Bacterial retention is assessed by challenging filters of the intended type having a range of integrity-test values and analyzing
the bacterial-passage results. Ideally, the retention pattern observed will allow identification of physical integrity-test
values above or below which, depending on the type of integrity test, there is virtually no probability of bacterial passage.
For example, with a series of filters having a range of bubble points and equivalently challenged, there would be a value
below which bacterial passage always occurred, a range where passage sometimes occurred, and a value above which passage never
occurred.
It is important to identify the integrity values above and below which bacterial retention and bacterial passage can be expected.
This ensures that the correlation between the integrity-test value and bacterial retention is valid and there are not other
factors such as pore-size distribution and anisotropy that are potentially influencing the perceived correlation.
During development of what he referred to as the "forward flow" test in 1973, Dr. Pall performed bacterial-challenge testing
on a series of 43 cartridges having water-wet forward air flow values ranging from 16 to 900 cm3/h at a pressure differential of 10 in of mercury (4.9 psi) (3). The results of this testing showed that no filter with a
flow of less than 199 cm3/h allowed bacterial passage. On the basis of those results, he established a maximum flow limit of 100 cm3/h for an acceptable production filter element, building in a safety factor. However, the testing also showed that there were
filters with forward-flow values of 210, 258, 450, and 645 cm3/h that retained the challenge organism and filters with forward-flow values of 199, 238, 471, and 600 cm3/h that allowed bacterial passage. The study did not establish a point above which bacterial passage always occurred; therefore
the correlation between the integrity-test value and bacterial retention was not fully elucidated.
Because the forward-flow test as described relies on diffusive flow, which in terms of the filter membrane is a function of
porosity, area, and thickness and is not directly related to pore size, the bacterial-retention results obtained for the higher
forward-flow values could be indicative of pore-size distribution differences (or possibly thickness variations) among the
tested membranes. Had these tests been carried out at pressures closer to the bubble point as is done today, differences in
pore-size distribution might have been revealed as a result of the pressure-induced thinning of the liquid layer in the larger
pores and better correlation obtained with bacterial retention at the higher diffusive-flow values. Nonetheless, Pall's efforts
served as the basis for developing the automated filter-integrity tests in use today. These tests operate at considerably
higher pressures, capturing the influence of the knee area and providing effective correlation between bacterial retention
and the integrity-test value.
It is important to note that the integrity-test values were obtained on clean filters, before commencing the bacterial-retention
tests, eliminating the influences of filter loading on filter porosity and diffusive-flow values.
Another validation consideration is to test the filters after sterilization and bacterial-challenge testing to evaluate the
influences of filter loading and the sterilization process on the integrity-test values.
Filter loading
The sterilizing filtration process is designed to remove viable and nonviable particles from the fluid passing through the
filter. The particles removed from the fluid either remain on the surface of the filter membrane or are trapped within the
membrane matrix.
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