Selecting The Best Deterministic Method For Your CCIT Project

Container Closure Integrity Testing (CCIT) is essential for maintaining drug product sterility, particularly in combination devices like prefilled syringes. Over the past 15 years, regulatory perspectives on CCIT have shifted, favoring validated integrity testing over sterility testing during stability studies. The FDA’s 2008 guidance recommended replacing sterility tests with validated CCIT methods, including vacuum decay, bubble tests, dye penetration, and trace gas leak detection.

In 2016, updates to USP <1207> significantly expanded CCIT guidelines, introducing key concepts such as the Maximum Acceptable Leakage Limit (MALL), set at 6E-6 mbar * L/sec. This threshold ensures product safety and may vary based on product requirements. Additionally, the concept of inherent CCIT emerged, emphasizing the need to test empty vials within validated packaging systems to confirm closure integrity.

Regulators now prefer deterministic methods, like vacuum decay and high-voltage leak detection, due to their reliability and sensitivity. While probabilistic methods (e.g., dye penetration) are not entirely dismissed, their use requires strong justification. With increasing regulatory expectations, manufacturers must develop comprehensive container closure system profiles and validate CCIT methods specific to each product-package combination.

USP <1207> provides a framework but does not prescribe specific techniques, recognizing that no single method suits all packaging configurations. To ensure compliance, manufacturers must understand various CCIT techniques, their advantages, and limitations, allowing them to implement the most effective and regulatory-compliant approach for their specific products.