Vaccinating the planet against COVID-19 is an unprecedented logistical challenge like never before. The closest thing would be to mobilize for a world war, but in this case the enemy is invisible and is everywhere.
Some vaccines need to be stored at very low temperatures at almost every point during their journey until they are inoculated into the person’s upper arm. And vaccines are being produced primarily in rich countries, even though the greatest needs (and especially now) are in poor ones.
While some rich countries have managed to vaccinate most of their citizens, just under half of the world’s population is still waiting for the first dose.
I have studied global supply chains for more than two decades, including those for drugs and other medical devices. To illustrate this process and show how complex and challenging it is, I will replicate the journey of a dose of Pfizer (which received full approval from the US Food and Drug Administration on August 23, 2021) from the Missouri factory where the arm of the person being inoculated is produced in Bangladesh.
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Although it is commonly referred to as the Pfizer vaccine, it was actually developed in association with BioNTech, a company based in Germany.
It is one of the two vaccines that have used the new messenger RNA technology, which provides genetic instructions that encode a certain viral protein. Once the vaccinated person’s cells begin to produce the virus protein, their immune system begins to massively generate powerful antibodies that can neutralize the virus should they ever have to deal with it.
The 60-day journey of dispensing a dose of the vaccine originates from raw materials at a Pfizer factory in Chesterfield, Missouri, near St. Louis. In this factory an essential raw material called plasmid is produced, which is basically made up of traces of DNA that have genetic instructions to build coronavirus proteins.
The bottles with the genetic material are frozen, packaged in sealed containers and placed in containers to be transported by boat to Andover, Massachusetts. There it is processed into messenger RNA, which is the active ingredient in the vaccine (also known as a “drug substance”).
The messenger RNA is then packaged in plastic bags (each containing enough material to produce ten million doses), frozen, and shipped to Kalamazoo, Michigan, where the vaccine is in the final phase of its elaboration: formulation and filling.
First, the drug substance is combined with lipid nanoparticles (which are basically fat) to protect the messenger RNA and facilitate its entry into human cells. This mixture is then filled into glass vials, six doses per vial, which are packaged and frozen for distribution.
I have just described the simplified process in just three steps. However, making a vaccine is much more complex, since it requires more than 200 different materials that have to be provided by factories scattered around the world.
Keeping vials at extremely low temperatures
While waiting to be distributed, Pfizer vaccine vials should be stored in deep freezers at temperatures ranging from minus 60-80 degrees.
To put it in perspective, the average annual temperature at the South Pole is around 50 degrees below zero, while ice cream and frozen steaks, during storage and transport, remain at about 29 degrees below zero.
Pfizer designed its own refrigerated boxes to facilitate the transportation of its vaccines across the United States and around the world. The vials are deposited in trays, 195 in each, and each box can hold five trays. Each box therefore contains 5,850 doses, and also has a GPS locator and a monitor that indicates the temperature.
Pfizer boxes do not require more specialized equipment to transport the vaccines, and to maintain the deep-frozen temperature in the boxes during transport, it is enough to use dry ice, which has to be replaced every five days.
The problem with dry ice is that it is carbon dioxide in solid form. The ice gradually turns into gas, which can be dangerous if there is not adequate ventilation.
Once the shipment is ready for shipment to a certain destination, Pfizer contacts one of the global freight companies with which it has a collaboration agreement, such as DHL or UPS, who collect a specified number of boxes and at one or two days takes them by sea directly to the indicated country.
The last mile of the road
In order for a country to receive vaccines from Pfizer, it must have the capacity to store medical supplies at extremely low temperatures.
And while this is not a problem in rich countries, it is in poor countries, where there is less infrastructure of this type.
When the cargo reaches the destination country it has to be kept at low temperatures, most of the time in an airport or in a storage infrastructure, until it is time to use it. Vaccines should be stored at deep-frozen temperatures for at least one month before being inoculated onto a person’s shoulder.
In poor countries with the necessary infrastructure, such as Bangladesh, distribution is still limited to a select few hospitals located in large urban areas where deep freezing facilities exist. For example, Bangladesh distributes the Pfizer vaccine to only seven hospitals in its capital, Dhaka.
The frozen journey of Pfizer’s vaccine is just one part of the process that ends when the person gets their shot. There are a number of secondary vaccination supplies that include special syringes capable of delivering 0.3 milliliter doses, needles, sterile alcohol patches, and personal protective equipment for the toilets administering the dose.
Preparing the Pfizer injection is a complex process. First, the nursing staff must liquefy the vaccines in a refrigerator at a temperature that ranges between two and eight degrees, where they can last up to 31 days. Just before vaccination, the vial should be brought to room temperature (that is, between two and 25 degrees), a temperature at which the vaccine can be stored for a maximum of six hours.
Since Pfizer’s vaccine is shipped as a concentrate, the nursing staff must dilute it in 1.8 millimeters of saline solution, from which they obtain a mixture that results in six doses.
The fact that single-use syringes that capture a fixed number of doses are used in many low- and middle-income countries is an additional complication. Under normal conditions this avoids errors. UNICEF is in charge of delivering additional medical equipment to poor countries; Countries that are getting their doses through COVAX, the global initiative created to distribute COVID-19 vaccines in low- and middle-income states.
An immense achievement
There are other vaccines that require a much less demanding cold chain, that do not need to be diluted and that accept syringes with standard dose sizes, which allows them to be used in more countries, and even in rural areas.
Most World Health Organization-approved vaccines, such as those from AstraZeneca or Johnson & Johnson, tolerate conventional low-temperature storage between two and eight degrees.
I have focused on Pfizer in large part because most of the doses donated by the United States to COVAX have been produced by this company.
As of December 6, 2021, 8 billion doses of COVID-19 vaccine had been administered worldwide, an unimaginable milestone in the fall of 2020. But global coverage is being hugely uneven. While in high-income countries much of the population has already been vaccinated, only 6.3% of the population in poor countries have received their doses. And most of these countries are in Africa.
The development of numerous vaccines (ten of which have already received the go-ahead from the WHO, many more than a year ago) has been a colossal achievement of both science and global collaboration, especially because on previous occasions actions thus they took half a decade.
But creating supply chains that make it possible to deliver these life-saving vaccines to people scattered around the world will be an equally colossal achievement.
Ravi Anupindi, Professor of Technology and Operations, University of Michigan
This article was originally published on The Conversation. Read the original.