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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

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
        There's a US government program that tests drugs' efficacy beyond the manufacturer dating to extend the life of the stockpiles. https://www.astho.org/Programs/Preparedness/Public-Health-Emergency-Law/Emergency-Use-Authorization-Toolkit/Federal-Shelf-Life-Extension-Program-Fact-Sheet/ https://www.astho.org/Programs/Preparedness/Public-Health-Em...
    - refurb 6y ago
      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.
  - tooltower 6y ago
    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.
  - coffeecat 6y ago
    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.
  - refurb 6y ago
    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.
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.

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
        There's a US government program that tests drugs' efficacy beyond the manufacturer dating to extend the life of the stockpiles. https://www.astho.org/Programs/Preparedness/Public-Health-Emergency-Law/Emergency-Use-Authorization-Toolkit/Federal-Shelf-Life-Extension-Program-Fact-Sheet/ https://www.astho.org/Programs/Preparedness/Public-Health-Em...
  - refurb 6y ago
    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.
- tooltower 6y ago
  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.
- coffeecat 6y ago
  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.
- refurb 6y ago
  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.

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.