The triumph of the COVID-19 mRNA vaccines resulted in a universal sigh of relief - followed by dismay at the lack of cold storage capacities to put these vaccines into use. With science in progress to develop mRNA vaccines for other diseases like Zika virus, metastatic cancers, and multiple sclerosis, what is the long view for sustainable cold storage?
Sustainable laboratory-grade cold storage is needed to make the best use of the massive advantage that mRNA vaccine technology has brought to fighting the SARS-CoV-2 pandemic. Heroically, Pfizer-BioNTech and Moderna have projected producing up to four billion doses combined of their safe and effective SARS-CoV-2 mRNA vaccines in 2021. Each and every vial will be a vital resource for saving lives.
Here is the long view. While putting these critical immunizations into immediate use in every geographical location worldwide is an unsurmountable undertaking - vaccine cold storage needs to be ramped up where ever it is feasible. The brilliance of mRNA vaccine biotechnology lies in its development speed. Today, it is acting as a tourniquet in the COVID-19 pandemic while the world is waiting for conventional vaccines to come to market. Tomorrow, it will enhance vaccine development for any SARS-CoV-2 variants of concern as they arise and possibly personalized genomics disease treatments. The caveat is that verified cold storage chains are a limiting factor.
Accounting for mRNA vaccines temperature sensitivity
Those of you working in molecular biology know the basic science behind RNA degrading more easily than DNA. Compared to DNA, RNA has a hydroxyl group in place of a hydrogen atom that promotes breakage of the phosphate bond in its nucleic acid molecular backbone. Keeping RNA samples cold in the lab slows down this hydrolysis potential. It is only one of the causes of RNA degradation. There are more. If you’re interested in exactly how much effort is normally required by scientists to prevent RNA degradation, watch this video from New England Biolabs on Avoiding RNase Contamination. Understanding the baseline for handling RNA samples makes the vaccine manufacture’s stabilization strategies using uracil modifications and protective lipid nanoparticle formulations even more impressive.
With those stabilization improvements acknowledged, it must be said that the cold storage logistics for RNA vaccines are still a bear.
The requirements to maintain mRNA vaccines highlight the hurdles for vaccine distribution. The CDC has shared storage and handling information for both the Pfizer and Moderna vaccines on its web site. The details draw a hard and fast picture. Thawed vaccines cannot be refrozen. Both vaccines will rely on constant temperature tracking with wireless RF powered sensors reported back to the vaccine manufacturer and then handed off to the government after delivery. There is no room for error in transportation, storage, and handling. Constant monitoring of the environment of vaccine vials is imperative.
The Moderna vaccine stability is nicely enhanced with RNA modifications and lipid nanoparticles. It still has a tighter freezer storage range than typical vaccines at -25°C and -15°C. After thawing, vials can last in the refrigerator unopened at 2°C to 8°C for 30 days. It can also be kept at room temperature for up to 12 hours. This tells us that at a minimum -20°C lab freezers must be functioning reliably and not having the doors opened and closed too often.
The Pfizer-BioNTech vaccine sets the bar higher for users to maintain its integrity. It may be stored at room temperature in undiluted vials for no more than 2 hours. It requires -70°C for long term storage. Pfizer has designed its own packaging, informally named “the pizza box”, to use as vaccine vial storage for a few weeks without specialized freezers. The pizza box is meant to be temporary storage and cannot be opened more than twice each day for less than three minutes in total. Specialty shippers that hold five pizza boxes must be replenished with dry ice every five days for a max of fifteen days by end-users.
The ULT freezer ordering bottleneck
Laboratory freezer capacity needs to be scaled up fast to make the best use of billions of vaccine doses. A broad range of organizations, from large hospital systems to small nursing home facilities, are increasing freezer capacities for immunization programs. The good news is that manufacturers make are making a variety of equipment sizes to right-fit needs. The bad news is that there are not enough units immediately available - in particular ultra-low temp (ULT) freezers. According to Reuters, pharmacies, health clinics, and large hospital systems in the U.S. do not have enough ULT freezer storage capacity in place for the rollout and can’t possibly place one in every clinic. Even though laboratory freezer manufacturers have ramped up production and added new remote monitoring services, many are on backorder until at least March 2021.
Thinking long term about freezer storage to avoid failure
ULT freezers able to maintain stocks of COVID-19 mRNA vaccines at -70C have always been a driver of high energy use in labs. When I say high energy usage, I mean unnecessarily high due to design and operational factors. Most people working in life science labs are very familiar with these freezers but perhaps less so with the associated sustainability issues. A typical ULT freezer can use 16 to 30 kilowatt-hours (kWh) per day - about the average for U.S. residence. Please visit the website for the International Freezer Challenge to learn how to use lab freezers sustainably.
Dry ice is really meant for short-term cold storage of vaccines and biological samples in general. Thankfully there is no shortage of dry ice in the U.S.A. as of this writing. However, dry ice makes the cold chain cumbersome to maintain and less reliable in practice. It is more labor-intensive and prone to human error. Imagine if you had to sore your own lab samples on dry ice only for weeks at a time.
It is worth noting that Energy-star certified freezers are more reliable in practice than dry ice cold storage, or older freezer designs. A typical ULT unit can store tens of thousands of vaccine stocks. They can range in price from $6,000 to more than $25,000. ULT freezers can fail and sadly this has already occurred several times in the United States during the vaccine rollout. All types of ULT Units must be located with an eye on manufacturer-recommended spacing and local HVAC capacity to handle their heat output. The wireless RF powered sensors collect data to centralize at the CDC. The immunization program end users are still responsible for monitoring their own freezers to prevent vaccine degradation. Adding a wifi-enabled alarm and door monitoring system is very worthwhile for precious lab materials.
Energy Star Laboratory Freezers for the vaccine rollout
This is all why I was so pleased to interview Steve Miller on energy provider, Eversource’s new program to support the vaccine rollout. According to Steve, who also manages for the International Institute for Sustainable Laboratories Utility Working Group, energy-efficient ultra low-temperature lab freezers are being put in place with an expectation for long term use. You learn about an incentive program to help expand cold storage in this green lab tip interview.
I hope that utilities everywhere will be able to model after this program and that sustainable lab cold storage manufacturing will meet demand as soon as possible!
