• Pfizer's Covid-19 vaccine, made in partnership with the German firm BioNTech, will need to be stored at subzero temperatures, and there are distribution challenges in rolling it out in the weeks ahead.
• The vaccine is based on a novel approach that targets the virus using synthetic mRNA to mount an immune response.
• Francesca Marzullo, manager of Pfizer global supply communications, said the company will use its cold storage chain management experience to help healthcare providers meet storage requirements for their vaccine.

A Covid-19 vaccine is expected to be made available to the public in the coming weeks, but some in the healthcare field are already asking about the practical logistics of shipping and storing one of the candidates. Pfizer's vaccine, made in partnership with the German firm BioNTech, will need to be stored at subzero temperatures, and cash-strapped medical facilities may not be able to afford such equipment.

 Don Hackett, founder and publisher of CoronavirusToday, said that cold chain vaccine storage itself is a standard requirement and shouldn't pose a challenge to U.S. hospitals or pharmacies. However, he was less sure how the effort would be outside of the U.S., where potential exists for large-scale vaccine waste. "In the developing world, cold chain requirements may be a show-stopper," he said.

The World Health Organization (WHO) has reported over 50% vaccine wastage globally every year, in part because some points of vaccination, such as healthcare providers in poor or rural areas, may not have the resources to support cold chain requirements.  "[C]ountries may receive correct quantities overall but have insufficient cold chain capacity to accommodate deliveries, with the result that vaccines are at risk of exposure to adverse temperatures," the WHO said.

"Cold chain distribution in pharma is complicated even in normal times," David Gitlin, president and CEO of Carrier Global Corp. told CNBC. "You have a clock ticking, you have an expiration date, you have multiple modes of transportation, multiple hand-offs, from [original equipment manufacturer] all the way to administration... The good news is public and private industry all coming together to be part of the solution through more capacity and new digital capabilities."

Temperature-controlled thermal shippers

 While Pfizer's vaccine candidate will need to be stored at subzero temperatures, the ones announced by Moderna and Oxford-AstraZeneca can be stored at temperatures that are within the reach of the average home refrigerator. How is Pfizer's vaccine different?

 "The vaccine is based on a novel approach that targets the virus using synthetic mRNA to mount an immune response," said Sunny Jha, anesthesiologist at the University of Southern California and co-creator of the LA Surge Hospital. "mRNA tends to be more fragile, which requires storage at a lower temperature to maintain the vaccine's stability. [This ensures] that the particles don't disintegrate to the point where the body won't recognize it or mount the correct immune response to it."

While Moderna's vaccine uses the same technology it only needs to be stored at minus 20 degrees Celsius.

 Francesca Marzullo, manager of Pfizer global supply communications, said that the company had anticipated the need to help doctors and hospitals meet storage requirements for their vaccine. She also said that the company was ready to use its cold chain management experience to help healthcare providers in poor and rural areas.

 "Our track record gives us confidence in our ability to quickly scale and manufacture and distribute large quantities of a high-quality Covid-19 vaccine, leveraging multiple sites in the U.S. and Europe," she said. "We have experience working with differing customers with different infrastructures in all markets to ensure success."

 She said that Pfizer had already developed plans for vaccine transport, storage, and continuous temperature monitoring and will ship frozen vials to the point of vaccination from its sites in Kalamazoo, Michigan and Puurs, Belgium. Pfizer will also use its existing distribution centers in Pleasant Prairie, Wisconsin and Karlsruhe, Germany.

 She said the company would also use temperature-controlled thermal shippers, which use dry ice to maintain storage temperatures of approximately negative 70 degrees Celsius for up to 10 days.

 "We will utilize GPS-enabled thermal sensors in every thermal shipper with a control tower that will track the location and temperature of each vaccine shipment across their pre-set routes," she said.

 Once the vaccine is delivered, the recipient can store it in an ultra-low temperature freezer, providing it with a shelf life of up to six months. It can also be stored for up to five days at two-to-eight degree Celsius conditions, which she described as "very commonly available in hospitals."

 She also said that medical facilities without subzero freezers could keep the vaccine in its thermal shipper, filled with dry ice. This impromptu storage unit would be good for up to 15 days.

 Danny Sanchez, vice president and general manager of EnlivenHealth, said that keeping vaccines at subzero temperatures is not at all unusual, citing the Varicella, MMRV, and shingles vaccines as common examples of medicines that must be stored at ultralow temperatures.

 "Our healthcare and pharmacy supply chain knows how to properly store, distribute and administer these kinds of vaccines," he said. "I do believe that our medication supply chain, anchored by 60,000-plus community pharmacies nationwide, can handle this."

Operation Warp Speed

 Even assuming pharmacies and hospitals can meet the requirements necessary to store and administer the vaccine, questions remain. How many doses can realistically be made, and how long will it take to get them all to the population?

 To get it out faster, the vaccine will be distributed as part of Operation Warp Speed (OWS). A Trump administration initiative, its initial goal is to produce and deliver 300 million vaccine doses.  

In an Oct.23 OWS briefing, Paul Mango, Deputy Chief of Staff for Policy in the immediate office of the Secretary at the U.S. Department of Health and Human Services (HHS), said that the Department of Defense (DOD) would work in conjunction with the Centers for Disease Control and Prevention (CDC) to guide and facilitate logistics.

Mango said that the military would facilitate logistics and organize supplies, such as "needles, syringes, swabs, band-aids, dry ice, trucks, U.S. Marshalls guarding those trucks, airplanes, flying in equipment, getting vaccines out." He clarified that the military would not be involved in the physical distribution of the vaccine itself, nor in administering it.

HHS Secretary Alex Azar said that OWS had enlisted the pharmaceutical distribution company McKesson to physically transport the vaccine. Administration will be handled by a network of independent pharmacies and pharmacy chains.

"The vast majority of Americans live within five miles of a pharmacy, so vaccination in pharmacies is a huge piece of ensuring easy access to vaccines," Azar said in a Nov. 18 OWS briefing "The ultimate goal here is to make getting a Covid-19 vaccine as convenient as getting a flu shot."

 Azar said that between Pfizer and Moderna, there would be enough vaccine doses by year's end for 20 million people. He added that the U.S. also has supply agreements in place for vaccines from Johnson & Johnson, Sanofi and GlaxoSmithKline, Novavax, and Oxford-AstraZeneca.

 The CDC has recommended that four groups of people get it first– healthcare workers, workers in "essential and critical industries," people with underlying medical conditions that may put them at risk for severe Covid-19 illness, and people aged 65 years and up. On Friday, the CDC also said that employees from the Bureau of Prisons, Department of Defense, Department of State, Indian Health Service and Veterans Health Administration might receive doses directly from the federal government in as little as eight weeks.

 According to an HHS spokesperson, OWS will also ensure that administration sites have the cold-storage resources they need, including fresh dry ice to extend vaccine storage.

Challenges for patients

 The effort to get this vaccine out has thus far been much faster than usual. Hackett said that in the past decade, the average vaccine took eight years to bring to market. However, there are still factors that may slow the process such as patient adherence. EnlivenHealth recently conducted a national survey which found that 67% of pharmacies, and 99% of health plans, are either  "somewhat concerned" or "very concerned" about people's willingness to go get the vaccine once it comes to market.

 Andrey Zarur is founder and CEO of GreenLight Biosciences, which is currently in the pre-clinical stages of developing its own Covid-19 vaccine. He said that the fact that it requires more than one dose might prove a significant hurdle.

 "The MMR jab combines three vaccines in a single dose, precisely because it is much harder to get a patient to visit the healthcare center three times than once," Zarur said. "In the USA, multi-dose vaccines for HPV and hepatitis have sometimes had only 40% of people get fully vaccinated."

 Zarur also said that even after the vaccine is available, there may still be hiccups ahead.

 "There may be supply chain bottlenecks," he said. "For instance, the people who supply Pfizer with their nucleotides will also supply Moderna. In addition, if the virus mutates, we may need to develop a new vaccine."

 Despite the tantalizing possibility of life returning to normal, Dr. Robert W. Amler, vice president and dean at New York Medical College and a former epidemiologist in CDC's immunization division stressed that the Covid-19 crisis is not over, and people still need to be as vigilant as they were at the beginning. He advised that people continue to practice the "Four Ws" until further notice. 

 "Wash hands, wear masks, watch social distance and walk away from groups of people," he said. "We must remain alert for symptoms, get tested when appropriate, and observe applicable isolation and quarantine guidelines."