In this comment on the parent question, David Manheim makes the case for building new vaccine production facilities before we have a vaccine ready to produce, and for this to be subsidized. I find this question interesting in its own right, but it's also an opportunity to dig into the nitty-gritty of producing something, which I wish happened more on LessWrong. I don't expect this to lead directly to a vaccine facility coming into existence- presumably the people who have the power to do that already have access to the knowledge as well- but I think it's a useful exercise in how things actually get done.

To recap, David's argument as I understand it is:

  • The world is under-capacity for vaccines as it is
  • Building a vaccine production facility takes a lot of time and money, so we need to start funding and building them now to have them ready when we have candidates ready.
  • We're likely to want to mass-produce multiple vaccines until we know which ones work the best, increasing the amount of capacity needed.

There's already a great discussion of this in the replies to his thread, and I encourage you to read it before commenting here. Some questions that came up in that discussion:

  • Is there such a thing as a generic vaccine production facility, or do different vaccines require different facilities?
  • What raw materials (e.g. sterile eggs) are we also likely to need large quantities of, and should perhaps start sourcing now?

Some additional questions I have are:

  • Are there costs besides the obvious financial ones to building these facilities ahead of time? Are they competing for a resource we need more elsewhere?
  • Who does have the power and knowledge to make these facilities?
  • What are some historical equivalents?

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To produce a vaccine, you will need at least:

  • Vaccine (or at least a rough idea what your vaccine will be going to look like)
  • Large scale production process (which is not the same as a bench scale process)
  • Raw materials
  • Facility (see below)
  • Staff (see below)
  • A working quality system (including an ok from the regulatory agencies)

In biopharmaceutical production you have two kind of extremes in the facility design:

  • "Stainless steel" facility: This is usually the option if you are going to produce the same product forever. It needs a higher upfront investment but comes with lower operating costs. If you take care of such a facility you should be able to use it for a long time. Construction time should be higher than for the option below, but will depend highly on the exact setup.
  • "Single use" facility: This facility design is sometimes referred to as a "ballroom" design because it just comes with the clean room and the needed media (e.g., water, gas, etc.) and uses single-use equipment for the production itself (i.e., plastic bag, tubing, etc.). This setup needs less upfront investments and has higher operating costs (usually due to the expensive single use equipment). There are also production systems which are built into containers.

Of course, everything between those two designs is possible. Both types can be designed to produce multiple products which is referred to as a "multi-product facility". Depending on the automation grade you will need more or less staff with more or less training and experience. For the ramp-up of the facility and for ongoing troubleshooting you will need (highly) educated stuff.

The vaccine production systems can be roughly classified into these variants:

  • Egg-based: Egg gets infected with virus, virus particle or parts of it are used for the vaccine.
  • Cell-culture-based: The same as above, but you infect cells.
  • Microbial/insect-based: Usually used to express subunits of the vaccine and no entire virus particles. Can be also used for DNA vaccines?
  • (Fully?) synthetic: Nucleic acid- (i.e., RNA, DNA) or poly-saccharide-based vaccines?

These outlined systems are quite different, and, therefore, the facilities will look different. However, a well-designed multi-product facility should be able to cover a wide range of the possible vaccine types because basic fluid handling and a lot of other steps are similar.

The most similar historical equivalent I can think of is the penicillin production, although there the circumstance where quite different.

Vaccines are one of the most cost-effective medical preventive measures but usually the margins are thin. This is why the investments in such products has not seen the levels of treatments of civilization diseases, e.g., cancer or diabetes.

Edit: Added large scale process to the points at the beginning.

There seem to be different technologies that can produce vaccines. On the one hand there's an old-fashionated way to create vaccines.

Then there are multiple different companies that make mRNA-based vaccines and as far as I understand they all use different technology to do so and are therefore not easily exchangable.

CureVac announced that they got a 80 million Euro loan from the EU that they use to build a facility that can produce ~1,000,000,000 doses of a possible vaccine if the dose is equal to what they found to be needed for their rapies vaccine candidate.

Moderna who started their human trial on March 16th made a SEC filing in which they wrote:

On March 20, 2020, Stephane Bancel, CEO of Moderna, was interviewed by representatives of Goldman Sachs regarding the Company’s work onCOVID-19. During such interview, Mr. Bancel indicated that while a commercially-available vaccine is not likely to be available for at least 12-18months, it is possible that under emergency use, a vaccine could be available to some people, possibly including healthcare professionals, in the fall of2020. In addition, Mr. Bancel confirmed that the Company is scaling up manufacturing capacity toward the production of millions of doses per month,in the potential form of individual or multi-dose vials. As has previously been disclosed, the ability of the Company to make millions of doses per month is contingent on investments in the scale up and further buildout of the Company’s existing manufacturing infrastructure.

I would predict that if Moderna starts giving out a million vaccines to health workers under emergency use any additional doses of vaccines they produce would also find willing patients whether or not the drug is offically commercially-available. Politically it wouldn't be defensible to let millions of doses of a vaccines that's good enough for health workers to lie around.

The highlited passage looks to me like Moderna needs cash to scale up their production.

According to the main investor in CureVac, there current plan is to make the vaccine generally available at the end of the year:

https://www.focus.de/finanzen/boerse/weil-biotech-leben-rettet-curevac-investor-im-fruehsommer-koennen-wir-mit-dem-test-des-impfstoffs-am-menschen-beginnen_id_11829181.html

Would be interesting to know how long they'd have to produce ~1,000,000,000 doses.

2ChristianKl4y
They said that currently they can produce 10,000,000 per campaign and with the new facility they can produce 1,000,000,000 per campaign in the press call. Unfortunately, they didn't specify how long a campaign is going to last. Last year they got some funds to develop a portable facility (The RNA Printer) that can produce 1,000,000 doses in two weeks.
2Davidmanheim4y
Unfortunately, 1bn doses is likely no more than a quarter of the world's need - less if COVID is stopped more places.

1 Related Questions

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micpie's answer here is good! I don't have a lot to add to it.

Here are a few related reference-links* and a tiny bit of commentary.

*...some of which I heard about via other micpie comments. Go figure.

** 60 days from the nCOV DNA sequence to mRNA vaccines starting clinical trials! mRNA is a relatively flexible/easy-to-modify platform, but new and a bit untested.

From this comment on a post to which I recently linked on this site:

Also: I don't know if you saw the article, but it's not just gardening supplies that have been wiped out. America's run through all the baby chickens too.

So, as a sort of sub-question to this one:

What are the costs, benefits, and logistics of opening new facilities for the entire supply chain for vaccine facilities?