Container/Closure Integrity Testing and the Identification of a Suitable Vial/Stopper Combination for Low-Temperature Storage at -80 {degrees}C.

Unlabelled: It was recently found that after storage of a live viral vaccine at -80 °C in glass vials closed with rubber stoppers, a phenomenon was revealed which had not been observed before with other viral products stored at -20 °C: overpressure in the vials. As this phenomenon poses a serious safety problem for medical personnel as well as for the product itself, an investigation was initiated to identify the root cause of the overpressure. After exclusion of possible root causes (differences in air temperature or atmospheric air pressure during filling and quality control testing, outgassing from the formulation buffer) the remaining hypothesis involved a possible container closure integrity issue at low temperature.