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Overcoming Obstacles in Automating Cryogenic Storage

Gloved hand using tweezers to remove a test tube from liquid nitrogen.
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Read time: 15 minutes

In life sciences, the success or failure of a new drug, treatment or cell therapy can hinge on the quality of a single sample. In this sense, every sample matters. Yet, it can feel like an insurmountable task to manage thousands of samples that require consistent handling, strict documentation discipline and careful tracking of their location in storage.

How can sample managers keep accurate records but also ensure the right samples are accessible when needed? How many hours of work are spent tracking down missing information or trying to find enough open space in a freezer to hold the next batch of samples?

Prioritizing scalable and dependable cryogenic storage solutions for biological samples is critical, yet many companies fail to make it a priority. Sample management often gets sidelined by more immediate concerns, prompting companies to postpone considering how to generate long-term efficiencies.

Transitioning to automated cryogenic storage systems represents a significant advancement for laboratories dealing with large storage volumes or with demanding standards for digital record-keeping and audit trails. Automated systems utilize sophisticated software and technology to streamline biological sample management processes.

Leveraging advanced robotics, automated sample handling and computerized monitoring and control systems, they can efficiently manage cryopreserved materials with heightened precision, significantly minimizing the occurrence of human errors and reducing incidents of transient warming.

This article explores the challenges and strategies involved in transitioning to automated cryogenic storage systems. From assessing current infrastructure to gaining organizational buy-in and selecting appropriate containers, follow these steps to help ensure a successful transition to automated cryogenic storage.

Assess the current storage infrastructure

Cryogenic storage infrastructure often evolves in an ad hoc manner, with organizations initially acquiring freezers based on immediate needs, only to find themselves contending with space constraints and inefficiencies later.

The initial step, an infrastructure assessment, involves gaining a thorough understanding of the current state of your facilities and resources. It includes identifying the location of storage units, determining who is responsible for their management, and who has access to them.

This initiative can be led from the very top of the organization, but it’s more commonly championed by middle management – a lab manager or director who heads up cryogenic storage. Often, this person will look around and realize, “All of my people are spending their time digging in freezers,” or “I can't physically fit another freezer in this room. This isn't scalable or sustainable for the future. How are we going to fix that?”

When you start opening freezers and looking at them, one of the things you may find is that they're not very efficiently organized for cryogenic storage. Some samples won’t have data associated with them, or the person who knows their purpose is no longer around. If you don't know the consent status of that sample, you generally can’t use it – so, why are you paying to keep it cold?

Just like your refrigerator or freezer at home, you may not be making the best use of space, and you might have a whole bunch of mystery items. Conducting an assessment begins the process of deciding how your repository or lab is going to handle samples as they age so you can put practices in place to prevent the freezers from filling up again with unusable samples.

Beyond sample management and storage efficiency, decisions about the biorepository's structure must be addressed. With a centralized, on-site automated biorepository everything is kept on hand, with a small group of people managing it.

Alternatively, an off-site distributed repository offers expertise, compliance and scalability, and each lab can have its own freezer that it manages. A third alternative is a hybrid approach to keep some samples on campus in your repository and some samples off campus at a third-party repository.

When planning for automated cryogenic storage, some companies handle this assessment on their own, or it can be done with the help of experienced consulting services. This is also the time to start specifications and cost estimates for the project. In addition to equipment, you need to account for the time, labor and energy to make this shift.

Cultivate a culture shift toward automation

How do you get buy-in for a large-scale change in process? It generally means garnering support from the C-suite, and that means highlighting the value. Leadership must weigh the benefits of maintaining the status quo against investing in a future state streamlined by automated processes. You can expedite this by quantifying the need for change and outlining the impact it will have on the organization in terms of time and money saved, as well as mistakes reduced, or fewer samples lost.

Lab personnel also need to recognize the value of automated cryogenic storage and how it will ease their workload without forfeiting control. Often, each lab seeks autonomy over its own freezer to maintain control of sample quality and usage. This siloed approach leads to a proliferation of freezers with duplicated samples held in multiple freezers rather than sharing resources. Some freezers sit empty while others are stuffed full, creating waste in space and energy.

However, transitioning to an automated platform enables greater access control while optimizing resource utilization. Automation as a shared resource can significantly reduce the need for duplicate freezers, resulting in cost savings on equipment, floor space and labor. Shifting toward automation with access control and traceability instills trust in sample security, giving lab staff more confidence to let their samples share space in a cryogenic freezer.

The benefits extend beyond operational cost savings. For example, in the context of high-value therapies like CAR T, automation minimizes the risk of human error or transient warming, safeguarding multimillion-dollar investments. Additionally, automated systems offer enhanced monitoring and traceability, protecting the integrity and security of stored samples through built-in reporting mechanisms.

Standardize container selection

It may be obvious, but changing to an automated system also means ensuring that the storage containers and racks used for storage are designed to support digital tracking and automation. Prioritizing compatibility with planned automation systems helps avoid complications down the line.

When selecting containers, look for features that facilitate automation, such as standard sizes, screw caps and bar codes. For instance, opting for cryovials that work seamlessly with decappers, but may not be compatible with the liquid handler or the robotic arm that moves them in and out of the freezer, will cause problems.

Barcoding plays a pivotal role in enhancing sample management efficiency. Traditional paper labels are prone to wear and loss, leading to sample identification challenges. Barcodes etched into labware or printed with special permanent ink that can withstand cryo temperatures provide a reliable means of sample tracking from the outset, ensuring long-term readability. Dual- or tri-coded barcodes on labware allow the bar codes to be read from various angles.

Selecting containers that align with current automation needs while remaining flexible for future expansions ensures scalability and adaptability. Ask your cryogenic storage system vendor which containers are most suitable for your system configuration and requirements to ensure a smooth transition to automated cryogenic storage.

Define sample data requirements

Next, assess your data management needs, both current and future needs as you move into additional phases of development. Consider the data associated with each sample, including consent forms, ownership and permitted usage. Implementing robust data management protocols protects each sample’s integrity and value throughout its lifecycle.

Typically, a laboratory inventory management system (LIMS) or similar software handles this information. The LIMS tracks what type of sample it is, what documents are attached to it, who can touch this sample, and possibly even its location in the freezer.

Attempting to manage this information manually for a large number of samples is impractical and may lead to errors. Therefore, investing in a system that automates this process improves sample integrity as well as data compliance, which can be essential for organizations reaching the trial stage of development.

You also want to consider integration between different data management systems, such as LIMS and automation systems, to ensure seamless operation. Requests for sample retrieval should be made through the LIMS, which serves as the "standard of truth," ensuring data accuracy and traceability across the sample’s lifecycle.

The collection of bidirectional data across all freezers in the system can help to identify bottlenecks, improve processes, maintain product quality and reduce costs. This enables continuous improvement based on data-driven decision making.

Integrate process development

As you transition from manual to automated cryogenic storage, you will need to develop standardized procedures and new processes. Process development typically begins with collaboration between the researchers and sample management teams to understand their workflows and identify areas for improvement. The goal is to integrate automation seamlessly into existing processes, alleviating burdens and enhancing efficiency for researchers.

For example, you will need to understand how storage fits into the wider workflow: how frequently are samples being accessed, how many are being generated for storage, and is it necessary for each researcher to manage their own samples?

In many cases, a centralized approach with strategically placed freezers can minimize travel time and disruptions to the critical work of research – finding the next cure or scientific breakthrough. By emphasizing how automation can simplify workflows and support research objectives for principal investigators, automation will be seen as an empowering tool by researchers, rather than a threat.

Additionally, involving operations and quality control staff in procedure development enables alignment with regulatory requirements and operational excellence. Collaborating with team leads helps ensure that the procedures for implementing and utilizing automated cryogenic storage systems are practical, effective and well-suited to the team's needs.

Once you have a new process ready, implement training sessions for each group and provide easy-to-understand documentation to ensure smooth adoption and continued usage of the new processes. As personnel receive training, be sure to demonstrate the benefits of the new process to gain buy-in from the wider team.

Plan for scalability to support future growth

The rapid advancements in cell and gene therapy highlight the importance of proactive scalability planning. Consider how you can address current cryogenic storage demands while preparing for the anticipated growth in sample volumes and types. By evaluating factors such as workflow design, facility layout and infrastructure readiness, you may more effectively accommodate increased workloads and evolving storage requirements.

Integrating insights from process development steps enables you to optimize user interactions with equipment and define access protocols. For instance, how do people interact with this equipment, and who is allowed to have access? How might this change over time, and how can the change be managed?

Collaboration with your automated cryogenic storage partner at an early stage can help you be more effective in this process. By understanding current needs and future projections, you can strategize and allocate resources accordingly. For instance, if a central biorepository model is adopted, plans for accommodating multiple freezers within designated spaces can be laid out from the outset. Moreover, ensuring infrastructure readiness is crucial. Preparing drops for electricity and other utilities in advance facilitates seamless integration of new equipment as the need arises.

Finally, proactive planning for scalability in automated cryogenic storage operations involves collaboration, foresight and leveraging industry insights. By laying the groundwork for future growth and flexibility, you can adapt to the dynamic landscape of advanced therapies and accelerate progress in this critical field.

In summary, successful implementation of automated cryogenic storage systems requires a comprehensive approach encompassing infrastructure assessment, container selection, data management, procedural standardization, scalability planning and strategic foresight. By adhering to these steps, companies can optimize storage efficiency, ensure sample integrity and drive innovation in cell and gene therapies.


About the author:

Erica Waller is a senior product manager for cryo automation and stores at Azenta Life Sciences, headquartered in Burlington, MA, USA.  She holds a BS in Mechanical Engineering from MIT and was a systems engineer for Brooks Automation (now Azenta Life Sciences) for several years prior to her current role.

Today, she oversees the cryo storage and automation portfolio for Azenta Life Sciences. She lives in the Boston area and is passionate about cryopreservation and innovation to support the next phase of medicine and research. In her spare time, she's an avid clay artist, specializing in ceramics thrown on a potter's wheel.