Present status
The pore sites of a filter are where the liquid flow manifests itself, where the particle removals take place, and consequently
where the throughput volume is defined by the filter blockage. Important though they be, pore sizes are not appraised by direct
measurements. They are determined by way of experimentally performed bubble points whose values are transmuted into pore-size
ratings. Each filter manufacturer confers its own pore-size designations to its filters. There is no industry standard. In
the process, the pore-size ratings, which in any case are not numerical description of the pores' dimensions, are reduced
in their significance to parts number in the fabricator's catalogue.
The bubble-point values identify the pores with the largest diameters, those through which suspended particles are most likely
to escape capture. In conjunction with information on organism sizes, a coupling of correct pore sizes can be used to attain
complete organism removals. It has been established that a correlation exists between bubble-point values and the log-reduction
values for the various membrane types. This enables the identification of the filters that can accomplish the removal of 1
× 107 cfu of B. diminuta per square centimeter of EFA, as confirmed by microbiological assays. Such filters are "sterilizing filters" as defined by
FDA. This designation qualifies the filter for sterilizing applications. Its actual performance as a sterilizing filter requires
validation.
The logic of the above is weakened by the absence of industry standards. The direct assessments of pore sizes are difficult.
The converting of bubble-point measurements into pore sizes is encumbered by the complexity of bubble-point values being so
highly peculiar to the pairing of the membrane (polymer) type with its particular wetting liquid and for being different again
for each pore-size rating of the solid–liquid couple.
It would seem that membrane users would be faced with considerable problems in their choosing the filters best suited for
given applications. On the basis of experience, however, the filter user finds that assigned pore-size numbers do offer a
level of practical guidance, for example, to particle retentions. Albeit indirectly, bubble points can be interpreted as bearing
a relationship to particle sizes. Moreover, although the guidance of formal standards is largely absent, the foci both of
filter manufacturers and users are strongly directed to the needs of a federally regulated industry. In this manner, even
proprietary actions undergo a peer review. In addition, the development of tools and techniques necessary to pharmaceutical
manufacture are shared through numerous technical communications: papers, books, lectures, courses, congresses, and so forth.
The need of the industry to meet the requirements set by the regulating agencies promotes shared experiences and cooperative
approaches to industry-wide problems. These technical contacts do compensate to an extent for the lack of formal standards.
Coupled to a user's experience, the assigned pore-size numbers can offer a level of practical guidance. Nevertheless, it is
the bubble points that can be and are measured experimentally. However complicated their values, they can be quantified. It
is upon these measurements that, on the basis of experience, the practical applications of filters should be ventured.
Maik W. Jornitz is the group vice-president of global product management, bioprocess of Sartorius North America and is a director of the
PDA, Russel E.
Madsen, Jr., is the president of The Williamsburg Group, LLC, and Theodore H. Meltzer* is a consultant for Capitola Consulting Company, theodorehmeltzer@hotmail.com
Mr. Madsen and Dr. Meltzer also are members of Pharmaceutical Technology's Editorial Advisory Board.
*To whom all correspondence should be addressed.
Submitted: Aug. 11, 2006. Accepted: Oct. 12, 2006.
Keywords: filtration, integrity tests, pore-size ratings
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