New Binary Gas Integrity Test Improves Membrane Quality Assurance - The authors developed a test for defects in filter membranes. - BioPharm International

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New Binary Gas Integrity Test Improves Membrane Quality Assurance
The authors developed a test for defects in filter membranes.


BioPharm International
Volume 24, Issue 4, pp. 24-28

The authors have developed a test for defects in filter membranes based on the principle of differing gas permeabilities through the liquid layer of a wetted membrane. Both the binary gas integrity test and the standard gas–liquid diffusion method were applied to a newly developed virus clearance filter. Results demonstrated that the binary gas test provided a significantly higher level of virus retention assurance compared to the air–water diffusion test. The authors conclude that the binary gas test provides superior defect detection sensitivity in virus filters.

Over the years, there have been a number of nondestructive integrity tests for filtration membranes conducted as part of manufacturing quality assurance. Tests are typically implemented by the filter manufacturer as an additional quality assurance test prior to shipping the product to users.

Millipore has developed a test designed to be more sensitive to detection of defects. The new high sensitivity binary gas integrity test is based on the principle of differing gas permeabilities through the liquid layer of a wetted membrane that results in a concentration enhancement of the faster permeating gas.

The test makes use of the fact that the permeate composition in an intact (integral) membrane, with no defects, can be predicted based on the transport properties of the gases permeating through the liquid layer and the known operating conditions. So, if the test spots a deviation from the expected concentration, it is a clear indication of a defect or the presence of open pores.

The binary gas test has low sensitivity to membrane porosity, liquid layer thickness, and membrane area. This means that integral devices will exhibit a relatively narrow range of test values, making it easier to spot defects.

To "test the test", researchers applied both the binary gas integrity test and the standard gas–liquid diffusion method to a newly developed virus clearance filter. Results demonstrated that the binary gas test provided a significantly higher level of virus retention assurance compared to the air–water diffusion test.

TESTING FOR DEFECTS THAT COMPROMISE PERFORMANCE

Integrity testing of microporous or ultraporous filters is routinely used to detect the presence of oversized pores or defects that can compromise the filter's retention capability. Test choices include the particle challenge test, the liquid–liquid porometry test, the bubble point test, the gas–liquid diffusion test, and diffusion tests measuring tracer components. Although each test has benefits, there are also compromises that must be made.

The particle challenge test is destructive and therefore not applicable as a pre–use test. The liquid–liquid porometry and bubble point tests are useful for ensuring that the user has selected a membrane with the proper nominal pore, but are not sensitive enough to identify small numbers of small defects, particularly for filters larger than 47 mm. With the gas–liquid bubble point test, a single or few small defects may add only a small amount of gas flow that cannot be distinguished from the background diffusive flow rate through the integral part of the membrane in a filter device.


Figure 1: Gas diffusion through a wetted membrane: (a) integreal and (b) non-integral membrane.
The most commonly applied nondestructive integrity test for membrane filters, especially virus filters, is the gas–liquid diffusion test. A wetted membrane provides a liquid layer across which diffusive air flow occurs (see Figure 1a).

As pressure is increased, diffusive flow increases linearly until either the liquid layer begins to thin or until the bubble point is reached, whereupon robust bulk air flow commences. As shown in Figure 1, a measured gas flow rate more than that predicted for an integral membrane signals the presence of a defect.

The sensitivity of this test is limited by the minimum detectable excess flow. There can be significant device–to-device variability in gas diffusion flow rates of integral membrane filter devices due to differences in membrane area, membrane thickness, membrane porosity, and pore tortuosity (twists and turns). Other factors such as thinning of the liquid due to evaporation, liquid retention of membrane support layers (porous non-wovens, for example), and membrane movement or compression can also affect measured gas diffusion rate. This variability in gas flow rate acts as "background noise" that can diminish the sensitivity of the gas–liquid diffusion test.


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