Neues Verfahren zur Bestimmung der Inaktivierung von Endotoxin bei der Trocken-Hitze-Sterilisation
Rainald Forberta, Lothar Gailb und Ulrich Pflugmacherc
Siemens AG, A&D SPa,b, Frankfurt/Main, Aventis Pharma Deutschland GmbHc, QODP/QCDP, Frankfurt/Main
New Procedure for Determining Dry-Heat Inactivation of Endotoxin
The dry-heat inactivation of endotoxin can be determined either by using biological indicators or by temperature measurement and calculation using a previously modelled inactivation process. Most of the modelling procedures are based upon a) local temperature measurement of the sterilising object and b) isothermal inactivation measurement within the relevant temperature range.
Most investigations, however, have demonstrated that for the constant D, indicating the heat sensitivity of the used endotoxin, different numbers for the initial and for the subsequent destruction period have to be used. Hence, for best fitting of experimental and calculated inactivation, the progress of inactivation should be introduced as a further variable. By analysing numerous inactivation measurements, an algorithm for the transition between the two inactivation periods has been developed. This algorithm considers not only the current temperature but also the heat exposure time and the progress of inactivation.
By testing this procedure with biologically measured and calculated non-isothermal inactivation cycles of various authors a satisfactory conformity has been found. By offering the advantage of a more efficient evaluation of local temperature data, the new procedure may considerably contribute to improving the safety of sterilisation process monitoring and validation.
Key words Entpyrogenisierung • Inaktivierung, Endotoxininaktivierung, Kinetik • Sterilisation, Trocken-Hitze Sterilisation • Sterilisationstunnel • Validierung