What Happens when Your Cryo Storage Can’t Keep Up?
Cryogenic storage rarely makes it onto the list of things that sink a cell and gene therapy program. And that’s exactly the problem.
By the time cryogenic storage becomes visibly unmanageable, with freezers multiplying down the hallway, operators spending hours tracking down a single sample, or a temperature excursion that no one caught in time, the damage is already done. Sometimes that means a catastrophic loss: a batch compromised, a patient without therapy, a program set back months. Just as often, it’s the slower damage that’s harder to see; transient warming events quietly degrading cell viability, inventory gaps that erode confidence in your chain of custody, and compliance risks that only surface at the worst possible moment.
In a recent webinar, Cell & Gene Therapy Insights and Azenta Life Sciences brought together four experts spanning process development, manufacturing, facility engineering, and automation to examine cryogenic storage from every angle. The conversation was live, candid, and packed with practical insight. Below are excerpts from the live Q&A as our experts interacted with the audience.
Q: What Are the Early Warning Signs that Signal Your Manual Cryo Storage Is Becoming Unsustainable?
A: This question landed differently for each speaker, which is exactly the point. The answer depends on your therapy type, your scale, and what you’re optimizing for.
Mudith Jayawardena, Associate Senior Scientist at the Cell and Gene Therapy Catapult, flagged something that often gets overlooked: sustainability in the literal sense. Every time operators open a cryogenic vessel without discipline around access frequency, more liquid nitrogen boils off, supply needs go up, and costs follow. For an organization with an active sustainability program, these opening events add up.
For Paola Perrini, Cell Process Development Manager at AGC Biologics’ Milan site, the tipping point is closely tied to therapy type.
“When you have to face an allogeneic product, it’s unthinkable to maintain a manual asset.” – Paola Perrini, AGC Biologics
Autologous programs, with a handful of containers per batch, can be managed manually for a while. Allogeneic manufacturing, with its higher volumes, multi-step fill and finish, and longer expansion phases, demands a different approach from the start.
Peter Walters, Fellow of Advanced Therapies at CRB, offered a facility-level perspective. His signals are operational: retrieval times[RP1.1] creeping up, and floor space consumed by row after row of freezers. If your freezer count is becoming a space planning problem, you’ve already crossed a threshold. Scott Reeves, Director of Sales Engineering at Azenta, added that under-utilized freezers are often the real tell, with valuable material spread thin across too many units, with no one quite sure which freezer holds how many of what.
Key Signal: If your operators are spending significant time locating samples rather than processing them, the system is working against you.
Q: When Evaluating Freeze-Thaw Robustness for Biologics, Is There a Typical Number of Cycles that Your Teams Consider a Standard Qualification Threshold? How Much Safety Margin do You Usually Build Beyond Expected Real-World Handling?
A: Mudith’s answer was direct: it depends on the material. There’s no universal number. What matters is building genuine understanding of how your specific cell type responds to thermal stress over time.
“It boils down to how much experience you have with the material. It’s all about building capability and know-how.” –Mudith Jayawardena, Cell and Gene Therapy Catapult
This is particularly relevant for pluripotent stem cell-derived products and primary cell types, where even small differences in formulation or starting material can change the thermal tolerance profile significantly. The implication for development teams: invest in freeze-thaw characterization early and treat it as a living body of data rather than a one-time box to check.
Q: Can the Automated Cryo Storage System You Presented (CryoArc) also Handle the Storage of Cryo Bags? And if Yes, Is It Possible to Store Both Cryo Bags and Cryo Tubes in the Same Unit?
A: Flexibility is a real concern for teams working across multiple product formats.
Scott confirmed that the system is designed with labware flexibility in mind. Different rack configurations can accommodate different container types, including cassettes, vials, and tubes, though very small formats have some constraints based on how the automation is designed to handle retrieval.
The broader lesson here applies to any transition toward automation storage: container selection decisions made early in development save significant time later. If your team is still mid-process on format selection, that’s the moment to loop in your automation partner, not after you’ve locked in a container that may require workarounds.
Q: What Aspects of the Freezing Phase in the Cell and Gene Therapy Processes Are Regarded as the Most Critical and How Might They Impact the Overall Quality of the Drug Product?
A: Paola addresses which elements of the freezing phase are most critical to drug product quality. Her answer centered on process control and reproducibility at every handoff.
“You have to start from the same temperature for each container, with a controlled slope for the freezer. And your controlled freezer should be very close to the storage tank, so the exposure of the DP is very limited.” Paola Perrini, AGC Biologics
The point about proximity matters more than it might seem. Every meter a drug product travels between the controlled rate freezer and its final storage environment is an opportunity for temperature deviation. Smart facility design accounts for this from the start rather than as an afterthought during commissioning.
Q: As Cryogenic Storage Infrastructure Expands for Cell and Gene Therapies, How do Companies Balance Centralized Storage Models with Geographic Redundancy to Mitigate Risks, such as Facility Outages and Supply Disruptions?
A: As programs scale toward commercial manufacturing, questions around where to store materials and how to protect against facility disruption become more pressing. Peter walked through how CRB approaches this with clients.
The short answer: active manufacturing materials want to stay close to where they’re made. The GMP space and adjacent warehouse areas typically house the freezers that directly support production, including incoming apheresis, drug product, and QC samples. The case for geographic distribution is strongest for longer-term retains.
“Having a more centralized repository to your networking where you can all these retains – it’s just a giant freezer farm for long-term storage – makes a lot more sense for those applications.” Peter Walters, CRB
This hybrid model of GMP-adjacent active storage and centralized long-term repository is increasingly common among maturing cell therapy programs, and it changes the automation calculus at each tier.
Q: Focus Is Placed on the Freezing and Storage of Cellular Products, but the Thawing Process Has Been Understudied, and Manual Thaw Introduces a Lot of Variability. How Could these Automated Systems Improve the Thaw and Recovery of Immune Cell Products?
A: One of the session’s most pointed exchange came around a part of the cold chain that’s too often deferred: thawing. The freezing process has received significant attention and investment. The thaw has not and that asymmetry shows up in outcomes.
Udith made a case for treating controlled thawing as process standard, not an optional upgrade.
“If I had it my way, I would probably just make sure all products undergo controlled thawing. It still fits into your QTPP and forms your entire data package for your drug product. Having that control and consistency each time should be made standard.” Mudith Jayawardena, Cell and Gene Therapy Catapult
Olga Bukatova extended this to the point of care, where water bath thaws are still common in hospital pharmacy settings, introducing variability and contaminations risks that no amount of upstream process rigor can compensate for, resulting in an increased possibility of falling out of compliance with GMP standards.
“Having a controlled, non-operator-impacted thawing process at the point of care definitely secures these last minutes of life of the drug product prior to administration.” Olga Bukatova, Azenta Life Sciences
Azenta’s Barkey thawing devices are designed to bring the same documentation and reproducibility standards to the thaw step that the field has largely adopted for freezing, closing the loop on a gap that shows up more often than people realize.
Q: Are most Organizations Still Relying Primarily on Printed Barcode Labels, or Are We Seeing More Adoption of RFID-Based Solutions?
A: The honest answer: most organizations are still running on barcodes. Printed 2D and 1D codes can carry a lot of information but they do also introduce identification and sample traceability challenges. Scott noted that RFID interest is growing, especially for larger patient population studies and organizations planning to scale. For laboratories working with frozen samples, RFID is the most reliable and effective solution for reading frost-covered tubes.
Peter offered a practice frame for when RFID becomes worth the investment:
“The very large patient population projects are looking at RFID as a means of getting away from a code that a human has to interact with – something that can be more roboticized and electronically picked up throughout the lifecycle of the process.” Peter Walters, CRB
The implication: RFID is a future-proofing decision, not a current-state requirement for most programs. But teams designing for future commercial scale (i.e., 50,000+ patients per year) should build a tracking infrastructure that can get there.
The Bottom Line
Cold storage is integral to the success of any cell and gene therapy program. Very few organizations are prioritizing it before they have to, and by then, the fixes are more expensive and disruptive than they would have been at the design stage.
What the panel made clear is that the decisions that matter most (container formats, digital integration, controlled freeze and thaw, automated storage and retrieval) compound over time. The earlier they’re made intentionally, the smoother the path to commercialization.
Azenta Life Sciences supports cryogenic storage across every phase of development, from clinical to commercial. Whether you’re evaluating your first automated storage system or designing infrastructure for a large-volume program, our solutions can help you think through the right approach for your specific needs.
To watch the full conversation, access the on-demand webinar.