A New Approach for Understanding Container Closure Integrity over Shelf Life

Container systems must protect parenteral drug products through the entire shelf life. To accomplish this, container components (vial, elastomer stopper, and metal seal) must fit together well, and maintain an impervious seal. In a sealed system, elastomers are under compression, and it is well known that under compression they undergo relaxation. This raises the question whether such relaxation will affect the seal performance over time, and thus container closure integrity (CCI).

The traditional way to evaluate CCI was experimentally – accelerated or real-time – either way, a long process.  Dr. Qingyu Zeng, Principal Scientist in the Scientific Insights Laboratory, addressed this issue in his presentation:  Critical Consideration in Time Dependent Evaluation and Modeling for Rubber Stopper Seal Performance, at Parenteral Drug Association Europe’s Conference in Barcelona, Spain (March 15, 2017). This research represents a new, multi-discipline approach to gain insight into how elastomer material properties can affect CCI – an area where little research has been done. Employing empirical data and modeling on standard vial/stopper systems, an in-depth understanding of time- and temperature-dependent effects is being developed.

Compression stress relaxation (CSR) and residual seal force (RSF) data show that relaxation follows a defined exponential decay that ultimately levels – a decay for which a mathematical expression can be written. Knowing what RSF an elastomer needs to maintain good seal, and knowing how RSF changes with time, enables proper setting of initial RSF to meet shelf life requirements, and reduces reliance upon time-consuming experimental studies. Furthermore, this work can be extended to understand the influences of other factors (e.g., fillers) on RSF change. 

Dr. Zeng’s presentation is an example of West’s commitment to effective delivery of drug products—fundamental research that results in better container system performance, and more important, better patient outcomes. To learn more about West’s key areas of expertise, visit the Knowledge Center.