Even though Mr. Market is over the moon about the prospects for a not-yet-approved-by-anyone Pfizer Covid vaccine, Naked Capitalism readers quickly pounced on the question of whether or not the unprecedented mass distribution of a vaccine that needs to be kept at roughly -100F for no more than five days before use might be a problem. As vlade underscored by e-mail, “I don’t think that anyone was expecting having to distribute literally billions of items that have to be held at -80C or less until earlier this year.”
The mainstream media has caught up with reader concerns. As we’ll discuss, building new super-cold distribution is so costly and daunting that developing economies are likely to turn down the Pfizer vaccine. And not only are rural areas expected to get the short shrift, but even US states are having trouble developing credible distribution plans, which suggests that even some cities may encounter delays in getting their hands on the vaccine (assuming it is approved quickly).
Keep in mind that the same distribution issues apply to another promising-looking vaccine, from Moderna, which is another messenger-RNA-based vaccine and also must be kept at very cold temperatures before use, although not as severely cold as the Pfizer candidate.
And yes, sports fans, no such cold-chain storage system exists now, anywhere in the world. Keep in mind that the problem isn’t just keeping the vaccine vials super cold till they get to where they will be used. They also need to be kept in a super-frigid state at close to their point of delivery, or delivered on a just-in-time basis.
ProPublica gives a good overview of the delivery and storage issue:
The Pfizer vaccine is unusually difficult to ship and store: It is administered in two doses given 28 days apart, has to be stored at temperatures of about minus 100 degrees Fahrenheit and will be delivered in dry ice-packed boxes holding 1,000 to 5,000 doses. These cartons can stay cold enough to keep the doses viable for up to 10 days, according to details provided by the company. The ice can be replenished up to three times. Once opened, the packages can keep the vaccine for five days but can’t be opened more than twice a day. The vaccine can also survive in a refrigerator for five days but can’t be refrozen if unused.
Note that this description focuses only on the requirements. Below is a graphic in the Wall Street Journal as to how Pfizer plans to pack its vaccine. Clive saw a presentation and just sent this e-mail:
BBC ran this last night (think Pfizer went on a PR offensive over it) https://www.bbc.co.uk/news/technology-54889084
Two things struck me: one is insulated boxes are only currently available certified for storage down to -8C (so not suitable for low temperature medicines which need around -18C, but probably a good option for medium temperature cold storage). The Bloomberg (and the WSJ article which lead coverage) referred to Pfizer’s solution being capable of maintaining -70C (so they’ve already been bartering themselves down from previous statements saying the vaccine needed -80C — I’m always on alert when what should be absolute technical details start getting fuzzied). They mention dry ice as a source of thermal absorption, which without built-in mechanical cooling on the storage box can’t reach down to -80C. Nor do Pfizer mention any testing or product certification having been carried out. The timeframe for maintaining box temperate was also vague — it will have to have, by the laws of thermodynamics, different performance curves in high ambient air temperature regions for instance and it wasn’t spelt out if the quoted temperature maintainability time was relying on being in placed either a medium or low temperature refrigerated environment.
The other thing Pfizer ‘fessed up to was the phials were only capable of withstanding 4 exposures to ambient air without compromising stability. A logical guess is that embrittlement of the pharmaceutical-grade seals on the phials caused by any repeated thermal stress eventually means there’s soo much risk of allowing any more. So, four strikes and you’re out. You can envisage one exposure to ambient air as the vaccine leaves the the vaccine finishing plant and gets packed for initial transportation to the bulk storage facility. Another exposure will occur when they’re unpacked and placed into bulk storage. Then another exposure when they’re lifted out of bulk storage and repacked for local distribution. There’s one “life” left after all that — unpacking and thawing prior to dispensing. So zero room for any errors or unintended ambient air exposure.
For a Big Pharma player who must know there’s going to be a lot of scrutiny about quality control and vaccine safety, I don’t get why they think vague musings to tame press outlets and “tah-dah!” hero techie fixes like the storage box are going to cut it.
As Clive and vlade discussed by e-mail, there’s a big “last mile” or perhaps more accurately, “last stop” problem. What happens if many vaccine injection sites can’t be put on “just in time” deliveries? Then the vaccine would need to be stored locally at super cold temps until it’s time for it to be thawed and used. Vlade and Clive discussed the requirements. First from vlade:
The low temperature sites _are_ in fact farms of big boxes like these https://cryometrix.com/product-t160 . This is specifically meant to hold 2ml vials like medical samples or vaccine doses. They are not really that hard to have, a neighbor of mine is in the cryo/liquid gas business and embryo/stem cells long term storage is one of the areas he does.
A walk-in vault ala meatpackers is just not viable at -60C.
Yes, all commercially-available ultra-low temperature boxes are reach-ins. I’ve never come across an ultra low temperature walk-in, nothing above a small cupboard size, anyway (i.e. just a slightly bigger reach-in with a separately-installed second-stage split evaporator). So it makes sense to get enough of these reach-ins together and network them to act as a static bulk-storage facility. They’re sill a niche product though, and while you can probably source them in the hundreds, if not from stock, then with fairly short-ish manufacturing lead times, trying to get hold of thousands (which would be needed for continental-scale operations) isn’t going to be easy. Even if manufacturing / production capacity was available, it’ll be the sub-components — especially compressors, lubricants and refrigerants — where the bottle necks will be.
And they (reach-ins) will be under more supply pressure because in addition to bulk storage applications, they’ll also be needed for district and local storage (county and city hospitals, local health centres and so on).
Bloomberg gives a higher-level picture of why many developing countries are set to give the Pfizer vaccine a pass:
When Pfizer Inc. and BioNTech SE’s Covid-19 vaccine rolls off production lines, Shanghai Fosun Pharmaceutical Group Co. will be waiting to distribute it through a complex and costly system of deep-freeze airport warehouses, refrigerated vehicles and inoculation points across China…
….ountries will need to build from scratch the deep-freeze production, storage and transportation networks needed for the vaccine to survive. The massive investment and coordination required all but ensures that only rich nations are guaranteed access — and even then perhaps only their urban populations.
“Its production is costly, its component is unstable, it also requires cold-chain transportation and has a short shelf life,” said Ding Sheng, director of the Beijing-based Global Health Drug Discovery Institute, which has received funding from the Bill & Melinda Gates Foundation…
“If there is a protein-based vaccine that could achieve the same effect as an mRNA vaccine does and there’s the need to vaccinate billions of people every year, I’d go for the protein-based shots in the long run,” Ding said….
“The requirement for extremely cold temperatures is likely to cause spoilage of a lot of vaccine,” said Michael Kinch, a vaccine specialist at Washington University in St. Louis.
The article discusses how India is just about certain not to deploy the Pfizer Covid vaccine. It barely has the capacity to handle measles vaccinations, which target a smaller population (literally and figuratively), children aged 3 or below, and required cold but not super cold storage. Another impediment is the need for mass training of technicians to make the injections.
Given that the Pfizer vaccine requires two shots, a month apart, how often will patients wind up getting one or more jabs with vaccine that’s gone bad, and think they have Covid protection when they don’t? And in rural areas, where people often have to travel to an injection center, they often skip the second shot.
Back to the US. The Wall Street Journal says Pfizer will handle its own distribution, while in the US, McKesson will manage the distribution of other vaccines.
However, the ProPublica story, on state plans, demonstrates that “distribute” may not mean “deliver to hospitals and big clinics” but appears to mean “deliver to state public health officials who decide what to do next”. In reality, I have to think that major health providers like hospital systems would deal directly with Pfizer, but even so, there looks to be tremendous variations at the state level as to what the drill will be. ProPublica focuses on the problem of getting the vaccine to rural areas, but its survey of state plans raised additional questions.From ProPublica:
As the first coronavirus vaccine takes a major stride toward approval, state governments’ distribution plans show many are not ready to deliver the shots….
Across the country, authorities are grappling with how to accommodate the Pfizer vaccine’s finicky specifications. So far, state plans show few have come up with clear solutions. Oregon, for instance, said it still needs to “develop [a] plan” for how to handle 1,000-dose orders in “remote Oregon locations, while maintaining the ultracold chain and avoiding wastage.”
Perna, the general leading logistics for Operation Warp Speed, told NPR that it’s up to states to buy more freezers. That contradicts the CDC’s instruction to not invest in more equipment. But many states said they’re doing so anyway, or at least looking into it. They’re also taking stock of what facilities already exist in their states at hospitals and universities, or where they can get dry ice.
North Dakota, where the virus has killed roughly 1 out of every 1,200 people, is considering whether to break down the 1,000-dose packages and, on its own, distribute smaller quantities to individual hospitals and clinics….
As Texas and other states consider the need to break down the 1,000-dose packages into smaller shipments, that’s an additional cost that they’d have to shoulder, since the federal government will only pay to move the vaccines once. Several states identified funding as a major problem.
Virginia’s plan included a “preparedness gap analysis” that estimates that it will need $71 million to establish and operate mass vaccination clinics, which would include hiring temporary staff and covering facility rental costs, translation services, signage and other operating costs.
The plan also calls for a further $2.5 million in equipment such as refrigerators and thermometers and $3 million for public education, including TV, radio and social media ads, as well as “targeted outreach to clinicians, vulnerable populations and other key groups.”
On the other end of the spectrum, Kansas simply assumes Pfizer will indulge them by shipping minimum dose sizes of 100 per order. The story also points out that expecting rural doctors and nurses to travel to get shots is costly, supporting the Kansas view that the Pfizer minimum size is way too high:
Even in the case where prioritized health care workers were physically capable of driving themselves to the city to get a vaccine, relying on doctors and nurses to get themselves to a vaccine “doesn’t compute,” said Tim Size, executive director of the Rural Wisconsin Health Cooperative, which represents 43 rural acute hospitals. Wisconsin is battling its worst outbreak of the pandemic, and every hospital is stretched thin on staff, he said. Requiring everyone to take time off, twice, to get the Pfizer vaccine “means two days of lost staff time at a time we’re desperately short of staff.”
Despite the Pfizer happy talk about the possibility of starting to ship the vaccine by year end, that assumes everything breaks its way. But even on a fast track, the roll-out will be largely or entirely a Biden Administration task. We’ll see soon if it lives up to its campaign promise of competence. While the Trump Administration set a very low bar, elite symbol manipulators and complicated real world situations with hard physical constraints are not a happy mix.