5 ms·

Does anyone here know the reason for the difference? They're both mRNA vaccines, right? So why does one need a deep freeze and the other one not?

by lisper 6y ago

m-ee 6y ago
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.
- garmaine 6y ago
  At higher temperatures, you mean.
  - m-ee 6y ago
    Yes at higher temperatures
bpodgursky 6y ago
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": https://www.npr.org/sections/health-shots/2020/11/17/935563377/why-does-pfizers-covid-19-vaccine-need-to-be-kept-colder-than-antarctica https://www.npr.org/sections/health-shots/2020/11/17/9355633...
- refurb 6y ago
  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.
  - seanwilson 6y ago
    > stable for X years from room temperature to 30C How do you get this data for a large value of X without having to wait X years?
    - Retric 6y ago
      The general rule is increasing temperature by 10C roughly doubles the rate of chemical reactions. https://www.ddltesting.com/package-testing/shelf-life-testing/ https://www.ddltesting.com/package-testing/shelf-life-testin... 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.
      - maxerickson 6y ago
        In practice it seems the expiration dates on even boring drugs aren't real far into the future.
        Retric 6y ago
        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. https://www.pharmacytimes.com/news/some-medications-last-long-past-expiration-date https://www.pharmacytimes.com/news/some-medications-last-lon...
        refurb 6y ago
        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.
        rainbowzootsuit 6y ago
- IncRnd 6y ago
  > 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.
gnicholas 6y ago
According to NPR [1] > 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. 1: https://www.npr.org/sections/health-shots/2020/11/17/935563377/why-does-pfizers-covid-19-vaccine-need-to-be-kept-colder-than-antarctica https://www.npr.org/sections/health-shots/2020/11/17/9355633...
- ehsankia 6y ago
  Are they saying it's possible the existing BioNtech vaccine will be stable at lower temps or that they could make it with the alternative lipid? The latter would require another phase2/phase3 trial I assume, and you'd think they would've tested the former by now thoroughly.
  - gnicholas 6y ago
    My reading of the article is that they are testing to see whether the current formulation is not as temperature-sensitive as currently believed.
- kart23 6y ago
  Read in between the lines for a moment. 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.
nerfhammer 6y ago
Pfizer wanted to release as quickly as possible and didn't want to bother doing another study to tell
hannob 6y ago
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.

Does anyone here know the reason for the difference? They're both mRNA vaccines, right? So why does one need a deep freeze and the other one not?

by lisper 6y ago

Does anyone here know the reason for the difference? They're both mRNA vaccines, right? So why does one need a deep freeze and the other one not?

m-ee 6y ago

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.

garmaine 6y ago
At higher temperatures, you mean.
- m-ee 6y ago
  Yes at higher temperatures

bpodgursky 6y ago

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": https://www.npr.org/sections/health-shots/2020/11/17/935563377/why-does-pfizers-covid-19-vaccine-need-to-be-kept-colder-than-antarctica https://www.npr.org/sections/health-shots/2020/11/17/9355633...

refurb 6y ago
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.
- seanwilson 6y ago
  > stable for X years from room temperature to 30C How do you get this data for a large value of X without having to wait X years?
  - Retric 6y ago
    The general rule is increasing temperature by 10C roughly doubles the rate of chemical reactions. https://www.ddltesting.com/package-testing/shelf-life-testing/ https://www.ddltesting.com/package-testing/shelf-life-testin... 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.
    - maxerickson 6y ago
      In practice it seems the expiration dates on even boring drugs aren't real far into the future.
      - Retric 6y ago
        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. https://www.pharmacytimes.com/news/some-medications-last-long-past-expiration-date https://www.pharmacytimes.com/news/some-medications-last-lon...
        refurb 6y ago
        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.
        rainbowzootsuit 6y ago
IncRnd 6y ago
> 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.

gnicholas 6y ago

According to NPR [1] > 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. 1: https://www.npr.org/sections/health-shots/2020/11/17/935563377/why-does-pfizers-covid-19-vaccine-need-to-be-kept-colder-than-antarctica https://www.npr.org/sections/health-shots/2020/11/17/9355633...

ehsankia 6y ago
Are they saying it's possible the existing BioNtech vaccine will be stable at lower temps or that they could make it with the alternative lipid? The latter would require another phase2/phase3 trial I assume, and you'd think they would've tested the former by now thoroughly.
- gnicholas 6y ago
  My reading of the article is that they are testing to see whether the current formulation is not as temperature-sensitive as currently believed.
kart23 6y ago
Read in between the lines for a moment. 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.

nerfhammer 6y ago

Pfizer wanted to release as quickly as possible and didn't want to bother doing another study to tell

hannob 6y ago

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.