馃敩 Filter Integrity Test: Assurance of Sterility in Critical Processes
A Filter Integrity Test (FIT)聽is a crucial, non-destructive validation procedure used predominantly in the pharmaceutical, biotechnology, and food and beverage industries.
Its primary purpose is to confirm the structural integrity of a filter membrane and the entire filtration assembly (including housing and seals) after sterilization and/or production. This testing ensures that the filter is capable of consistently removing contaminants, particularly microorganisms like bacteria, down to the required level, thus guaranteeing the sterility聽and quality of the final product. Regulatory bodies, such as the FDA and EMA, mandate that sterilizing-grade filters must be tested post-use聽to confirm their performance during the batch run.
The Science: Correlating Physical Tests to Bacterial Retention
Since directly challenging a production filter with live bacteria is a destructive and impractical method, Filter Integrity Tests rely on validated non-destructive physical tests. These tests measure a physical parameter of the filter, such as flow rate or pressure, which has been mathematically correlated by the filter manufacturer to the filter's minimum retention capability (the ability to hold back a specific size of bacteria, typically Brevundimonas diminuta聽for 0.22 $\mu\text{m}$聽sterilizing filters). Testing is often recommended pre-use聽(Pre-Use, Post-Sterilization Integrity Testing or PUPSIT) to prevent the use of a damaged filter, but is always required post-use to ensure no damage occurred during processing.
Primary Types of Integrity Tests
The choice of test depends on the filter material and its properties (hydrophilic or hydrophobic):
Bubble Point Test (BP):聽This is the most widely used test. A wetted filter is subjected to gradually increasing gas pressure. The pressure at which the gas begins to form a continuous stream of bubbles on the downstream side (due to the gas overcoming the capillary forces holding the liquid in the largest pores) is the Bubble Point. This pressure directly correlates with the largest pore size. A low BP indicates a defect or a larger-than-specified pore size.
Diffusion/Forward Flow Test (FF):聽This test measures the bulk flow of gas that diffuses through the water-filled pores of the wetted membrane at a pressure typically around 80% of the Bubble Point. At this pressure, any bulk flow beyond the expected diffusive flow indicates a defect (a large hole or leak). The Pressure Hold (or Pressure Decay)聽test is a variation where the pressure drop over time is measured instead of the flow.
Water Intrusion Test (WIT):聽This test is specifically used for hydrophobic聽(water-repelling) filters, such as those used for air or gas filtration. Water is pressurized against the filter; an integral, hydrophobic filter will repel the water. The test measures the minimal amount of water intrusion (flow) that occurs. An increased flow indicates damage or a loss of hydrophobicity.