The wet testing involved is usually proprietary. Presumably, the test values of any of the integrity tests, including the
forward flow, based on diffusive airflows, may be serving this purpose. Experimentally determined bubble points are the guiding
measuring units known to the authors to be used. Although the membrane is classified in terms of pore-size ratings, the category
is determined on the basis of bubble-point values. The higher the bubble-point value, the smaller the pore-size rating and
the more likely the retention of smaller organisms. The grouping by bubble point inexorably gives rise to a spectrum of values
for each pore-size rating.
Care is taken that membranes intended for sterilization filtrations are not of too low a bubble-point value; this would signify
a too open pore arrangement susceptible to organism passage. On the other hand, tighter filters are seen as a guarantee against
violating the threshold value that was experimentally established as being capable of removing 1 × 107 cfu of B. diminuta per square centimeter of EFA. In fact, in a responsible address to dependable quality membrane, manufacturers add a (nonstandard)
safety margin to the threshold value of the product that is released to the market.
Figure 9: Correlation of bubble points and organism retention.
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After meeting the bubble-point requirements and the ASTM bacterial challenge test, the filters intended for sterilizing applications
are labeled as being of the 0.2/0.22 μm pore-size rating. No industry standards guide the filter purveyor. Each manufacturer
is free to use the numbers and limits he considers appropriate. The bubble-point value set by the filter manufacturer for
his filter, whether with safety margin or not, is considered the defining number by FDA investigators. It is beyond questioning
by the filter users. Pharmaceutical houses, however, may develop and validate their own LRV–bubble point correlations for
the filters they use. This is accepted by regulators.
Bubble point, organism retention
The bubble point had been shown by several experimenters to correlate directly with the log reduction values (LRV) characteristic
of a given filter type confronted by a particular type organism (25, 41–43) (see Figure 9). B. diminuta ATCC 19146 was the organism whose different degrees of retention, expressed as LRVs, was shown to correspond to specific
bubble-point pressure levels. Establishing the capability of a filter to sustain a challenge level of 1 × 107 cfu of B. diminuta per cm2 of efa, expressed as its bubble point, defines its qualification as a "sterilizing filter." This performance accords with
FDA's definition of a sterilizing filter (2). The following equation describes the relationship of the bubble point to the
pore's diameter, the dimension most influential on its retention properties:
in which θ represents the angle of wetting, λ is the liquid's surface tension, D signifies the pore diameter, and P is the bubble-point pressure in psi.
The equation is correct in indicating the reciprocal relationship of the bubble-point pressure with the restrictive pore width.
The critical sensitivity of the wetting action, however, disallows calculating the dimensional size of the pore by way of
the equation. Obtaining retentions of 1 × 107 /cm2 requires more than a particular pore-size rating. It is dependent also on the suspending fluid's compatibility with both
organisms and filter in terms of size alterations of the microbes and pores; on the filtration conditions, especially the
differential pressure, temperature and viscosity; and on the numbers, shapes, and size distributions of both the pores and
the organisms.
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