Grow-Through and Penetration of the 0.2/0.22 "Sterilizing" Membranes - Pharmaceutical Technology

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Grow-Through and Penetration of the 0.2/0.22 "Sterilizing" Membranes


Pharmaceutical Technology


None of the 0.1-μm-rated membranes that were examined showed evidence of grow-through. Five nylon 66 filters tested yielded sterile effluent over the entire duration of the test (120–196 h), up to challenge levels from 5.7 X 107 to 2.0 X 108 cfu/cm2. Similar results were obtained with the PVDF filters tested: No R. pickettii were detected at challenge levels from 5.9 X 107 to 6.0 X 108 cfu/cm2. The organisms were sufficiently small to penetrate the corresponding 0.2-μm-rated membranes, however, and all 0.1-μm-rated filters tested provided consistent and complete retention of R. pickettii for the entire duration of the test (120–192 h).These results demonstrate that 0.1-μm-rated filter membranes provided sterile effluents under conditions that allowed bacterial penetration to occur through conventional 0.2- and 0.22-μm-rated sterilizing grade filters (9).

Choosing the pore-size rating

On the basis of the above data, one can argue that 0.1-μm-rated membranes would quell grow-through concerns and would permit longer-term formulation and filtration operations. Indeed, the authors believe that long-term filtrations should incline toward a reliance on the 0.1-μm-rated filters. Nevertheless, it is recognized that significant penalties are incurred by the unnecessary use of tighter membranes (11–13). Objections to the tighter filters are the consequences that derive from their lower rates of flow. It should also be noted that longer term operations would promote endotoxin production, usually a matter of some importance.

A responsible choice requires that both the 0.1-μm-rated membranes and the 0.2/0.22-μm-rated membranes be validated. If both prove appropriate, the higher pore-size rating should be used to avoid the penalties of reduced flows. If, however, the validation data do not permit a clear resolution, the 0.1-μm-rated membranes should be selected. Retention is more important than flow rate or flux.

It has been stated that advances in filter manufacture have resulted in 0.1-μm-rated membranes that are faster flowing than their 0.2/0.22-μm-rated counterparts. Contrary to common experience, however, it is noteworthy, and substantiating data are awaited. Its publication would accord with Lord William Thompson Kelvin's famous dictum, long a guiding principle of the scientific approach, "When you can measure what you are speaking about and express it in numbers, you know something about it." This condition, necessary to the removal of objections to the use of the 0.1-μm-rated membranes, remains unfulfilled.

Summary

It is hypothesized that the occurrence of grow-through and the diminution in the size of certain organisms when in contact with given liquids are the same phenomenon manifested under different circumstances. If this be so, the identification of liable organism types and the elucidation of the kinetics of their size diminution will be of considerable practical value. It will resolve the uncertainties of grow-through, will dissipate its concerns, and will contribute to a more reliable usage of the 0.1-μm-rated membrane. Moreover, process validation requirements defined 10 years ago reduce the fear of grow-through to an unresolved phenomenon instead of a safety issue.

Maik W. Jornitz is group vice-president for product management at Sartorius North America, 131 Heartland Blvd., Edgewood, NY 11717. Theodore H. Meltzer* is principal of Capitola Consulting Company, 8103 Hampden Lane, Bethesda, MD 20814-1244, tel. 301.986.8640. He also is a member of Pharmaceutical Technology's Editorial Advisory Board.

*To whom all correspondence should be addressed.


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