [the ultra-cold chain], we said: ‘If one day Pfizer is available, we need to have capacity to store it.’ So, the Ministry of Health equipped the country. And you know what? It’s not so expensive,” she said, adding it is “more a matter of organization. For less than US$200,000, Rwanda purchased the necessary freezers and the material needed to transport vaccines safely.”

But on the day we spoke to Dr. Binagwaho, Rwanda – a country of 12 million – had only administered 400,000 doses of COVID-19 vaccine. “Bring Rwanda 10 million vaccines. And I will assure you that the Ministry of Health will vaccinate Rwanda in a month,” she said.

The reason she was so confident? “Because we love science. Whatever science is there, and if we say it is science, we are trusted. And also, because you cannot do things that are not evidence-based.”

When we asked her about vaccine hesitancy, which continues to be a challenge in many parts of the world, she said it too is a failure of implementation science.

Implementation science, according to the University of Washington, is the “scientific study of methods and strategies that facilitate the uptake of evidence-based practice and research into regular use by practitioners and policymakers.” The NIH calls it “the scientific study of methods to promote the systematic uptake of research findings and other evidence-based practices into routine practice, and, hence, to improve the quality and effectiveness of health services.”

Dr. Binagwaho said it is ultimately a science rooted in planning. “It’s very simple. Planning in the supply chain and after that, the preparation logistics, and after that the service delivery chain, and after that the service delivery management of waste, and after that, monitoring and evaluation of all the steps, so we can do better the next time.”

In Zambia, Dr. Felix Masiye, Dean of the School of Humanities and Social Sciences at the University of Zambia, and an affiliate assistant professor at the Institute for Health Metrics and Evaluation at the University of Washington, said his country had planned for that “next time.”

In 2017, Zambia applied and received funding from Gavi, The Vaccine Alliance to expand its cold chain, particularly in rural areas, where cold storage was still kerosene or diesel-based . “We had to replace about half of our national cold chain at the district level, and the advent of COVID came at a point where we’d already made investments in expansion,” he said.

Today, Zambia has an adequate cold chain, something it was able to leverage when it applied for COVAX, by showing its cold chain was not a binding constraint to delivering eventual doses.

And when those doses arrive? Lieberman recalls that the networks Congo set up to combat Ebola, deploying the Arktek from locations outfitted with ultra-cold freezers. He said that for COVID-19, the Arktek could follow a similar “hub and spokes” model. “Vaccine storage can be centralized, and then with tools like the Arktek, distribution can be regionalized."

According to Our World in Data, on July 13, 2021, only 25.4 percent of the world’s population had received at least one shot of a COVID vaccine. In low-income countries, the figure was only one percent. For a pandemic that caught the world off guard, and a vaccine development that broke all speed records, the delays in implementation have created an odd paradox: countries that are still waiting for the vaccine may still have time to prepare. Looking to Rwanda and Zambia, both ready to deliver the COVID-19 vaccine to the last mile, may help other countries forge a path to receive and implement theirs, effectively.