Many things have to work out to end the coronavirus pandemic. Pharmaceutical companies need to develop a safe and effective vaccine. Billions of people have to consent to a vaccination.
But there are also more prosaic challenges. Among other things: Companies may have to move tiny glass vials thousands of miles while staying as cold as the South Pole in the dead of winter.
Some of the leading Covid-19 vaccines under development must be stored at temperatures as low as minus 80 degrees Celsius (minus 112 degrees Fahrenheit) from filling to injection into the patient's arms.
That will not be easy. Vaccines can be made on one continent and shipped to another. They will move from fulfillment center to fulfillment center before ending up in the hospitals and other facilities that they manage.
While no vaccine has yet been approved by health authorities in the United States, preparations are underway for a mass vaccination campaign. The U.S. military and a federal contractor are expected to have roles in coordinating the distribution. But a multitude of companies are trying to figure out how to keep hundreds of millions of doses of a vaccine very, very cold.
Aircraft, trucks and warehouses need to be equipped with freezers. Glass vials have to withstand icy climes. Someone has to do a lot more dry ice.
"We are only just beginning to understand the complexities of the delivery side of all of this," said J. Stephen Morrison, senior vice president at the Center for Strategic and International Studies, a research firm. "And there is no getting around it. They have high temperature requirements that limit access and delivery."
President Trump claimed Friday that hundreds of millions of doses of an unidentified vaccine will be available to all Americans by April. This schedule is more ambitious than what his own consultants have described. Dr. Robert R. Redfield, director of the Centers for Disease Control and Prevention, told a Senate committee Wednesday that a vaccine would not be widely available until mid-next year.
Of the three vaccines enrolled in Phase 3 trials, two – one from Moderna and the National Institutes of Health, the other from Pfizer and BioNTech – require near-constant freezing. (They're made of genetic material that falls apart when thawed.) Another lead vaccine candidate developed by AstraZeneca and Oxford University requires refrigeration, but not frozen storage.
McKesson, a major drug distributor, won a major federal contract to distribute a coronavirus vaccine last month. Much of the work, however, will go to companies outside the medical and pharmaceutical industries. The major US logistics companies, including UPS and FedEx, already have networks of freezers that they use to ship perishable food and medical supplies. The companies have experience shipping vaccines against other diseases, including seasonal flu.
But the Covid-19 vaccination efforts are likely to dwarf all previous campaigns.
UPS announced that it is building a freezer farm in Louisville, Kentucky, the company's largest hub, to store millions of cans at sub-zero temperatures.
Creating an entire warehouse that could maintain this freezing would have been too complex and expensive. Instead, rows of upright industrial Stirling Ultracold freezers are arranged in a warehouse, each of which can hold 48,000 vials. There are 70 freezers so far, but the warehouse could fit a few hundred. A similar UPS center is in the works in the Netherlands.
"I've never seen anything like it," said Wes Wheeler, UPS health director. "Nothing was that global."
At FedEx, vaccine preparation is led by Richard W. Smith, son of founder Fred W. Smith. The younger Mr. Smith, who heads the company's flight operations in America, was responsible for the life science business of FedEx flight operations during the 2009 H1N1 pandemic. At that time, the U.S. government asked FedEx to prepare to ship vaccines, Smith said, and the company doubled the number of freezers worldwide.
"Fortunately, H1N1 hasn't reached the level of the pandemic we thought it could be," he said. "But that has allowed us to really improve our cold chain infrastructure."
In the years following that fear, FedEx expanded its range of freezers and worked with the Federal Aviation Administration to get approval for its planes designed to carry more dry ice. (When dry ice melts, it emits carbon dioxide, potentially making the air on planes unsafe for pilots and crew members.)
Now FedEx is adding freezers that can maintain temperatures as low as minus 80 degrees Celsius in cities like Memphis, Indianapolis and Paris. Additional refrigerated trailers will be installed in Oakland, California, Dallas, and Los Angeles that can be used for vaccines that must be served chilled rather than frozen.
"The demand for this is huge," said Mr Smith. "We know it will be a very important market." Citi analysts agreed that the vaccine shipping business is likely to be profitable in a recent notice that FedEx stock was a good investment.
As if the challenge wasn't massive enough, the world is facing an impending dry ice shortage – an unexpected side effect of the pandemic.
Dry ice, which emits cool smoke and excites school-age scientists, is made from carbon dioxide, which is most commonly a by-product of the manufacture of ethanol.
However, ethanol production is dwindling due to the demand for gasoline. That spring, when home stay orders went into effect, people started driving less. As a result, ethanol production collapsed, as did the supply of carbon dioxide.
In April, Richard Gottwald, executive director of the Compressed Gas Association, sent a letter to Vice President Mike Pence warning of "a significant risk of carbon dioxide starvation".
Five months later, "the ethanol industry has still not recovered," said Gottwald in an interview. "We see a shortage." And that makes it difficult to get dry ice.
Marc Savenor, owner of Acme Dry Ice in Cambridge, Massachusetts, which supplies the medical company, is low in carbon dioxide for most of the summer. The supply was the tightest he had seen in his 42 years, and it forced Mr. Savenor to ration his dry ice.
"It was like a McDonald's without a hamburger," he said, adding that carbon dioxide appeared to be abundant for the past few weeks.
UPS and FedEx take matters into their own hands. FedEx already has machines in warehouses that can produce dry ice, and UPS was considering adding them.
Companies must also provide their delivery workers with specialized training and equipment such as gloves for handling their icy goods.
Pfizer designed a special box to transport the vaccine they were hoping for. The boxes, about the size of a large cooler, hold a few hundred glass vials each containing 10 to 20 doses of vaccine. The boxes are equipped with GPS enabled thermal sensors so Pfizer knows where the boxes are and how cold they are. (If they get too warm, workers can add dry ice.)
All of this leads to another problem: glass often cracks in extreme cold.
Earlier this year, Corning, a 169-year-old glass manufacturer in New York State, reached out to officials at the Department of Health and Human Services with a warning stating that there wouldn't be enough cold-resistant glass vials to handle a frozen vaccine. said Brendan Mosher, Corning's director of pharmaceutical technologies.
Corning suggested a solution. With a new type of pharmaceutical grade glass that can withstand the lowest temperatures, millions of vials could be made. In June, the government awarded the company a $ 204 million contract to increase production of the specialty vials. The new glass is made without boron, a common ingredient in conventional glass that can contaminate the materials in the vials.
Mr Mosher said Corning used the federal money to quadruple the capacity of its Big Flats, New York facility. expedite construction of a glass furnace in New Jersey; and to expedite the construction of an additional facility in North Carolina. Corning hires 300 people and says it is on track to produce hundreds of millions of glass vials over the next year.
Even with enough dry ice, refrigerated warehouses, and sturdy vials, it is unlikely that everyday pharmacies will be able to store large amounts of vaccines that need to be stored ultra-cold. Even so, they may be able to keep Pfizer's cooler boxes ready, and Moderna's vaccine can be stored in less extreme temperatures for the days prior to administration.
In a presentation to the White House coronavirus task force last month, Kathleen Dooling, a disease expert with the C.D.C., said strict temperature requirements "will make storage and administration very difficult for community clinics and local pharmacies". She said the vaccine must be dispensed "in central locations with adequate equipment and high throughput". It's not clear where these locations are or who is giving the vaccines.
That's only in the United States. A vaccine that required strict temperature controls would be banned in much of the developing world. A recent study by DHL and McKinsey found that a cold vaccine would be available to approximately 2.5 billion people in 25 countries. Large parts of Africa, South America, and Asia where super-cold freezers are scarce would be left out.
"The consequence is that the astonishing tendency in favor of the few rich and powerful countries is intensified," said Morrison of the Center for Strategic and International Studies.