Some of the most anticipated vaccines in decades, many COVID-19 vaccine candidates require special temperature handling, including at ultra-low temperatures (around -80°C or -112°F) in order to remain viable and effective. Previously approved vaccines have never required such low temperatures, but innovations in vaccine creation in recent years have resulted in research with these robust yet fragile vaccines which require this cold environment. International health groups have noted that as much as 50% of life-saving vaccines are wasted each year, due in part to failures in the cold chain, so proper care is critical.
Why Do COVID-19 Vaccines Require Ultra-Low Temperatures?
As many recent news stories have noted, the development of vaccines to prevent COVID-19 infections caused by the novel coronavirus SARS-CoV-2 has proceeded at an unprecedented pace. This rapid creation of vaccines is due, in large part, to new techniques in how these vaccines work.
A Brief Intro to Cells, Viruses, and the Immune System
Each cell in our bodies contains a nucleus filled with DNA or RNA (genetic instructions) coated in a layer of proteins which carry out the DNA or RNA's specific instructions. Messenger RNA (mRNA) ferries instructions from the DNA/RNA to the proteins, telling them what to do, performing most of our bodies' functions at a cellular level. mRNA messengers are broken down by enzymes after their tasks are complete. Viruses work in the same way, with mRNA carrying messages from the virus DNA to its proteins. Viruses attempt to invade our cells to force our own cells to replicate the virus cells instead. Cells in our immune systems are always alert for invader (antigen) cells, identified by their proteins. If we have antibodies for a particular virus, they recognize the specific protein structure of the antigen and reproduce rapidly to neutralize it, halting the infection.
Traditionally, vaccines have been developed using weakened, inactivated, or partial versions of the virus, bacteria, or toxins they are designed to protect against, and teaching our immune systems what antibodies to create if that antigen appears again. These are tried-and-true methods, but they require many years for vaccine creation and testing.
Messenger RNA (mRNA) Vaccines
Taking advantage of advances in genetics, mRNA vaccines have been in development for multiple diseases in recent decades. They work by giving our immune systems precise instructions using genetic details from the virus itself, resulting in a faster, stronger immune response. mRNA vaccines do not require live virus for creation, and can be produced much more quickly than traditional vaccines, requiring only the genetic code of the virus.
The Vaccine Cold Chain
Because each vaccine has a specific formulation, it will have a particular range of temperatures and lifespan for effective use. Most conventional vaccines are stored in refrigerated units with an optimal temperature of 5°C (40°F), though a few require freezing temperatures at -50°C to -15°C (-58°F to -5°F). The physical structure of mRNA vaccines in conjunction with modifications to make them more effective has the downside of also making them more delicate than traditional vaccines. This more fragile nature requires lower temperatures, ranging from -20°C (-4°F) to -70°C (-94°F), depending on the vaccine's specific formulation, to prevent mRNA's natural deterioration. Vaccines must be maintained constantly at these temperatures, neither too hot nor too cold, throughout their existence, from manufacturing through point-of-care. Decades of experience have resulted in effective cold chain techniques for storage and delivery of conventional vaccines, even in very remote areas.
Challenges to a Proper Vaccine Cold Chain
At the best of times, maintaining vaccines at their proper temperatures presents obstacles, and in fact, the cold chain can account for up to 80% of a vaccine's cost. Increased difficulty can result when there are additional challenges including:
Undersized, inappropriate, or poorly maintained equipment
Unreliable or inadequate electrical supply
For multi-dose vaccines, the need to properly store a greater number of individual doses
Challenges for the COVID-19 Vaccine Cold Chain
When vaccines, such as some COVID-19 mRNA candidates, require handling and storage that deviates more significantly from conventional vaccine storage, the picture becomes even more complicated. One of the primary challenges with some COVID-19 vaccine candidates is accommodating ultra-low temperature requirements. In particular:
The Pfizer/BioNTech COVID-19 vaccine candidate must be stored at -70°C (-94°F). It can last up to 6 months with consistent, proper storage at that ultra-low temperature. After thawing,it can be stored at standard vaccine refrigeration levels for up to 5 days before it begins to deteriorate.
The Moderna COVID-19 vaccine candidate must be stored at -20°C (-4F). With proper, consistent storage, it can remain effective for up to 6 months. After thawing, it can remain at standard vaccine refrigeration temperature for up to 30 days, and can be held at room temperature for up to 12 hours.
Initial challenges to maintaining a safe cold chain when such vaccines leave the manufacturer are in preserving their consistently cold environment during transport from the production facility to the next step in their journey.
Once these vaccines reach their destinations, those requiring ultra-low temperature (ULT) storage will present the greatest difficulties.
Lack of Appropriate Equipment — While large facilities such as universities and major medical centers, may have enough ULT equipment to accommodate these vaccines, many smaller health providers, physicians' offices, and pharmacies will not. Many who don't may also lack the funding to obtain needed ULT freezers.
Undersized Equipment — Even when suitable equipment is available, it may not have the capacity to house the volume of doses needed, particularly for those vaccines which require two doses, and when manufacturers have high minimum order requirements.
COVID-19 Vaccine Cold Chain Solutions
Researchers, vaccine developers, manufacturers, cold chain and logistics specialists, and countless others have come together to find effective solutions to ensure these critical vaccines are maintained safely, so they can be administered to those in need.
Pfizer, whose vaccine, which requires ULT handling, developed special packaging with dry ice to keep vials safely cold for up to two weeks without requiring ULT equipment. One concern, though, is that these containers must be repacked with fresh dry ice every five days, can only be opened twice per day, and must be closed within 60 seconds of opening.
Experience with an Ebola vaccine which requires ULT handling was used successfully in several countries in Africa, providing valuable experiences to inform handling of similar vaccines.
At American Biotech Solutions, we are proud to offer a full array of cold storage solutions, including vaccine-appropriate refrigeration, freezer, and ULT freezer units.
In related news, SC Governor Henry McMaster toured our plant recently, and gained valuable insight on how our products are essential in the fight against Covid-19. Please click here to view the article in its entirety.