Vaccine manufacturing is just a way more involved process than anything what an average organic synthesis shop can handle. Dealing with antibodies, proteins, plasmids, or RNA requires real factories rather than garage labs.
What one need is a complete process transfer: instructions on setting up every process, along with supplies needed, and operation training, and supervision.
Conventional vaccine production is a highly biological process... chicken eggs being used to make the flu vaccines and so forth. I was under the impression that the mRNA vaccines are chemically much simpler -- just strands of a particular RNA sequence (swapping Pseudouridine for Uracil), encapsulated in a very clever lipid coat.
Presumably the biotech industry is really really good at manufacturing strands of RNA by now, right? I mean that seems like it's something they would've been doing every day for the last 20 years.
So are the only novel manfuacturing steps the Pseudouridine substitution and the lipid coat?
I would want to know how they do it (mRNA isolation) too, but nobody will share that knowledge for free.
Even most simple methods like inactivation require a cell culture tech, which means lots of expensive bioreactors, and extreme levels of sterility.
The DNA sequence is then cut out of the plasmids and transcribed into mRNA.
https://www.nytimes.com/interactive/2021/health/pfizer-coron...
I bet getting that batch of bacteria to grow and make lots of the desired plasmids is a nice trick to pull off.
Getting sufficient production of the target isn't easy. The guy at your link includes 'countless failures' in his intro!
Why do they do it that way?
When you order DNA plasmids from places like Addgene the stuff they ship you is chemically synthesized using enzymes rather than and entire complete living cell, right? I would've thought Pfizer would do the same thing and then transcribe that DNA into mRNA.
Is it because of the massive quantities of material they need to produce?
[1] https://blogs.sciencemag.org/pipeline/archives/2021/02/02/my...
[2] https://blogs.sciencemag.org/pipeline/archives/2021/02/22/mo...
Okay, this is the best article of them all, the one I was wishing for. Congratulations, you win ten thousand Internets!
Best part (although the whole thing is totally worth reading):
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. ... Everyone is almost certainly having to use some sort of specially-built microfluidics device ... 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.
The Economist isn't a technical publication but it is known to do its homework and get details like this right.
Supplies of raw materials such as nucleotides are also tight. According to Dr Zarur, Thermo Fisher, an American chemical-supplies company, has spent $200m on a new facility in Lithuania to make these molecules, though the firm itself would not confirm this.
I would not have expected this, but it definitely explains a whole lot of otherwise-cryptic claims being made in the WTO debate. I guess it does sort of make sense. The worldwide demand for pure bulk nucleotides probably shot up hundreds or thousands-fold as a result of COVID-19 vax manufacturing.
https://www.nytimes.com/interactive/2021/health/pfizer-coron...
No details on which ingredients are the ones causing so much consternation at the WTO right now, nor any answer to the obvious question "why aren't the DNA plasmids made the same way other commercial plasmid services make them"?
But hey, it's the NYTimes. They have to hold the attention of an audience that mostly has no science background.
Good on them. I wish patents on medication were disregarded universally.
I very much doubt we’d have these fancy new mRNA vaccines if that had been the case the last 20 years.