How To Build A Vial-Stopper Combination Suitable For Drug Product Storage At -80°C

By Jennifer Roark, Technology Manager, Container Closure Integrity, Analytical Labs

Advanced therapies are rapidly becoming a reality, targeting unmet patient needs and treatments for diseases with limited therapeutic options. Some advanced therapies, such as gene therapy and mRNA, require frozen storage due to their fragile nature at ambient temperature, putting unprecedented expectations on the vial-stopper-seal combination to maintain container closure integrity (CCI) during storage at low temperature conditions. The quality, patient safety, and high value of these therapeutics can be jeopardized if the chosen vial-stopper-seal combination doesn’t maintain a sterile barrier from when the drug is packaged through to administration to the patient. During cooling from ambient temperature to temperatures below -80°C, packaging components such as glass vials, elastomeric closures, and aluminum seals exhibit contraction and changes in physico-mechanical properties. These changes in material properties and component dimensions may affect their ability to maintain CCI, resulting in the formation of transient leaks.

The objective of this joint study conducted by West and Corning Incorporated was to determine if the chosen vial-stopper-seal combination will remain integral while frozen at -80°C, under studied conditions, when the appropriate materials, processing, and sealing conditions are applied. The study was conducted in four separate experiments to explore the influences of capping force, cooling rate, dimensional changes, and long-term storage at -80°C on the vial-stopper-seal combination’s ability to maintain closure integrity.