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Comment by ancymon | Hacker News Reader

As I understand, for example in Europe Pfizer is producing vaccines in single factory and not in sufficient number. Why production doesn't happen in more places? Couldn't they sell license to other European pharmaceutical companies to produce it? Is production process so unique it can't be replicated in other places?

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I've been wondering this myself too. Lockdowns are so expensive that I'd assume every unconventional method to expand the production is taken into use. The situation is bad but not so bad that competitors could be forced to work together it seems.

I expect that the amount of angry people in EU will peak in spring or early summer when UK, US, and Israel are mostly back to normal and we are not.

Yes, I was wondering that very much myself. I remember talks about ramping up production preemptively, starting from spring, to have large stock of vaccine available when they are approved. Bill Gates talked about that specifically, taking like first 5 most promising vaccine candidates and starting production ramp up immediately, even risking the possibility they will not be approved and wasting some money. I thought "Finally, some good strategy". Money risked with such an approach would still be minuscule compared to losses due to pandemic and covid relief funding. But looks like that didn't happen, which is just another sign how badly world handled the pandemic. There's an article related to this: https://www.lesswrong.com/posts/SruhzksSgHWSuxm7b/covid-bill...

Pfizer and moderna were not in the most promising vaccines list. MRNA was too new and untried. I'm not sure why Oxford/az wasn't ramped up more though, they were the ones everyone was waiting for.

Moderna received WARP funding though, I think they definitely were on the list of most promising vaccines. There were 6 most promising western vaccines: Biontech, Moderna, J&J, Oxford, Novavax and Sanofi. It was clear they were the ones needing preemptive production. Sanofi didn't play out, but others are doing ok.

I think currently the main reason why not more factories produce the BionTech/Pfizer Vaccine is that it is quite difficult to manufacture and so it takes time to set up additional capacity. As far as I know several competitors are in discussion to build additional capacity. Of course there is the question why this has not been done earlier.

It kinda reminds me of the current cutting edge chip shortage - eq. the special microfluidics machines needed for mRNA vaccines VS EUV machines needed for cutting edge ASIC manufacturing.

The American factories are only producing for Americans. The European ones are producing for the whole world.

Some American factories are export restricted, Pfizer has set up production in the US which is cleared for export as they didn’t took any government funding for those production lines.

Israel is getting most of their doses from US factories not EU ones.

And pays more than 10x as much per dose.

And that really doesn't matter compared to the cost of locking down a country and the lives saved by quicker vaccination.

Agreed. But given the lack of production this was an easier deal to make for Israel than for say all of the EU, no matter what the price, those vaccines are not available in that quantity.

Chicken and the egg if the EU would’ve handed out 50 billion € a year ago to setup production and stockpiles it would’ve made a difference...

Israel is paying about $30 a dose about twice the Pfizer listed price in the US and EU not 10 times more.

It’s paying 10 times more when comparing to the AZ vaccine but that’s not apples to apples.

https://www.jpost.com/israel-news/the-cost-of-vaccinating-is...

says $47 / dose

No, it says $47 per person that’s under $30 per dose.

doesn't explain why European ones are happening in one factory

> in one factory

This is not true;

Not sure if i can find the source i read (at spiegel.de) but i will have a look and post it if i find it.)

So apparently the main EU plant for production of the vaccine is in Puurs, Belgium.

The second one (already producing today) is in Marburg, Germany. Source in German: > "In the first half of 2021, 250 million doses of the vaccine are to be produced..."

https://www.spiegel.de/wirtschaft/unternehmen/corona-impfsto...

I don't know if there are more factories...?

Are they? Didn't the EU put up a vaccine export ban? https://www.bbc.com/news/world-europe-55860540

No, they are currently just requiring export licenses "to get an overview". Up to now, all export requests have been granted and there are large parts of the world where no license is required: https://www.tagesschau.de/wirtschaft/weltwirtschaft/eu-impfs...

Overall I would call it useless EU blustering, there won't be an export ban, no matter what happens. It is just the minimum required measure to save face.

Also lets not forget that this was specifically targeting the UK, not the rest of the world.

That is not quite true, it doesn't only target the UK. The export requirements apply to basically everyone except third-world countries through Covax and Switzerland/Norway/Ukraine/Israel due to existing treaties.

But it is true that the AstraZeneca/UK-situation was the trigger event that lead to the public noticing that something was amiss.

Are you saying EU specifically tried to ban export to UK while export to the rest of the world is ok?

There is/was a contract dispute between the EU and AstraZeneca regarding supply of the Oxford-AstraZeneca vaccine. The EU wanted AstraZeneca to supply additional vaccine from it's UK-based factories, which are already contracted to supply the UK.

The export registration requirements (not an export ban) are, at least in part, in response to this dispute.

https://www.theguardian.com/business/2021/jan/30/lawyers-dis...

Well, the contract with the EU included the UK factory(ies) as a (potential?) supplier to the EU.

UK signed the contracts slightly earlier and jump-started the programme by issuing an emergency approval a few weeks earlier than the regular approval by the EMA.

And above all, it seems despite all efforts of coordination and treaties (COVAX), almost all players (except Norway) are playing the auction game and hoarding.

This is a global pandemic and these "selfish" actions will have global effects :(

The rest of the world will get it's vaccines after the first-world states are all vaccinated. And while it sucks to live in a third-world country where vaccinations will come 2022 or 2023 maybe, I can't see any other way, except if the third world would do their own production. Letting more people in the first world die to save some in the third world would be politically impossible.

The problem is that letting the virus continue to circulate unchecked in the developing world just gives it more opportunities to mutate into new, possibly vaccine-resistant variants. Variants can then spread back to infect the first world, and as we've already seen, this can happen quite quickly.

A global vaccination strategy is needed if we really want to get on top of Covid for the long term.

There are two possible strategies for the problem you describe:

Either you vaccinate everyone world-wide at the same time as quickly as possible. Then mutations that make the virus resistant to vaccinations only have the time to occur during the time it takes to vaccinate. However, we do not have sufficient production capacity for doing this. We would have to wait a few years before even starting the vaccinations, otherwise the virus would "mutate away" from the vaccine. Or it would mutate away, if the campaign took too long, because everyone is waiting for the slow drip of doses...

Or you do divide and conquer: Put up travel restrictions, quarantine and testing regimes to split up the problem into smaller areas and subsets of the global population. Quickly vaccinate each of those, so that the virus doesn't have time to mutate away. If possible eradicate the virus in those regions. Then start with the next set of regions and populations, possibly adapting the vaccine to the variants that have occured there. Eradicate the virus there. Then lift the travel restrictions between the regions where the virus has been eradicated. Repeat until done.

Accidentally, the latter one is what we are doing. However, I fear the travel restrictions are too lax to really make it work, because it isn't really planned, just accidential.

There was misunderstanding and arrogance from EU bureaucrats about how business works. They have already tracked back ( Von Der Leyen in EU parliament, Merkel in media ).

A Dutch facility is producing vaccines ( AZ ) for the UK, as they have been financed from the UK deal.

That factory is in Belgium right? Or do we have one too? (I don't really follow much covid news)

https://nos.nl/artikel/2367290-eu-erkent-wel-degelijk-nederl...

Halix in Leiden.

The US just signed two contracts for additional deliveries of 100 million doses each of two vaccines (Pfizer & Moderna, I believe?)

I doubt that these companies can make such deliveries without first fulfilling the contracts they have with the EU. I looked it up at the time, and they have. contracts with hundreds of millions of doses for the EU.

So what I believe will happen is that deliveries will grow extremely fast at some point before July, when new production capacities come online.

Consider what would happen if capacities increased dramatically: any advantage some countries have right now will shrink, when measured in time, from "months" to maybe just a few weeks. The real end of lockdowns may well still coincide.

Sanofi is starting production of the Biontech / Pfizer stuff this summer. They have delays in their own mRNA vaccine. So yes, competitors are cooperating. And it gives you an idea of the production difficulties.

> The situation is bad but not so bad that competitors could be forced to work together it seems.

And yet this should have been the plan from the very beginning.

Considering the vast numbers needed in Europe and the whole world, forcing all available production facilities to produce vaccines should have been part of the plan.

Absolutely, however the EU's politicians are playing dumb and claim that they couldn't foresee that mass production could be a problem.

The EU ordered too late and simply not enough. Now they are trying to blame everyone else for their failure.

Yes, that's true, but it also has to be said that producing these vaccines is not so simple. It's all new technology, no mRNA vaccine was ever approved before, and you can't just dial up production so easily. Unfortunately. You can't just convert any old pill-factory into a factory that produces these vaccines. Apparently there are supply chain issues as well - some of the things that are needed for the production of this vaccine are in not available in the numbers that are required.

But all that being said, I think we should move to war-time production here.

I can absolutely imagine that scaling production is extremely hard.

However I don't have confidence that the same politicians that just claimed that they couldn't foresee problems with mass production did everything in their power to help here last summer. I mean the EU ordered only in November from Biontech and Moderna (and less doses than the companies offered). That doesn't really look like an incentive for companies to look into opening another factory already in summer.

Just throwing the same numbers in here: The EU ordered 4+ doses per inhabitant by Q4 2020. Deliveries were intially scheduled through Q3 2021, with enough doses to be delivered to reach herd immnity by end of Q2. Not sure how ordering even more, without knowing when said doses would have been available, had helped.

EU politician really screwed up in summer 2020, so. They had, besides ordering (which was outsourced to the EU anyway), one job. Planning and setting up operations to vaccinate millions of people in the first 6 months of 2021. That would have included coordination between patient appointments, manufcturing and deliveries (invlving the EU ideally), making sure back-up plans are in place, getting processes up and running to make it as easy as possible to get vaccinated, making sure manufacturers can get necessary support in securing their upstream supply chains when needed and so on.

None of that happened. Instead, everyone was so, so happy that Europe had a great summer vacation. And then everyone so so hoped the unsurprising increase in cases starting in October would be just go away. And then everybody so so hoped they could safe Christmas shopping and christmas markets, And then everybody fell back to the only lesson they learned during the first wave: people like politicians that act tough. They just din't realise that back then acting tough, read lockdowns, was inline with expert advice. Basically, the EU had over six months to get ready for an EU-wide vaccination campaign. Member states had also 6 months. And did, it seems, by no means enough, if they did anything at all.

This now shows, and everyone is just happy to point at manufacturers and the EU. We'll see how long that story is going to hold water.

I can confirm the Czech government did basically nothing to prepare for vaccinations till the very last moment - something resembling a mass vaccination plan was only published on Dezember 22th (!) and only now the system seems to be in somehow working state, likely due to not having that many vaccines to process yet.

I just hope whatever solutions are in place are able to cope once the vaccine deliveries kick in.

FWIW Canada did the same thing and our federal gov't is paying the same political price.

Trump reserved the US manufactured supply for themselves, only, so Canada is reliant on EU exports, which is kind of crazy to think about, geographically.

My understanding is many Canadian officials were caught off guard by the fact that the vaccine became available Q1 2021, they were thinking Q2/Q3 2021 was more likely and so much of the purchase deals were geared around that.

They ordered one slightly later than the UK and the US (let's ignore Israel which is basically a large scale trial). The main difference: the EU used normal certification processes, just sped them up considerably. The UK and US used emergncy certification.

The volumes the EU ordered initially were absolutely sufficient with 4+ doses per EU inhabitant. Manufacturing capacities were sufficient for that as well. It all started to go south as soon as memeber states looked for scape goats why vaccination happened so slowly. First the manufacturers, then the EU, then the federal government (where applicable). It is a last-mile distribution issue if you will now, not a manufacturing one.

I think that's a very charitable interpretation of events. Realistically the EU negotiated on behalf of the 27 member countries to try to get the best deal on price, and perhaps more importantly, to avoid the inevitable tensions which would follow from one member country securing more than another member country. This process slowed down the negotiation process.

Whether there is any truth in the EUs certification being conducted differently is a bit moot given they have approved the same vaccines based on the same trial data.

I don't think it is charitable. The EU had to juggle 27 individual countries, one central certification and Brexit. They had to avoid a situation in which rich countries, e.g. Germany, outbids poorer countries, e.g. Hungary or Greee. They managed to do that. They over purchased, they split orders betwen suppliers thus further minimizing the risk.

And they did all that using normal certification. They even pointed out, quite clearly, that the actual managemen of vaccination campaigns, the vaccine ordering and the national distribution is up to the member states.

The last part shows very different results, e.g. in germany Mecklenburg-Vorpommern is far ahead in per capita vaccines. Bavaria for example is behind them. All we won with focusing on the supply of vaccines so far in a shutdown of Pfizer's pant in Belgium to produce more doses, which are not needed, at a later point of time. And a nasty contract dipute with AZ after the media and, at least IMHO, politians singled out AZ as a scape goat.

Marburg started production a few days ago: Brand new factory just came online: https://investors.biontech.de/news-releases/news-release-det...

This process started in September already. It was founded partly with EU and German money, and will be producing vaccines for the world.

It's important to keep in mind that COVID is a danger for the entire planet at least until every nation on the planet is vaccinated.

As long as this virus can spread in unvaccinated populations, mutations are bound to happen and sooner or later they will be knockout mutations, circumventing current vaccine effects.

So no one on this planet is truly safe from future lockdown/pandemic status until we are all vaccinated. And even that is debatable.

Short answer: apparently, yes. The process is too unique and new to just be replicated in other factories.

Derek Lowe has an in-depth and readable explanation:

https://blogs.sciencemag.org/pipeline/archives/2021/02/02/my...

Came here to share this exact link. In The Pipeline has been a uniformly excellent source of information on vaccines and therapeutics development throughout the pandemic and is absolutely worth a look for curious laymen. As all of us are, under the circumstances.

Exactly! Also one more thing to keep in mind - the sooner we can help end the pandemic the sooner will Derek have time to write about other stuff, like crazy unstable, explosive and toxic compounds! :)

He identified the microfluidic liquid nanoparticle assembly machines as the bottleneck but didn't specify why their manufacture can't be spread up. We should be purchasing the IP for hundreds of billions of dollars and open sourcing the technology, not leaving it up to the companies to slowly set up their facilities and build manufacturing partnerships.

It wouldn't even required to purchase or transfer the IP at all, the governments should just fund the setup of the necessary production capabilities and lease them to BioNTech/Pfizer and Moderna at basically zero costs.

Vaccine production is still far to low to vaccinated the whole world population any time soon and only then we can prevent the creation of new mutant strains.

Producing vaccines is difficult and it takes time to ramp up production. But the German government also failed miserably here. Probably they did not believe in the success of the mRNA technology in the first place. But once it became obvious that it is a success they also showed no interest in ramping up production and ramping it up fast. The German law would allow to take away the patent of BioNtech and allow anyone to help with the production. So they would have some leverage if BioNtach were the ones that would slow down the ramp up. They decided to not go this path and I am not sure why. I can understand when a company says, look we have limited resources and we do as much as we can. I cannot understand that when it comes to the government as it has basically unlimited resources when it comes down to money. This is a huge failure of the EU administration / German government. Ursula van der Leyen should step down. Angela Merkel will not run again anyway.

There was an article about that on HN 2 weeks ago:

https://news.ycombinator.com/item?id=26014616

Pfizer does most of the production of the vaccine, but in Europe a large part of the vaccines is also manufactured by their German partner BioNtech. BioNtech is setting up a new factory in Marburg Germany right now.

https://investors.biontech.de/news-releases/news-release-det...

From their press release: "Facility will become one of the largest mRNA manufacturing sites in Europe and the third site in the BioNTech manufacturing network in Germany expected to produce BNT162 for global supply Expected to be fully operational in the first half 2021 with an annual production capacity up to 750 million doses of potential COVID-19 vaccine"

They already started production.

https://investors.biontech.de/news-releases/news-release-det...

It should be noted that BioNTech developed the vaccine and partnered with Pfizer for testing and worldwide production/distribution.

Producing medical products is all about managing risk. Whatever you do there's got to be a comprehensive risk assessment of every possible outcome of that action

If a company were to outsource the risk assessment and documentation effort would be huge and potentially open them up for a lot of legal liability if their third party manufacturer causes harm to a patient

For many manufacturers, it's much easier to use your documented in-house manufacturing, supply chain, training, machinery, etc. that you have risk documented up to the eyeballs so that if the product does cause harm, you have enough paperwork to show that you've done your due diligence

If you bring in a third party, it's incredibly difficult to prove that every aspect of their company meets the standards to which you're happy to hold yourself legally responsible.

Remember that even if you have a thousand factories, one will be first. Meaning that there will be a time when there appears to be just one.

That's why it feels like that right now. There are many factories around the world gearing up to mass-produce various vaccines. Some will inevitably take a few more months than others to start shipments. Others were being prepared to produce vaccine candidates that ended up failing and are now being re-engineered to produce the vaccines that turned out to work. And the factories that are already producing are constantly working to expand their throughput as well.

Right now the world is being supplied entirely by the first factories. Over the next few months that will change and the total rate of production will be much higher than it is right now.

French competitor Sanofi is about to produce the vaccine, too.

https://www.reuters.com/article/health-coronavirus-vaccines-...

Biontech is ramping production at a new site, Marburg in germany I think (too lazy to Google right now). Sanofi will start manufacturing in summer as their own mRNA vaccine is delayed.

As all ramp ups, I don't care that much about initial speed, but rather about how fast the goal, in our case a vaccination rate of 60+%, is reached. Justhaving doses produced isn't any good when these doses aren't getting into peoples arms.

All your points should be addressed in this (IMHO excellent) blog post:

https://blogs.sciencemag.org/pipeline/archives/2021/02/02/my...

In short - mRNA vaccines are cutting edge & require the most high tech machines and processes in some of their stages, which create the bottleneck. As for partnering/licensing - that's preatty much a thing & has been for a while, still there is quite some time to get a new production line working in a safe and predictable manner.

BTW, there is also a companion article about the bottlenecks for adenovirus based vaccines (Astra Zeneca and others), which have a different set of bottlenecks:

https://blogs.sciencemag.org/pipeline/archives/2021/02/08/ho...

Derek Lowe has a nice short article explaining how the mRNA vaccines require very specialized manufacturing processes that are a bit of a bottleneck.

https://blogs.sciencemag.org/pipeline/archives/2021/02/02/my...

Lowe ascribes the speed of vaccine development to mRNA vaccine technology. Given that adenovirus vector and inactivated virus vaccines were also developed within a year, this seems to me to be simply incorrect:

> mRNA as a vaccine technology has been worked on for some twenty to twenty-five years now, from what I can see, and (as I never tire of mentioning) we’re very fortunate that it had worked out (and quite recently) several of its outstanding problems just before this pandemic hit. Five years ago we simply could not have gone from sequence to vaccine inside of a year. And I mean that “we” to mean both “we the biopharma industry” and “we the human race”.

By far, the longest step in development was running the trials, not actual development of the candidate vaccine itself.

first of all, while Pfizer might just be producing at their factory in Belgium, that vaccine is produced in multiple factories in Germany by Biontech, most notably in Marburg (which is going to become Biontech's largest production site)

And secondly, 'just' producing the vaccine isn't the only bottleneck. Currently the biggest bottleneck seem to be two molecules that are produced earlier on in the production-process, and they're scarce.

So adding more production capacity upstream doesn't help if production capacity in factories downstream aren't scaled as well.

Good point with upstream availability issues. I never really looked those up, simply because I have zero idea how vaccine manufacturing works. Until now, I only focused on the downstream side, everything after manufacturing. And I don't like what I see on that end, especially in Germany.

It is almost like the world at are is getting a crash course in supply chain management. One could have asked experts on that before, sure, but why bother when local politians need credits for their election campaigns, right?

AFAIK they just started production in another factory in Marburg.

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