Clearly it is not money, as there cannot be much limit on how much states are willing to pay.
From what I understand, it’s mostly because the precursors to the vaccines themselves are finicky and high-tech and can only be produced so fast at specific facilities, and then the vaccines themselves can be produced only so fast as well, in equally specific facilities and using specific processes.
It’s not like we can repurpose one of Anheuser Busch’s breweries and crank these vaccines out by the hectoliter; these are extremely specialized facilities, industrial processes and feed stocks in both stages.
It’s almost certainly not a question of cash, but existing facilities and processes. And I’m sure they’re repurposing everything they can and even building new, but that takes time.
Even if you could double the amount of vaccine being produced there are only so many people who can perform the vaccinations and only so many people willing to line up for them.
In my state (Montana) some counties have more vaccine then they need due to a lack of demand and are shipping their extra vaccine to counties that have higher demand. I don’t think there is a general lack of supply in the US, it’s just that the demand varies depending on local need.
Distributing vaccine based on a state’s population made sense in the beginning but there are probably more efficient ways to distribute it now based on the demand at each vaccination site in the country.
There are a host of supply chain bottlenecks, such as shortages of the glass vials that the vaccines go in. Or since there is (was?) a limit of 5 Moderna doses per vial, and each vial takes x seconds to fill, and there are only so many hours in a day per vaccine filling line. Moderna then applied for permission to put 10 doses per vial simply to speed up this single bottle neck.
These are new production processes and production lines, and there are always teething issues. In addition to that, there is a global disruption to the air and sea shipping industry. And even if you’ve got the planes to airship the vials to the factory, you might run into the global shortage of container shipping units (ie, you have boxes of vials, but don’t have a 20 foot container for the boxes, so can’t get it on the plane).
Step One: Produce the appropriate stretch of DNA, containing the sequence that you need to have transcribed into mRNA. This is generally done in bacterial culture.
Step Two: Produce that mRNA from your DNA template using enzymes in a bioreactor.
Step Three: Produce the lipids that you need for the formulation. Some of these are pretty common (such as cholesterol), but the key ones are very much not (more on this below).
Step Four: Take your mRNA and your lipids and combine these into lipid nanoparticles (LNPs). I have just breezed past the single biggest technological hurdle in the whole process, and below you will learn why it’s such a beast.
Step Five: Combine the LNPs with the other components of the formulation (phosphate buffers, saline, sucrose and such) and fill those into vials.
Step Six: Get those vials into trays, into packages, into boxes, into crates, and out the door into trucks and airplanes
more cetails
Ah, but now we get back to Step Four. As Neubert says, “Welcome to the bottleneck!” Turning a mixture of mRNA and a set of lipids into a well-defined mix of solid nanoparticles with consistent mRNA encapsulation, well, that’s the hard part.
Moderna appears to be doing this step in-house, although details are scarce, and Pfizer/BioNTech seems to be doing this in Kalamazoo and probably in Europe as well.
Everyone is almost certainly having to use some sort of specially built microfluidics device to get this to happen – I would be extremely surprised to find that it would be feasible without such technology.
Microfluidics (a hot area of research for some years now) involves liquid flow through very small channels, allowing for precise mixing and timing on a very small scale. Liquids behave quite differently on that scale than they do when you pour them out of drums or pump them into reactors (which is what we’re used to in more traditional drug manufacturing). That’s the whole idea.
My own guess as to what such a Vaccine Machine involves is a large number of very small reaction chambers, running in parallel, that have equally small and very precisely controlled flows of the mRNA and the various lipid components heading into them. You will have to control the flow rates, the concentrations, the temperature and who knows what else, and you can be sure that the channel sizes and the size and shape of the mixing chambers are critical as well.
These will be special-purpose bespoke machines, and if you ask other drug companies if they have one sitting around, the answer will be “Of course not”.
This is not anything close to a traditional drug manufacturing process. And this is the single biggest reason why you cannot simply call up those “dozens” of other companies and ask them to shift their existing production over to making the mRNA vaccines.
There are not dozens of companies who make DNA templates on the needed scale. There are definitely not dozens of companies who can make enough RNA. But most importantly, I believe that you can count on one hand the number of facilities who can make the critical lipid nanoparticles. That doesn’t mean that you can’t build more of the machines, but I would assume that Pfizer, BioNTech, Moderna (and CureVac CVAC, +5.04% as well) have largely taken up the production capacity for that sort of expansion.
When I got my second Pfizer vaccination I had a conversation with the nurse who actually poked me. She said the syringes were prefilled when she got them and the needle retreated into the body of the syringe after use, both features really handy when you’re working under a pop-up in a parking lot.
In my lab we make mRNA all the time from cDNA as described above, but the Pfizer and Moderna vaccines are not made this way - they have modified nucleotides incorporated into them which reduces the bodies immune response to the mRNA molecule itself (which would destroy it before it had a chance to work).
The modified vaccine mRNA is synthesized artificially; in essence it is printed by RNA synthesis machines. These are expensive and specialized.
On edit: this also makes it very easy to develop new vaccines for new strains or new pathogens. You just feed the new sequence into the computer and print a different vaccine. If nothing else comes out of this COVID fiasco, we’ve had a paradigm-shift in vaccine technology that may, over time, save more lives that have been lost to COVID.
Still too bloody expensive for my taste, but one must find what silver linings one can