[HN Gopher] Myths of Vaccine Manufacturing
       ___________________________________________________________________
        
       Myths of Vaccine Manufacturing
        
       Author : undefined1
       Score  : 126 points
       Date   : 2021-02-03 15:41 UTC (7 hours ago)
        
 (HTM) web link (blogs.sciencemag.org)
 (TXT) w3m dump (blogs.sciencemag.org)
        
       | joe_the_user wrote:
       | Here's a general article:
       | 
       | 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.
        
       | readams wrote:
       | 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.
        
         | 13415 wrote:
         | This is narrow-minded thinking influenced by recent events
         | instead of a realistic risk assessment. Imagine you spend
         | trillions on vaccines for possibly deadly diseases, and then
         | the Yellowstone supervolcano breaks out and general disaster
         | control is in a bad shape because you've spent trillions
         | elsewhere.
         | 
         | You can prepare for everything but it needs to be done on the
         | basis of balancing many different concerns.
        
           | ClumsyPilot wrote:
           | Why should we imagine highly contrived scenario, most risks
           | are known, we underinvest in prevention and then pay 10x when
           | shit hits the fan
        
         | hef19898 wrote:
         | 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.
        
         | FabHK wrote:
         | > we see the utter lack of the ability to think big in the drug
         | community
         | 
         | I don't know what you are talking about. Speculatively building
         | out capacity for as yet unproven vaccines was suggested and
         | planned back from the beginning already.
         | 
         | (Here for example the Gates foundation in April 2020:
         | https://www.businessinsider.com/bill-gates-factories-7-diffe...
         | )
         | 
         | > There basically no amount of money that it would not have
         | been worth it to spend.
         | 
         | The Economist calculated, based on a Goldman Sachs study, that
         | "an American wearing a mask for a day is helping prevent a fall
         | in gdp of $56.14. Not bad for something that you can buy for
         | about 50 cents apiece." - so, basically a 10000% ROI in a day!
         | 
         | Yes, then, money could have been sensibly employed, but on
         | what? Maybe it would have been better employed on PR to
         | persuade people to wear masks, or maybe a DDOS shutting down
         | social media. How to allocate money optimally in real time
         | remains a difficult question.
         | 
         | I don't think things could have been substantially faster,
         | though things could have been much less painful if not for the
         | intransigence and recklessness of many covidiots.
         | 
         | EDIT to add the source: https://www.economist.com/finance-and-
         | economics/2020/08/22/w...
         | 
         | and outline if paywalled: https://outline.com/yCeVzn
        
         | fabian2k wrote:
         | 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.
        
           | readams wrote:
           | By now the scale could be far larger than it is currently.
           | Moving up vaccine timetables by just a few months would be
           | enormously valuable. I never said it was easy, but the answer
           | was not "let's do nothing because it's hard."
        
             | bluGill wrote:
             | You are speaking from hindsight. Just a few months ago the
             | smart money was on the mRNA vaccines not completing phase-3
             | before some of the more conventional vaccines that we
             | already have the ability to produce in large quantities.
             | 
             | That mRNA completed phase-3 trials first was a big shock to
             | everyone. That they are significantly better than the
             | conventional vaccines is also a big shock. If we knew about
             | these shocks 1 year ago we would have invested a lot more
             | money in mRNA (and none at all in all the other vaccines -
             | some failed trails, some are in progress, and the rest are
             | are not as good) and had more manufacturing as a result.
        
               | abacadaba wrote:
               | we certainly knew there was a potential for this "shock"
        
               | bluGill wrote:
               | Yeah, but it was a long shot potential. If it hadn't
               | worked out you would be mad at the government for
               | allocating money to this stupid bet instead of something
               | else (probably J&J which wouldn't have come out any
               | sooner)
        
         | epc wrote:
         | The market clearly decided that investing a trillion dollars in
         | speculative capacity was not valuable. Absent Federal
         | intervention (in the US at least), where would the money come
         | from? Had the Trump Administration utilized the Defense
         | Production Act to nationalize the necessary resources, then
         | perhaps we would have had the necessary capacity by now, but it
         | decided to go with "Warp Speed" instead.
        
           | readams wrote:
           | Obviously this would not happen with purely private
           | investment.
        
           | bluGill wrote:
           | Even if Trump had done that, he would have invested in the
           | wrong vaccines. This is NOT incompetence, nobody had any
           | reason to think mRNA would be the way to go 9+ months ago
           | when the money was allocated.
        
           | robocat wrote:
           | > The market clearly decided that investing a trillion
           | dollars in speculative capacity was not valuable
           | 
           | Somehow the investors need to get back their investment,
           | cover their risk, and make a profit on top of that.
           | Impossible?
           | 
           | Even worldwide, the median per-capita household income is
           | $2,920. 1 trillion is a lot of money.
           | 
           | Edit: is there a name for the fallacy "something costs an
           | individual $x, therefore the individual can afford to pay
           | $x", or the similar fallacy "something costs people an $x
           | GDP, therefore the government should pay $x to fix it".
        
       | jbullock35 wrote:
       | 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
       | 
       | [2] https://doi.org/10.1198/016214504000001790
        
         | foobiekr wrote:
         | We have a vaccine in February in the same way that we have 5nm
         | fabs this year.
         | 
         | After all, all the technology is there, it's just the
         | investment and those pesky actual manufacturing process that's
         | standing in the way.
        
           | bluGill wrote:
           | Not exactly. If you have a 5nm fab you can produce chips
           | today that you know work. (the yield might be terrible, but
           | you can get some functional chips every day). In February
           | what we had was something that completed the process, but we
           | had no idea if it worked at all.
        
             | foobiekr wrote:
             | From a manufacturing perspective, the equipment was there
             | because they've been working on it 20Y; whether the vaccine
             | worked is a separate question.
             | 
             | By analogy, it's one thing to have a fab, a working fab can
             | make 5nm chips as designed at some yield, however, the fab
             | is not responsible for whether the chip designs work or are
             | valid.
             | 
             | My point here really was that tech people, and especially
             | people in the software industry, ignore that the bulk of
             | the work isn't the equipment, it's the long tale of supply
             | chain, manufacturing process and QA. All of the 5nm
             | equipment exists today, it's the other parts that are the
             | hold up.
             | 
             | Essentially, in our own domain we know better, and we
             | should really understand this and stop making this mistake
             | in other domains.
        
         | angry_octet wrote:
         | 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.
        
       | tptacek wrote:
       | 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 wrote:
         | 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.
        
           | timr wrote:
           | The technology is pretty standard. I can't imagine that
           | there's any tech-driven bottleneck to development, but
           | rather, issues surrounding licensing, IP transfer, liability,
           | etc (in other words: legal concerns).
           | 
           | Once those are resolved, there's still a fixed amount of time
           | that it takes to convert existing production facilities to
           | some new purpose that you can't really eliminate (the old
           | saying about 9 women having a baby in 1 month applies
           | here...)
           | 
           | Basically, it's the sort of thing HN readers don't like to
           | hear: the complexities of the real world create obstacles
           | that are difficult to surmount with technology alone. If I
           | had to guess, even if you got approval to have N partners
           | manufacture the vaccine _today_ , it would still take a few
           | months to ramp those partners up to capacity.
        
           | BasinAndRange wrote:
           | This is exactly what's happening at Royalmount in Canada.
        
       | andred14 wrote:
       | 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/
        
       | twoslide wrote:
       | 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 wrote:
         | Oxford/AstraZeneca vaccine is indeed being produced around the
         | world:
         | 
         | https://www.biopharma-reporter.com/Article/2020/08/06/AstraZ...
         | 
         | 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-vacc...
        
       | jancsika wrote:
       | > My own guess as to what such a Vaccine Machine involves
       | 
       | In a global pandemic, why are we guessing?
        
         | _Microft wrote:
         | It's a thing he does not work with.
        
           | jancsika wrote:
           | Sorry, that wasn't clear.
           | 
           | Are the specs for the design of the "Vaccine Machine"
           | machine-- as he terms it-- public knowledge?
        
       | [deleted]
        
       | GavinB wrote:
       | _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.
        
         | gus_massa wrote:
         | > _And we refused to risk any individual life in order to
         | potentially save hundreds of thousands or more._
         | 
         | Are you volunteering? Will you sign all the paperwork?
         | 
         | If you die in the trial or get a severe reaction, would your
         | family be happy with the paperwork, or they will claim that
         | they fooled you?
         | 
         | If you die and the vaccine candidate fails, will the TV claim
         | that they should have used a good old method like a modified
         | adenovirus instead of playing god and creating a frankenvirus
         | in the lab?
        
           | d7ryerh wrote:
           | You make it sound as though no one would volunteer. I think
           | you're severely underestimating the altruism of some people.
        
           | ClumsyPilot wrote:
           | People have voluntered for fucking one way trip to Mars.
           | Maybe you think they are mad, but thats a different problem.
        
           | Symmetry wrote:
           | I and a ton of other people signed up for challenge trials
           | through 1 Day Sooner (https://www.1daysooner.org/). Sure,
           | there was some risk to me but it was small compared to the
           | potential to save the lives of older friends and family even
           | before considering strangers.
        
         | tass wrote:
         | Doesn't this raise the same problem with the current
         | manufacturing process?
         | 
         | There was limited capacity to manufacture back then, probably
         | less so than there is today. Which vaccine candidate would
         | Pfizer have manufactured? All of them?
        
           | GavinB wrote:
           | Yes, all of them. Or possibly expanding capacity for each of
           | the major vaccine types, to be ready when we know which one
           | is the winner.
           | 
           | And then, yes, a lot of those factories would have ended up
           | sold for scrap (or mothballed for future pandemics or
           | mutations). But the few that worked then save trillions of
           | dollars of value and hundreds of thousands of lives.
           | 
           | It's a simple matter of calculating expected values and
           | investing accordingly. But thats not how our civilization
           | works.
        
             | tass wrote:
             | I'm going off the assumption that the capacity has been
             | expanding as much as possible, so scrap factories wouldn't
             | be a problem.
             | 
             | The Pfizer vaccine seems to have a shelf life of 6 months,
             | so realistically the earliest they could have begun mass
             | manufacture and have an effect today would have been June.
             | That's right around the time they narrowed down to a single
             | vaccine candidate.
             | 
             | I'm surprised that mass manufacturing didn't begin back
             | then with the only possible candidate, especially since the
             | US government also put their order in around that time. I
             | can't find a whole lot of info on when they did ramp up
             | (something I saw said October), and what reasons they had
             | for not starting earlier.
        
             | natechols wrote:
             | Last year Bill Gates talked about doing exactly that (I
             | don't know if this actually happened):
             | https://www.businessinsider.com/bill-gates-
             | factories-7-diffe... The fact that someone like Gates is
             | throwing the idea around suggests that it's not really
             | incompatible or inconsistent with our civilization. (EDIT:
             | saw your other comment with the follow-up, sigh.)
        
               | [deleted]
        
         | milliondollar wrote:
         | EXACTLY my question. How much would it have cost to make some
         | bets against the various types of vaccines that could come out.
         | Make a "generic" manufacturing facility that could then help
         | scale up. So what if we "wasted" $10B on facilities that didn't
         | pan out?
        
         | [deleted]
        
         | Gatsky wrote:
         | The virus can be controlled with appropriate measures to limit
         | the death rate - see Taiwan, SK, Australia, New Zealand etc. If
         | you want to argue that we could have saved hundreds of
         | thousands of lives I would probably start there instead of
         | experimenting on billions of people.
        
         | chuckcode wrote:
         | Agree that relative to the cost in lives and global GDP leaders
         | have drastically under invested in production and distribution
         | of vaccines. Arguments about what ethical and incentive
         | policies should be will continue forever. Certainly though we
         | shouldn't be blocked at this point by availability of a few
         | machines, shipping and inventory tracking, etc. Especially in
         | the US we have really wasted 9-10 months to work on public
         | health in general and vaccine delivery in particular. History
         | will not be kind
        
         | standardUser wrote:
         | To be fair, part of the reason we establish rules of ethics is
         | so that when an emergency happens, we don't just wing it and
         | start making up the rules. Situations like this pandemic are a
         | very good reason to revisit established rules of ethics, but
         | using it as justification to overrule existing rules negates
         | the entire idea of establishing rules of ethics in the first
         | place.
        
           | GavinB wrote:
           | I agree in principle. On the other hand, global crises have
           | always called for extraordinary measures.
           | 
           | Even in this pandemic, we've (correctly, I would say)
           | basically thrown out important principles like freedom of
           | movement and freedom of association during lockdowns. I think
           | that allowing volunteers to put themselves at a relatively
           | low risk to speed up vaccine trials would have been a
           | relatively small transgression, compared to the lockdowns and
           | travel bans (which, again, I think were justified).
           | 
           | But I do take your point.
        
             | cameldrv wrote:
             | This is a very good point. The lockdown measures, while
             | very arguably necessary, are an extremely severe measure.
             | They were perhaps the only measure that would have been
             | effective at the beginning when there was no preparation.
             | 
             | Yet, things like enforced mask wearing, or enforced out of
             | home quarantine/isolation somehow were off the table. It is
             | a weird path-dependent quirk of the fact that we had no
             | testing at the beginning, that instead of quarantining and
             | isolated the exposed and infected, we are effectively
             | quarantining everyone.
        
         | Florin_Andrei wrote:
         | > _We did have it, we just didn 't know which one it was._
         | 
         | What we had was the ending of Indiana Jones and the Last
         | Crusade.
         | 
         | A table full of cups. Some of those have the Water of Life.
         | Some just water. Some will outright kill you. Pick one.
         | 
         | It's only when you go through the trial process that you can
         | separate the life-giving stuff from the rest.
        
         | azangru wrote:
         | > And we refused to risk any individual life in order to
         | potentially save hundreds of thousands or more
         | 
         | But we are risking individual lives now. Vaccines have side
         | effects. It's never about an individual life, always a calculus
         | of number of lives risked vs number of lives saved, I would
         | think.
        
           | mortehu wrote:
           | I think the point is that we chose and are still choosing to
           | wait for a hundred people to get infected at random in each
           | efficacy trial, instead of just deliberately infecting a
           | hundred people immediately.
           | 
           | The cost of our approach is that roughly the same proportion
           | of the country's population must bet infected as in the
           | trials.
        
             | Digit-Al wrote:
             | So, would you volunteer to be deliberately infected with a
             | disease that might or might not kill you in order to save
             | many other lives?
        
               | doliveira wrote:
               | Honestly, I would. The way things are going down here in
               | my country (Brazil) I will get infected eventually, at
               | least by participating in challenge trials it would help
               | other people.
        
               | mortehu wrote:
               | Tens of thousands of people have signed up for this at
               | 1daysooner.org. I didn't even volunteer for any of the
               | ongoing trials myself.
        
               | ClumsyPilot wrote:
               | That's an difficult and potentially eternal question -
               | some people volunteer to go to space or cross the ocean
               | on a canoe because to them its worth the risk. Some do it
               | for the money. Some are just mad or obsessed.
               | 
               | Back in my time at uni, volunteers had to be unpaid to
               | ensure they do it kf their own free will. Its unclear
               | which is better / worse.
        
               | nickpp wrote:
               | For a nice sum, a whole bunch of people would probably
               | volunteer.
        
               | pgodzin wrote:
               | An ethical consideration is whether it is ethical to
               | disproportionately place the poorest (those most in need
               | of a nice sum) at this unknown risk
        
               | ls612 wrote:
               | I'm 25 and healthy. If they paid me $1000 and provided
               | medical treatment if necessary I would have volunteered
               | for such a trial last spring.
        
         | sna1l wrote:
         | +1
         | 
         | It was clear the US government made the wrong decision when
         | they backtracked and tried to buy more doses from Pfizer +
         | Moderna[1]. Given how much the US has spent on stimulus, you
         | would think even like 10-15 extra billion would be nothing.
         | 
         | [1]: https://www.nytimes.com/2020/12/07/us/trump-covid-vaccine-
         | pf...
        
         | jimbokun wrote:
         | > 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.
        
           | maxerickson wrote:
           | The economists that put together this working paper estimated
           | that we left a lot on the table. Several months and hundreds
           | of billions of dollars in the US (that invested a relatively
           | large amount) and nearly a year and over a trillion dollars
           | for the globe. Table 1 on page 6 summarizes it.
           | 
           | https://bfi.uchicago.edu/wp-
           | content/uploads/2021/01/BFI_WP_2...
        
           | GavinB wrote:
           | 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...
        
             | natechols wrote:
             | Oh thanks I was looking for followup on the Gates thing,
             | that blog post is superb. And depressing.
        
       | Animats wrote:
       | 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".
        
         | foofoo55 wrote:
         | Here's a commercial RNA encapsulation system:
         | 
         | https://www.precisionnanosystems.com/platform-technologies/p...
        
           | Animats wrote:
           | Right. That's the next stage up, pumps, plumbing, and
           | instrumentation. The "cartridge" mentioned is the hard part.
           | 
           | Here's a company which makes the "chips" which go in such
           | cartridges.[1] And here are some chips.[2] Making those
           | involves etching tiny patterns in glass, lining the channels
           | with various coatings, and assembling the layers of glass
           | into devices. All this has to be done in a very clean
           | environment. Note the similarity to the processes in a wafer
           | fab.
           | 
           | The point here is that the semiconductor industry has many
           | processes and tools which might be helpful if there's a need
           | to manufacture microfluidic components in quantity.
           | 
           | [1] https://www.dolomite-microfluidics.com/
           | 
           | [2] https://www.dolomite-microfluidics.com/product-
           | category/micr...
        
         | Accujack wrote:
         | 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.
        
         | xjlin0 wrote:
         | There are many fancy kitchen machines out there. But even you
         | buy me one, it's impossible for me to cook great dishes
         | overnight. Same things goes to wafer fab, buying me the most
         | advanced limask alignerhography machine can not make me to be
         | able to produce great 5nm chips in a few years.
         | 
         | Also the instrumental parameters from manufacturer A probably
         | cannot be applied directly to the instrument from manufacturer
         | B. It is an entire process/system that can not be reproduced
         | overnight. It takes time.
        
         | danvoell wrote:
         | "Part of the problem may be that wafer fab people and drug
         | production people don't talk to each other much." - Another
         | part of the problem is probably regulation. Water companies
         | don't want to inadvertently bypass FDA regulation. Drug
         | production folks don't want to teach water folks the FDA
         | approval process, such that, they could become future
         | competition.... Sheer speculation.
        
         | rossdavidh wrote:
         | If we had a long-term bottleneck here, there might be some
         | possibility here, but then again if there were a long-term
         | bottleneck we could just build more capacity. However similar
         | they are, I doubt you can just turn this on in a month or two
         | without serious potential issues, and given how many people the
         | vaccine is going into you have way more potential downside than
         | potential upside.
         | 
         | Which is really the issue with all potential fixes: either they
         | are unknown and thus unacceptably risky for something we will
         | use on hundreds of millions (or billions) of people, or if we
         | take the time to get to acceptable risk it will be too late to
         | really help with this issue.
        
       | ericb wrote:
       | 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?
        
         | tpm wrote:
         | He is responding to a tweet that explicitly mentions Pfizer and
         | Moderna.
        
         | bluGill wrote:
         | 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)
        
           | ericb wrote:
           | I don't think it will be clear that Pfizer is "more
           | effective" until we see the two-dose J&J study come in.
           | 
           | > J&J doesn't really need to be scaled up because they alone
           | have the ability to produce so much of it.
           | 
           | I'd bet 100 dollars that J&J ships less than a billion doses
           | before July.
           | 
           | Are you willing to take the other side of the bet? If I'm
           | right, that means that they could have "used help" even
           | though they "have the ability to produce so much of it."
           | 
           | Edit: Before you take my bet, which I'm happy if you do, you
           | may want to read this:
           | 
           | https://www.nytimes.com/2021/01/13/health/covid-vaccine-
           | john....
        
           | whycombagator wrote:
           | > I'd prefer to get the mRNA vaccines as they seem much more
           | effective
           | 
           | I am still unsure which route seems best.
           | 
           | Don't mRNA vaccines target the spike protein?
           | 
           | The spike is a topic of debate currently as mutations/changes
           | to the spike (South African variant etc) may affect mRNA
           | vaccines more?
           | 
           | Moderna themselves are developing a booster shot targeting
           | the SA variant & a separate booster for all the other
           | variants (U.K. et al) for this very reason (read: you'll need
           | 2 doses of vaccine & 2 booster shots for full protection
           | against all current forms of COVID/virus)
           | 
           | So the mRNA route might well be 4 shots for just the variants
           | we know about.
           | 
           | That isn't to say non mRNA vaccines (AstraZeneca, J&J) won't
           | also have the same issues (decreased effectiveness against
           | the mutated virus ) but from what I've read it seems more
           | likely to affect mRNA
        
         | chaganated wrote:
         | 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 wrote:
           | 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 wrote:
         | Derek's blog is great but he's a bit of a stooge for his
         | industry, so he plays dumb sometimes.
        
       | firebaze wrote:
       | 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
       | 
       | 2https://en.wikipedia.org/wiki/Influenza_vaccine
       | 
       | 3https://coronavirus.jhu.edu/data/mortality
        
         | EthanBar wrote:
         | 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 wrote:
         | > I do want to question the effect on the society, and the
         | personal responsibility of everyone involved.
         | 
         | What does this mean?
         | 
         | There are many factors at play here. Aside from mortality, you
         | also have to look at the R0. Covid 19 has a significantly
         | higher R0 than seasonal flu (estimated 1.5 vs 2.5+).
         | 
         | In addition, many people have some immune resistance to
         | seasonal flu, but there was no existing resistance to Covid 19.
         | 
         | You only have to look at the health situation in Italy,
         | Portugal, UK and elsewhere to see the difference between the
         | two. Or look at the excess death graphs.
        
           | firebaze wrote:
           | Covid19 is a new disease, noone is primed (by natural
           | immunity) against it. It will be more deadly _by nature_
           | since this is what nature is.
           | 
           | I _doubt_ our response is good. We _must_ protect vulnerable
           | people, and we have the means to. But this is what we are
           | neglecting, and this is what causes deaths.
           | 
           | And while we're not protecting vulnerable people, we're also
           | harming (to a not yet known degree) people who are not
           | vulnerable at all: the young. The're being deprived of their
           | education (at least in europe), of their young years, of
           | living their young life. Even my parents in their 60s say
           | they'd rather protect themselves or die instead of causing
           | depression among the young.
           | 
           | But who cares.
        
             | [deleted]
        
         | sfteus wrote:
         | This is like using only GDP to compare economies; it's a useful
         | data point, but it doesn't tell the whole story.
         | 
         | From what we've seen, yes, the mortality rate of COVID19 is
         | similar to the flu. However, the mortality rate of the flu is
         | without other interventions aside from the flu vaccine. In a
         | regular flu season the public doesn't social distance; they
         | tend to group even closer indoors because of the cold weather.
         | The US has never normalized mask wearing; people in the
         | beginning stages of the flu will go about their lives, and work
         | places actively encourage people to continue to work in-person
         | unless they are too unwell to do so. I would wager most people
         | in the US don't improve their hygiene during a regular flu
         | season either. We've done all that (to an extent) with COVID19
         | and we've barely managed to make an impact.
         | 
         | Look at some other important data points. Average US flu deaths
         | / year: 36k [1]. COVID19 deaths in the US in only 11 months:
         | 445k. [2] If we assume the first COVID19 death in the US was in
         | early February as some report, that's over 12x the deaths/year
         | than the flu. If current trends hold (~3k deaths/day for the
         | next 27 days) until March 2 (the first officially confirmed
         | COVID19 death in the US), we'd be at 526k deaths, or more than
         | 14x as many deaths/year as the flu. If this ran at this rate
         | for the entirety of the next 365 days, we'd hit nearly 1.1
         | million deaths, or over 30x as many deaths/year as the flu.
         | That's assuming we don't have any massive improvements with
         | vaccine rollout.
         | 
         | The contagiousness of the two is also orders of magnitude
         | different. Flu is estimated to have an R0 value of ~1.5 [3].
         | Some estimates put COVID19 at an R0 value of 5.7 [4].
         | (Remember, R0 is without interventions). The way to estimate
         | "herd immunity" rates is the Critical Vaccination Threshold
         | formula: (1 - (1/R0)) / E, where E is the effectiveness of a
         | vaccine. With an R0 of 1.5 and an efficacy of 67% (from your
         | second link. Remember, this is the effectiveness of the
         | vaccine, not the effectiveness in a real-world population,
         | which factors in vaccine rates), we would need roughly 50% of
         | the population to vaccinated to start preventing illnesses in
         | those that are unvaccinated. With an R0 of 5.7 and an efficacy
         | of 94% (Pfizer vaccine), COVID 19 would require nearly 88% of
         | the population vaccinated to achieve the same rate. Even using
         | the lower-quoted R0 value of 2.5 (R-value _with_ other
         | interventions, such as social distancing, mask wearing,
         | improved hygiene), we'd need nearly 64% of the population
         | vaccinated.
         | 
         | You're also ignoring the fact that, despite our interventions,
         | there are currently 3 other strains of COVID19 spreading, all
         | of which are speculated to be both more contagious _and_ more
         | deadly. [5] While the current vaccines are _effective enough_
         | against the strains, there's nothing saying a new variant
         | couldn't emerge that is resistant to the current vaccines,
         | starting a new pandemic. And you're also ignoring the long-term
         | cases of COVID19 [6] as well as the long term effects post-
         | infection outside of death [7], including chronic
         | cardiovascular damage, kidney damage, neurological effects,
         | among many others.
         | 
         | So yes, the mortality rates are similar, but literally nothing
         | else is. We don't know enough about this virus to let it run
         | rampant, and the world should have done more from the get-go to
         | keep it contained.
         | 
         | [1]: https://www.cdc.gov/flu/about/burden/past-seasons.html
         | 
         | [2]: https://covid.cdc.gov/covid-data-tracker/#datatracker-home
         | 
         | [3]:
         | https://www.vdh.virginia.gov/coronavirus/2020/12/07/covid-19...
         | 
         | [4]: https://wwwnc.cdc.gov/eid/article/26/7/20-0282_article
         | 
         | [5]: https://en.wikipedia.org/wiki/Variants_of_SARS-CoV-2
         | 
         | [6]: https://en.wikipedia.org/wiki/Long_COVID
         | 
         | [7]:
         | https://en.wikipedia.org/wiki/Coronavirus_disease_2019#Longe...
        
         | Robin_Message wrote:
         | The wikipedia page you reference gives all-age mortality of
         | 0.096% for the US 18-19 flu season.
         | 
         | So, with your 0.3%-3% CFR, Covid-19 is three to thirty times as
         | deadly as flu. Call it ten times as deadly; it is also more
         | virulent (R0 of 1.4 vs 3-5 for Covid-19).
         | 
         | That's why it is being treated more seriously than flu.
        
         | inglor_cz wrote:
         | CFR isn't the main problem about Covid, the 5 per cent of cases
         | that end up in hospital is - and for how long they stay there.
         | 
         | People with bad cases of Covid routinely spend weeks in ICU
         | before they either get better or die. This is an enormous
         | workload for doctors and nurses.
         | 
         | Also, we do not know for sure how long haulers will fare. I
         | myself had heart arrythmia after an otherwise very mild case of
         | Covid. Fortunately, a simple beta blocker helped me and there
         | are no traces of anything worse on my heart, but the doctors
         | that took care of me told me that they have a surge of youngish
         | patients with myocarditis and similar problems. Some of those
         | are actually sportsmen.
        
         | DeRock wrote:
         | > 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 wrote:
           | 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.
        
         | mcguire wrote:
         | " _The CFR of influenza..._ "
         | 
         | Case Fatality Rate, in case anyone else lost their acronyms.
         | 
         | According to worldometers.info, the US has reported 27,101,847
         | cases of COVID19 and 460,398 deaths, giving a CFR of about
         | 1.70%, so that's about right.
         | 
         | I have reservations about your influenza mortality number of
         | 0.8%. Most of the numbers I've seen have been significantly
         | lower. If you look at [1], there were an estimated 29,000,000
         | _symptomatic_ cases of influenza in the US in 2016 and an
         | estimated 38,000 deaths, giving an estimated CFR of 0.1%,
         | including any effects of vaccination. Correcting for
         | vaccination and making the assumption that everyone were
         | vaccinated, that would result in a unvaccinated CFR of around
         | 0.2-0.3, right?
         | 
         | " _If you disagree, please be so kind and educate me why._ "
         | 
         | We've been dealing with COVID19 for about a year, no? We've had
         | 27,000,000 cases and 460,000 deaths, right? That's about the
         | same number of cases and _10x_ the number of deaths.
         | 
         | You may not be trying to downplay COVID19, but I suspect you
         | are doing it.
         | 
         | [1]
         | https://en.wikipedia.org/wiki/United_States_influenza_statis...
        
       | godtoldmetodoit wrote:
       | 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 wrote:
         | This already exists, it's called BARDA
        
         | peytn wrote:
         | 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 wrote:
           | 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).
        
         | atleta wrote:
         | 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.)
        
       ___________________________________________________________________
       (page generated 2021-02-03 23:01 UTC)