The @Dereklowe piece sort of misses the point. Yes, there is no idle mRNA vaccine production capacity in the pharma industry that could simply be repurposed to make more COVID-19 vaccines. But we could rapidly *build* more capacity, as we did across the world last year. 🧵
Before we get deep into the weeds, lets remember, in January/Feb, the world had basically no commercial scale mRNA vaccine production capacity. By December, private industry (with a lot of public funds) built 3 billion+ doses / year scale capacity
So what happened? Companies like @pfizer, @BioNTech_Group, and @LonzaGroup (which makes the bulk of finished drug substance for @moderna_tx ) rapidly built mRNA vaccine production capacity inside existing manufacturing facilities.
To see how fast this can happen, let's look at @BioNTech_Group purchase of @Novartis biologics manufacturing plant in Marburg, Germany on 28 Sep 2020. (h/t @LeaozinhoM for this example)…
Purchased at the end of Sept, with no built in mRNA vaccine production capacity. In Oct\Nov BNT installed equipment for mRNA vaccine production. In Dec the plant was approved by environmental authorities for operation. On 28 Jan 2021, the plant was approved for cGMP production.
The plant starts commercial production this month. So a very new German company, in less than 6 months, was able to convert an existing plant w/ no mRNA vaccine production capacity into a plant that can produce 750 million doses per year.
Almost certainly if an entity like the USG was involved, this process could go faster (albeit not much faster), because of basically unlimited capitol, labor and special powers like the DPA and 28 USC 1948.
Now lets talk about the step that @Dereklowe argues is the rate limiting one, lipid nanoparticle (LNP) encapsulation. The LNP are the tiny (prob. ~100 nm), roughly spherical particles made of lipid (a fat is a lipid) that enclose the modRNA payload.
The LNP is incredibly important for mRNA vaccine efficacy. It allows the RNA to get into the inside of the cell, allowing the RNA to be converted (translated) into the (modified) spike protein that elicits the immune response. Obviously simplifying a lot here.
Quality control is super important here, in vitro results show that tiny differences in LNP composition/size/morphology - may have big impacts on
efficacy. So we need to make sure that the LNPs generated are within narrow set of parameters. e.g…
The process of generating LNPs is called "nanoprecipitation" and generally involves precisely mixing the lipids (dissolved in semi-polar solvent, like EtOH) with the RNA (dissolved in a buffered polar solvent). The dynamics of this mixing process must be carefully controlled.
@DerekLowe assumes that LNP generation for vaccines uses microfluidics to generate the LNPs. This is a reasonable assumption, but not necessarily correct. Recall that there are macrofluidic processes that can generate RNA containing LNPs.
For example, T-junction mixing is commonly thought to be able to produce RNA containing LNPs with pretty precise size control and good encapsulation efficiency. E,g….
In fact, @pfizer itself seems to imply that their production process uses a macrofluidic process for LNP generation.…
But the assumption that both vaccines uses a microfluidic process for at least part of the nanopreciptation process is reasonable and probably correct. But so what? There is a certain amount of hand waving going on here, like it uses microfluidics ergo we can't scale it up.
@Dereklowe says that these microfluidic nanopreciptation macihnes are not lying around in existing pharma plants, therefore we can't scale it up. True, but they weren't lying around @LonzaGroup, @pfizer plants in February either. But we were able to rapidly *build* that capcity
The manufacturing processes used in the production of most microfluidic "chips" are relatively easy to scale up. Recall that most microfluidic devices for LNP generation use soft lithography for manufacturing using e.g. PDMS for molding. e.g…
This is *similar* to the process used to fab semiconductors. And recall that the feature size of these chips is generally way above 1 micron, we can use standard transparencies for the fabrication process.…
Tl;dr the world scaled mRNA vaccine production capacity by more than 6 orders of magnitude in less than a year. there is nothing that stopping us from scaling up more now, except our will.

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More from @jbkrell

3 Feb
I am a little confused by this @nytimes reporting by @MarcSantoraNYT and @RebeccaDRobbins on the new AZD1222 data. First of all, the claim that this data is the “first” to document evidence that a COVID vaccine can result in a reduction in transmission seems to be wrong. Image
In fact, just last week, Israeli researchers documented a 50% reduction in both symptomatic and asymptomatic infections in individuals who took a single dose of the Pfizer mRNA shot in a retrospective cohort study.…
This is a preprint, but so is the new Astra data! Furthermore, the original AZD1222 publication in the Lancet in December *also* reported on preliminary PCR positivity in asymptomatic individuals in COV002 as well.… Image
Read 5 tweets
2 Jul 20
When I was 22, I watched a friend become HIV+ cuz he couldn't afford Truvada PrEP which cost s$1,300/m but costs <$6 to make. CDC invented & patented PrEP, but they refused to stop Gilead's price gouging for yrs. Today, the the same thing is happening with remdesivir for COVID.
Last month, @cmorten2 & I showed that not only did (h/t @zainrizvi ) the US government spend >$70 million on developing & inventing the drug, the government is legally entitled to be co-owners of the patents for remdesivir.
This means that USG can license remdesivir to generic manufacturers while paying no (or very little) $ to Gilead. Remember remdesivir costs less than $1 to make a dose, yet Gilead charges over $350 a dose for it. Our government could stop this price gouging today, but will they?
Read 4 tweets
6 May 20
This is an important q from @mynameisjro. The convo around physical distancing reminds me a lot of the pre-PrEP conversations about HIV prevention. THREAD but tl;dr u can shame as much u want, but it doesn't change the fact that our methods of COVID control are not sustainable.
I am NOT saying we should stop physical distancing. But the idea that we can ask people to not see friends, lovers, family etc. for a basically unlimited period of time is BS. Let's not repeat the mistakes of the HIV epidemic in our response to this plague. 2/n
1 of the reasons the HIV epidemic was allowed to run out of control in US queers starting in the early 90s is because we were more focused on shaming queer ppl than finding effective ways to prevent HIV. And a lot of that had to do with the shame around "barebacking". 3/n
Read 11 tweets
15 Feb 19
@Surgeon_General @POTUS @NIAIDNews @HRSAgov @IHSgov @VP @gregggonsalves @fcraw4d Respectfully, that is bullshit. HIV epidemics in PWIDU are not "unprecedented" and interventions to bring them under control, like needle exchange, have been well understood since the 1980s. You and @VP could of implemented needle exchange sooner, but didn't, so Hoosiers suffered
@Surgeon_General @POTUS @NIAIDNews @HRSAgov @IHSgov @VP @gregggonsalves @fcraw4d 2. The idea that you did not know that SC was at risk for an HIV epidemic is also BS. Increases in overdoses had been happening in IN since 2004, local officials recommended needle exchange in 2008, there was a huge HCV outbreak in IN in 2010-11, but still no needle exchange.
@Surgeon_General @POTUS @NIAIDNews @HRSAgov @IHSgov @VP @gregggonsalves @fcraw4d Even in the midst of the peak of the epidemic, more than two months after it was identified @VP refused to allow needle exchanges, preferring to "pray", rather than understand science. This is not success.
Read 4 tweets

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