Comparison between two types of water baths (wet and dry) in the context of the CAR-T cell reinjection circuit

Introduction
CAR-T cells are Advanced Therapy Medicinal Products that follow a specific circuit within hospital pharmacy. Given the increasing activity related to their use (+148% between 2022 and 2023 in our center), the pharmaceutical team sought to optimize the thawing step of CAR-T cell bags using a water bath (WB). The objective was to compare a currently used wet water bath (WWB) and a dry water bath (DWB).

Materials and Methods
Various parameters related to water baths were identified using manufacturer technical sheets and classified according to 9 characteristics: operating mode, dimensions, empty weight, time to reach 37°C, cost, maintenance, sterile water consumption, filling and draining system, and safety system. This process enabled the creation of a comparative table. A comparison of different usage times of these two water baths (filling, thawing, draining) was conducted. For thawing time measurement, a factitious bag of 68 ml provided by a CAR-T cell laboratory was thawed in both the WWB and DWB. Then, 6 test bags representing another laboratory were created to closely replicate the cell dispersion environment (50 ml empty bag, 23.75 ml of 0.9% NaCl, 1.25 ml or 5% of CryoStor CS10). Three test bags were thawed for each WB.

Results
WWB thaws a bag by immersing it in water at 37°C, whereas in DWB, the bag is placed between two heating cushions without direct contact with water. Water consumption for the WWB averages 3 plastic containers of 5L sterile water per week (about 780L per year) versus 9L of demineralized water once a year for the DWB. WWB has a manual filling and draining system (posing maneuverability challenges due to weight), while DWB offers an automatic system. WWB’s price is 2 to 3 times lower than DWB. Time to reach 37°C, maintenance, and safety system are similar for both water baths. Measurements showed that total average usage time (filling, thawing, draining) for WWB is 22 minutes, whereas for DWB, it ranges from 11.5 minutes to 8.2 minutes depending on different CAR-T cells. Thawing time for the factitious bag is longer for DWB at 9 minutes compared to 4 minutes for WWB and 5.7 minutes versus 3.7 minutes for test bags.

Conclusion/Discussion
Despite a higher cost, DWB offers several advantages. It is easier to use due to its automatic system and it is more ecological by limiting plastic and water consumption. The overall thawing step (filling, thawing, draining) is optimized, saving time for the user. The main disadvantage is the longer thawing time, which may need to be considered for CAR-T cells with short stability durations.

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