Browsing by Subject "Bioindikator"

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Dekontamination von pharmazeutischen Isolatoren mit verdampftem Wasserstoffperoxid : Charakterisierung von Einflussparametern und Optimierung des Maschinendesigns
(2010) Unger-Bimczok, Beatriz; Kottke, Volker
In the pharmaceutical industry sterile drugs, which can not be terminally sterilized, have to be prepared and handled under aseptic conditions. The application of isolator technology with physical separation of the process from the environment and the operator is commonly used. Prior to the aseptic processing, the inner isolator surfaces have to be treated with a sterilant to reduce the microbial contamination to a defined acceptable level. Today vaporized hydrogen peroxide (VPHP) is most commonly used for this purpose. Different parameters like hydrogen peroxide concentration, humidity, and condensation have an influence onto the microbicidal activity of the decontamination cycle. Also isolator design factors (e.g. material of construction, geometrical structure) can impact the inactivation results. The objective of the presented thesis was to investigate the mode of action of the VPHP and the relationship between different influencing cycle parameters in order to develop a recommendation for optimum decontamination conditions. An additional goal was to analyze the impact of different construction materials, surface finish and geometrical structures onto the inactivation efficiency of the sterilant to improve the design of aseptic processing machines regarding VPHP decontamination. For the studies an pharmaceutical isolator connected to a VPHP generator was used. Standard decontamination cycles with varying combinations of hydrogen peroxide and water concentration, cycle time and condensation levels were developed. Biological indicators (BIs) with defined initial spore population of Geobacillus stearothermophilus were exposed to the different VPHP cycles. By determination of inactivation kinetics for the microbial test challenge, the sporicidal activity for each set of cycle conditions was evaluated. The applied microbial methods were Most Probable Number (MPN) technique as well as the determination of decimal reduction times (D-values). BIs were not only tested when openly exposed to the sterilizing atmosphere, but also inside of defined gaps to challenge the penetration capability of the VPHP into small lumens under diffusive conditions. Different construction materials were inoculated with defined spore populations to investigate the resistance behaviour of the spores on varying surfaces. Supplementary the physico-chemical characteristics of the respective materials were analyzed in detail to draw conclusions regarding correlation of surface quality and inactivation properties. The results demonstrate that the decisive factor for a successful decontamination is the overall microscopic interaction with the bioburden on the surface. It is shown, that the microcondensation in the sub-visible range is effective for good inactivation performance and that further condensation in the visible range does not enhance the microbicidal activity. The data illustrate that the microbial inactivation is accelerated by increasing hydrogen peroxide concentration. An H2O2 level of 800 ppm ensures a sufficient deposition of sterilant onto the surface and results in excellent and reproducible kill. For sterilant levels > 800 ppm no further improvement in inactivation is detectable. It is shown that for openly exposed BIs a lower H2O2 level (400 ppm) can be compensated by higher humidity. The elevated water content in the decontamination atmosphere promotes the sterilant deposition. The higher the hydrogen peroxide level is, the more independent from humidity becomes the inactivation effect. For H2O2 levels of 800 ppm, the microbicidal activity of the VPHP is found to be independent from the water concentration. In contrast to the openly exposed BIs, for the inactivation of spores exposed under diffusive conditions inside of gaps, a lower hydrogen peroxide level can not be compensated by higher humidity. Solely the hydrogen peroxide concentration and the overall cycle duration are able to influence the decontamination success inside of the trenches. It is demonstrated that in principle complex structures can be decontaminated by the means of VPHP but the penetration capability is limited. The inactivation is impeded with decreasing gap cross section and with increasing gap depth. It is shown that different construction materials and surface textures have an impact onto the resistance behaviour of spores towards VPHP.