Such studies are difficult because many parameters may influence results, and very little work has been done to develop control
procedures to verify the quality of marketed or self-grown spore suspensions or to standardize the procedures for the inoculation
of product or equipment, the exposure to sterilization conditions, and the recovery of survivors.
Once the effect of a sterilization process at the worst-case position is known, a sterilization cycle can be defined in consideration
of the heat sensitivity of the product, the expected bioburden, and the necessary biological effectiveness to be achieved.
It may be that a process that is considered an overkill process in most parts needs special precautions to reduce the bioburden
at worst-case positions.
Test pieces that simulate worst-case positions (e.g., vials inoculated between the stopper and the glass) may then be used to verify that the sterilization processes used in
the production of pharmaceuticals correctly deliver the conditions needed to achieve the necessary sterilizing effect. Such
customized test pieces are product and process oriented but otherwise similar to the conventional worst-case devices used
in the ISO approach. Whether commercially available BIs on carriers are suitable to simulate worst-case conditions must be
decided for each specific case.
A process characterized and validated with such an approach would then be routinely monitored by physical tests, and the biological
effectiveness could be deduced from the measured physical parameters.
Klaus Haberer, PhD,* is the managing director and Korinna Vreden is the head of laboratory, both at Compliance Advice and Services in Microbiology GmbH, Robert-Perthel-Str. 49, D-50739 Cologne,
Germany, tel. +49 (0) 221 957457 0, fax +49 (0) 221 957457 25, k.haberer@compliance-asim.de
*To whom all correspondence should be addressed.
Keywords: sterilization processes, biological indicators, steam sterilization
References
1. S.L. Rubio and J.E. Moldenhauer, "Effect of Rubber Stopper Composition, Preservative Pretreatment and Rinse Water Temperature
on the Moist Heat Resistance of Bacillus stearothermophilus ATCC 12980," PDA J. Pharm. Sci. Technol.
49, 29–31 (1995).
2. I.J. Pflug and G.M. Smith, "Survivor Curves of Bacterial Spores Heated in Parenteral Solutions," in Selected Papers on the Microbiology and Engineering of Sterilization Processes, 5th ed., I.J. Pflug, Ed. (Environmental Sterilization Laboratory, Minneapolis, MN, 1988), pp. 25–65.
3. J.E. Moldenhauer et al., "Heat Resistance of Bacillus coagulans Spores Suspended in Various Parenteral Solutions," PDA J. Pharm. Sci. Technol.
49, 235–38 (1995).
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66 (12), 5509–13 (2000).
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54, 398–412 (2000).
6. T.J. Berger et al. "The Effect of Closure Processing on the Microbial Inactivation of Biological Indicators at the Closure-Container Interface,"
PDA J. Pharm. Sci. Technol.
52, 70–75 (1998).
7. The United States Pharmacopeial Convention, Chapter ‹1035›, United States Pharmacopeia 30, CD edition (2007).
8. I.J. Pflug, Microbiology and Engineering of Sterilization Processes, 10th ed. (Environmental Sterilization Laboratory, Minneapolis, MN, 1999), p. 9.6.
9. ISO 18472, "Sterilization of Health Care Products—Biological and Chemical Indicators—Test Equipment," 2005.
10. EMEA, "Decision Trees for the Selection of Sterilisation Methods," Annex to Note for Guidance on Development Pharmaceutics,
2000.
11. European Pharmacopoeia, Chapter 5.1.1 "Methods of Preparation of Sterile Products," 5.7th ed. (Council of Europe, Strasbourg, 2007).
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