Integrity testing membrane filters

The integrity of membrane filters with a pore size of 0.2 and 1.2 pm should be verified using a bubble-point test after use as an in-process control. During this test a 0.2 pm membrane filter should resist the air pressure produced by moving the plunger over 80-85 % of the total syringe volume and in the case of a 1.2 pm membrane filter over 50-60 % without continuous bubble formation on the opposite of the membrane (see also Sect. 30.6.5). 

Filters for use in sterile gas filtration must conform to standards similar to those mandated for sterile hquid filtration. Nondestmctive integrity tests may be apphed. The tests are performed by wetting the filter with an appropriate solvent, commonly 60/40 isopropyl alcohol/water for hydrophobic membranes, and applying air or nitrogen gas at a preset pressure. 

Integrity testing of vent filter membranes associated with the sterilizer... 

The bubble point test is a popular single-point physical integrity test for disc filter membranes based on Eq. (21). A fdter medium is wetted with a liquid, and test gas pressure is slowly raised until a steady stream of bubbles appears from a tube or hose attached to the downstream side of the filter and immersed in water (Fig. 9). The pressure at which the bubbles first appear is recorded as the bubble point and is related to the largest pores in the fdter medium. A pore size can be calculated from Eq. (21) however, it must be realized that the bubble point test does not measure the actual pore size, but only allows correla-... 

Another integrity test referred to as the pressure hold test makes use of the fact that below the transition pressure no bulk flow of the test gas takes place. Therefore, in a pressure hold test, once a filter system is in place and the filter medium wetted, pressure is applied to the system and then shut off and sealed. If there are no leaks in the system or holes in the membrane larger than the corresponding test pressure used, the pressure should remain constant. If the pressure drops, there is a leak somewhere in the system that should be corrected. The pressure hold test is popular in testing filter assemblies and systems in... 

Retention is a function of the pore size distribution of the membrane, solution properties, and operating conditions. For critical applications such as sterile or virus filtration, retention should be tested with the actual solution under different operating conditions. Typically, membrane filters are tested for integrity before use to ensure the required retention is obtained during operation. Integrity tests are based on bubble point or diffusion [6]. 

When the wetting fluid is expelled from the largest pore, a bulk gas flow will be detected on the downstream side of the filter system (Fig. 7). The bubble point measurement determines the pore size of the filter membrane, i.e., the larger the pore the lower the bubble point pressure. Therefore, filter manufacturers specify the bubble point limits as the minimum allowable bubble point. During an integrity test, the bubble point test has to exceed the set minimum bubble point. 

Tarry, S.W. Henricksen, G. Prashad, M. Troeger, H. Integrity testing of EPTFE membrane filter vents. Ultra-pure Water 1993, 10 (8), 23-30. 

It is essential that the microbiological particle passage test is performed as part of the development of new sterile formulations. Because of its very specialized nature, the test is normally performed only by the filter manufacturers, who then provide limits for secondary physical tests (e.g., bubble point, pressure decay, forward flow, etc.), which can be applied to verify the pore size rating and integrity of the membrane filters. 

A bubble test to check the integrity for the membrane filter immediately after filtration but prior to release of the product. (This is done by applying air pressure through the filter until the validated bubble point is reached. Filter integrity is indicated by the absence of a steady stream of bubbles.)... 

Filter tests must be performed by the manufacturer before release to the market and by the individual user also, to ensure that the membrane filter complies with the specifications, is undamaged, and is eventually placed correctly in the filter case by the user. As described before in this chapter, such a test should in fact be performed with Brevundimonas diminuta. However, in daily practice this is not possible for the user in the pharmacy, and thus test methods have been derived, which are based on the physical properties of the membrane filter. Such test methods are called filter integrity tests. 

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