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The hidden cost of the mRNA cold chain

The first mRNA vaccines had to be kept frozen, one of them far colder than an ordinary freezer can go. Here is what that means for cost, for logistics and for who can be reached.

By Samkit Shah3 min read

The first mRNA vaccines were developed faster than almost any vaccine before them. Getting them to people, once they were made, was a different problem. Both of the first widely used mRNA vaccines had to be stored frozen, and one of them needed temperatures far below what an ordinary freezer can reach.

How cold

When the World Health Organization described the Pfizer-BioNTech vaccine in early 2021, it required ultra-low temperature storage between −80 °C and −60 °C. Once thawed, it could be kept at 2 to 8 °C for five days, or for two hours below 30 °C.1

Moderna’s vaccine was supplied as a frozen suspension at −25 °C to −15 °C. WHO’s guidance allowed unopened vials to be kept refrigerated at 2 to 8 °C for up to 30 days. Once the first dose had been drawn, the vial had to be discarded after six hours.2

Storage windows have since been extended. A 2023 review in the Journal of Pharmaceutical Sciences notes that regulators extended refrigerated storage of Comirnaty from up to one month to ten weeks, while long-term storage stayed at around −80 °C. The same review notes that long-term storage integrity of both Comirnaty and Spikevax is only achieved at subzero temperatures.3

Why mRNA needs the cold

RNA is chemically fragile. Its backbone can break through a reaction within the molecule itself, and the rate of that breakage rises with heat and with alkaline pH.3 Storage near neutral pH in a freezer keeps it to a minimum.3 That is why storage temperature and integrity, the share of molecules still intact, are so closely linked.

What an ultra-cold chain takes

WHO’s overview of ultra-low temperature storage and transport is frank: establishing an ultra-cold chain is not easy.1 It sets out what is involved.

  • Freezers. Ultra-low temperature freezers have stringent operating conditions, including a controlled ambient temperature below 27 °C, and high energy demands. WHO notes that a 700 litre ultra-low freezer consumes as much as a 20 cubic metre walk-in cold room. They need a reliable power supply.1
  • Transport. Moving vaccine at −80 °C to −60 °C needs special phase change materials or dry ice, and newer types of insulated containers.1
  • Handling. On arrival, WHO’s guidance asks teams to move vaccine packs from their shippers into ultra-low freezers within three minutes, to prevent exposure to room temperature.1

The same overview says ultra-low storage for mRNA vaccines is challenging without transport links, refrigeration facilities or stable power supplies.1

Who gets left out

These requirements do not fall evenly. In a 2023 report on mRNA technology, WHO’s Science Council observed that the benefits of mRNA COVID-19 vaccines were not distributed equally around the world. Among the reasons it gave were ultra-cold-chain requirements and high costs for low- and middle-income countries.4

Heat makes every part of the chain harder. The freezers themselves need a cool, controlled room to run in, and keeping a room cool takes power too. In places where outside temperatures are high and the grid is unreliable, each of those requirements becomes a separate problem to solve.

The cold chain is not just a logistics line item. It decides which clinics a medicine can reach.

The cost you do not see on the label

Some costs are easy to count: freezers, dry ice, insulated shippers, backup power. Others are not. Every handover is a chance for a temperature excursion, and every excursion raises a question about whether the product is still good. That question needs an answer before the product can be used, or the product is thrown away. WHO lists managing on-site storage to minimise wastage as part of running the cold chain in practice.1

Where this is heading

Formulation changes have already lengthened some refrigerated storage windows, but long-term storage of the first mRNA vaccines still depends on freezing.3 WHO’s Science Council put it directly: improving the stability of mRNA vaccines at higher temperatures should be a key target for research and the money that funds it.4

As mRNA moves from pandemic response toward routine use, the distance between where medicines are made and where they are needed will matter more, not less. mRNA that keeps without refrigeration is one of the most useful problems in the field to solve. It is also one of the hardest.

Footnotes

  1. World Health Organization. Ultra-low temperature (ULT) storage and transport for vaccines: an overview of options and challenges. February 2021. who.int ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7

  2. World Health Organization. Interim recommendations for use of the Moderna mRNA-1273 vaccine against COVID-19. Interim guidance, updated 18 August 2022. who.int ↩

  3. Oude Blenke E, Örnskov E, Schöneich C, et al. The storage and in-use stability of mRNA vaccines and therapeutics: not a cold case. Journal of Pharmaceutical Sciences. 2023;112(2):386 to 403. doi.org/10.1016/j.xphs.2022.11.001 ↩ ↩2 ↩3 ↩4

  4. World Health Organization. WHO’s Science Council issues report on mRNA vaccine technology. 13 December 2023. who.int ↩ ↩2

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