An increasing number of pharmaceuticals including vaccines, stem cells, and proteins require cold storage to maintain efficacy prior to use.
However, the ability to maintain container closure integrity (CCI) during cold storage is still not completely understood. Concerns about CCI failure have been raised for the storage and shipment of pharmaceutical products in rubber-stoppered vials under cold conditions (such as -80°C or dry ice).
Commonly used butyl stoppers are believed to lose their elastic properties below their glass transition temperature (Tg) posing a risk to sealability. The temporary loss of CCI under cold conditions can allow cold, dense gas from the surrounding low-temperature storage environment to leak into the stored vial.
Ingress of the gas can contribute to loss of efficacy of the stored drug product due to interaction with the gas as well as overpressurisation of the vial. Overpressurisation occurs when cold, dense gas becomes trapped within the vial as the rubber stopper warms to a temperature above its Tg after it is removed from the cold storage conditions.
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