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



Figure 2: Multiround housing 5 x 30-in. cartridges A, B, C, D, and E. (ALL FIGURES ARE COURTESY OF THE AUTHORS.)
To verify the mathematically simulated test results, the 30-in. filter elements (i.e., A, B, C, D, and E) with no break in integrity were installed into the multiround housing and tested with the bubble point and multipoint diffusion tests. All cartridges were tested three times and rinsed between each test (see Figure 2).


Figure 3: Multiround housing and 10-in. housing, 4 x 30-in. cartridges A, B, C, and D; 1 x 20-in. cartridge F; and 1 x 10-in. cartridge G or H. ( (ALL FIGURES ARE COURTESY OF THE AUTHORS.)
One 30-in. cartridge (cartridge E) was then replaced by a 20-in. cartridge. A 10-in. filter housing, containing the bubble-point failing cartridge, was connected in parallel with the multiround housing, consequently representing a five-round 30-in. setup in terms of membrane surface. The system containing cartridges A, B, C, D, F, and G was tested with bubble-point and multipoint diffusion tests. All cartridges were rinsed between each of the three tests (see Figure 3).

The bubble-point failing cartridge (cartridge G) in the 10-in. housing was then replaced by the high-diffusion cartridge (cartridge H), and the same tests and rinses were performed. Instead of performing a separate single-point diffusion test at 2500 mbar (36.25 psi), the authors considered the diffusion value at the same pressure during the multipoint diffusion test was representative.

Individual test result

The expected difference in diffusion between five 30-in. cartridges (i.e., A, B, C, D, and E) (137.9 mL/min) without loss of integrity and an equivalent setup including the bubble-point failing 10-in. cartridge (i.e., A, B, C, D, F, and G) (139.4 mL/min), at the standard test pressure of 2500 mbar (36.25 psi) was <2 mL/min, thus being not possible to detect with a high degree of confidence.

An equivalent setup including the failing 10-in. high-diffusion cartridge (i.e., A, B, C, D, F, and H) would require the maximum allowable diffusion value to be lowered by more than 40% as compared with the cumulated individual maximum diffusion values to be detected at all. Using such a high safety margin creates a high potential risk of getting false-failure test results with filters that otherwise have no break of integrity.

Based on the typical diffusion profile of a cartridge with no loss of integrity, it was possible to define a maximum allowable diffusion curve, which made it possible to get a clear multipoint-diffusion test failure when the bubble-point failing 10-in. cartridge was included in a multiround setup (cartridges A, B, C, D, F, and G). The same approach showed that it should be possible to get a clear test failure when having the 10-in. high-diffusion cartridge in a multiround set-up (cartridges A, B, C, D, F, and H).


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