20 ms·

Myths of Vaccine Manufacturing

219 points by undefined1 6y ago

twoslide 6y ago
This article discusses why mRNA vaccine manufacturing cannot be outsourced to third parties, but there are other vaccines that might be be produced in this way (Oxford/AstraZeneca). Not sure if this is authorized in the US, but it is in many other locations experiencing shortage (e.g. the EU).
- smnrchrds 6y ago
  Oxford/AstraZeneca vaccine is indeed being produced around the world: https://www.biopharma-reporter.com/Article/2020/08/06/AstraZeneca-taps-20-plus-partners-to-hit-goal-of-2bn-COVID-19-vaccines https://www.biopharma-reporter.com/Article/2020/08/06/AstraZ... https://www.reuters.com/article/health-coronavirus-canada-vaccine/verity-pharma-and-serum-institute-of-india-apply-to-distribute-astrazeneca-vaccine-in-canada-idUSKBN2A21JS https://www.reuters.com/article/health-coronavirus-canada-va... Another traditional vaccine, Novavax, is signing licensing deals as well: https://globalnews.ca/news/7613878/covid-made-in-canada-vaccines-agreement/ https://globalnews.ca/news/7613878/covid-made-in-canada-vacc...
jancsika 6y ago
> My own guess as to what such a Vaccine Machine involves In a global pandemic, why are we guessing?
- _Microft 6y ago
  It's a thing he does not work with.
  - jancsika 6y ago
    Sorry, that wasn't clear. Are the specs for the design of the "Vaccine Machine" machine-- as he terms it-- public knowledge?
    - _Microft 6y ago
      He's not working in drug manufacturing but in research. The details of these machines will be trade secrets. The pun in my statement was that Mr. Derek Lowe is writing a popular series of blog postings on dangerous chemicals. It is called "Things I Won't Work With". https://www.bing.com/search?q=derek+lowe+things+i+won't+work+with https://www.bing.com/search?q=derek+lowe+things+i+won't+work...
      - jancsika 6y ago
        So here's the unambiguous version of my original question: Why are we guessing about trade secrets in a pandemic? Seems to me that an advanced society would have the sense to say that while trade secrets are obviously an important part of the economy, in the case of a global pandemic we can suspend them specifically for the design specs of the bottleneck in vaccine production.
deleted 6y ago
[deleted]
ericb 6y ago
I love Derek's writing, but aren't we likely within a few weeks of non-RNA vaccines in the US via Johnson and Johnson, though? He didn't really answer--can that one be scaled since it has more standard dependencies? If so, isn't the "naive" question perfectly valid in that case?
- chaganated 6y ago
  Even though I know very little about vaccines, this article has a paid PR smell. These kinds of technocratic problems have short and long answers. He skipped one, and danced around the other.
  - natechols 6y ago
    He's been writing on these subjects for years, and nothing in this article would be a surprise to anyone who has read him before or has even a passing familiarity with the pharma industry. (Also, he's always been totally up-front about his conflicts of interests and political views, and acknowledges when pharma companies screw up.) I think there are fewer serious long answers to this problem than you expect - they tend to hinge on "wave hands and solve central planning problem".
- vernie 6y ago
  Derek's blog is great but he's a bit of a stooge for his industry, so he plays dumb sometimes.
- tpm 6y ago
  He is responding to a tweet that explicitly mentions Pfizer and Moderna.
- bluGill 6y ago
  J&J doesn't really need to be scaled up because they alone have the ability to produce so much of it. That said, I'd prefer to get the mRNA vaccines as they seem much more effective, so any scaling up done there is still useful even if J&J alone could get rid of Covid in the US in a few months. (pending need to vaccinate kids for herd immunity, Pfizer is the farthest along that path, but not close to mass vaccination)
GavinB 6y ago
So no, we did not “have the vaccine” in February. We did have it, we just didn't know which one it was. And we refused to risk any individual life in order to potentially save hundreds of thousands or more. We also could have invested single digit billions early on to build capacity for all of these different potential vaccines, but we decided to play if "safe" and will now be spending over a trillion again to try to save the economy. I don't blame the pharma companies for this. Our government and medical establishment was not intellectually prepared to make the hard decisions required to save us. And we need to be building momentum to learn how to do better.
- jimbokun 6y ago
  > We also could have invested single digit billions early on to build capacity for all of these different potential vaccines Are we sure "we" didn't? I don't know the actual numbers behind what was spent ahead of time for the various vaccines, but I believe the manufacturing process was ramped up before the trials completed.
  - GavinB 6y ago
    There was discussion of it early on, but there's no evidence that it was done on any significant scale outside of the efforts of individual pharma companies working on their own supply chains. It's possible that I'm wrong! Maybe we invested everything possible and couldn't have done significantly more. But it's striking that this article doesn't even address that question. Basically, I haven't seen any evidence that this take is wrong: https://thezvi.wordpress.com/2021/01/28/covid-bill-gates-and-vaccine-production/ https://thezvi.wordpress.com/2021/01/28/covid-bill-gates-and...
    - natechols 6y ago
      Oh thanks I was looking for followup on the Gates thing, that blog post is superb. And depressing.
    - _carbyau_ 6y ago
      I am not entirely sure I agree with the thinking though. While initial production ramp up would get the richer countries vaccinated quickly it seems like Gates has a more holistic picture and wants to see the whole world vaccinated faster. I agree with this thinking. It won't matter if rich countries are vaccinated if other countries are coming up with new variations all the time. We want to eradicate this by having everyone in the world on the same page, not have it hanging around like the flu.
andred14 6y ago
Stay away from these untested drugs. The satan1c ped0phile eugenicists that made them are trying to kill you. Please learn about these dangerous new vacc1nes: https://www.bitchute.com/video/KAzUeDrgijM3/ https://www.bitchute.com/video/KAzUeDrgijM3/
readams 6y ago
Derek is a smart guy but here again we see the utter lack of the ability to think big in the drug community. It would have been worth it to spend a trillion dollars and speculatively build out capacity and manufacturing for every vaccine candidate. We should have built megafactories and employed a million people. And we should have done large-scale phase 3 trials by randomizing distribution of large fractions of the output of these megafactories. It's just completely wrong to say that everything was done as well as it could possibly have been and there's no way it could have been faster. There basically no amount of money that it would not have been worth it to spend.
- hef19898 6y ago
  There are problems that cannot be solved by simply throwing money at them. Sure, invest billions in new manufacturing capacity. That capacity probably wouldn't been ready now, ramping manufacturing is hard enough, starting from scratch even harder. This whole vaccine availability "scandal" is driving me nuts. It was clear that nobody knew which vaccine would work. It was prudent to buy all of the potential candidates. It was also clear that there would be a ramp up phase, in each country and for each vaccine. The EU pretty much delivered on part one, sourcing. And I don't care what the press writes, 5 doses for each EU citizen regardless of age is enough. EU member states screwed up on managing part two. And communication. I think, things will tun smoother once we have a vaccine that can be handled and used by every doctors practice. That supply chain works for millions of vaccinations every year. Before that, it is hit and miss.
- fabian2k 6y ago
  I don't see any realistic way to expand manufacturing capacities at that kind of scale in such a short time. There are a lot of things that are potential bottlenecks because the stuff you need isn't produced at that scale and there aren't unlimited numbers of people that have the right experience. And with producing a vaccine it is extremely important that the production results in exactly what you intend to produce, to ensure it is safe and effective. That part is done by designing processes, carefully checking that they work and then strictly adhering to them. That is not an activity that is easy to scale up.
jbullock35 6y ago
The blog post is mainly about the difficulty of producing vaccines. I don't see much in it that is objectionable. But this line may be misleading: So no, we did not “have the vaccine” in February. The author is arguing that, because it's difficult to produce of the Moderna vaccine, we couldn't have disseminated it on a wide scale in February or shortly thereafter. That argument may be fine, but it diverts attention from the critical role that the U.S. regulations in general, and the U.S. FDA in particular, played in slowing the process of widespread vaccine dissemination. Specifically: the process could have been sped by months if the U.S. had been willing to conduct human-challenge trials [1] and to integrate tests of safety (Phase 2) and efficacy (Phase 3) [2]. To my knowledge, understanding of how to integrate the safety and efficacy trials has only recently developed; perhaps the FDA shouldn't be faulted on that front. But the benefits of human-challenge trials have long been understood. [1] https://doi.org/10.1093/infdis/jiaa152 https://doi.org/10.1093/infdis/jiaa152 [2] https://doi.org/10.1198/016214504000001790 https://doi.org/10.1198/016214504000001790
- angry_octet 6y ago
  Firstly, it wasn't produced in large quantities in February. They have to do trials against the mass produced article, not lab samples. Secondly, it would be extremely unethical to overlap phase 2 & 3 trials, when there are effective NPIs. The lessons of unethical medical science, like Tuskegee and experimentation on armed forces personnel, must not be ignored. And yet that is precisely what your ref Eyal[1] is proposing, because practically none of the safeguards can be achieved. Efficacy trials require a much larger participant group, given the still low infection rates. I don't see how one can justify giving a candidate to 100k people before safety screening, especially when the downside risk is significant risk of death if they ever catch COVID.
  - jbullock35 6y ago
    > Firstly, it wasn't produced in large quantities in February. They have to do trials against the mass produced article, not lab samples. Yes, I’m not disputing this point. My claim is that even after we account for the difficulties of mass production, the FDA-controlled licensing process should have taken less time than it did. > Efficacy trials require a much larger participant group, given the still low infection rates. This is the major benefit of human-challenge trials [1]: if you intentionally infect healthy, well-informed, low-risk volunteers with low doses of a virus, the size of the requisite participant group falls dramatically. Note also that “Any volunteers in whom infection was confirmed would receive excellent care for COVID-19, including priority for any scarce life-saving resources, in state-of-the-art facilities.” You can say that it’s unethical to run such trials. But it seems hard to make that argument if the volunteers are informed about the risks and if safeguards are in place (e.g., limiting the dose to which volunteers are exposed). Consider also the cost -- many thousands of lives -- of refusing to run such trials and thus delaying the licensing of a vaccine by months. > The lessons of unethical medical science, like Tuskegee [...] must not be ignored. And yet that is precisely what your ref Eyal[1] is proposing No, not at all. In the Tuskegee experiment, people infected with syphilis were promised medical care that they were later denied. When they were diagnosed with syphilis, they weren't even told of the diagnosis. (One of the purposes of the experiment was to study what happens when syphilis isn't treated.) These conditions are a world apart from what Eyal et al. are proposing in [1]. You don't need to take my word for it: the article is short and easy to read. [1] https://academic.oup.com/jid/article/221/11/1752/5814216 https://academic.oup.com/jid/article/221/11/1752/5814216
tptacek 6y ago
So this explains why recruiting other firms to produce Pfizer or Moderna mRNA vaccines is difficult (because the limiting factor is probably microfluidics devices built specifically for processes only Pfizer and Moderna had a reason to scale). But what's the bottleneck on scaling up J&J's adenovirus design?
- Exmoor 6y ago
  I cannot speak specifically for J&J, but by the number of adenovirus licensing agreements I've seen for Oxford, Sputnik V, etc. I would guess that existing facilities can be converted to produce a viral-vector vaccine much easier than an mRNA vaccine. From there I would suspect that the scaling issues are mostly related to QA and repeated cycles of ensuring what you're producing is actually exactly what you intended to produce.
  - BasinAndRange 6y ago
    This is exactly what's happening at Royalmount in Canada.
    - sudosysgen 6y ago
      Yup, à biotech research lab is going to produce 2 million doses à month of the Novavax vaccine (which is essentially as effective as the mRNA ones).
      - refurb 6y ago
        https://nrc.canada.ca/en/covid-19-response-building-infrastructure https://nrc.canada.ca/en/covid-19-response-building-infrastr... Color me a little skeptical. This looks like a big GMP bioreactor facility. Once the vaccine is made, how does it get into vials? Fill and finish production lines are usually another massive complex. Are they going to transfer it offsite for packaging? And this facility won't be finished until July 2021. Then the tech transfer has to happen, trial runs completed, everything validated. They might start actual production at the end of 2021. Tech transfer of pharmaceutical processes is no joke. I've done it before.
Animats 6y ago
The article says that RNA encapsulation is the big bottleneck. This is a touchy microfluidic process. That needs to be accelerated. While few companies make those parts, more could. They're made by a process similar to that used in a wafer fab. A low-rez wafer fab, like the ones used to make MEMS gyros and such. Part of the problem may be that wafer fab people and drug production people don't talk to each other much. Someone should get them talking. Might come to nothing. Might lead to "oh, we can make that easily".
- Accujack 6y ago
  A chip isn't a complete device. What about the rest of the machinery? The software? Construction of the devices, calibration, testing and commissioning? There are probably less than 10 people worldwide capable of determining if machines like this (that probably only exist within the vaccine manufacturers) are set up correctly and working right. I suspect if you track down what's needed, you'll find that all the manufacturing capability for making more of those machines is already in use by the vaccine makers. Bespoke microfluidics devices aren't common or easy to make, although some components are.
  - silexia 6y ago
    The argument in the article for why the vaccine could not be produced is that there are new technical innovations that can't be done by other companies. I believe this to be a straw man argument. Each new human innovation is based on a massive mountain of previous human innovation. Many, many companies are on the edge of this innovation and allowing them to use the innovations of other companies without fear of patents litigation would allow them to make that last step now. Patents are one of the most insidious harms we have in our society today. Patent defenders claim that patents protect innovators. The truth is actually the exact opposite: patents are a monopoly legal tactic most often used so that the patent obtainer does not have to innovate further or execute. Patents kill all further innovation in the area they are in. A great example of this is that hundreds of companies used to manufacture aircraft. Boeing and Airbus bought up all the companies that own patents, and now it's nearly impossible to start a new aircraft manufacturing business due to Boeing's monopoly on the patents. Aircraft have changed very little ever since. We need to eliminate the patent system and allow free trade to actually work.
godtoldmetodoit 6y ago
One thing I hope we take away from this is that just like we way over provision food production here in the States as a matter of national security, we should build out massive amounts of vaccine manufacturing capability. The federal government should massively invest in MRNA manufacturing or whatever other vaccine technologies make the most sense and lease the facilities out at a loss if need be to pharma during normal times. Or just subsidize pharma to have massive amounts of capacity ready to churn out 5-10 million doses a day. I don't really care how it happens, I just want the capability as a society and I'm willing to pay for it.
- m-ee 6y ago
  This already exists, it’s called BARDA
- atleta 6y ago
  It's partially a transient problem: mRNA vaccines is new technology that has never seen commercial use, so it's expected that initially you'll have production capacity problems. (Not to say that countries should not prepare for future pandemics.)
- peytn 6y ago
  We could have a futures market for doses. That way the government doesn’t have to pick winners in the drug development arena, something it historically isn’t very good at.
  - maxerickson 6y ago
    We could have ordered 300 million courses each of the top 5 or 10 vaccine candidates for, in essence, peanuts. $2 billion for Oxford. $3 billion for J&J. $20 billion for Novavax. $24 billion for Pfizer (at worst price). $48 billion for Moderna (again, worst price). You end up with a billion vaccines you don't need, you give them away. This is likely an over-investment if you consider the US in isolation (for instance, all 5 vaccines work well to reduce symptomatic and serious infections).
    - 6y ago
firebaze 6y ago
Influenza typically has a mortality of around 0.8%¹. There usually is a vaccine against the current strain of influenza, which usually hovers around 45%² efficacy (tops out at ~60%). With covid, we have a mortality rate of something between 0.3% and 3%³. The CFR of influenza includes - to the best of my knowledge, since i can't find any sources - vaccinated people. So without vaccination, influenza would have a CFR around 0.8% * (100% / 45%) ~= 1.78%. This is within the error bars of covid19 CFR, since there was no vaccine until now. I don't want to downplay covid19. I do want to question the effect on the society, and the personal responsibility of everyone involved. @Downvoters: just state why please. If you disagree, please be so kind and educate me why. ¹https://en.wikipedia.org/wiki/Influenza https://en.wikipedia.org/wiki/Influenza ²https://en.wikipedia.org/wiki/Influenza_vaccine https://en.wikipedia.org/wiki/Influenza_vaccine ³https://coronavirus.jhu.edu/data/mortality https://coronavirus.jhu.edu/data/mortality
- DeRock 6y ago
  > Influenza typically has a mortality of around 0.8% The Wikipedia article has a graph, which I assume you're referring to with this figure, which shows the mortality rate of 0.8% only applies to those ages 65+. The blended rate for a typical flu season, given in a table below, is <0.1%.
  - firebaze 6y ago
    This is the (approximately) same graph for covid19 patients. If influenza was a "new" disease to the immune system of western people, it quite probably would be way more deadly. Original american natives would probably agree.
- EthanBar 6y ago
  Do you mean influenza typically has a mortality of around 0.8% for those 65 and older? It has a mortality of < 0.1% for everyone from the same Wikipedia article. And CFR, case fatality rate, won't include vaccinated people who didn't get sick so your final calculation doesn't make sense.
- agd 6y ago
joe_the_user 6y ago
Here's a general article: https://www.statnews.com/2020/12/11/covid19-vaccine-timeline-keeps-slipping-experts-say-it-will-change-again/ https://www.statnews.com/2020/12/11/covid19-vaccine-timeline... "“Vaccine manufacturers hold their production capacity pretty close to their vest because it’s a point of a negotiation.” he said. Companies want to have flexibility in their contracts so they can balance production of various drugs and vaccines. “These companies are businesses and want to maximize their revenue. They’ll continue to make other products they can sell while manufacturing their vaccine.”" I know less than either Lowe or the State News author. I don't know where the particular bottlenecks might be. But it seems hard for me to believe that "ramping up is impossible" doesn't mean "ramping up is impossible under standard procedures, where we keep proprietary information proprietary, where we don't spend massively on capital equipment we might not need down the line (etc etc)" That is to say that we're far and far from a Manhattan Project intended to push vaccine manufacture to the logistical maximum. That's just how just any institutional process works.
- BurningFrog 6y ago
  The Pfizer and Moderna vaccines are the first mRNA vaccines to ever be mass produced, and they're needed for the biggest vaccination effort in human history. It seems very credible to me that ramping up from (guessing) thousands of doses to billions will take a long time. As I understand it, once the industry is set up, producing mRNA vaccines should be substantially faster than traditional techniques, since there is no biological step to wait for. They're "printed, not grown".
- xyzzyz 6y ago
  > “These companies are businesses and want to maximize their revenue. They’ll continue to make other products they can sell while manufacturing their vaccine There is an extremely easy solution to this problem, which is, just paying drug companies so much that it’s not worth for them to make anything else. Unfortunately, the governments around the world have failed the easiest cost-benefit analysis in the history, that is, trillions > billions, and so they negotiated the vaccine prices to be rather low, saving billions, while at the same time, spending trillions in stimulus money. Imagine if they just allowed the companies to sell the vaccines at the prices dictated by the market. Also imagine if they allowed AstraZeneca vaccine in the US without jumping through extra hoops, which cannot possibly give us more valuable information than we already have, now that millions of doses have already been administered in UK. Alas, the regulatory state has failed us in the pandemic the worst it has ever had.
worker767424 6y ago
I suspect Biden talking up the defense production act was mostly for show. Reading this post, there aren't any easy bottlenecks, and everyone knew this was coming, so they did what they could to ramp up production.
brunoTbear 6y ago
This is the same author as who wrote the HILARIOUS series of "Things I won't work with". Highly entertaining reading: https://blogs.sciencemag.org/pipeline/archives/2010/02/23/things_i_wont_work_with_dioxygen_difluoride https://blogs.sciencemag.org/pipeline/archives/2010/02/23/th...
alex_young 6y ago
The scale of thinking here is amazingly constricted. Imagine if we had approached this like we did WWII. We would have nationalized the effort to produce vaccines, building entire production chains and staffing them with anyone in need of work. We would have built infrastructure to produce n95 masks and shipped them to every address. What would this mean? We would have saved hundreds of thousands of lives, employed millions of people, strengthened our economy, and would now be wrapping up vaccinating everyone. Our response to the crisis should be noted as a failure of monumental proportions. The lack of leadership at all levels of government continues to be astounding.
- thechao 6y ago
  The US response to WW2 took years. We’re still in the months range. You can’t parallel use the early sequential phases; you can’t fabricate this equipment — nor the expertise to manufacture it from nothing in just a few months.
  - Robotbeat 6y ago
    Yes, actually, you can. (A well-endowed manufacturer can produce this equipment.) But it takes coordination, leadership, unlimited funding, and federal authority to step across red tape and corporate veils and IP to get things done. I was involved with some of this stuff. I know first hand how uncoordinated and un-led much of it was. We needed technocrats on private jets flying around the country tooling up production and solving every supply chain bottleneck like they were Elon trying to squeeze out luxury car production at the end of a quarter. And vaccine production ABSOLUTELY could've been parallelized with approval. In fact, it was. They were stockpiling doses before approval. But the effort was at least an order of magnitude smaller than it ought to have been. We constantly make excuses for this lack of effort. We shouldn't. We know what is possible. We can read history books.
    - visarga 6y ago
      I'm wondering how we'd fared if Elon was in charge.
xwvvvvwx 6y ago
Perhaps this is my bias showing but I find it totally unbelievable to suggest that production would not be significantly faster had the vaccines been open sourced from the start.
ckemere 6y ago
Please read through the comments on the blog. Info content is very high.

219 points by undefined1 6y ago

This article discusses why mRNA vaccine manufacturing cannot be outsourced to third parties, but there are other vaccines that might be be produced in this way (Oxford/AstraZeneca). Not sure if this is authorized in the US, but it is in many other locations experiencing shortage (e.g. the EU).

smnrchrds 6y ago
Oxford/AstraZeneca vaccine is indeed being produced around the world: https://www.biopharma-reporter.com/Article/2020/08/06/AstraZeneca-taps-20-plus-partners-to-hit-goal-of-2bn-COVID-19-vaccines https://www.biopharma-reporter.com/Article/2020/08/06/AstraZ... https://www.reuters.com/article/health-coronavirus-canada-vaccine/verity-pharma-and-serum-institute-of-india-apply-to-distribute-astrazeneca-vaccine-in-canada-idUSKBN2A21JS https://www.reuters.com/article/health-coronavirus-canada-va... Another traditional vaccine, Novavax, is signing licensing deals as well: https://globalnews.ca/news/7613878/covid-made-in-canada-vaccines-agreement/ https://globalnews.ca/news/7613878/covid-made-in-canada-vacc...

jancsika 6y ago

> My own guess as to what such a Vaccine Machine involves In a global pandemic, why are we guessing?

_Microft 6y ago
It's a thing he does not work with.
- jancsika 6y ago
  Sorry, that wasn't clear. Are the specs for the design of the "Vaccine Machine" machine-- as he terms it-- public knowledge?
  - _Microft 6y ago
    He's not working in drug manufacturing but in research. The details of these machines will be trade secrets. The pun in my statement was that Mr. Derek Lowe is writing a popular series of blog postings on dangerous chemicals. It is called "Things I Won't Work With". https://www.bing.com/search?q=derek+lowe+things+i+won't+work+with https://www.bing.com/search?q=derek+lowe+things+i+won't+work...
    - jancsika 6y ago
      So here's the unambiguous version of my original question: Why are we guessing about trade secrets in a pandemic? Seems to me that an advanced society would have the sense to say that while trade secrets are obviously an important part of the economy, in the case of a global pandemic we can suspend them specifically for the design specs of the bottleneck in vaccine production.

deleted 6y ago

[deleted]

ericb 6y ago

I love Derek's writing, but aren't we likely within a few weeks of non-RNA vaccines in the US via Johnson and Johnson, though? He didn't really answer--can that one be scaled since it has more standard dependencies? If so, isn't the "naive" question perfectly valid in that case?

chaganated 6y ago
Even though I know very little about vaccines, this article has a paid PR smell. These kinds of technocratic problems have short and long answers. He skipped one, and danced around the other.
- natechols 6y ago
  He's been writing on these subjects for years, and nothing in this article would be a surprise to anyone who has read him before or has even a passing familiarity with the pharma industry. (Also, he's always been totally up-front about his conflicts of interests and political views, and acknowledges when pharma companies screw up.) I think there are fewer serious long answers to this problem than you expect - they tend to hinge on "wave hands and solve central planning problem".
vernie 6y ago
Derek's blog is great but he's a bit of a stooge for his industry, so he plays dumb sometimes.
tpm 6y ago
He is responding to a tweet that explicitly mentions Pfizer and Moderna.
bluGill 6y ago
J&J doesn't really need to be scaled up because they alone have the ability to produce so much of it. That said, I'd prefer to get the mRNA vaccines as they seem much more effective, so any scaling up done there is still useful even if J&J alone could get rid of Covid in the US in a few months. (pending need to vaccinate kids for herd immunity, Pfizer is the farthest along that path, but not close to mass vaccination)

GavinB 6y ago

So no, we did not “have the vaccine” in February. We did have it, we just didn't know which one it was. And we refused to risk any individual life in order to potentially save hundreds of thousands or more. We also could have invested single digit billions early on to build capacity for all of these different potential vaccines, but we decided to play if "safe" and will now be spending over a trillion again to try to save the economy. I don't blame the pharma companies for this. Our government and medical establishment was not intellectually prepared to make the hard decisions required to save us. And we need to be building momentum to learn how to do better.

jimbokun 6y ago
> We also could have invested single digit billions early on to build capacity for all of these different potential vaccines Are we sure "we" didn't? I don't know the actual numbers behind what was spent ahead of time for the various vaccines, but I believe the manufacturing process was ramped up before the trials completed.
- GavinB 6y ago
  There was discussion of it early on, but there's no evidence that it was done on any significant scale outside of the efforts of individual pharma companies working on their own supply chains. It's possible that I'm wrong! Maybe we invested everything possible and couldn't have done significantly more. But it's striking that this article doesn't even address that question. Basically, I haven't seen any evidence that this take is wrong: https://thezvi.wordpress.com/2021/01/28/covid-bill-gates-and-vaccine-production/ https://thezvi.wordpress.com/2021/01/28/covid-bill-gates-and...
  - natechols 6y ago
    Oh thanks I was looking for followup on the Gates thing, that blog post is superb. And depressing.
  - _carbyau_ 6y ago
    I am not entirely sure I agree with the thinking though. While initial production ramp up would get the richer countries vaccinated quickly it seems like Gates has a more holistic picture and wants to see the whole world vaccinated faster. I agree with this thinking. It won't matter if rich countries are vaccinated if other countries are coming up with new variations all the time. We want to eradicate this by having everyone in the world on the same page, not have it hanging around like the flu.

andred14 6y ago

Stay away from these untested drugs. The satan1c ped0phile eugenicists that made them are trying to kill you. Please learn about these dangerous new vacc1nes: https://www.bitchute.com/video/KAzUeDrgijM3/ https://www.bitchute.com/video/KAzUeDrgijM3/

readams 6y ago

Derek is a smart guy but here again we see the utter lack of the ability to think big in the drug community. It would have been worth it to spend a trillion dollars and speculatively build out capacity and manufacturing for every vaccine candidate. We should have built megafactories and employed a million people. And we should have done large-scale phase 3 trials by randomizing distribution of large fractions of the output of these megafactories. It's just completely wrong to say that everything was done as well as it could possibly have been and there's no way it could have been faster. There basically no amount of money that it would not have been worth it to spend.

hef19898 6y ago
There are problems that cannot be solved by simply throwing money at them. Sure, invest billions in new manufacturing capacity. That capacity probably wouldn't been ready now, ramping manufacturing is hard enough, starting from scratch even harder. This whole vaccine availability "scandal" is driving me nuts. It was clear that nobody knew which vaccine would work. It was prudent to buy all of the potential candidates. It was also clear that there would be a ramp up phase, in each country and for each vaccine. The EU pretty much delivered on part one, sourcing. And I don't care what the press writes, 5 doses for each EU citizen regardless of age is enough. EU member states screwed up on managing part two. And communication. I think, things will tun smoother once we have a vaccine that can be handled and used by every doctors practice. That supply chain works for millions of vaccinations every year. Before that, it is hit and miss.
fabian2k 6y ago
I don't see any realistic way to expand manufacturing capacities at that kind of scale in such a short time. There are a lot of things that are potential bottlenecks because the stuff you need isn't produced at that scale and there aren't unlimited numbers of people that have the right experience. And with producing a vaccine it is extremely important that the production results in exactly what you intend to produce, to ensure it is safe and effective. That part is done by designing processes, carefully checking that they work and then strictly adhering to them. That is not an activity that is easy to scale up.

jbullock35 6y ago

The blog post is mainly about the difficulty of producing vaccines. I don't see much in it that is objectionable. But this line may be misleading: So no, we did not “have the vaccine” in February. The author is arguing that, because it's difficult to produce of the Moderna vaccine, we couldn't have disseminated it on a wide scale in February or shortly thereafter. That argument may be fine, but it diverts attention from the critical role that the U.S. regulations in general, and the U.S. FDA in particular, played in slowing the process of widespread vaccine dissemination. Specifically: the process could have been sped by months if the U.S. had been willing to conduct human-challenge trials [1] and to integrate tests of safety (Phase 2) and efficacy (Phase 3) [2]. To my knowledge, understanding of how to integrate the safety and efficacy trials has only recently developed; perhaps the FDA shouldn't be faulted on that front. But the benefits of human-challenge trials have long been understood. [1] https://doi.org/10.1093/infdis/jiaa152 https://doi.org/10.1093/infdis/jiaa152 [2] https://doi.org/10.1198/016214504000001790 https://doi.org/10.1198/016214504000001790

angry_octet 6y ago
Firstly, it wasn't produced in large quantities in February. They have to do trials against the mass produced article, not lab samples. Secondly, it would be extremely unethical to overlap phase 2 & 3 trials, when there are effective NPIs. The lessons of unethical medical science, like Tuskegee and experimentation on armed forces personnel, must not be ignored. And yet that is precisely what your ref Eyal[1] is proposing, because practically none of the safeguards can be achieved. Efficacy trials require a much larger participant group, given the still low infection rates. I don't see how one can justify giving a candidate to 100k people before safety screening, especially when the downside risk is significant risk of death if they ever catch COVID.
- jbullock35 6y ago
  > Firstly, it wasn't produced in large quantities in February. They have to do trials against the mass produced article, not lab samples. Yes, I’m not disputing this point. My claim is that even after we account for the difficulties of mass production, the FDA-controlled licensing process should have taken less time than it did. > Efficacy trials require a much larger participant group, given the still low infection rates. This is the major benefit of human-challenge trials [1]: if you intentionally infect healthy, well-informed, low-risk volunteers with low doses of a virus, the size of the requisite participant group falls dramatically. Note also that “Any volunteers in whom infection was confirmed would receive excellent care for COVID-19, including priority for any scarce life-saving resources, in state-of-the-art facilities.” You can say that it’s unethical to run such trials. But it seems hard to make that argument if the volunteers are informed about the risks and if safeguards are in place (e.g., limiting the dose to which volunteers are exposed). Consider also the cost -- many thousands of lives -- of refusing to run such trials and thus delaying the licensing of a vaccine by months. > The lessons of unethical medical science, like Tuskegee [...] must not be ignored. And yet that is precisely what your ref Eyal[1] is proposing No, not at all. In the Tuskegee experiment, people infected with syphilis were promised medical care that they were later denied. When they were diagnosed with syphilis, they weren't even told of the diagnosis. (One of the purposes of the experiment was to study what happens when syphilis isn't treated.) These conditions are a world apart from what Eyal et al. are proposing in [1]. You don't need to take my word for it: the article is short and easy to read. [1] https://academic.oup.com/jid/article/221/11/1752/5814216 https://academic.oup.com/jid/article/221/11/1752/5814216

tptacek 6y ago

So this explains why recruiting other firms to produce Pfizer or Moderna mRNA vaccines is difficult (because the limiting factor is probably microfluidics devices built specifically for processes only Pfizer and Moderna had a reason to scale). But what's the bottleneck on scaling up J&J's adenovirus design?

Exmoor 6y ago
I cannot speak specifically for J&J, but by the number of adenovirus licensing agreements I've seen for Oxford, Sputnik V, etc. I would guess that existing facilities can be converted to produce a viral-vector vaccine much easier than an mRNA vaccine. From there I would suspect that the scaling issues are mostly related to QA and repeated cycles of ensuring what you're producing is actually exactly what you intended to produce.
- BasinAndRange 6y ago
  This is exactly what's happening at Royalmount in Canada.
  - sudosysgen 6y ago
    Yup, à biotech research lab is going to produce 2 million doses à month of the Novavax vaccine (which is essentially as effective as the mRNA ones).
    - refurb 6y ago
      https://nrc.canada.ca/en/covid-19-response-building-infrastructure https://nrc.canada.ca/en/covid-19-response-building-infrastr... Color me a little skeptical. This looks like a big GMP bioreactor facility. Once the vaccine is made, how does it get into vials? Fill and finish production lines are usually another massive complex. Are they going to transfer it offsite for packaging? And this facility won't be finished until July 2021. Then the tech transfer has to happen, trial runs completed, everything validated. They might start actual production at the end of 2021. Tech transfer of pharmaceutical processes is no joke. I've done it before.

Animats 6y ago

The article says that RNA encapsulation is the big bottleneck. This is a touchy microfluidic process. That needs to be accelerated. While few companies make those parts, more could. They're made by a process similar to that used in a wafer fab. A low-rez wafer fab, like the ones used to make MEMS gyros and such. Part of the problem may be that wafer fab people and drug production people don't talk to each other much. Someone should get them talking. Might come to nothing. Might lead to "oh, we can make that easily".

Accujack 6y ago
A chip isn't a complete device. What about the rest of the machinery? The software? Construction of the devices, calibration, testing and commissioning? There are probably less than 10 people worldwide capable of determining if machines like this (that probably only exist within the vaccine manufacturers) are set up correctly and working right. I suspect if you track down what's needed, you'll find that all the manufacturing capability for making more of those machines is already in use by the vaccine makers. Bespoke microfluidics devices aren't common or easy to make, although some components are.
- silexia 6y ago
  The argument in the article for why the vaccine could not be produced is that there are new technical innovations that can't be done by other companies. I believe this to be a straw man argument. Each new human innovation is based on a massive mountain of previous human innovation. Many, many companies are on the edge of this innovation and allowing them to use the innovations of other companies without fear of patents litigation would allow them to make that last step now. Patents are one of the most insidious harms we have in our society today. Patent defenders claim that patents protect innovators. The truth is actually the exact opposite: patents are a monopoly legal tactic most often used so that the patent obtainer does not have to innovate further or execute. Patents kill all further innovation in the area they are in. A great example of this is that hundreds of companies used to manufacture aircraft. Boeing and Airbus bought up all the companies that own patents, and now it's nearly impossible to start a new aircraft manufacturing business due to Boeing's monopoly on the patents. Aircraft have changed very little ever since. We need to eliminate the patent system and allow free trade to actually work.

godtoldmetodoit 6y ago

One thing I hope we take away from this is that just like we way over provision food production here in the States as a matter of national security, we should build out massive amounts of vaccine manufacturing capability. The federal government should massively invest in MRNA manufacturing or whatever other vaccine technologies make the most sense and lease the facilities out at a loss if need be to pharma during normal times. Or just subsidize pharma to have massive amounts of capacity ready to churn out 5-10 million doses a day. I don't really care how it happens, I just want the capability as a society and I'm willing to pay for it.

m-ee 6y ago
This already exists, it’s called BARDA
atleta 6y ago
It's partially a transient problem: mRNA vaccines is new technology that has never seen commercial use, so it's expected that initially you'll have production capacity problems. (Not to say that countries should not prepare for future pandemics.)
peytn 6y ago
We could have a futures market for doses. That way the government doesn’t have to pick winners in the drug development arena, something it historically isn’t very good at.
- maxerickson 6y ago
  We could have ordered 300 million courses each of the top 5 or 10 vaccine candidates for, in essence, peanuts. $2 billion for Oxford. $3 billion for J&J. $20 billion for Novavax. $24 billion for Pfizer (at worst price). $48 billion for Moderna (again, worst price). You end up with a billion vaccines you don't need, you give them away. This is likely an over-investment if you consider the US in isolation (for instance, all 5 vaccines work well to reduce symptomatic and serious infections).
  - 6y ago

firebaze 6y ago

Influenza typically has a mortality of around 0.8%¹. There usually is a vaccine against the current strain of influenza, which usually hovers around 45%² efficacy (tops out at ~60%). With covid, we have a mortality rate of something between 0.3% and 3%³. The CFR of influenza includes - to the best of my knowledge, since i can't find any sources - vaccinated people. So without vaccination, influenza would have a CFR around 0.8% * (100% / 45%) ~= 1.78%. This is within the error bars of covid19 CFR, since there was no vaccine until now. I don't want to downplay covid19. I do want to question the effect on the society, and the personal responsibility of everyone involved. @Downvoters: just state why please. If you disagree, please be so kind and educate me why. ¹https://en.wikipedia.org/wiki/Influenza https://en.wikipedia.org/wiki/Influenza ²https://en.wikipedia.org/wiki/Influenza_vaccine https://en.wikipedia.org/wiki/Influenza_vaccine ³https://coronavirus.jhu.edu/data/mortality https://coronavirus.jhu.edu/data/mortality

DeRock 6y ago
> Influenza typically has a mortality of around 0.8% The Wikipedia article has a graph, which I assume you're referring to with this figure, which shows the mortality rate of 0.8% only applies to those ages 65+. The blended rate for a typical flu season, given in a table below, is <0.1%.
- firebaze 6y ago
  This is the (approximately) same graph for covid19 patients. If influenza was a "new" disease to the immune system of western people, it quite probably would be way more deadly. Original american natives would probably agree.
EthanBar 6y ago
Do you mean influenza typically has a mortality of around 0.8% for those 65 and older? It has a mortality of < 0.1% for everyone from the same Wikipedia article. And CFR, case fatality rate, won't include vaccinated people who didn't get sick so your final calculation doesn't make sense.
agd 6y ago

joe_the_user 6y ago

Here's a general article: https://www.statnews.com/2020/12/11/covid19-vaccine-timeline-keeps-slipping-experts-say-it-will-change-again/ https://www.statnews.com/2020/12/11/covid19-vaccine-timeline... "“Vaccine manufacturers hold their production capacity pretty close to their vest because it’s a point of a negotiation.” he said. Companies want to have flexibility in their contracts so they can balance production of various drugs and vaccines. “These companies are businesses and want to maximize their revenue. They’ll continue to make other products they can sell while manufacturing their vaccine.”" I know less than either Lowe or the State News author. I don't know where the particular bottlenecks might be. But it seems hard for me to believe that "ramping up is impossible" doesn't mean "ramping up is impossible under standard procedures, where we keep proprietary information proprietary, where we don't spend massively on capital equipment we might not need down the line (etc etc)" That is to say that we're far and far from a Manhattan Project intended to push vaccine manufacture to the logistical maximum. That's just how just any institutional process works.

BurningFrog 6y ago
The Pfizer and Moderna vaccines are the first mRNA vaccines to ever be mass produced, and they're needed for the biggest vaccination effort in human history. It seems very credible to me that ramping up from (guessing) thousands of doses to billions will take a long time. As I understand it, once the industry is set up, producing mRNA vaccines should be substantially faster than traditional techniques, since there is no biological step to wait for. They're "printed, not grown".
xyzzyz 6y ago
> “These companies are businesses and want to maximize their revenue. They’ll continue to make other products they can sell while manufacturing their vaccine There is an extremely easy solution to this problem, which is, just paying drug companies so much that it’s not worth for them to make anything else. Unfortunately, the governments around the world have failed the easiest cost-benefit analysis in the history, that is, trillions > billions, and so they negotiated the vaccine prices to be rather low, saving billions, while at the same time, spending trillions in stimulus money. Imagine if they just allowed the companies to sell the vaccines at the prices dictated by the market. Also imagine if they allowed AstraZeneca vaccine in the US without jumping through extra hoops, which cannot possibly give us more valuable information than we already have, now that millions of doses have already been administered in UK. Alas, the regulatory state has failed us in the pandemic the worst it has ever had.

worker767424 6y ago

I suspect Biden talking up the defense production act was mostly for show. Reading this post, there aren't any easy bottlenecks, and everyone knew this was coming, so they did what they could to ramp up production.

brunoTbear 6y ago

This is the same author as who wrote the HILARIOUS series of "Things I won't work with". Highly entertaining reading: https://blogs.sciencemag.org/pipeline/archives/2010/02/23/things_i_wont_work_with_dioxygen_difluoride https://blogs.sciencemag.org/pipeline/archives/2010/02/23/th...

alex_young 6y ago

The scale of thinking here is amazingly constricted. Imagine if we had approached this like we did WWII. We would have nationalized the effort to produce vaccines, building entire production chains and staffing them with anyone in need of work. We would have built infrastructure to produce n95 masks and shipped them to every address. What would this mean? We would have saved hundreds of thousands of lives, employed millions of people, strengthened our economy, and would now be wrapping up vaccinating everyone. Our response to the crisis should be noted as a failure of monumental proportions. The lack of leadership at all levels of government continues to be astounding.

thechao 6y ago
The US response to WW2 took years. We’re still in the months range. You can’t parallel use the early sequential phases; you can’t fabricate this equipment — nor the expertise to manufacture it from nothing in just a few months.
- Robotbeat 6y ago
  Yes, actually, you can. (A well-endowed manufacturer can produce this equipment.) But it takes coordination, leadership, unlimited funding, and federal authority to step across red tape and corporate veils and IP to get things done. I was involved with some of this stuff. I know first hand how uncoordinated and un-led much of it was. We needed technocrats on private jets flying around the country tooling up production and solving every supply chain bottleneck like they were Elon trying to squeeze out luxury car production at the end of a quarter. And vaccine production ABSOLUTELY could've been parallelized with approval. In fact, it was. They were stockpiling doses before approval. But the effort was at least an order of magnitude smaller than it ought to have been. We constantly make excuses for this lack of effort. We shouldn't. We know what is possible. We can read history books.
  - visarga 6y ago
    I'm wondering how we'd fared if Elon was in charge.

xwvvvvwx 6y ago

Perhaps this is my bias showing but I find it totally unbelievable to suggest that production would not be significantly faster had the vaccines been open sourced from the start.

ckemere 6y ago

Please read through the comments on the blog. Info content is very high.