The preparation of the COVID-19 mass vaccination campaign currently underway requires a cold supply chain built around the storage temperature requirements of the two vaccines: -70°C±10°C for Pfizer's BNT162b2, and -20°C±5°C for Moderna's mRNA-1273. The ultralow temperatures of Pfizer’s vaccine pose additional supply chain challenges.
Keeping the ULT supply chain intact
For the US and Canada, most doses are being shipped by road and air from the production site in Kalamazoo, MI, and the distribution center in Pleasant Prairie, WI. Depending on the distance, they will either directly reach the point of use, or FedEx’s and UPS’ distribution hubs in Memphis, TN, and Louisville, KY, respectively. From there, the supply chain might include one or more stops at intermediate storage facilities. In some cases, states (like New York, for example) may even set up additional regional storage facilities.
To maintain ultralow temperatures, distribution will use minus 80 freezers for storage, and thermal-controlled containers for transporting the vaccine from one point to the next. Both will be equipped with temperature monitors and data loggers that keep track of any temperature fluctuations out of the allowed range.
“ULT freezers provide long-term preservation at precise temperatures and have a typical life span of 10-15 years. Chest freezers last longer and are more efficient than upright models,” says Swati Patel, senior project manager at Clarkston Consulting. “The downside is that they use a significant amount of energy, the equivalent of a single-family home, which can mean higher running costs. Space can also be an issue, depending on how many are needed.”
Temperature-controlled containers have a capacity of 195 vials (almost 1,000 doses) and can be moved around more easily. They use dry ice to maintain ultralow temperatures, and are dependent on the local supply. However, they also have more restrictions—they should be opened no more than twice a day for one minute maximum and dry ice must be refilled every five days.
In the final leg of the distribution, one or the other may be used depending on their availability. Throughout the campaign, the points of vaccination will be a mix of large health care facilities in areas with high population density, and smaller facilities in more remote areas. According to New York's vaccination plan, for example, dispensing points include rural health clinics, private provider offices, schools, homeless shelters, social service offices, and food pantries.
The challenges of ULT storage for widespread vaccine delivery
While minus 80 freezers would ensure longer storage, they may not always be available, especially in smaller and public health facilities. In California, for example, capacity for ultralow temperature storage in local health departments is limited. In fact, the Centers for Disease Control and Prevention (CDC) advised jurisdictions not to purchase them at this time.
Because of the scarcity of ULT freezers in the last mile of the cold supply chain, temperature-controlled containers are more likely to be used. Considering their limitations, however, timing becomes particularly important. “With temperature-controlled containers, the vaccine has to be administered within a shorter time frame in order to not lose its potency. The challenge is making sure you have the patients lined up when the time comes,” says Patel.
While ULT freezers can store Pfizer’s vaccine for up to six months, with temperature-controlled containers, the maximum storage time is 30 days. After that, vials can be thawed and stored in 2-8°C refrigerators for up to five days. Once thawed, they cannot be frozen again. This would give a total of 35 days’ time to distribute the vaccine without using ULT freezers.
In its guidelines however, the CDC advises that once they reach the point of use, vaccines should be kept in the coolers for a maximum of 15 days and in refrigerators for up to five days, effectively reducing the time frame to 20 days.
“Since Pfizer vaccine containers are broken into 975 doses each, currently they are being shipped to locations that can administer all of them to the essential workers in the area. Many regional facilities are banding together so they can share them across their facilities, while others have procured the cold storage equipment needed to store them. Lastly, others are lining up the people so they can administer the doses within five days of receiving it,” says Patel.
COVID-19 vaccines without ULT storage requirements
Right now, these stringent ULT cold chain requirements are unique to Pfizer's vaccine. Moderna's has a storage temperature of -20°C—above the ultralow range—and can remain stable at 2°-8°C for 30 days and at room temperature for up to 12 hours.
“In terms of distribution strategy, I think Moderna’s vaccine might be better suited for smaller rural towns, as they often don't have the ability to handle the really low temperatures required by Pfizer’s,” says Patel.
The other phase 3 candidates likely to be distributed in the US won’t need ultralow temperatures either:
- AZD1222 by AstraZeneca can be stored, transported, and handled at normal refrigerated conditions (2-8°C) for at least six months
- NVX-CoV2373 by Novavax can be distributed in unfrozen, liquid formulation between 2°C and 8°C
- Ad26.COV2.S by Janssen (J&J) is expected to be stable for two years at -20°C and for upwards of three months in the 2°-8°C range
In the coming months, we can expect a larger use of 2-8°C fridges in the COVID-19 cold supply chain. This will allow any point of use to store doses for a longer time frame, and might help reduce vaccine wastage, which the WHO estimates to be at 50 percent worldwide.
However, Patel warns, when vaccines are stored in 2-8°C fridges, the temperature range is much narrower and there is much less room for fluctuations. This will require more stringent monitoring of these fridges to ensure stability of the vaccines.
At the same time, as the mass vaccination campaign continues and new candidates are authorized for distribution, the role of ULT freezers in the cold supply chain will be less important. That, however, doesn’t mean that they will remain empty: “I don't think that the need for ULT freezers is going to go away,” says Patel. “The medical advances of mRNA technology and personalized medicine will require some level of refrigeration as you transport them to patients, so they’re going to continue to be used.”