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Pharmaceutisch Weekblad

, Volume 13, Issue 3, pp 130–136 | Cite as

Microbiological aspects of heat sterilization of drugs

III. Heat resistance of spore-forming bacteria, isolated from large-volume parenterals
  • F. A. Boom
  • M. A. E. Van der Heijden Van Beek
  • A. C. A. Paalman
  • A. Stout-Zonneveld
Articles

Abstract

In order to calculate the minimum sterilization process conditions to obtain the generally accepted sterility level (less than 1·10−6 probability of microbial survival), we determined the bioburden and its heat resistance of 500 ml large-volume parenteral bottles over a period of 5 years. For the bioburden determination 1,832 bottles were examined by the membrane filtration method. Mean bioburden was 9.36 colony-forming units/bottle. Of the colony-forming units isolated 118 were heat resistant (0.69%). These were spore-formingBacillus species. Of the isolatedBacillus species heat resistance was determined in 5% glucose, 0.9% sodium chloride and 8% amino acids solution.D values greater than 1 min at 105°C were found for 2, 5 and 4 differentBacillus species in glucose 5%, sodium chloride 0.9% and amino acids 8%, respectively. 2Bacillus species showed aD value over 2 min at 105°C in all three media.D values at 110°C in sodium chloride 0.9% for these 2Bacillus species were 1.8 and 2.6 min and in amino acids 8% 0.9 and 1.7 min, respectively. The minimum sterilization process time at 110°C, calculated with the experimentally determined bioburden andD values is less than 25 min. When introducing reduced exposure times/temperatures, each individual manufacturer should assess the bioburden. The time-consuming determination of the heat resistance of bioburden isolates is not always necessary. By dividing the isolated colony-forming units in a ‘heat-resistant’ group and a ‘not-heat-resistant’ group, changing from standard overkill sterilization procedures to processes with lowerF0 values is possible.

Keywords

Bacillus Colony-forming units, assay Heating Infusions, parenteral Spores, bacterial Sterilization 

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Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1991

Authors and Affiliations

  • F. A. Boom
    • 1
  • M. A. E. Van der Heijden Van Beek
    • 2
  • A. C. A. Paalman
    • 3
  • A. Stout-Zonneveld
    • 4
  1. 1.Department of PharmacyHospital de HeelEE Zaandamthe Netherlands
  2. 2.ACF Chemiefarma NVBB Maarssenthe Netherlands
  3. 3.Department of PharmacySlotervaart HospitalEC Amsterdamthe Netherlands
  4. 4.Department of Medical MicrobiologySlotervaart HospitalAmsterdam

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