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Microbiological aspects of heat sterilization of medicines

II. A method for the determination of the effectiveness of a sterilization process using the bioburden and the bioburdens heat resistance

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Abstract

In order to verify whether the sterilization process of 60 min at 100°C for invert sugar 20% is sufficiently effective to attain the generally accepted probability of survival of maximum 1×10−6, we determined the bioburden and the bioburdens heat resistance for this product.

We examined 98 bottles by the membrane filtration method and found 84 bottles with o colony forming units (CFU's) and 14 bottles with 1–9 CPU's. Because none of the isolated CPU's was heat resistant (Bacillus species), we isolated heat resistant CPU's from the environment and determined the heat resistance in invert sugar, water and NaCl solution 0.9% of four differentBacillus species. The results in invert sugar for the most heat resistantBacillus species were a D-value of 0.92 min at 100°C.

For the determination of the D-value the end-point method is the most practical one, and the D-value calculation with the most probable number method is sufficiently accurate. Because of unavoidable inaccuracies in the experimentally determined D-value, safety margins of 100% have to be taken into account in the sterilization process calculations in which these D-values are used. Hence, in our case, we have to use a D-value of 2×0.92 min in the sterilization process calculation for invert sugar 20%.

The maximum bioburden in the examined 98 test bottles was 9 CFU's. The maximum heat resistant bioburden which must be used in sterilization process calculations may be safely fixed at 10% of the total bioburden, therefore we have to use 0.9 micro-organisms in our calculation. Hence using these values of 0.9 microorganisms and the maximum bioburden heat resistance (D-value=2×0.92 min at 100°C), the minimum sterilization process time for invert sugar 20% in our hospital pharmacy is calculated to be 10.96 min at 100°C.

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Author notes

  1. F. A. Boom

    Present address: Stichting Hospital de Heel, P.O. Box 210, 1500, EE Zaandam, The Netherlands

Authors and Affiliations

  1. Department of Pharmacy, Slotervaart Hospital, Louwesweg 6, 1066, EC Amsterdam, The Netherlands

    F. A. Boom & A. C. A. Paalman

  2. Department of Medical Microbiology, Slotervaart Hospital, Louwesweg 6, 1066, EC Amsterdam, The Netherlands

    A. Stout-Zonneveld

Authors
  1. F. A. Boom
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  2. A. C. A. Paalman
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  3. A. Stout-Zonneveld
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Boom, F.A., Paalman, A.C.A. & Stout-Zonneveld, A. Microbiological aspects of heat sterilization of medicines. Pharmaceutisch Weekblad Scientific Edition 6, 209–215 (1984). https://doi.org/10.1007/BF01999944

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