Abstract
The diffusion test in combination with the BP test provides decisive information for the acceptance of a filter element in sterile filtration. The single point diffusion test as usually performed is capable of detecting a flaw of 5 to 10 μm in size for large area membrane filters. Because of the amount and variability of gas flow through large area membrane filters, flaws can be masked which have impact on filtrate quality. The detectability of such hidden flaws can be improved by the proposed "Flow Ratio" method, where test gas flow through the wetted membrane filter element is determined at two different challenge pressures. The Bubble Point test is capable of detecting oversize pores also in large area membrane filters provided that the BP is determined with highest sensitivity. Integrity tests can be performed at temperatures and in wetting agents different from what is specified by the membrane manufacturer provided that temperature can be maintained stable for the duration of the test and that changes in diffusion rate and BP are considered. Theoretical computations show that the minimum retention value which can be considered realistic is directly proportional to the water permeability of the filter element and proportional to the sensitivity of the diffusion test employed. Integrity tests performed from the upstream side of the filter system have the advantage of not interfering with the clean, sterile downstream side. They can substitute downstream volumetric methods provided their sensitivity is comparable. As the upstream pressure loss rate caused by gas loss through the filter element depends also on the size of the upstream volume of the filter system, pressure loss data should be converted to decisive filter dependent volumetric gas loss data. Even slight temperature changes cause significant pressure changes in the filter system. Thus the upstream integrity test must be capable of detecting such disturbances. In critical applications where the desired degree of integrity cannot be ensured by the integrity test method, two, equally rated filters should be used in series.
- Received February 6, 1984.
- Accepted July 28, 1984.
- Copyright © Parenteral Drug Association. All rights reserved.
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