Mechanical Container Closure Integrity Test: A Method for Cartridge Systems

Abstract

A cartridge container closure integrity control strategy may leverage a combination of test methods to ensure drug products in the assembled container system are protected from an exchange with the external environment. These methods provide evidence supporting the suitability of the container closure system; however, some methods involve extended test times, complex setups, subjective interpretation and are destructive. A method that mitigates such factors was developed to improve upon testing utilized within the control strategy. Reviewing the underlying principles of internal methods and external standards resulted in two potential paths, a Force Decay method and Constant Force method, to improve on the cartridge control strategy using a linear mechanical testing system. The Force Decay method monitors the force decay signal obtained from applying a pre-determined force and holding the displacement constant for a desired timeframe. The Constant Force method monitors the displacement signal obtained from applying a predetermined force and holding the force constant for a desired timeframe. Supplementing experimental data generated for both methods with finite element analysis along with a first principles derivation of the system response aided in a recommendation to utilize the constant force method for cartridge container closure integrity leak testing. The constant force method was then optimized to attain the best signal response for leak detection and ensure a robust method. The data generated in this article supports the viability of using the constant force mechanical container closure integrity test method for improving the in-process CCI testing strategy for solution products.