How Do I Perform a Filter Integrity Test?

Integrity testing is used to demonstrate the integrity of a filter (usually sterilizing) to ensure that it will prevent the passage of contaminants (usually microorganisms) downstream of the filter, thereby protecting the process from the targeted contaminants.

Two tests must be performed:

1. The bubble point test is used to confirm that no pore in the filter exceeds the size quoted by the manufacturer. The smaller the ports, the higher the air pressure must be for bubbles to pass through the filter; and
2. The diffusion test is also used to confirm the integrity of the filter, i.e., that it is intact and that there is no leakage other than through its pores.

Terminology

Bubble point: the pressure at which bubbles appear in the effluent (steady stream of bubbles) of a wet filter under test (the bubble point quoted by the manufacturer should be used as the standard for verification);

Diffusion rates: the rate of air (or other sterile gas if applicable) escaping by diffusion from the wet filter under test measured at 80% of the bubble point pressure (quoted by the manufacturer) for 1 minute;

As found: A test performed on a filter before it is removed from service. It is used to confirm that the filter still had integrity before it was removed and therefore must have had integrity throughout its lifetime of service.

As left: Test performed on a filter before it is put into service. It is used to confirm that the filter is in good condition and therefore ready for use.

Note: Sterilization procedures may vary depending on your operations and industry. Before reactivating the system, please rely on your internal standards to ensure that the sterilization process meets your standards.

Bubble Point Test

The bubble point test is based on the premise that liquid is retained in the pores of a filter by surface tension and capillary forces. The pressure required to dislodge the liquid is related to the pore size. In fact, the smaller the pore, the greater the pressure required. The bubble point is the minimum pressure required to expel liquid from the largest pore in the filter.

Procedure

1. Wet the filter (hydrophilic filter: water, hydrophobic filter: isopropyl alcohol and water);
2. Pressurize the system (via the filter inlet) to approximately 80% of the manufacturer's quoted bubble point pressure;
3. Place a tube connected to the filter outlet in a basin of water; and
4. Gradually increase the pressure until constant and rapid bubbles appear at the filter outlet.

When a bubble point test fails, one of the following causes is possible:

1. Membrane not completely wet;
2. Test fluid with different surface tension than recommended test fluid (e.g., glycol vs. water vs. alcohol);
3. The filter is intact, but has the wrong porosity;
4. Higher temperature than recommended for the test; or
5. Membrane is damaged or incomplete sealing.

Scattering Test

The gas diffusion rate is proportional to the pressure differential and the surface area of the filter. At approximately 80% of the bubble point, the gas diffusion rate can be measured to verify the integrity of the filter. A maximum allowable gas diffusion rate is specified by the manufacturer to predict the filter's ability to retain microorganisms.

Procedure

1. Wet the filter (hydrophilic filter: water, hydrophobic filter: isopropyl alcohol and water);
2. Gradually increase the pressure at the filter inlet to the recommended manufacturer's test pressure, typically at least 80% of the manufacturer's specified bubble point.
3. Allow the system to reach equilibrium (i.e., wait a few minutes); and
4. Measure the gas flow rate at the outlet by displacing water in an inverted graduated cylinder in a container of water and towards which the outlet tubing is directed (note: measure for 1 minute and compared to the manufacturer's allowable volume).

When a failed scatter test happens, one of the following causes is likely:

1. Membrane not completely wet;
2. Insufficient equilibration time;
3. Test fluid different from recommended test fluid (e.g., glycol vs. water vs. alcohol);
4. Filter is intact, but has the wrong porosity;
5. Higher temperature than recommended for the test; or
6. The membrane is damaged or incomplete sealing.