Cryopreserved cell therapy products are usually stored in vapor or liquid storage tanks to maintain long-term viability. Storage tank (ST) failure can lead to the loss of cryopreserved cell therapy (CT) products, which means the only possibility of treating serious illnesses. We aimed to describe a serious vapor ST failure, as well as the improvements implemented in the storage procedure to increase the safety and quality of cryopreserved CT products.

This is a case report of a vapor ST failure (CBS, isothermal V5000-AB series). The records were reviewed to obtain information regarding the frozen units.

On 07-dec-2021, the technical staff observed the accumulation of liquid nitrogen (LN2) at the bottom of the ST. The engineering team was contacted and adjusted the ST's maximum LN2 level. The problem recurred on 23-dec-2021. The engineering and maintenance company carried out a series of tests on the ST. On 06-Jan-2022, it was requested emptying and defrosting of the ST for 48 hours for corrective maintenance of the LN2 level sensor. Planning to transfer the inventory to another ST was started, including bags with serology/NAT reagent overwrapping. However, on 23-Jan-2022 (Sunday), the LN2 level sensor stuck at level zero leading the automated LN2 filling of the ST to start and not stop. There was an overflow of LN2 inside the vapor ST, and 3 of 4 rack positions were submerged in LN2. The engineering team performed the filling interruption manually, after being called by the concierge. There were 553 frozen bags from 307 patients/donors stored in the ST at the time of failure. Out of the 553 bags, 87 (15.7%) had positive serology or NAT tests. Of these, 11 (1.9%) were anti-HIV positive (NAT HIV negative) and two (0.3%) were HBsAg and NAT HBV reagents. Out of the 553 bags, 10 (1.8%) had a positive microbiological test, including four (0.7%) for multi-sensitive Salmonella sp. Excess of LN2 was manually removed from the ST and the actions to transfer the inventory to the backup ST were intensified, including changing the bags with positive tests (PT) to positions A or B of the racks, as well as finishing these bags overwrapping. The inventory was transferred and stored in the backup ST for approximately 72 hours. Surveillance actions were performed, including virtual meeting and discussion with the Brazilian National Health Surveillance Agency, visual examination to disclose leaking or breakage of seals, thawing of the unit with positive HBV NAT (authorized disposal) to confirm the absence of leaking or breakage of seals, monitoring external signs of vacuum loss, and discussion of the possibility of cross-contamination with the bag supplier.

The data provided by this study are unique and should be considered when evaluating the cryopreserved cell therapy products storage procedure, including ST monitoring, detection of a failing ST, and contingency plan. After this ST failure, improvement actions in the storage procedure were implemented in our institution, including the modification of the storage location of the bags in quarantine and those with PT (positions A and B of the rack) and implementation of the routine use of overwrap in bags with PT. All activities conducted to resolve the issue and the improve actions were documented in non-compliance.

Vapor ST may fail, leading to an unexpected accumulation of LN2. Improvements in the storage procedure can avoid the serious consequences of this failure, including cross-contamination.