Container Closure Integrity of Vial Primary Packaging Systems under Frozen Storage Conditions: A Case Study

Abstract

As the complexities of the pharmaceuticals needed to prevail over serious diseases continue to grow, the need for technologies to enable their efficient storage and delivery are as essential as ever. Lately, drugs such as vaccines, proteins, and stem cells are increasingly requiring frozen storage to maintain their efficacies before use. Notably, the advent of cellular therapy products has invariably elevated the need for cryopreservation and frozen storage of cellular starting materials, intermediates, and/or final product. The container closure integrity (CCI)—which is a major requirement for aseptic or sterile packaging systems—at these extremely low temperatures has not been fully understood. For vial-based systems particularly, the commonly used rubber stoppers are expected to lose their elastic properties below their glass transition temperatures, suggesting a potential temporary loss of sealability under frozen storage conditions and posing a risk to CCI. The measurement of the CCI at these conditions such as −80°C is therefore critical; a process that can be very challenging. Previous works had explored the use of Oxygen Headspace Analysis to measure CCI at low temperatures. Here, we present the evaluation of the CCI of rubber-stoppered aluminosilicate glass vials (Valor®) and plastic vials (Crystal Zenith®) using the helium leak CCI test method at −80°C, with correlation to residual seal force (RSF). The results and their implications are then discussed with regard to the suitability of certain packaging components as frozen storage container closure systems.