Addressing Growing ULT Storage Demands With More Efficient, Automated, Sustainable Solutions

In the world of biopharmaceutical and biomedical research, maintaining precise storage temperatures isn't just about preserving samples and products – it's about safeguarding hope. Ultra-low temperature (ULT) storage, essential to maintain the integrity of sensitive biological samples, is expanding to accommodate the growth in treatments based on biologics. And as we stand on the brink of a new era in biological understanding and advanced therapies, the role of ULT storage will only continue to grow.

In this article, we explore the rising demand for large-scale ULT storage solutions, the challenges faced by traditional cold storage approaches and the innovative automated systems revolutionizing how we preserve precious biological samples and medicines.

The growing demand for large-scale ULT storage

Demand for ultra-low temperature storage capacity is growing at a significant pace. Recent analyses show that the market reached a value of $547 million in 2019, and is projected to reach $994.7 million by 2032, growing at a CAGR of 4.4%.

This soaring demand is driven by a couple of key factors:

• The rise of ULT-dependent medicines: the biopharmaceutical industry is increasingly focusing on the development of biologics, such as some vaccines, immunotherapies and antibodies, that require ultra-low temperatures for preservation. Naturally, as more of these innovative therapies progress through development, a greater number are entering clinical trials and advancing to commercial production. This progression entails larger production volumes, significantly increasing the need for larger ULT storage.
• The growth of biorepositories: as our understanding of human biology increases, so does the complexity of research. This evolution translates to a growing need for high-quality biospecimens, which in turn fuels demand for ever larger biobanking facilities – facilities that require vast amounts of ultra-low temperature storage to maintain the integrity of these invaluable samples.

The cold truth: Addressing growing ULT demand with “freezer farms”

Many companies seek to address their large-scale ultra-low temperature (ULT) storage needs using so called "freezer farms” – collections of numerous individual manual ULT freezers arranged in rows.

But while manual freezers undoubtedly have – and will continue to have – a crucial role to play in biomedical research and biopharmaceutical development, using them for large scale storage in freezer farms presents several challenges.

Slow, labor-intensive management and workflows

The location and physical retrieval of correct products and samples in freezer farms can be slow and cumbersome. For instance, in a large biobank with hundreds of freezers, samples might be dispersed over multiple units across various locations. Finding the samples might involve consulting multiple paper logs or basic inventory systems, coordinating with different teams and significant travel within and across sites, as well as manually searching through boxes or racks within each freezer – which can be a very tedious and convoluted undertaking.

Additionally, if the farm consists of different units from various manufacturers, maintenance, troubleshooting and repairs can become more complex and time-consuming. Technicians may need to be familiar with multiple systems and protocols, increasing the likelihood of errors or delays in addressing issues.

As a result, companies relying on freezer farms for their sample and product storage could face:

• Increased time to complete tasks, potentially causing costly research delays, or delayed product delivery.
• Higher full-time equivalent (FTE) resource requirements.
• Increased risk of human error, such as misplacing samples or recording incorrect storage locations.
• Greater risk of injury during manual handling, particularly when accessing samples in hard-to-reach areas of freezers, such as at the back of the top shelf. The risk is even greater when it comes to manual cryogenic units, too.
• Higher sample risk due to more frequent manual retrievals and door openings, potentially exposing sensitive materials to temperature fluctuations.

Visibility and traceability challenges

With thousands of samples or products distributed across multiple units and potentially multiple sites, maintaining visibility and traceability of product location and handling becomes increasingly difficult, too.

Traditional tracking methods, such as paper logs or basic spreadsheets, can be highly error-prone in large-scale operations. And, even with more advanced inventory management systems, the sheer volume of manual data entry that might still be required in a freezer farm can increase the risk of discrepancies between what is recorded and reality.

As a result, meeting rigorous data integrity requirements can become unnecessarily challenging in freezer farms.

Sample integrity put at risk

Many manual freezers have large doors that, if opened frequently and for extended periods, can lead to increased temperatures and higher risk of frost in the freezer chamber. When managing numerous manual freezers (as is the case in freezer farms), enforcing good door opening practices becomes even more challenging, potentially exposing samples and products to higher temperatures and compromising their integrity.

Moreover, some manual freezers may not have energy backup systems to maintain temperatures in the event of a power outage. Prolonged power cuts in a freezer farm room relying on such freezers could therefore compromise the integrity of thousands of samples and products.

Inefficient use of space

For large-scale storage requirements, vast numbers of individual manual ULTs also deliver a poor sample-to-space ratio. In such setups, floor space is quickly consumed, and it can be challenging to expand capacity as storage requirements increase, potentially limiting operational growth.

High energy consumption and environmental impact

The pharmaceutical industry is a significant contributor to greenhouse gas emissions, and so many companies have set ambitious sustainability goals. However, most ULT freezers are highly energy-intensive, resulting in freezer farms having a significant carbon footprint and elevated running costs.

Furthermore, older ULT freezers often use hydrochlorofluorocarbon (HCFCs) refrigerants with high global warming potential (GWP), contributing significantly to climate change when released into the atmosphere. While most newer ULT freezers use hydrocarbons (HCs) with a lower GWP, these refrigerants are highly flammable.

Crucially, as storage needs grow, these limitations become even more apparent, leaving many organizations seeking alternative solutions for large-scale ULT storage.

An emerging alternative

Thankfully, an attractive alternative is emerging for companies with large-scale ULT storage needs: large, centralized, high-density, environmentally friendly automated ULT storage systems (Figure 1). These systems offer a stark contrast to traditional freezer farms, providing a single, integrated unit that automates ULT sample retrieval and is easy to operate. Indeed, many large pharmaceutical organizations have already deployed, or are actively exploring the deployment of, such solutions.

Figure 1: Large, centralized, high-density, environmentally friendly automated ULT storage systems offer an attractive alternative to manual ULT freezer farms. Credit: Azenta.

Centralized and automated large-scale ULT systems address many of the concerns associated with freezer farms.

Increased operational efficiency and reduced labor requirements

Automated precision sample retrieval is a key feature of these units. Such capabilities enable effortless, quick and accurate retrieval of the right sample, significantly reducing end-user burden as well as the risk of human error. The most advanced systems also boast intuitive, information-rich displays with modern graphics, making them easy to operate with minimal training required.

Moreover, as a single unit from a single vendor, these systems drastically simplify maintenance, troubleshooting and repair processes, saving both time and money, minimizing downtime and enabling more efficient studies and operations.

Figure 2: Advanced automated sample retrieval systems offer precise, efficient and user-friendly alternatives to manual sample handling. Credit: Azenta.

Enhanced product traceability and visibility

With all samples and products stored in a single, centralized location, traceability is greatly improved in these systems. Additionally, easy-to-use controller software that supports 21 CFR Part 11 compliance can provide teams with meticulous and detailed tracking capabilities, and full chain of custody and audit trail reports. Some of these systems also offer easy integration with laboratory information management systems (LIMS), too.

Overall, this combination of features and capabilities enables more convenient inventory management and tracking with full visibility, without the need for disparate sample management systems.

Better temperature control, superior sample integrity assurance

Automated picking workflows, in a fully enclosed system, help keep samples and products at the designated storage temperature throughout the entire picking procedure. This feature safeguards sample viability and integrity by eliminating the risk of cold air loss and temperature increases posed by large manual freezer doors.

Optimized space usage

Automated ULT storage systems can offer significantly higher sample density relative to manual freezer farms. Some systems achieve a sample density of 112,000 tubes per square meter (for 0.9 mL tubes), with a single unit providing the same capacity as 160 manual ULT units. This translates to a ~72% footprint reduction compared to equivalent manual freezers. What’s more, these centralized automated systems offer easier scalability, allowing an organization’s storage capacity to grow with requirements.

More energy efficient, more environmentally friendly

Large-scale automated storage systems can significantly reduce energy consumption relative to equivalent storage using manual ULT freezers, in part because they are fully enclosed, which eliminates the need for frequent door openings. Some systems on the market can deliver up to 75% less power consumption than equivalent manual storage options, drastically reducing operating costs. Of course, such significant energy consumption reductions also help to create a reduced carbon footprint – which can be up to 75% less total equivalent warming impact (TEWI) in some cases.

More eco-friendly refrigerants are another benefit. For example, some systems are available now that employ natural refrigerants derived from clean air, with zero GWP. These refrigerants don’t just offer a significantly reduced environmental impact, though; they also provide greater efficiency at lower temperatures than conventional refrigerants, translating to additional cost savings.

Centralization: benefits at the expense of increased risk?

While the advantages of large-scale automated centralized ULT storage systems are clear, a common concern is whether the benefits of centralized storage come at the cost of increased risk to samples and products – if a unit containing all of your samples breaks, all of your samples are potentially compromised. However, the advanced technology employed in these systems offers several layers of protection and redundancy to minimize such risks.

For example, many systems offer tertiary backup – primary refrigeration, a secondary back-up refrigeration unit, and a tertiary liquid nitrogen back-up – helping to ensure continuous operation if refrigeration units fail. What’s more, back-up energy systems enable continued operation for 3–4 days in the event of a power outage, safeguarding valuable samples during emergencies.

Advanced monitoring capabilities further enhance sample and product security. Environmental and temperature monitoring and notification systems – complete with email alerts, visible beacon alarms, Building Management System (BMS) connections, and remote monitoring escalation – ensure that any issues are promptly identified. Moreover, intelligent diagnostics and error recovery systems work to swiftly resolve problems that could impact samples and products.

Finally, meticulously controlled access through usernames and passwords not only restricts unauthorized entry but also allows for comprehensive tracking of user access and activity.

A new era for large-scale ULT storage

As the biopharmaceutical and biomedical sectors advance, the demand for large-scale ultra-low temperature will continue to grow.

Traditional freezer farms, while relied on by many, present significant challenges that will only intensify as storage requirements grow. But large-scale automated ULT storage systems provide a compelling solution to these challenges, offering enhanced operational and energy efficiency, better use of space, and reduced environmental footprint – without compromising product or sample integrity.

As we look to the future, these innovative systems are poised to play a crucial role in supporting the next generation of biopharmaceutical research and development. By addressing key industry challenges, they will pave the way for optimized research, and more efficient product development and commercialization, all while facilitating a more sustainable pharmaceutical ecosystem.