The Past, Present and Future of Ultra-Low Temperature Storage

From PCR testing to vaccine distribution, ultra-low temperature storage became a commonplace technology during the pandemic, and its future is looking equally exciting.

Ultra-low temperature (ULT) storage has evolved from a specialised piece of hardware in the backrooms of laboratories and biorepositories to a daily topic of conversation. These freezers, which traditionally store their contents at temperatures as low as -86°C, have presented a variety of uses throughout the rise of COVID-19 – from storing the tests that enabled us to diagnose the virus accurately, and understanding the spread of the virus, to providing the supply chain infrastructure that continues to support delivery of mRNA vaccines to millions of people.

Prior to the pandemic, ULT was (and still is) a mainstay in the laboratory space for storage of injectable drugs and biological samples for clinical research and testing. Many injectable treatments and vaccines require constant storage at ULT temperatures to maintain their safety and efficacy, as dictated by the local regulatory body. Additionally, at -80°C, degeneration of biological samples slows significantly and can be tested for longer periods of time. Based on these capabilities, the broader benefit of a ULT infrastructure has been clear – extending from long-term storage facilities to transportation hubs, to pharmacies and hospitals at the last mile of distribution. However, there was never a need big enough to fully operationalise on a global scale – until the COVID-19 pandemic.

The Rise of Pandemic Related ULT

In January 2020, COVID-19 was not yet an epidemic, and the possibility of delivering one effective vaccine, let alone multiple, was not yet a conversation being had on the world stage. Instead, the immediate focus was on testing, diagnosing, and contact tracing to understand disease spread and consider how best to mitigate it. Backlogs in test processing, brought on by the sheer volume of tests that were being performed, created a three-day waiting period or more for results. A means of storing tests to maintain samples was essential for an accurate read. Many labs and biorepositories, which were already equipped with ULT infrastructure, partnered with hospitals in their regions to store and process test samples. This capability was the cornerstone of being able to get through backlogs and provide accurate reads of COVID-19, not just to the individual patients, but to researchers and government entities who were working to gauge the growing magnitude of the virus.

Chronologically, the testing backlog that required ULT storage of test samples actually occurred after COVID-19 was classified as a pandemic. As lockdown orders emerged, in-person medical visits halted, clinical trials were put on hold, and pre-pandemic research applications of ULT freezers largely paused in favour of this new, more essential use.

Flashing forward to December 2020, the EMA issued approval of the Pfizer-BioNTech mRNA vaccine, and the FDA issued an emergency use authorisation (EUA) of the vaccine, quickly followed by Moderna’s. Data were suggesting that these could be incredibly effective against the virus and came with the added benefit of not introducing a sample of the virus into the recipient’s system. However, due to the fragility of the formula, the industry at large was aware that these vaccines would require storage at ULT temperatures.

Stability testing could potentially allow for reformulations that would enable storage and distribution at warmer temperatures, but this could take many months, and these were the first mRNA vaccines of their kind. With that, in the months leading up to the anticipated EUA of vaccines, the global supply chain network for the pharmaceutical industry was hard at work erecting an end-to-end infrastructure for manufacturing and distribution, with ULT freezers at its heart.

The next wave of pandemic-related ULT use came as vaccines were rapidly manufactured and stored in freezer farms by third party logistics providers like UPS. Dry ice was also a solution, though challenging to implement as it required a vast supply chain, special training, and frequent refilling to consistently maintain the necessary temperatures for efficacy and safety. If vaccines were outside of these temperatures for several hours, they had to be immediately thrown out. Although biorepositories would again step in to help, local health system and pharmacy networks largely had to build their own ULT infrastructures to store vaccines in the last mile once they were in distribution. As large-scale distribution began, the next major challenge was underway: last mile distribution and storage.

ULT Storage One Year Later

Strategies for last mile distribution have varied around the world, but persist to the present day as the biggest challenge for vaccine delivery. Many areas, such as Puerto Rico, established hub and spoke models where vaccines could be stored using ULT in a central repository and moved to pharmacies, medical centres, and vaccination clinics (1).

Today, countries like the United Kingdom and the United States have been able to operationalise their infrastructure quickly to achieve total vaccination rates of 60 percent or more. However, as distribution has expanded from developed countries with stable electric grid infrastructure to areas of the world with less reliable grids and less developed terrain, mobility and energy efficiency have become increasingly critical capabilities of the ULT temperature being employed. Mobile ULT freezers are enabling last mile logistics providers to maintain ULT temperatures for longer treks to deliver vaccines to inoculation locations, and newer freezers are able to run on less energy while also being brown-out tolerant.

Looking forward as the pandemic continues and the need for vaccination persists, long term storage remains a crucial need in countries where vaccine hesitancy persists and the ability to deploy vaccines quickly and reliably where they have demand is similarly important. The likelihood of booster shots is also growing as the Delta variant rages on around the world. This will put pressure on the whole infrastructure to deliver as quickly as it did for the initial vaccine campaign.

Beyond COVID-19, we have also begun to see the restart of active clinical trials. Furthermore, the remote capabilities that the pandemic inadvertently enabled has spurred growing widespread adoption of decentralised clinical trials. Out of this growth, ULT is already seeing a new emerging use case in mobile and local infrastructure to enable these trials, particularly as the focus on new cell and gene treatments, as well as precision medicine, becomes more and more prevalent.

The Future of ULT Technology

The technology behind ULT storage is undergoing advances that will have a powerful impact on the use cases it serves in the end-to-end supply chain. Integrating ULT freezers with supply chain platforms via cloud connectivity will increasingly become the foundation for tracking vials throughout distribution to ensure safety, efficacy, and regulatory compliance.

Furthermore, integrating freezers with information and sample management systems via connectivity will enable guided, and even fully automated, access and retrieval of ULT-stored therapies and doses. This ensures the right samples are being retrieved and returned to cold storage before their quality is impacted. All the while, this data can be captured and maintained in a virtual audit trail for regulatory purposes. Furthermore, there is also a growing focus on the data protection layer that sits above these capabilities, ensuring sensitive information does not fall into the wrong hands.

The formulation of medicines is improving in parallel to become more personalised and, consequently, higher value. Many of these treatments increasingly include stringent ULT temperature requirements for storage and distribution. It is absolutely essential that tracking and handling capabilities are equipped to maintain these treatments, and these advances in ULT technology will directly support that mission.

Empowering the Future of Medical Innovation

Delivery of vaccines around the world continues to be the most imminent and pressing task for the global ULT infrastructure as new variants continue to emerge. Should new vaccines or boosters be needed in the near future or on an annual basis, stability testing for every new vaccine could add months to the timeline that we don’t have. As such, mitigating the need for stability testing entirely will serve to hasten the control of COVID-19 spread.

That said, the urgency we have seen for treatments on such a broad scale with the pandemic is not a new experience for some patient groups. Those in areas suffering from life-threatening viruses like Ebola have long faced challenges with accessing vaccines and treatment. Flexible ULT infrastructure will be instrumental in preventing spoilage and increasing access to these vaccines.

Furthermore, ULT technology will become the foundation for clinical research and scaled delivery of precision and biologic medicine for rare and life-threatening illnesses. Mitigating stability testing will equally serve the patients with life-threatening cancers who need these treatments most. Finally, the global scale and flexibility of this infrastructure will ensure that, when these new treatments are approved, they are accessible to patients globally – not just to a small few.

The circumstances of the pandemic shone a spotlight on ULT that is not going away. This infrastructure helped the industry surmount the manufacturing and logistics challenges of the largest vaccine campaign in history. That same infrastructure will ensure preparedness to deliver boosters for COVID-19 variants, as well as vaccines for future pandemics and epidemics. It will also be the underpinning for the supply chain to deliver precision medicines at scale. Looking forward, the work done to put this infrastructure in place will holistically serve the pursuit of greater medical innovation for the foreseeable future.

This article is taken from Pharmaceutical Manufacturing and Packing Sourcer October 2021, pages 18-20. © Samedan Ltd.

Reference

  1. Visit: www.wsj.com/articles/mass-vaccination-sites-will-mean-scaling-up-logistics-coordination-11612004400

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