Defect Detection Sensitivity of Bubble-Point-Type Tests for Sterilizing-Grade Membrane Cartridge Filters

Area of Science:

• Filtration and Separation Science
• Microbiology
• Biopharmaceutical Manufacturing

Background:

• Bubble point tests are standard for sterilizing-grade membrane cartridge filter integrity.
• Previous studies highlighted bubble point test limitations, but bacterial retention assurance from automated integrity testers (AITs) remained unquantified.

Purpose of the Study:

• To quantify the bacterial retention assurance provided by bubble point tests using AITs.
• To determine the sensitivity of AITs to filter defects and correlate defect size with bacterial retention.

Main Methods:

• Utilized three AITs to test 10-inch (25.4 cm) sterilizing-grade cartridge filters with controlled laser-drilled defects.
• Quantified the minimum defect size causing a bubble point test failure and bacterial log reduction values.

Main Results:

• AITs' bubble point tests were insensitive to defect sizes until gross leak failure.
• Minimum defect diameter causing failure ranged from 30 to 60 µm, correlating to bacterial log reduction values of 4.0–4.5.
• Defect size sensitivity varied by filter type and test conditions.

Conclusions:

• Bubble point tests with AITs do not reliably detect small defects that compromise bacterial retention.
• Recommended practice is to pair bubble point tests with complementary gas-liquid diffusion tests for comprehensive filter integrity assessment.
• This combined approach enhances bacterial retention assurance in critical filtration processes.