> Moderna spokesperson Colleen Hussey explained to NPR in an email that its vaccine doesn't need to be kept so cold because of its particular "lipid nanoparticle properties and structure," and because the company has learned from experience — it's developed ten mRNA vaccine candidates already. "Now we don't need [ultra-cold conditions] as the quality of product has improved and [it] doesn't need to be highly frozen to avoid mRNA degradation," Hussey explained.
and
> It's possible that Pfizer's vaccine could eventually be shown to be stable in somewhat warmer conditions — or for longer times out of the freezer.
They're saying that the differences are secret, and they're not gonna release the specific structure of the LNPs and why the differences are there. The equivalent of having two proprietary binaries that both accomplish the same task, but have different code, and the reasons why are secret as well.
And we're accepting this on the first mRNA vaccine ever to be used on a massive scale, all to protect their profits before the rest of the world can start producing vaccines. Yes they spent a lot of money and time creating the vaccine. Now open source it and let the rest of the world save their citizens.
> Yes they spent a lot of money and time creating the vaccine. Now open source it and let the rest of the world save their citizens.
And who’s going to pay for it? The whole PPE shortage was exactly because of this entitled attitude. If you artificially limit prices, you’ll only limit the supply (to possibly nothing, as vaccines have high upfront costs), and enable scalpers.
One obvious solution is to have a UN initiative that buys the IP and opensources it. I don’t know how hard this is. Generally, one big problem is the lack of gratitude on the part of freeriders. Otherwise, the goodwill it generated for the sponsors would probably be enough to make it happen.
PS: I live in Iran. I am not defending my privilege here.
Ideally, they would realize that moral responsibility to save lives is greater than money in this case. I don't think money would even be a problem, public pressure would be enough if everyone knew what was at stake. The companies capable of manufacturing would still make money by selling the vaccine to governments and people.
Probably every doctor and nurse feels moral responsibility to save lives is greater than money in any specific case. But if you cut all their compensation to minimum wage plus a bit, I doubt many will keep working in health care for very long.
It doesn't matter now because that's not some ingredient you can bolt on. It was part of the initial design process.
Sure, they could have shared all their secrets, and BioNTech theirs. Then, they would have come up with the same vaccine candidate and run two identical trials. Which would've been quite useless and far more risky.
Those LNPs have historically caused adverse reactions, per their 2018 SEC filing, hopefully their upgraded versions are improved and do not cause those reactions; I am hopeful.that they have, because of the reported results of their current clinical trials, but it is a data point:
"Most of our investigational medicines are formulated and administered in an LNP which may lead to systemic side effects related to the components of the LNP which may not have ever been tested in humans. While we have continued to optimize our LNPs, there can be no assurance that our LNPs will not have undesired effects. Our LNPs could contribute, in whole or in part, to one or more of the following: immune reactions, infusion reactions, complement reactions, opsonation reactions, antibody reactions including IgA, IgM, IgE or IgG or some combination thereof, or reactions to the PEG from some lipids or PEG otherwise associated with the LNP. Certain aspects of our investigational medicines may induce immune reactions from either the mRNA or the lipid as well as adverse reactions within liver pathways or degradation of the mRNA or the LNP, any of which could lead to significant adverse events in one or more of our clinical trials. Many of these types of side effects have been seen for legacy LNPs. There may be resulting uncertainty as to the underlying cause of any such adverse event, which would make it difficult to accurately predict side effects in future clinical trials and would result in significant delays in our programs"
I read that Pfizer/Biontech is currently testing whether they can go with higher temperatures, but those tests aren't finished yet, because the first priority was to get the patient data, and there they did what they expected will be safest and most likely to work.
It may very well be that later on they'll change the freezing requirement later.
Different lipid nano particles, or maybe just stability testing. The vaccines could be stable at lower temperatures but the companies haven’t had time to prove it by letting the vaccine sit in a fridge for months.
The answer is "there is probably no difference, but Moderna has more experience with mRNA vaccines and felt good about the -20 requirement, but Pfizer is new to mRNA, and didn't":
As someone who has been involved in stability testing before, I doubt this is really the case.
In order to justify your stability, you need data to submit to the FDA (they don't take your word for it). When doing your initial stability studies, you try and collect data for the most ideal conditions - no refrigeration needed, stable for X years from room temperature to 30C (to account for conditions during shipment).
No doubt Pfizer lined up a number of early stability studies testing -80C, -50C, -20C, 0C, etc. They recognize that needing a -70C cold chain is a logistics hurdle. If they could avoid it at all, they would have pushed for it and had data to back it up.
Though in practice it’s more complicated. Basically, make predictions based on accelerated testing and then validate them in real time tests. So, if things hold up at 3 and 6 months real time you can probably trust them over longer timeframes.
Exactly. Plus dating tends to get extended post-approval.
If Pfizer has a short-list of candidates back in May, they could have had 6 months of stability data at approval.
They can keep those studies going and by next May have 12 months of data for the FDA to review and potentially update the transportation and storage requirements.
Yea, prescription drug manufacturers have little incentives to seek multi year shelf lives. Combined with the slow approval process real time testing is likely considered sufficient.
I think you summarized it well. There is little incentive to test the limits of stability as manufacturers typically control channel inventory quite tightly. I know my company targeted maybe 14 days on hand? So going much beyond 2 years stability didn’t make much sense as most product was consumed well before it expired.
Not OP, but this is the same way lightbulb or hard drive manufacturers can claim "greater than 50,000 hours of operation". Instead of testing for over a decade, they test many samples over a shorter time duration, and then they extrapolate. Like any other extrapolation, these estimates have their caveats. But for biological reagents, something like an exponential decay is often considered reasonable.
Accelerated studies. Usually you test stability for shorter periods of time under harsher conditions. It’s not perfect, but if your product is fine at 50C for 2 months, it’ll probably be fine refrigerated for 12 months.
Assume that the reaction rate (shelf life) versus temperature relationship is described by the Arrhenius equation or some other model; perform experiments at elevated temperatures, and extrapolate to lower temperatures.
> but Moderna has more experience with mRNA vaccines
Let's keep things in perspective, please. This EUA is for Moderna's first product with any approval whatsover from the FDA. The lipid coating is a way for encasing the mrna vaccine in a kind of plastic for entering the cell.
