Container Closure Integrity Testing For Sterile Vial Products In Deep Cold Storage

Storage of sterile pharmaceutical product vials at -80°C is sometimes practiced to increase shelf life, especially for cell and gene therapies and live viral vaccines. In addition, vials are sometimes stored on dry ice during transport to achieve a cold storage shipment. Storing vial product samples at such low temperatures can, however, result in practical problems such as (temporary) closure integrity failures.

A vaccine-focused biotechnology company approached LIGHTHOUSE to help investigate a phenomenon observed in liquid vaccine product stored at -80°C. During QC testing, a number of vials were found to have an overpressure. The vaccine samples, frozen in glass vials with rubber stoppers, were thawed to room temperature prior to QC testing. When the rubber stopper was punctured with a syringe needle, the syringe pistons in some of the samples moved backwards. After removal of the needle, vaccine product shot out of the needle insertion holes indicating a considerable overpressure in these vials. This phenomenon represented a serious safety risk and LIGHTHOUSE was asked to support an investigation to identify the root cause. The working hypothesis was a potential container closure issue during cold storage at -80°C. Working closely with the client, LIGHTHOUSE carried out a series of studies to investigate this hypothesis using headspace analysis systems. These laserbased platforms enable rapid non-destructive characterization of the headspace gas conditions inside a sealed container.