The primary purpose of filter integrity testing is to ensure that the filters used in pharmaceutical manufacturing processes are functioning correctly. This is essential to prevent contamination and ensure the sterility of the final product.
In this test, the integrity of the filter membrane, disk filters, capsules/cartridges are checked. The machine that performs this task is called filter integrity machine, filters require integrity testing both before and after use.
Testing shall comply according to the method outlined in ASTM F838-05 (formerly ASTM F838-83), Standard Test Method for Determining Bacterial Retention of Membrane Filters Utilized for Liquid Filtration.
The FDA considers a filter as “Sterile” when it retains the challenge of bacteria Brevundimonas Dimunita at least 1×107 per cm2 of filtration area.
The following are the most common methods for non-destructive filter integrity testing:
- Bubble Point Test,
- Diffusion (forward flow) Test and
- Water Intrusion Test
1. Bubble Point Test
- This test works on the principle of capillary action and surface tension.
- Liquid when passed through the filter, fills inside the pores with the help of surface tension and capillary action.
- The minimum amount of pressure required to remove the liquid out from the pores helps measure the pore size.
The bubble point test goes like this:
- Filter is wetted with suitable solvent (‘water for hydrophilic filters’ and ‘water+alcohol for hydrophobic filters’) uniformly.
- Pressure is applied to the upstream of the filter. The amount of minimum pressure expected from the recommendations provided by filter manufacturers.
- If bubbling appears at a lower pressure than the set pressure, the test is considered a fail.
Possible reasons for failure:
- Incorrect installation of the filter inside the housing
- Filter wetting is non-uniform
- The unsuitable solvent used for wetting the filter is causing compatibility issues due to different surface tension than recommended.
2. Diffusion Test (forward flow)
This test works on the principle of Fick’s Law of Diffusion, where the rate of diffusion is directly proportional to the membrane’s surface area.
The procedure goes like this:
- Filter is wetted uniformly with a suitable solvent.
- Pressure is applied upstream of the membrane, gradually increased up to the recommended value and allowed for stabilization.
Possible reasons for failure:
- Incomplete wetted membrane
- Insufficient stabilization
- Filter failed integrity due to damaged pore size
3. Water Intrusion Test
This test is typically performed to detect the quality of defects of hydrophobic filters. These filters are installed as air vent filters.
GxP Requirement for Filter Integrity Units
- 21 CFR Part 11, Electronic Records, and Signatures , back up to be taken at interval time.
