[high_derivative]

My understanding used to be that this will not change much on an immediate basis since the nano-particle delivery system + its manufacturing chain are quite complicated and not easily scalable. Does anyone know if this is not the case?

[pas]

For anyone interested: https://blogs.sciencemag.org/pipeline/archives/2021/02/02/my...

Around the time of this post I tried to get a bit more information on this, and ... well, here's the rabbit hole:

- https://www.youtube.com/watch?v=68p3qAm4i7U

Use lithography to create the mold, then cure it, then put it into a pure O2 enivornment, then drop it on a glass plate and you just plasma glued the silicone and the glass.

- https://www.youtube.com/watch?v=EYuyRUjnTgc

- https://www.youtube.com/watch?v=EjyM8sNplm4

- https://www.youtube.com/watch?v=wTmgqFCIbsA

I still have no idea where the bottleneck actually is. Derek Lowe claimed that the manufacturers of the microfluidics devices are. Which is likely, because hacking together something in/for a lab is very different than getting it ready for "FDA GMP [good manufacturing practices] approval" ... but at the same time there are thousands of people dying every day, and I'd like to see the extraordinary evidence to support the extraordinary claim that it's "impossible" to scale up vaccine manufacturing. (Impossible here meaning that it's impossible to get to the same necessary purity and control.)

[rossdavidh]

What is possible given sufficient time, is very different from what is possible in a few months. Even in non-medical situations, getting a high-tech manufacturing process up and running takes years, not months, normally, and working long hours doesn't help as much as you think because the rate of mistakes goes up.

But, having more capacity in a year's time, doesn't necessarily save any lives, since the mRNA vaccines are not the best fit for most of the world anyway, as they require two doses per person and are more demanding in the refrigeration requirements. The adenovirus vaccines, despite the one-in-a-quarter-million side affects, are much more likely to be usable in quantity in most of the world.

So, you could get more capacity up in a year's time, when it won't be needed in the rich world and won't be useful in the rest of the world.

My guess is Moderna just made this announcement to try to dispel the idea that their patent enforcement was somehow getting people killed.

[whatisthiseven]

Your post is good overall but I am not so sure about this part:

"as they require two doses per person and are more demanding in the refrigeration requirements."

Moderna doesn't require overly deep refrigeration, that is Pfizer. The difference is a technical one and one that Pfizer believes they can solve. So while it is true of the current Pfizer vaccines, it isn't true of mRNA vaccines generally.

Secondly, the two dose regimen is unnecessary, IMO. Pfizer and Moderna have higher efficacy with one dose than J&J or Astrazeneca have after their one shot. The FDA and others insisting on two doses is because of Pfizer and Moderna's original process called for two doses as they wanted to be sure of the efficacy and that is what they got approval for. Given many doctors are looking at the pandemic from the perspective of a patient rather than that of a population and a disease, they aren't willing to admit that two doses for Pfizer and Moderna is unnecessary and putting far more lives at risk.

The rest of the world can benefit, as those countries that can afford the higher priced vaccine may do so as they are more effective and available now, which helps to get them out of the market of the lower cost vaccines. That decrease in demand for J&J and others can then be filled by countries that don't have the funding or the infrastructure for the current mRNA vaccines, thereby keeping their price low.

[rossdavidh]

Interesting! Looks like you're right about that: https://www.modernatx.com/covid19vaccine-eua/providers/stora...

I have read that J&J also had a two-dose phase 3 going in parallel, but because the one-dose worked well enough they dropped it.

Really, given the shortage of vaccines in the world, and the fact that the U.K. essentially ran a 12-week one-dose experiment on a massive scale, I would think that we have enough data now to make the call. But, everything is more complicated than it seems from afar, so I am sure they have reasons.

[rossdavidh]

Although it does look to me like J&J is a bit less demanding in regards refrigeration; it never requires below freezing storage: https://www.cdc.gov/vaccines/covid-19/info-by-product/jansse...

But still you're right, Moderna does not require anything all that exceptional.

[bluGill]

The impossible part is time. You can make a car from ore that you dig yourself - if someone provides you food and shelter you could finish this task in 30 years or so. You could even make the atoms in a super collider given enough time (well energy is probably the limit).

But we need vaccines today. That means we are limited to what can be manufactured today by existing processes and factories. If you need a round iron part accurate to .001 inch (or similar metric) I know plenty of machinists. Need it more accurate and you have eliminated a large part of that supply chain, but I can still get you to .0001 inches, more than that is hard to find anyone who can handle (possibly impossible - temperature becomes a factor).

[refurb]

Yup. Moderna doesn’t have much to worry about. Most of the volume of vaccine will be sold in the next 6-12 months, not enough time for another manufacturer to develop the manufacturing capability, validate it and get FDA approval.

Even if new vaccines are needed for new variants, it won’t be easy for another company to catch up when the cycle are 12 months long and then you’re onto the next version.

[thaeli]

Plus, once the pandemic is "over" at least officially, their best case scenario is that other manufacturers did implement their parents.. because they can start collecting license fees, and those manufacturers are likely to have made investments in ways that commit them long-term to using processes covered by Moderna's patent portfolio.

[bluGill]

Moderna would probably be happy to license their next vaccine to someone who did invest in a factory. The price would be probably be affordable. I'm not sure it is worth it though, only time will tell if a booster shot is needed.

[achenatx]

booster shots for variants are almost guaranteed to be needed.

[bluGill]

Everyone says that, and work is ongoing, but so far the current vaccines are holding against variants. Time will tell.

[majewsky]

"Their next vaccine" does not need to be a SARS-CoV-2 vaccine.

[meepmorp]

Yeah, that's what I've read. Basically, even if you could make the necessary mRNA particles properly, the it's useless without the delivery mechanism. Only a few companies even produce the necessary lipid products needed to deliver the vaccine, and they (and their suppliers) are already doing everything they can.

The IP concerns had basically zero effect on the availability of vaccines.

[contravariant]

Well it won't have much of an effect unless they price the vaccine exorbitantly. So you can also view this as a binding promise to keep margins reasonable.