Ermittlung realitätsnaher Sterilisationsbedingungen
Produkte, die mit mehr als nur einer Keimart verkeimt sind / Berechnung ausreichender und realistischer Sterilisationsdosen anhand von ermittelten D-Werten / am Beispiel der Sterilisation mit ionisierenden Strahlen
Originale
Key Words Bioburden | Strahlensterilisation | D-Wert(e) | Compliance- Anforderungen
ABSTRACT
Determination of realistic sterilisation conditions for products contaminated with a bioburden of various species / Calculation of realistic sterilisation doses based on experimentally determined D-values, e. g., sterilisation with ionising irradiation
Ionising radiation sterilisation is an accepted procedure and described in the European Pharmacopoeia [1]. The reference dose is laid down to be ≥ 25kGy absorbed dose in order to achieve a sterility assurance level (SAL) of ≤ 10-6. In the text of the European Pharmacopoeia it is also mentioned, that alternative sterilisation doses (above/below 25 kGy) may be used for sterilisation, provided that the resulting SAL will not exceed 10-6.
In case biological indicators (BI) are used (for the validation and) for the monitoring of sterilisation, the number of indicator organisms, spores of Bacillus pumilus, shall exceed 107/BI, and the resistance (= D-value) against ionising radiation shall be equal or above 1,9 kGy. With these preconditions m. a., sterilisation doses of 13–14 kGy (7 x 1,9 = 13,3) can be validated/monitored (see below). Either it is incontrovertibly proven that the natural bacterial flora of the products to be sterilised (bioburden) will not exceed the values of the indicator organisms m.a. quantitatively and qualitatively (D-value) or, if this cannot be proven, the reference dose m.a. has to be used for sterilisation.
It makes more sense to investigate the bioburden qualitatively and quantitatively in order to determine a realistic sterilisation dose. This can be done by determining the number of bacteria on the products quantitatively (assuming the bioburden is ∼10/product), logarithmising (logarithm to a basis of 10) the result, adding 6 (because of a reachable SAL of 10-6) to this logarithmised result and multiplying the resulting sum with the experimentally determined overall D-value of the bioburden on the products. The result is the realistic sterilisation dose for the product and should fulfill all compliance requirements (compliance, i. e., fulfillment of regulatory requirements).
The procedure described above is a bit theoretical, and from an experimental point of view it might be difficult to demonstrate: This is due to the fact that, on the one side, necessary experiments for the determination of D-values are complex to perform, and, on the other side, products are normally not contaminated with a homogenous bacterial population, but with a “mixture” of bacteria, yeast and bacterial spores, which individual D-values have to be determined for.
In this publication, it is described how to master the challenge mentioned in the previous paragraphs, determination of a realistic sterilisation dose, with a simple experimental approach and with (a bit of) mathematics.
Korrespondenz:
Dr. Michael Pfeiffer, c/o Boehringer Ingelheim Pharma GmbH & Co. KG (HPZ 4329-EG-03), Binger Straße 173, 55216 Ingelheim (Germany);
e-mail: michael.pfeiffer@boehringer-ingelheim.com
Zusammenfassung
Die Sterilisation mit ionisierenden Strahlen ist ein vom Europäischen Arzneibuch anerkanntes Verfahren [1]. Als notwendige Sterilisationsdosis werden ≥ 25kGy absorbierte Dosis angegeben (Referenzdosis), um einen Sterility Assurance Level (SAL) von ≤ 10-6 zu erreichen. Bereits im nächsten Satz des entsprechenden Arzneibuchtexts wird jedoch darauf hingewiesen, dass
