Sterile filter integrity testing is a fundamental requirement for critical applications, with regulatory agencies worldwide establishing specific guidelines for its execution. So, what methods are available for integrity testing?
Destructive Testing
The bacterial challenge test, conducted in accordance with ASTM F838-15, is the optimal method for determining the bacterial retention capability of sterile filters. However, because this test introduces a high concentration of challenge microorganisms, the filter cannot be cleaned or reused afterward; hence, it is termed a destructive test. As the gold standard for bacterial retention testing, manufacturers typically employ this method to perform sampling inspections on filter membranes and housings during the production process.
Non-Destructive Testing
Due to the limitations of destructive testing, users typically employ non-destructive alternative methods for the integrity testing of sterile filters. Common methods include the bubble point test, diffusion test, and water intrusion test. The commonly referred to diffusion flow test, pressure hold test, and pressure decay test are all classified as diffusion tests due to their similar underlying principles.
Furthermore, it must be noted that regardless of the method employed, such physical tests must be correlated with bacterial retention capability.
Bubble Point Test
The bubble point test is the most widely applied non-destructive test. Liquid is retained within the membrane pores due to surface tension and capillary forces. The minimum pressure required to expel the liquid from the largest membrane pore is defined as the bubble point value. When the measured bubble point value exceeds the specified minimum standard, the filter passes the integrity test.
Diffusion Test
01 Diffusion Flow Test
A diffusion flow test pressure is set at a percentage (typically 80%) of the minimum bubble point pressure. With the filter membrane fully wetted, gas molecules migrate through the water-filled membrane pores in accordance with Fick’s Law of Diffusion. The gas diffusion flow rate of a filter is directly proportional to the pressure differential and the filtration area. If the measured result at the given test pressure is below the standard diffusion flow limit, the filter passes the integrity test.
02 Pressure Hold Test
Also known as the pressure decay test, this is another form of diffusion testing. This test requires the installation of a high-precision pressure gauge to detect pressure changes on the upstream side of the filter caused by gas diffusion. Since it does not require measuring gas flow on the downstream side, it significantly reduces the risk of downstream contamination. The pressure hold value is correlated with the diffusion flow and the upstream volume. Typically, if the measured pressure decay value is below the specified standard limit, the filter passes the integrity test.