Imagine this conversation:
Small doctor’s office at the heart of a coronavirus hotspot: “A mRNA-based coronavirus vaccine has been approved? Fantastic! Can you please send some to us? We’re in dire need!”
State health department: “Sure, as long as you have multiple ultra-low freezers to store them in before distribution. And a way to transport them to your office without breaking the cold chain. You have that, right?”
Small doctor’s office: “No.”
While that may be an oversimplification, delivery, distribution and storage of the possible first and second coronavirus vaccines will be much more complicated than any previously approved pharmaceutical treatment.
The novelty of it all
The initial vaccine candidates from Pfizer and Moderna are both mRNA vaccines, and if one gets approved for the treatment of coronavirus, it would be the first mRNA ever approved. Traditional vaccines contain small or inactivated doses of the disease-causing organism, which are introduced into the body to provoke the immune system into mounting a response. In contrast, mRNA vaccines contain a synthetic version of the mRNA that a virus uses to build its infectious proteins. This mRNA is delivered into the human body, whose cells read it as instructions to build that viral protein, creating some of the virus’s molecules themselves. The immune system then detects these viral proteins and starts to produce a defensive response to them.
“mRNA is naturally an unstable molecule that is prone to degradation when exposed to dramatic temperature fluctuations, even at ultra-low temperatures. In vaccine form, the importance of mRNA’s temperature stability is heightened exponentially,” Carl Radosevich, Senior Manager of Scientific Applications & Collaborations at PHC Corporation of North America, told Laboratory Equipment.
mRNA is a novel way to create a vaccine—of course, it’s a novel virus. So, it stands to reason that delivery and distribution would be novel, as well.
Delivery near and far
Last week, Pfizer announced it will seek Emergency Use Authorization for one of its coronavirus vaccines at the end of November. Knowing their mRNA vaccine requires ultra-low temperatures of -70˚ to -80˚C—and anticipating a shortage of ultra-low temperature (ULT) freezers—Pfizer designed temperature-controlled shipping packages that use dry ice to keep the vaccine vials at -75˚C for 10 days. According to the pharmaceutical giant, the shippers are roughly the size of a suitcase and weigh about 70 pounds fully loaded.
However, federal distribution of cold-storage vaccines is anticipated to be sent in 1,000-dose shipments, raising concerns about storage and wastage of an already critically low resource.
“Wastage is a huge thing,” Raja Rao, Director of Cold Chain Strategy & Markets at B Medical Systems told Laboratory Equipment. “There is just limited experience at this scale and this storage temperature.”
Rao said one of the things that can help with wastage and overall immunization efforts is employing the use of vaccine vial monitors. A vaccine vial monitor is a label that can be affixed to the outside of a vaccine that contains a heat-sensitive material. The material can register cumulative heat exposure over time. So, if a vaccine that needs to be kept at or below -75˚C rises above that temperature, the color of the label visibly and irreversibly darkens, altering healthcare personnel.
“It’s not just an anti-vaxxer issue, it’s an issue with people wanting to make sure they are being safely injected with a very, very new set of vaccines that have been quickly developed,” Rao said. “This could help big picture with getting everyone immunized on time.”
Noting that Pfizer is already planning to ship its vaccine in custom cold cases, the CDC, last month, advised states not to purchase ultra-low freezers—prompting questions about if the public health agency is worried about a shortage, as the U.S. experienced with PPE at the beginning of the pandemic. While that is one possibility, there could be other reasons.
At the moment, it looks like Pfizer and Moderna’s mRNA vaccines will be ready first. After that, however, is likely to be AstraZenca and Oxford’s vaccine that needs -20˚C temperatures to ensure efficacy, followed by liquid vaccines that can be stored at traditional temperatures, like flu vaccines.
“There has to be some scenario planning to answer questions as to how many refrigerators and freezers are needed,” Rao said. “You want to be efficient about your cold chain. Maybe we just deal with it using existing equipment and capacity. But then if there is a hiccup or delay with the [non-mRNA] vaccines, that can be risky.”
That can also easily lead to disparities in distribution—both domestically and globally. Small towns with limited infrastructure that cannot support ULT equipment may be relegated to wait for vaccines that do not require such resources.
When looking outside the U.S., the picture becomes even more grim. Rao, who has over a decade of experience delivering vaccines to remote areas of the world through his work with The Bill and Melinda Gates Foundation, says it’s nearly impossible to keep the cold chain spectrum intact for developing countries.
“Even to reach a modicum of immunization, the developing world will need to wait until the vaccine volume reaches a certain level, as in 2 to 3 vaccines are approved by health authorities,” he said. “They may even have to wait for a liquid vaccine, or at least a -20˚C vaccine that is widely available. The logistics of the frozen mRNA vaccines are mind-blowing for developing countries.”
The Associated Press estimates vaccine storage issues could leave 3 billion people in developing countries without access to a coronavirus vaccine.
Benefits of ULT freezers
For laboratories, hospitals and other health facilities looking to invest in ULT freezers, there are a few ideal characteristics to look for.
“Keep in mind that the difference between the room temperature and the storage temperature is often over 100˚C. Therefore, it is important to focus on cold performance: uniformity of temperature in the chamber when the door is closed and the ability to recover cold temperatures after door openings. A critical balance of low energy consumption, longevity and temperature performance the best COVID-19 vaccine ULT freezers,” said Radosevich.
Versatility is another key feature of these instruments. For example, B Medical Systems has units that can go from +2˚C to -20˚C with the turn of a dial. Ultra-low freezers that can go from -86˚C back down to -20˚C also provide flexibility and efficiency.
“Remote temperature monitoring that is equipped with real-time temperature information as well as historical information is very helpful,” Rao said. “A monitoring system can tell you if the door is open on one of the fridges. Additionally, if a freezer drops below a certain temperature, alarms are sent out.”