The integrity of filters is a key point in the confirmation and batch release of sterile drug production. For critical sterilization level filtration processes, integrity testing is a certification to control the quality of filter production and ensure the safety of the sterilization process. At the same time, conducting integrity testing is also a requirement of regulations and audits in various countries.
Integrity testing classification:
The integrity testing of sterilization filters is divided into destructive testing (bacterial/particle challenge testing) and non-destructive testing (mainly including bubble point and water intrusion testing based on capillary principles, as well as diffusion flow and pressure maintenance/attenuation testing based on diffusion principles).
The purpose of destructive testing is to determine whether the filter is a sterilization grade filter. The testing method is based on the FDA‘s definition of sterilization grade filters (e.g. ASTM F838), which is the gold standard for bacterial retention testing. For sterilization grade filters, after adding a large number of challenging bacteria in the experiment, the filter cannot be cleaned and used again, so it is called destructive testing.
Non destructive integrity testing is an alternative test associated with bacterial challenge testing. The purpose of non-destructive testing is to determine whether there are defects that may jeopardize the retention capacity of the filter without damaging it. The testing method is as follows:
Bubble Point:
The minimum pressure required for gas to be extruded from the largest pore of a fully wetted porous membrane and form a continuous, stable, or large amount of gas. When the measured bubble point value is greater than the standard minimum bubble point value, the filter integrity test is qualified.
Features: 1. Detect the maximum opening diameter of the filter membrane
2. It is unrelated to the porosity, thickness, and usage status of the filter membrane
3. It is difficult to distinguish the changes in filter membrane material
4. Integrity testing of disc filter membranes and small filter cartridges
5. Sensitivity decreases at higher pressures and larger membrane areas
Diffusion Flow:
Apply a gas pressure below the bubble point, and the gas molecules diffuse through the fully wetted membrane pores to the downstream gas flow rate of the filter membrane. If the measured result is lower than the standard diffusion flow limit under the given test pressure, the integrity test is qualified.
Features: 1. Directly detected traffic values
2. Constant and gentle detection pressure
3. Can detect ultra large area filter membranes
4. Can reflect the thickness and usage status of the filter membrane
5. Can be continuously detected
6. Can reflect changes in filter membrane material and process
Pressure Hold/Pressure Decay:
It is another form of diffusion testing. A high-precision pressure sensor is used to monitor pressure changes caused by leaks or gas passing through filters. This test is conducted to verify the integrity of the sealed casing or system, or to check the integrity of the filter. If the measured pressure attenuation value is lower than the given standard value, the integrity test is qualified.
Water Invasion/HydroCorrTM:
The water intrusion method is specifically designed for testing hydrophobic filter cartridges. It is to measure the resistance of a dry hydrophobic filter membrane to water wetting under a certain pressure, that is, to measure the "apparent" water flow rate formed by a small but measurable liquid level drop below the breakthrough pressure of water. If the measured water intrusion flow rate is lower than the given maximum allowable flow rate (i.e. standard test index), the integrity test is qualified.
Features: 1. Compliant with FDA‘s integrity testing requirements for sterilization grade filter cartridges
2. No need to introduce flammable or potentially polluting solutions
3. It can keep the filter membrane dry and shorten the time required to blow dry the filter after testing, without the need for downstream operations
The test results of filter integrity are an important basis for making batch release decisions. SGS uses automated integrity testers to perform filter integrity testing and generate various records that comply with data integrity regulations, providing you with professional quality control services.