Container closure systems (CCS) for parenteral products must maintain sterility and product quality throughout their shelf life until final use. Traditionally, there is a tendency to demonstrate appropriate control of the integrity of a CCS through testing, e.g., by sterility and/or container closure integrity (CCI) testing of drug products.
A holistic approach to CCI is recommended and, in line with current regulations, a science- and risk-based approach in (bio)pharmaceutical product development and manufacture.
This approach is more robust and aims to build quality into the design and processes rather than testing or inspecting the finished product – and this is why we have published this paper.
It provides an industry perspective on ensuring CCI throughout the product lifecycle and includes discussions on development, validation, routine manufacturing, shipping and stability, and the ongoing monitoring of holistic CCI strategy. It also includes appendices on qualification activities, a process performance qualification readiness checklist, CCS assembly steps (and associated preventions and detections), and analytical considerations.
This paper is intended to trigger technical and scientific discussions. Key topics include:
- Building CCI of a parenteral drug product into the overall process and assuming CCI through a holistic approach, rather than relying solely on final release/stability testing of the product
- Taking a robust ‘quality by design’ approach with formalized risk assessments to de-risk CCI by the tailored design of critical component interfaces and confirming the robustness of design with characterization data.
To our knowledge, it is the first publication of an industry-wide view of a holistic approach to CCI for a parenteral product.