Why storage resilience will protect the future of CAR-T

Cell and gene therapies are changing the way pharmaceutical organisations think about sample storage. From autologous starting material and engineered cell products to viral vectors, retained manufacturing samples and long-term stability studies, these therapies depend on biological materials that are often irreplaceable.

Few organisations expect a storage failure to become the cause of a major development setback. Yet, the loss of critical samples can undermine years of research, manufacturing, and regulatory work.

Although these challenges are particularly visible in CAR-T and other advanced therapies, the underlying principles extend across biologics and pharmaceutical development more broadly. Every programme depends on samples that generate the scientific evidence supporting product quality, regulatory submissions, and manufacturing decisions. The resilience of the systems protecting those samples, therefore, becomes increasingly important as pipelines grow more complex.

For many organisations, sample storage planning has focused on capacity and equipment. The more important question is whether those systems could withstand a major disruption.

Sample storage is an active process

Sample storage depends on far more than a freezer. Equipment, monitoring systems, maintenance, documentation, and trained personnel all contribute to maintaining the conditions those materials require. Weakness in any one area can compromise an entire collection, whether that involves patient-derived starting material, retained manufacturing samples, or long-term stability programmes.

Routine operational issues can quickly escalate into significant failures. A missed alarm, delayed response, or equipment fault may be manageable in isolation. Left unresolved, those issues can allow valuable material to remain outside validated conditions for longer than expected.

The widely reported 2023 incident at the Karolinska Institutet illustrates how quickly this can happen.¹ Interruptions to the liquid nitrogen supply, combined with delays in alarm escalation, resulted in the loss of stored biological samples. While the incident involved cryogenic storage, it offers a broader lesson for pharmaceutical organisations: storage failures rarely stem from a single point of weakness, and successful recovery relies on coordinated infrastructure, processes, and decision-making.

For advanced therapies, those consequences can be particularly severe. Autologous cell therapies depend on material collected from individual patients that may be impossible to replace, while retained manufacturing samples and stability programmes provide evidence required throughout development and commercial manufacture. The same principles increasingly apply across biologics, where replacing compromised material may consume valuable time, resources, and scientific effort.

Beyond backup freezers

The scale of those consequences has prompted a broader rethink of storage resilience. Backup freezers and additional storage capacity remain important, but they cannot protect against every type of failure. This is particularly relevant for cryogenic storage supporting cell and gene therapy manufacturing, where maintaining validated conditions throughout recovery is critical.

After all, equipment rarely fails in isolation. A prolonged power outage can affect multiple storage units simultaneously. Building services failures may interrupt cooling systems, environmental monitoring, or site access. Even where backup equipment remains operational, organisations still need trained personnel, validated transport arrangements, and qualified contingency storage to recover critical material before storage conditions are compromised.

Events such as Hurricane Sandy demonstrated how dependent storage infrastructure can be on the resilience of the wider operational environment.² Flooding at NYU Langone Medical Center disrupted infrastructure supporting backup generators during prolonged power outages, placing frozen research specimens at risk, despite contingency measures being in place. The incident reinforced a lesson that remains relevant today: successful recovery depends on the resilience of the wider storage operation.

That broader perspective is reshaping how organisations approach resilience. Success is no longer measured by the number of backup freezers available, but by how effectively infrastructure, people, quality systems, and contingency planning work together to protect critical samples when something unexpected happens.

Recovery starts before anything goes wrong

Equipment failures, utility outages, and human error are an unavoidable part of managing laboratory infrastructure. The question is how quickly an organisation can respond when an incident occurs.

Effective disaster recovery starts long before an alarm sounds. Organisations identify the samples that would be most difficult to replace, review where they are stored, and establish clear recovery procedures before storage conditions are compromised. For CAR-T and other patient-specific therapies, those priorities may already be defined because every collection represents a unique manufacturing opportunity. Backup power, geographically separate storage, validated contingency capacity, and predefined decision-making enables a faster, more coordinated response, allowing teams to focus on protecting samples, rather than sourcing storage, arranging transport, or defining responsibilities during an incident.

Preparation also requires testing. Recovery procedures that exist only on paper may not perform as expected during a real incident, while scenario exercises often expose practical challenges such as transport availability, communication pathways, and the time needed to relocate large sample collections under validated conditions.

For irreplaceable or high-value material, that preparation can make the difference between a manageable operational incident and the loss of years of scientific evidence.

Compliance depends on evidence

Maintaining the correct storage conditions is only part of the challenge. Organisations also need to demonstrate that samples remained within validated conditions throughout their storage lifecycle.

Current Good Manufacturing Practice (cGMP)³ and ICH guidance⁴ set clear expectations for how samples are stored, monitored, and documented. Storage environments must remain qualified, monitoring systems must perform as intended, and organisations need complete, reliable records to demonstrate that materials remain suitable for their intended purpose.

During an inspection, organisations may be asked not only whether samples remained within specification, but how they know that to be true. Environmental monitoring records, maintenance logs, inventory systems, and chain-of-custody documentation provide the evidence needed to answer that question. Missing or incomplete records can undermine confidence in sample integrity, even where no temperature excursion has occurred.

Protection doesn't end at the storage room door

Protecting samples does not end once they enter storage. Cell and gene therapy materials frequently move between collection centres, manufacturing facilities, analytical laboratories, and long-term storage sites. Similar transfer pathways increasingly exist across biologics and other complex pharmaceutical products. Every movement introduces another opportunity for delays, handling errors, or temperature excursions.

As development programmes become increasingly global, maintaining sample integrity depends on consistent standards across both storage and transport. Validated shipping methods, robust chain-of-custody procedures, and complete traceability help ensure samples remain suitable for their intended purpose wherever they are stored or transferred.

Building resilience for the next generation of therapies

The demands placed on sample storage are unlikely to decrease. Cell and gene therapies, alongside increasingly complex biologics, are generating larger, more diverse sample collections while placing greater emphasis on traceability, regulatory compliance, and business continuity.

Maintaining contingency capability across multiple temperature ranges is not always practical for organisations whose primary focus is research, development, or manufacturing. Storage infrastructure, environmental monitoring, quality systems, and recovery resources all require ongoing investment, regardless of how frequently they are used.

Many organisations, therefore, combine internal capability with specialist external support to strengthen resilience and improve disaster recovery preparedness. Working alongside a single outsource partner that offers reliable monitoring, regulatory expertise, and robust backup systems can be advantageous. Rather than working with separate vendors, organisations such as these can help streamline operations from stability and biorepository storage to disaster recovery across validated temperature-controlled environments ranging from +60°C to -196°C.

As advanced therapies continue to mature, storage resilience will increasingly become part of manufacturing resilience. Every pharmaceutical organisation already has a storage strategy. The more important question is whether it has a recovery strategy.

The two are no longer the same thing.

References

About the author

Philip Bradley is the general manager at Astoriom, bringing nearly a decade of experience within the life sciences industry. Specialising in stability storage services, Bradley oversees operations across Astoriom’s multiple locations, ensuring the delivery of high-quality, temperature-controlled solutions that meet stringent compliance standards.