Non-destructive integrity testing is meaningful only when correlated with the bacterial retention capability of a specific filter.
Under standard test conditions, bacterial retention challenges are performed on a series of specific filter membranes with progressively “tighter” structures. Based on the test results, the retention capability of that type of filter membrane can be determined. Typically, by observing the retention pattern, a standard value for physical testing can be established; above this standard, no bacterial penetration is observed.
The integrity test metrics determined through this series of tests can represent the bacterial retention capability of the filter.
One chart to summarize.
The integrity testing method for production filters should be selected based on filter characteristics, product, and process conditions to ensure reliable test results.
The non-destructive tests described previously, including the bubble point test, diffusion flow test (also known as forward flow test), and pressure hold test, can all be used to determine test standards based on the aforementioned trials and serve as detection methods for production filters. However, each testing method has its own advantages and limitations.
Simply put, the resolution of the bubble point test decreases as the filter area increases because the increased diffusion flow interferes with bubble point detection. The diffusion flow test is not directly related to the membrane pore size; therefore, it requires determining the test pressure conditions based on the minimum bubble point value to provide quantitative detection. When the filter area is too small, the diffusion flow is too low, which may affect detection accuracy.
• For large-area filters, the diffusion flow test is recommended.
• For small-area filters, the bubble point test is recommended.
Integrity testing of sterilizing-grade filters is a fundamental element in ensuring sterility assurance levels. However, due to the limitations of detection methods, relying solely on integrity testing is insufficient to guarantee sterility assurance levels; other factors must also be considered:
• The process control and quality system of the filter manufacturer should ensure quality assurance and product uniformity of the filter membranes and filters.
• Filter users should perform validation based on the product, process conditions, and specific filter to ensure bacterial retention capability under specific conditions.
• Filter users should ensure appropriate product/process control (e.g., operating parameters, microbial burden, etc.).