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Comment by cashsterling | Hacker News Reader

-80C storage is an issue, you are definitely right, but it is a common requirement for many biological samples and protein-based drug therapies. -80C lab freezers are not that expensive and all over the place. I used to work in biotech and, at one company, all of our intermediate drug substance storage was -80C. we had freezers big enough to drive a forklift into; one such a freezer could store millions of doses... and we had several.

There are numerous companies which specialize in -80C transport and shipping. These containers can be used as temporary (3-7 day) storage at destinations where they do not have infrastructure.

So this vaccine can be distributed to regions with the infrastructure to store it and we can preserve vaccines with less stringent requirement for developing countries, etc.

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Why, biologically speaking, does it need to be that cold? I'm guessing something breaks down at higher temperatures?

(That's -112 F, for anyone else wondering.)

It’s an RNA vaccine. RNA degrades at room temperature.

Yes, but why that low?

Because it degrades at higher temperatures.

They do stability studies on these molecules, holding samples at different temperatures and measuring how much "is left" after a period of time.

This particular RNA sequence and carrier might be particularly unstable, so it require -80C if you want it to last longer than a few weeks.

Because RNA is not a stable molecule. At lower temperatures, it's less likely for a given bond to reach the Gibbs free energy of activation, thus preventing degradation.

In a biological context, the vast majority of RNA use falls within the 'central dogma' of DNA -> RNA -> Protein. It is merely an intermediate, albeit one with important and complex regulatory processes.

In RNA viruses and other contexts where stability is required, the RNA is stabilized by its environment, namely by associating with special proteins.

Is that literally 1.5C colder than dry ice?

If that temperature could be obtained with dry ice, that would simplify things a bit. But AFAICT dry ice sublimates at -78.5C.

Could you name some of the companies? Are any of them public?

> There are numerous companies which specialize in -80C transport and shipping. These containers can be used as temporary (3-7 day) storage at destinations where they do not have infrastructure.

But what kind of capacity can they handle? I imagine the scale of a Covid vaccine rollout would overhelm prior existing infrastructure

There are a lot of other things that need this treatment. There is also limited ability to make doses. If you don't already have the infrastructure in place, then you will get notified when you shipment is arriving, and you get a few days to administer it. You schedule everyone who will get a dose for their shot and they are in and out quickly. If it takes more than half a day to use up their entire shipment it is because some dosages are reserved for 3rd shift and will be administered 12 hours later. Then repeat 3 weeks latter.

Of course larger institutions already have everything in place and will get shipments with less warning (but they will also get smaller shipments since they don't have to get everyone done at once)

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