COVID-19 vaccines are miracles of science and supply chains

A single dose of Pfizer-BioNTech's COVID-19 vaccine is barely enough to cover the average pinky nail but is made up of more than 280 components and requires at least three manufacturing plants to produce.

By the time that dose is injected, it has travelled to at least six different cities in four countries, across the Atlantic Ocean twice, and monitored by a 24-hour watchtower in Iceland every step of the way.

A marvel of both science and supply-chain heroics takes the vaccine from the factory floor to the arms of grateful patients all over the world.

"It's really very complex," said Germain Morin, Pfizer's vice-president in charge of global supply chains for the company's rare-disease medications and vaccines.

The messenger ribonucleic acid (mRNA) vaccines being made by Pfizer and its German partner BioNTech, as well as Moderna, are a novel technology that before COVID-19 had never been approved for widespread use in humans.

While DNA is the large and complex molecule that stores all of genetic coding that makes us who we are, RNA carries individual pieces of that code out into the body with the instructions on how to carry out the body's work.

In the case of mRNA vaccines, they are carrying the genetic code for part of the SARS-CoV-2 virus, which teaches our bodies to mount a defence against the virus.

A year ago, the materials for these vaccines were being made for research purposes only, enough for maybe a few hundred doses at a time. Now Pfizer expects to pump out two billion doses by the end of this year.

It has made scaling up the manufacturing process a herculean feat, said Morin. There are 25 different suppliers involved, spanning 19 different countries. Some of them, said Morin, were making milligrams of liquid at the start. Then they were asked to make kilograms of it, and finally hundreds of kilograms.

The 475,000 doses Canada received last week began their lives before Christmas. Morin said it used to take four months to make a single dose of the vaccine, which is officially called BNT162b2. Morin said the process has recently been streamlined to half that time.

Every dose of the Pfizer-BioNTech vaccine is born in a Pfizer lab in Chesterfield, Mo., a suburb of St. Louis. That's where small DNA molecules called plasmids are made with the beginnings of the code for the SARS-CoV-2 spike protein.

It takes about two weeks, followed by a quality assurance process. Every step of production has quality checks and rechecks, from the bags and boxes used to store and transport the vaccine components to the temperature in the lab and the protective clothing worn by any workers.

Then comes the first major chill, as the plasmids are put in bags and frozen to that famous ultralow temperature Pfizer's product needs: -80C.

From Missouri, the plasmids are shipped to two labs, one a Pfizer facility in Andover, Mass., and another a BioNTech facility in Germany, where they are used to make the mRNA.

A single batch of mRNA takes about four days to make, in a high-tech process with numerous enzymes and chemicals. The mRNA is then frozen again and shipped off for finishing.

In the U.S. that happens in Kalamazoo, Mich., and for Canada's doses, currently made in Europe, they go to Puurs, Belgium, Pfizer's biggest plant in the world.

Messenger RNA is not a very stable product and will disintegrate quickly if not protected, so every bit of mRNA is encased in a tiny amount of fat called a lipid nanoparticle.

"Imagine a very, very small egg, so a very small eggshell of lipids that would protect the mRNA," said Morin. "This is part of the magic of making this vaccine as well."

Over the course of three or four more days the mRNA gets its lipid coating, and is filled into vials containing enough vaccine for six doses. The vials are then packed into boxes, and immediately put into "those famous freezers" which turn the lipid-coated mRNA molecules into mini blocks of ultracold ice.

"This was, by the way, one of the challenges," said Morin. "You can imagine that those freezers are not very common in the world. Laboratories buying them would typically buy them one or two at a time. We went to the suppliers and the first time we've asked for 650 of them in one shot, and then we went for more after that."

The vials stay in those freezers for two to three weeks, while every lot is tested with more than 40 different quality-control measures.

Then come the thermal shipping boxes Pfizer and BioNTech developed for this vaccine. Each vial is packed into a tray about the size of a pizza box with 195 vials total. Five trays are packaged together into the special box, which is filled with dry ice, and sealed.

Every box contains a tracking unit to know its location and internal temperature at all times. A control site in Iceland monitors the boxes, which are all uniquely labelled. If any box records a problem between Belgium and the delivery site, it will be investigated and most likely discarded.

Morin said at first there were many concerns about the complexity of the freezer requirements but the supply chain has been so successful that only one per cent of the product around the world has been lost because of temperature concerns.

Pfizer contracted with UPS to deliver the boxes. Those are picked up by UPS in Belgium, and sent through Germany and Kentucky on their way to Canada.

UPS delivers the batches to dozens of delivery sites in each province, where provincial health officials take over possession and prepare to inject them into arms.

Moderna hasn't released as many details about its manufacturing process, but has said the vaccine is largely produced for Canada in Switzerland, sent to Spain to be mixed with a diluent and filled into vials, and then shipped to a warehouse in Belgium.

Canada has hired FedEx and Innomar Strategies to manage the shipping and distribution of Moderna's and all other vaccines except Pfizer-BioNTech's.

Guy Payette, the president of Innomar, said they too use specially designed boxes. Moderna's vaccine doesn't have to be frozen as deeply but does have to be kept at about -20C.

The other vaccines Canada is likely to get will mostly need to be kept at about 6 C.

Payette said each box is also labelled and tracked with a GPS and thermal sensor. The shipments arrive at Innomar's warehouse, where workers repackage them to match the quantities being sent to each province.

He said except for one spot in northern British Columbia, the trackers have worked beautifully. Where they did not, due to the altitude, boxes are equipped with a second device with data that can be downloaded later.

He said so far, the temperature has been fine and all products delivered successfully.

Those involved in the vaccine process have expressed awe at the speed with which everything turned around. Moderna's vaccine was in clinical trials less than two months after the SARS-CoV-2 virus was fully sequenced.

Pfizer and BioNTech signed a partnership agreement in March 2020, and 266 days later the vaccine was approved in the United Kingdom. More than 50 countries have since followed suit and more than 100 million doses of Pfizer-BioNTech's vaccine have now been distributed.

It's a pace of development the company has never seen in its 173-year history.

"Oh, no, no, no, no, no, no, not even close," said Morin.

He said most products take three to five years to get this far.

"We're very proud," he said. "Every new market that we launch is a celebration."

He said when the first Canadian was vaccinated on Dec. 14, "I had goosebumps."

This report by The Canadian Press was first published Feb. 27, 2021.