Cell therapy clinical trial storage means keeping investigational doses, retention samples and patient samples continuously below –150 °C in the vapour phase of liquid nitrogen, with complete records, and moving them to clinical sites in qualified dry shippers. How much capacity, which locations and which retention periods you need depends on trial phase, product type and GMP rules for investigational products.
Cell therapies are advanced therapy medicinal products (ATMPs), and they behave very differently from small molecules in a supply chain. A batch of living cells cannot simply be re-manufactured. In autologous therapies such as CAR-T, the starting material comes from the patient, and each batch belongs to exactly one person. A temperature failure in storage or in transit therefore costs more than material: it can cost a treatment option and months on the trial timeline. This article covers what is stored, how requirements change from Phase I to Phase III, how long retention samples must be kept, central versus site storage, and how investigational ATMPs are shipped.
A cell therapy study generates several sample types, each with its own handling rules:
For living cells, vapour-phase storage above liquid nitrogen is the accepted standard. At –196 °C in the liquid and below –150 °C in the vapour phase, no relevant biological activity takes place, and the vapour phase lowers the risk of cross-contamination through liquid nitrogen. For keeping material of different quality grades apart, see our guide to separating research-grade and clinical-grade samples.
Storage and logistics needs grow as a programme moves through development. A set-up that works for one site in Phase I has to scale across countries by Phase III.
Early studies treat few patients at one or two sites, often with manufacturing in an academic or hospital GMP facility. There are few batches and heavy analytics per batch. One or two cryogenic tanks with clearly separated zones for investigational product, retention samples and research samples are usually enough. Qualified equipment with IQ/OQ documentation already matters here, because Phase I data feeds into the eventual marketing application.
As enrolment grows, so does the number of sites and the number of shipments. Every dose travels from the manufacturing site to the clinic, and in autologous programmes the apheresis material travels the other way first. The trial now needs a robust logistics design with qualified shippers, temperature recording and defined hand-over points.
Pivotal trials treat hundreds of patients in several countries. Storage capacity, redundancy and monitoring need to approach commercial operation. Many sponsors build central cryogenic depots at this stage that later supply the market. What regulators look for in those facilities is covered in our FDA and EMA cryogenic storage inspection checklist.
For investigational medicinal products, EU GMP for IMPs (formerly Annex 13, now set out in Commission Delegated Regulation (EU) 2017/1569 and the accompanying Commission guidelines) requires reference and retention samples of each batch to be kept for at least two years after completion or formal discontinuation of the last clinical trial in which the batch was used. The trial master file itself must be archived for at least 25 years after the end of the trial under the Clinical Trials Regulation (EU) No 536/2014.
ATMPs get a specific allowance. The EU GMP guidelines for ATMPs (EudraLex Volume 4, Part IV) recognise that material is scarce for autologous products and very small batches. Retention samples can then be reduced or replaced with other material such as intermediates, provided this is justified, risk-based and described in the trial application.
For the storage infrastructure, the practical point is simple: retention samples occupy positions for many years, often well beyond the trial itself. Build those years into capacity planning from day one rather than squeezing samples into full tanks later.
Every multicentre trial has to decide where doses and samples live. Both models are valid.
All batches, retention samples and often trial samples sit in one central depot at the manufacturer or a specialist provider. Sites receive a dose shortly before the scheduled infusion.
Strengths: uniform conditions, one monitoring system, one set of records, fewer containers overall. Weaknesses: every dose has to be shipped, and the schedule depends on the logistics chain.
Clinical sites hold doses locally, for instance in the hospital pharmacy or a stem cell facility. Response times shorten, but every site needs qualified tanks, trained staff, monitoring and emergency procedures.
Strengths: flexible scheduling, fewer time-critical shipments. Weaknesses: many locations to qualify and audit, and more scope for inconsistent conditions.
In practice, many sponsors combine the two: retention samples and reserve stock centrally, individual doses moved to the site at short notice. For the wider context of storing clinical material, see our article on proper sample storage in clinical trials.
Transport is the most exposed link in the cold chain. For cell therapies, the dry shipper is the established solution: liquid nitrogen is absorbed into a porous material, so there is no free liquid, the payload stays cryogenic for the duration of the journey, and the shipper can travel by air under IATA rules.
Four things make investigational product shipping safe:
A qualified shipper: hold time and temperature profile proven for the longest realistic journey, delays included.
Continuous temperature data: a data logger records the whole journey. Without that record, a delayed dose cannot be released.
Chain of identity and chain of custody: every hand-over is recorded, and the link between dose and patient is never in doubt.
Defined receipt at the site: acceptance, review of temperature data, transfer into a cryogenic tank or thaw according to SOP.
ISO 21973 sets out general requirements for transporting cells for therapeutic use and is a useful frame for shipper qualification. For container selection and temperature validation in detail, read our guide to cryogenic sample shipping with dry shippers.
Clinical trials follow Good Clinical Practice (ICH E6); manufacturing of the investigational product follows GMP. For cryogenic storage that translates into specific evidence:
The weak spot is usually the interface between manufacturing, storage and transport. When each stage runs its own systems, gaps appear in the record. One continuous concept from freezing to storage to shipping closes them. For product-specific requirements, see our article on cryogenic storage for CAR-T cell therapies.
Consarctic® is a market-leading German provider of cryogenic systems for the life sciences and supplies the building blocks of a trial cold chain as one integrated system:
Consarctic has been certified to EN ISO 13485 since 2003 and works to ISO 9001:2015. References in cell and gene therapy include Minaris Regenerative Medicine.
Under EU GMP for investigational products, at least two years after completion or formal discontinuation of the last clinical trial in which the batch was used. For ATMPs with scarce material, such as autologous cell therapies, the amount and type of retention sample can be adapted with a documented justification.
Central storage gives uniform conditions and less qualification work, but every dose has to be shipped. Site storage shortens the path to the patient but needs qualified equipment and trained staff at every site. Many sponsors combine both.
Usually in qualified dry shippers, in which the liquid nitrogen is absorbed, with a data logger recording the full temperature history. Every hand-over is documented as part of the chain of identity and chain of custody.
Typically in the vapour phase above liquid nitrogen, below –150 °C. The exact storage temperature is set by the manufacturer based on its stability data.
Planning the cryogenic infrastructure for a cell therapy trial? Consarctic's specialists support you from capacity planning and qualification to the transport concept.