Experimental and numerical investigation of container closure integrity in prefilled syringes at ultracold...

The increasing demand for deep-frozen pharmaceutical storage intensified by mRNA-based therapeutics poses new challenges for Container Closure Integrity (CCI) in prefilled syringe systems. This study presents a comprehensive investigation of CCI failure mechanisms at ultracold temperatures, combining micro-tensile characterization, advanced numerical modelling, and validation via a modified dye-ingress method. Results reveal that CCI failure consistently occurs below the rubber glass transition temperature, initiating with contact loss at the plunger ribs and progressing to complete leakage past the trimmed edge. These failures follow reproducible patterns confirmed by both experiments and simulations. The underlying mechanism arises from the interplay between thermal contraction, viscoplastic response, and loss of contact at the rubber-glass interface, with simulation results supporting plastic "freezing" of deformation as the dominant failure mode. The findings underscore the need to re-engineer elastomeric materials and sealing strategies for reliable performance under ultra-low temperature conditions and provide a predictive framework for future CCI assessment.