This concept of “leaks of concern” is directly related to the maximum allowable leakage limit (MALL). There tends to be much confusion around the MALL, though at its core, it is a fairly straightforward concept: What is the leak size / rate at which there is a risk to product quality or safety over its intended shelf-life and use?
Furthermore, as part of a comprehensive risk assessment and mitigation strategy, the chapter describes package integrity verification during three product life cycle phases: 1) package development, and package processing and assembly validation; 2) product manufacturing; and 3) commercial product shelf-life stability assessments. This is a critical distinction to be made from historical practices, in which a finished product-package system was “verified” for integrity using a microbial or dye ingress test. Under current best practices, integrity assurance should be built into the package system and an integrity profile generated throughout the lifecycle.
Often times, a comprehensive CCI strategy includes implementing numerous CCI methods to address unique study goals. A strong preference is placed on deterministic methods based on predictable physicochemical phenomena quantitative in nature, compared to probabilistic methods, which rely on a series of probabilistic events (such as microbial ingress and growth), and tend to be qualitative in nature. Other assays, control strategies, and procedures that do not directly test CCI, but may directly characterize or influence it, can and should be included in a comprehensive CCI package. Package component vendor qualification, incoming lot inspection, and in-process residual seal force (RSF) testing are examples of this, defining and ensuring good “inputs” to create container systems.
Understanding the complex inter-workings of requirements, product-package limitations, CCI test options, and broader control and risk mitigation strategies requires an experienced team. CS Analytical consists of founding members of the world’s first cGMP, FDA-registered contract CCI laboratory housing all deterministic technologies as listed in USP <1207>. The resulting laboratory set standards and best practices for industry still used today, many of which are directly incorporated into USP <1207>. CS Analytical is the most trusted source for designing and implementing a comprehensive container closure integrity strategy to industry best practices that reduce organizational risk and exceed regulatory expectations.