Container Closure Integrity Testing of Finished Sterile Injectable Product

Abstract

Note that, quite generally, a container that is gas-tight will also be tight against microbial ingress. [...]the requirement to maintain headspace gas conditions imposes higher standards on CCI than the requirement to maintain sterility. Test method parameters are optimized during method development and confirmed during validation. [...]a final leak test method is specific to a particular container-closure or product-package system." The framework described in the chapter is currently driving changes in industry best practices for CCI testing, including: * Implementation of a 'toolbox' of CCI test methods optimized and chosen on a per product configuration basis rather than the application of a single legacy test method in a one-size-fitsall approach * Generation of science-based CCI data in robust method validation studies, which demonstrate the detection of a critical leak represented by various types of positive controls. New concepts introduced in the regulatory guidance are changing industry best practices and include the following: * Generate science-based CCI data throughout the product lifecycle to build up a package integrity profile database that can be used as input for risk management. * When possible, use deterministic CCI test methods that have been validated to detect a critical leak. * There is no one-size-fits-all CCI test; a toolbox of CCIT technologies that can be optimized on a per-product package configuration is necessary for a robust CCIT program. Because industry best practices will be evolving as the impact of new guidance becomes clearer, a certain amount of uncertainty in CCIT best practices is to be expected in the near term.