Improving the Integrity Test Assurance of Multiround Housings Assessments - Pharmaceutical Technology

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Improving the Integrity Test Assurance of Multiround Housings Assessments
The authors describe a novel approach for the integrity testing of large sterile filter systems such as multiround housings and describe a multipoint diffusion test capable of detecting minor failures.

Pharmaceutical Technology

Integrity testing multiround filter housings is difficult and inaccurate because of the multitude of filter elements involved. The diffusive flow sum of all of the filter elements can make it difficult to detect a single flawed filter or determine the bubble point which is bulk flow point.

The single-point diffusion test reflects the overall diffusion rate of the cartridges being tested, thus increasing the risk for a minor failure (e.g., one single filter element with a loss in integrity) being potentially masked by the overall low diffusion values of the surrounding cartridges. A statistical approach with a reduced maximum allowable diffusion test limit would reduce this potential risk.

The bubble point will reflect the biggest pore-size area. Its accuracy depends on the capacity of the integrity test unit to detect the over-proportional increase of gas flow when passing from the diffusive flow region to the bulk flow region. For a large filtration area this transition phase potentially will be masked because of the overall high diffusion rate. In addition, the bulk flow through possible flaws does not increase exponentially as the test pressure increases, thus making bubble-point determination difficult.

The multipoint diffusion test will create a diffusive flow profile (diffusion versus applied pressure) of the filter system over a broad range of test pressures all the way up to the characteristic bulk flow of the bubble point. The combination of multipoint diffusion test and bubble point leverages the advantages of the combination and increases a higher accuracy of detection.

Some automated multipoint diffusion-test systems allow programming of a specific maximum allowable diffusion value for every pressure step, thus setting a maximum diffusion profile.

Test material

The following materials were used: automated integrity-test unit (Sartocheck 4, Sartorius Stedim Biotech GmbH); five pieces of 30-in. PESU 0.2-Ám cartridges (Sartopore 2, Sartorius Stedim Biotech GmbH), referred to as A, B, C, D, and E, respectively; one piece of 20-in. PESU 0.2-Ám cartridge (Sartopore 2), referred to as F; one piece of 10-in. PESU 0.2-Ám cartridge (Sartopore 2) failing cartridge (low bubble point), referred to as G; one piece of 10-in. PESU 0.2-Ám cartridge (Sartopore 2) failing cartridge (high diffusion), referred to as H; one multiround (5 x 30 in.) housing; one single-round 30-in. housing; and one single-round 10-in. housing.

Test methodologies

All filter cartridges were individually tested three times with a multipoint diffusion test over a range of pressure points. The lowest point was at 2500 mbar (36.25 psi), which is the traditional single-point diffusion test pressure for the filter used. The highest point was 3250 mbar (47.13 psi), which is 50 mbar (0.73 psi) above the specified minimum allowable bubble point of the filter tested. The filter cartridges were thoroughly rinsed with demineralized water at room temperature before each integrity test.

Figure 1: Individual values of cartridges A, B, C, D, F, and H and their sum. (ALL FIGURES ARE COURTESY OF THE AUTHORS.)
After the diffusion profile curves (from the multipoint diffusion test) and the individual bubble point values were generated, the data were analyzed. The individual cartridge values were used to mathematically simulate different filter combinations in a multiround housing (see Figure 1).


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