As multiple COVID-19 vaccines have become available globally, we are struck by how many innovations in the life sciences are direct byproducts of the pandemic. One such byproduct was the construction of a global infrastructure for ultra-low temperature (ULT) storage practically overnight. Without establishing an ecosystem for thermal protection into the existing end-to-end vaccine supply chain, stability testing of vaccines in transit and storage likely would have added another six to eight months to their delivery date, and the world would still be impatiently awaiting inoculation.
 
ULT capabilities are growing across many regions of the global supply chain, and biorepositories, freezer farms, and manufacturing facilities have exploded as a direct result of the pandemic. Looking beyond, there are key areas where this infrastructure will be useful beyond the pandemic to support ongoing processes to rapidly accelerate the future of medical innovation.  
 
Supporting upstream drug research and manufacturing
While supply chains made a significant difference in the commercialization of COVID-19 vaccines, they are not the only, or even primary, function of ULT storage. Before the pandemic, ULT storage was primarily a critical tool much earlier on in the drug development, research and manufacturing process.
 
All drugs are made up of two components: the active pharmaceutical ingredients (APIs) that bring about their effects, and the excipient, or the other substances that help deliver the medication to your system. APIs often require ULT storage to prevent biological change or spoilage in storage and must maintain an active state while these substances are researched. This is particularly true for cell and gene therapies, which require test specimens, tissue samples and blood samples to produce.
 
Poorly manufactured or compromised APIs have been connected to serious issues such as illnesses or even death. Furthermore, bulk storage facilities for APIs face stringent regulations and oversight that often require ULT storage at -80°C or colder to maintain efficacy until the final product is manufactured with the excipient.
 
Moving forward, biorepositories and pharmaceutical manufacturers will continue to rely on ultracold storage throughout research, development and manufacturing processes to ensure the creation of safe, efficacious and compliant therapies for patients.
 
Commercializing more mRNA vaccines
While stability testing of the Pfizer-BioNTech messenger RNA (mRNA) vaccine did lead to regulatory confirmation that the vaccine could remain safe and effective for up to two weeks in standard freezer temperatures, the flexibility that ULT infrastructure offered made the industry ready for anything that may have come from the first ever commercialized mRNA vaccines. Many regions across the globe are beginning to build out their support structure.
 
mRNA vaccines have been a revolutionary breakthrough in immunizing people against disease without actually delivering a piece of the virus into their system, as is the case with traditional vector vaccines. However, these vaccines have proven to be very fragile and potentially unstable at regular freezer temperatures, with more easily broken molecular bonds. The speed to which these vaccines have been brought to market means freezing storage temperatures are required for stability until more testing can be completed. Furthermore, Pfizer-BioNTech COVID-19 vaccine vials that must be stored for longer than two weeks still require ULT storage.
 
Following the remarkable efficacy of both Pfizer-BioNTech and Moderna’s vaccines in immunizing against COVID-19, researchers are already exploring new opportunities for mRNA vaccines and therapies going forward. The same ultracold chain infrastructure made necessary by the pandemic will become instrumental in both advancing the delivery of more vaccines in this class, as well as potentially upending their process and timeline for stability testing all together. The reliability of ULT storage will offer a confidence level across these more temperature-sensitive treatments to guarantee their efficacy in transit even without extensive stability testing, as it did for COVID-19 vaccines.
 
Realizing the promise of personalized medicine
Buzzwords like mRNA, CAR-T, cell & gene, CRISPR, regenerative medicine and precision medicine have been present in the industry for years. These innovative concepts for medicine exist under an umbrella idea that therapies can be personalized to every individual’s genetic code or that their genes can be edited altogether for a desired medical outcome. As such, they are popular in fields such as oncology and rare disease where blockbuster treatments either do not exist or have largely failed their patient populations. Still, there has yet to be a real-world example that truly pushes these treatment classes beyond buzzwords in the industry – until the COVID-19 mRNA vaccines. 
 
The emergency use authorization and mass commercialization of these vaccines has invigorated the scientific community with an influx of new financial capital, as well as a newfound confidence that new treatments in these classes can in fact be developed, produced and marketed at scale. That means researchers, engineers and scientists are working faster than ever to safely commercialize advanced therapies to address rare diseases, cure cancers and ultimately extend the health and longevity of the world’s population. 
 
Personalized medicine depends on their chemical perfection for the patient they are created for, which has long rendered it a pipe dream for the mainstream. In order to create more accessibility around these treatments as they do come to fruition, drug developers must be able to guarantee their stability as they are commercialized. All of these advanced treatments will require some level of ULT storage to research, to produce, or to preserve long-term for maximum effectiveness. Furthermore, because no two treatments are the same, their storage requirements may vary greatly. Some will have -20°C storage requirements while many will fall into the territory of cryogenics at -135°C or colder. Some temperature requirements for a given treatment will vary depending on the stage of clinical development. Stability testing to confirm effectiveness and lessen stability conditions in this case would be a massive hindrance, taking years to complete and leaving patients waiting for cures.
 
In creating a global ULT storage infrastructure, the industry has incidentally set itself up to finally deliver on the future of precision medicine that has long been promised. In the continued expansion of a flexible ultracold chain infrastructure, a primary focus on implementing ULT solutions capable of accommodating a wide range of temperatures will be the underpinning to deliver personalized and precision treatments for cancer, rare disease, and eventually all medicines in a post-blockbuster drug world.