from Hacker News

Exploring the Supply Chain of the Pfizer/BioNTech and Moderna Covid-19 Vaccines

by palcu on 1/19/21, 7:46 PM with 56 comments

• by kart23 on 1/19/21, 9:23 PM

  Like many others, I find the LNPs to be the most interesting part. It seems like Moderna was having issues with accumulation and toxicity issues, but changed something to make it safely degrade in the body. [0] Heres an interesting paper that shows some of the challenges. [1] 99% of it went over my head, but I still find the research intriguing.

  [0] https://www.sciencemag.org/news/2017/12/can-multibillion-dol...

  [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7329694/

• by at_a_remove on 1/19/21, 11:38 PM

  Here's something I can only speculate on with the cold chain.

  I have mentioned it elsewhere on HN, but I've handle dry ice and liquid nitrogen quite a bit, first in college and then just later for fun. Several years back, I noticed a very large price hike in dry ice, as well as a drop in availability (less available in my city, vanishing from small towns). I was told by someone in my supply chain that federal regulations around dry ice had changed, resulting in only a few players being left in the game and of course the price going up.

  I wonder if now, a decade or so later, the law of unindented consequences has reared its often invisible head.

• by hef19898 on 1/19/21, 9:22 PM

  This is one of the best supply chain articles I ever read. Cudos!

  As the article is mainly describing the supply chain, I'd like to add some of the challenges, especially downstream / last mile. The Biontech vaccine seems to be a royal pain to distribute. Cold chains are tricky to maintain, let alone at -70 C. Having doses packed in numbers larger than one makes it challenging to vaccinate people at the centers, the unfreezing takes some time, and the vaccine cannot be stored eternally once unfrozen. So you have to closely schedule appointments with the treatment of the vaccine itself for batches of people. Which cannot be allowed to wait in line because of COVID-19. It also means that existing infrastructure, doctors and care and nursing services, cannot be used to get the Biontech vaccine to the people. Yet another pain.

  At yet, we are only discussing the purchased doses. Not even the delivery schedules, just the total quantity. As if that was the real bottle neck right now.

• by cheese_van on 1/20/21, 3:56 AM

  The research cooperation by the scientific community seems unprecedented. The Bomb had terrific focus as did the Apollo program. But those were proprietary for the most part, not a world-wide effort. This seems new.

  It would be grand if this spirit continues and provides a model for the other sciences. I would like to think this is a potential silver lining that could have wonderful consequences.

• by MichaelRazum on 1/19/21, 9:08 PM

  Wow amazing article. Thanks a lot. Interesting to see that most of the technology comes from Europe and US. Also interesting to see that it is complete independent from Asia.

• by satya71 on 1/19/21, 8:00 PM

  I have been trying to find out why the supply of mRNA is limited. This article gives me hope that it can be scaled up with the right focus. As long as there is no fundamental science to be discovered, industrial processes can be scaled with enough money.

  It is not possible to grow chicken eggs faster. So it's been impossible to have anything less than a years lead time to get flu vaccines made in sufficient quantities.

  Planet money even did a show on the emergency chickens [1] (have they been called into service already ?). So we have the chickens, but no COVID vaccine that can be grown in eggs.

  [1] https://www.npr.org/2020/03/13/815307821/planet-money-why-th...

• by wegs on 1/19/21, 11:55 PM

  > Next to it is a picture of a CodexDNA BioXP device that is advertised as producing “custom DNA fragments of up to 7,000 base pairs”. Could this be the next distributed manufacturing revolution? This time with DNA printers making COVID-19 vaccines in our garages instead of 3D printers and plastic widgets?

  > I’ll start with the bad news: Nobody will be making an mRNA vaccine in their garage any time soon.

  ... We're not there in time for COVID19, but technologically, I think we're less far away than this article presumes. Cost of both sequencing and synthesis has been dropping like a rock, albeit not very smoothly. I can get DNA synthesized for less than what I was paying for amateur PCBs as an undergrad.

  A lot of the other complexity, I suspect, is specific to getting this out in <1 year. It's worth remembering the earliest vaccines took no technology beyond what I have in my garage. With a little more time and patience, I'm sure some of the other complexity will go down. We can't spare time and patience when we're bleeding billions of dollars from our economy and thousands of lives each day, but....

• by GuB-42 on 1/19/21, 11:57 PM

  The most mind boggling fact for me is that glass vials are a bottleneck.

  We have all these high tech stuff, $50k a gram chemicals, custom built machines, DNA printers and nano-scale technologies producing a substance where every atom is at the right place.

  And all that is produced at a scale where we are limited by glass vials. That's literally ancient technology, and commodity stuff. Ok, it is a bit fancier than what the Romans had, but these are still just glass bottles.

  The glass vial part is expected, things get complicated when multiplied by a billion, but it gives a sense of how much vaccine is being produced and how fast it is done.

• by linuxftw on 1/19/21, 8:29 PM

  Interesting bits about the 'bottleneck' being the lipid envelope. This sounds highly proprietary and very, very new (eg, not widely tested). How can these products be QA'd by an independent lab to be free from significant defects?

  Are the doses being distributed produced on the same line with the same procedure as the doses in the trials?

• by bawolff on 1/19/21, 8:07 PM

  "The Moderna vaccine is also known as “mRNA-1273”, but appears to lack a brand name other than “Moderna COVID-19 vaccine” which is what it says on the product label"

  Anyone else find that really refreshing?

• by vimy on 1/20/21, 1:26 AM

  I remember at the start of the pandemic Bill Gates was funding mass production of, I'm not sure but I believe 8, several vaccines before trials were completed. The idea was that there wouldn't be a delay between testing and having enough doses for everyone. He said some of the vaccines would fail their trials and the money would be wasted but he said it was worth it to kickstart production.

  I wonder if it made a difference? Does anyone know more how his plan turned out?

• by rediguanayum on 1/19/21, 8:59 PM

  Fantastic write up on the supply chain which is the overlooked challenge to these vaccines. I'll need to reread it (and again). Also good are the "In the pipeline" blog posts by Derek Lowe in Sciencemag about vaccine development: https://blogs.sciencemag.org/pipeline/

• by 8thcross on 1/20/21, 3:34 PM

  most interesting post in a while.

• by dirtyid on 1/20/21, 9:59 AM

  Question, which vaccine to choose given option.

  Moderna has 100mg per dose and standard freezer storage

  Pfizer has 30mg per dose and extreme cold chain storage.

  Seems like there's more potential for Pfizer to spoil along logistics chain.