Feasibility of Using Fluorescence Spectrophotometry to Develop a Sensitive Dye Immersion Method for Container Closure Integrity Testing of Prefilled Syringes.

摘要

Ensuring container closure integrity of injectable pharmaceutical products is necessary to maintain quality throughout the shelf life of a sterile drug product. Container closure integrity testing has routinely been used to evaluate closure integrity during product development and production line qualification of prefilled syringes, vials, and devices. However, container closure integrity testing has recently gained industry attention due to increased regulatory agency scrutiny regarding the analytical rigor of container closure integrity testing methods and expectations to use container closure integrity testing in lieu of sterility tests in stability programs. Methylene blue dye is often used for dye ingress testing of container closure integrity, but we found it unsuitable for reliable detection of small breaches in prefilled syringes of drug product. This work describes the suitability and advantages of using a fluorescent dye and spectroscopic detection for a robust, sensitive, and quality control-friendly container closure integrity testing method for prefilled syringes.