Development of Probabilistic Model to Predict Residual Seal Force of Crimped Vial Seals

Abstract

One of the most important requirements for a sterile packaging system is container closure integrity (CCI). For vial-based systems comprised of a vial, a hyper-elastic stopper, and a rigid crimp seal, CCI testing is an integral part of the drug development process.  During the vial-capping process, the component dimensions and materials play a critical role in creating a robust and adequate seal that will satisfy CCI. Although these properties are manufactured within certain tolerances there exist lot to lot variabilities and aging effects. If not taken into consideration during initial design, these factors can potentially impact the Residual Seal Force (RSF)  for a container closure system (CCS). Residual Seal Force (RSF) of the vial, while not predictive or causal, is correlated with CCI. For example, is possible that containers with sufficient RSF can contain defects that compromise CCI, including but not limited to fibers, cracks, and folds.

A robust and efficient deterministic finite element model capable of predicting RSF for fixed displacement crimping systems was developed for this study. A probabilistic analysis was conducted, and stopper top dimensions (height and outer diameter (OD)) were found to be the most important drivers of seal force magnitude and variation. Seal force was positively correlated with both stopper height and OD. The effect of 2-year accelerated aging of the stopper, prior to assembly, was an increase to material stiffness and corresponding seal force. However, this increase in force was small (~3%). This corresponds well with practical findings where shelf aging is typically associated with increased material stiffness over time as well as an increase in RSF.