[This is a continuing series beginning with #1 and #2].

There is yet a third vaccine coming on the market, let’s call it PFZ. It uses technology similar to MDN, injecting messengerRNA into the body, with instructions for building a part of the COVID19 virus necessary for the virus to function, but which by itself is not dangerous. The supply chain will be similar to MDN’s, with a major difference. PFZ must use a subset of cold chain logistics called super-cold chain, among other things. PFZ must be stored at -70C, or -94 Fahrenheit. This is close to the coldest surface temperature ever recorded on earth, -89.2 Celsius (-128.6 Fahrenheit), in Antarctica in 1983.

Manufacturing PFZ is done in a super-cold environment. The amount of energy needed to cool an entire manufacturing plant to -70 Celsius is significant, and the equipment isn’t easily maintained by a shade-tree mechanic. A lot of automation will be required, because humans don’t do well at those temperatures. Putting humans in heated suits runs the danger of heating the entire plant. Automated machinery will load vaccines into vials and vials into cold-storage sealed boxes. If dry ice is used, there are often two or three layers of boxes surrounding the 200 or 1,000 vials.

The packages are transported via truck or train to an airport/seaport for forwarding. Here is where the functions of manufacturing, distribution and retail probably deserve some information. Manufacturing produces products in quantity. It rarely sells single products to individual consumers, because it isn’t equipped to do so. It has no displays, no cash registers, no way to keep retail customers out of manufacturing areas once allowed inside the facility, it has no large call center to take orders, it cannot process credit card purchases – all of those are handled by retail organizations, which do them well. Manufacturers who sell directly to the public usually find that they’re competing with their own best customers, distributors.

The purpose of distribution is to deliver and buffer manufactured goods to retailers. Manufacturers produce in quantity, and distributors break down the quantity into bite-size chunks, store it, and send it to retailers when they need it. A retailer, such as a pharmacy or doctor’s office, has no use for a box of 1,000 vials of a vaccine, or 5,000 doses, because the retailer cannot serve that many customers for an injection in one day, especially of a vaccine that can’t be warmed, cooled, warmed. They rely on distributors to handle storage, breakdown and delivery.

With PFZ, retailers need to order exactly the number of doses needed for one day, and keep the boxed vials in refrigerated storage fortified by dry ice. Super-cold storage is expensive and rare. It is found in large hospitals for use with some laboratory specimens and some pathologists’ testing; it is also found in limited quantity in research institutions. Huge distributors, pharmacy chains and hospital groups are building new super-cold storage capability and have been for months.

I don’t pretend to know how the problem of sparsely-populated rural areas will be covered. The problem is called “The Traveling Salesman” by mathematicians and is different in every case. This has addressed PFZ in the First World, where a lot of cracks can be papered over with money and reallocation of resources. Cracks in Second- and Third-World countries are broader, deeper and more difficult to resolve. With enormous resolve and herculean effort, India can meet much of its need for MDN; it lacks the super-cold storage needed for PFZ.

The best-case scenario is for a future ATZ vaccine. Another, let’s call it MDN, cannot warm above -20 Celsius (-4 Fahrenheit) between manufacturing plant and the syringe. This is usable in almost every part of every First World country, because most refrigerators’ freezers can handle that. So, we can transport it in cold storage, in a refrigerated truck or refrigerated shipping container from the manufacturing plant to the seaport or airport. The refrigeration unit requires power while on its way to the ship or plane, and continuous power on the vessel. None of this can be ordered from Amazon or Ebay.

Speed is important, as is security, as is continuous temperature regulation for MDN. Most pharmaceuticals are shipped via passenger airline flights, but their schedules are severely disrupted. Certainty will require cargo flights or ocean containers for intercontinental shipments. The old stand-by, dry ice, has limited use on aircraft because it is solid carbon dioxide. The solid sublimates directly to gas, which is dangerous to the crew. Individual insulated boxes will require continuous monitoring for temperature and leaks.

MDN is delicate, as it is principally RNA, which falls apart under little provocation. It also is an artificial thing that doesn’t self-replicate. It’s a set of instructions for the body to create a defense against some weakness in the virus, such as a protein spike. That’s a two-step process, because the instruction actually causes the body to create just the protein spike, necessary for the virus to enter a cell, but harmless without the rest of the virus attached. Step two is the body’s immune system recognizing the protein spike as a potential threat and creating specialized cells to block or destroy the spike.

In manufacturing MDN, it can’t be allowed to rise above -20C. The manufacturing has to be done under freezing conditions. The delicate RNA can’t be treated roughly or it falls apart. Think of threading a needle while doing jumping jacks, standing on a hammock in a snowstorm. We know how to do this, and will do it well. The vials have to be filled while still doing jumping jacks and packed into cases of 200 or 1,000 vials. The cases then cannot be opened to the atmosphere for more than one minute at a time, likely once a day.

As soon as the cases leave the manufacturing plant in a refrigerated truck or container, they are at the mercy of strong forces, such as curious export inspectors who just want to take a peek. Or thieves thinking they can steal vaccines that will still be worth something. Or traffic accidents, or malfunctioning cranes, or longshoremen on strike, and the possibilities are limited only by imagination.

[More . . . ]

"The Long Pole in the Tent" is a common term used by the US Army to describe the most difficult, or time-consuming, or resource-intensive task in getting a job from start to finish. Often, it is all three. We are in the midst of a nearly year-long effort to develop a vaccine that will fix the pandemic. Victory is in sight.

Not so fast. Vaccines don’t save lives. Vaccinations save lives. For that to occur, far more is needed than developing the molecules for a messenger RNA (mRNA) virus, or manipulating a cold virus (adenovirus) to carry elements of another cold virus (COVID19) that will prompt the human immune system to develop the necessary tools to kill the latter virus. That work is critical, and can only be done by highly-educated and disciplined scientists familiar with how to work at the molecular level with biology, how to develop and choose among candidate vaccines, how to establish testing methods and protocols, and thirty thousand other things few people on earth are qualified to do. We owe them a debt of gratitude.

Their work is in vain, though, until a vaccine becomes a vaccination, which is a vaccine that is injected into a patient. This brings us to the long pole in the tent: getting a manufactured vaccine safely and securely into the syringe to be injected into the patient.

The next step is manufacturing the vaccines. Why we need more than one is a story guaranteed to cure insomnia. Each vaccine uses a separate mechanism to interfere in the virus’s nefarious activities. None is “the best” for everyone, and some carry risks for certain groups but not risks for others. Why that is so will cure insomnia relapse.

Vaccine manufacturing isn’t like home-cooked meth. Very strict procedures, highly technical machinery, well-trained workers and pure ingredients are needed. Each batch must undergo quality assurance. When the vaccine is finished, it must be carefully measured into individual vials, usually of five doses each. Vials go into cartons of either 200 or 1,000 vials. Three vaccines are on the verge of being approved for manufacturing.

Each of these three vaccines each operates a bit differently, and each follows a different track in the supply chain. Obviously, all are tamper-evident sealed, bar-coded, receipted all the way through. Only one of them can remain effective at room temperature, let’s call that one ATZ. Ideally, everybody takes ATZ. Except it carries different risks for different people than the other two. And, ATZ, will have to re-enter Stage III trials to correct a testing error, so it won’t be ready immediately.

When it is ready, it’s easily handled with existing secure processes. On arrival at port it is offloaded, undergoes customs inspection and payment of any import fees, turned over to the consignee who is probably a Third-Party Logistics (3PL) provider. Because the vaccine does not require refrigeration, the contents are broken down in a warehouse for separate shipments to hospitals, pharmacy chains, group practices, distribution centers and government stockpiles. This will work well in First World Counties, even in landlocked countries such as Switzerland, Andorra, San Marino, the Vatican, and small nations such as Singapore, New Zealand, Iceland and Monaco.

The Third World is not so lucky. Much of the world is tribal, and vaccines entering a tribal country are likely to be kept by the ruling tribe to keep subjugated tribes in line. Keloptocracies and mob-ruled countries will make equitable distribution problematic. Lack of reliable roadways or railways will delay deliveries and lose some vials. Stops at international and intranational borders offer opportunity for mischief. And, keeping track of where things are is difficult enough in First World countries; in Third-World countries, the basics are still aspirational.

Even first-world countries such as Bahamas face a daunting task reaching individual islands. Small countries, such as Palau or Samoa, will never be a priority for scheduled air travel nor ocean cargo. Then, there are dozens of areas of active conflict, ranging from Donbass in Ukraine to war of starvation in Yemen. And India still struggles with the basics.

All of this is for the best case. The other two vaccines present much greater logistical challenges and will be dealt with in Chapters Two and Three. Where we are will then be addressed in Chapter Four.