Abstract 25
Introduction
Transient warming events (TWE) are brief exposures of a cryopreserved product to temperatures above the critical storage temperature. Cord blood units (CBUs) are routinely stored in liquid nitrogen at –196°C. The viability and potency of CBUs may be reduced because of TWEs during operational activities. Ultimately, this loss of viability and potency may affect the clinical effectiveness of CBU transplants.
Study Design and Methods
A TWE study was conducted that consisted of three phases; first, the kinetics of transient warming to 0°C were studied using temperature probes on CBU bags. Second, the processing time to reach an allowable (−135°C) and deviant (−120°C) temperature in the CBU was determined based on (a) phase I kinetic data and (b) an assessment of ambient room temperature and exposure durations during operational activities. Third, a pool and split study was performed to assess the effect of TWE scenarios in CBU post‐thaw quality criteria (CD45+ and CD34+ cell viability and recovery, colony‐forming unit [CFU] growth).
Results
Kinetic and operational data supported our selections for the warming scenarios; the 5‐ml compartment warmed faster than the 20‐ml compartment, taking a minimum of 130 seconds to reach –135°C and a minimum of 176 seconds to reach −120°C. The post‐thaw data showed that warming events can affect the quality of the CBU, with several significant differences between the control and either the typical TWE scenario (5 ml bag CD45+ viability [p = .0469], CD45+ yield [p = .0406], and CFU‐GM [p = .0388]) or worst case TWE scenario (20 ml CFU‐total yield [p = .0205], 5 ml CFU‐GM yield [p = .0388]). All segment samples met CD34+ and CFU potency criteria but several segment samples failed to meet requirements for CD45+ viability.
Discussion
Transient warming events were shown to affect product quality, but the effects were small for the scenarios tested and, while in some cases the segments failed to meet quality thresholds, the results in the 5 ml and 20 ml bag compartments met our post‐thaw acceptance criteria. Therefore, efforts should be taken to establish critical processing constraints for CBB to minimize the impact of TWE on product quality.