Microbiological aspects of heat sterilization of drugs. III. Heat resistance of spore-forming bacteria, isolated from large-volume parenterals

Pharm Weekbl Sci. 1991 Jun 21;13(3):130-6. doi: 10.1007/BF01981530.

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-forming Bacillus species. Of the isolated Bacillus 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 degrees C were found for 2, 5 and 4 different Bacillus species in glucose 5%, sodium chloride 0.9% and amino acids 8%, respectively. 2 Bacillus species showed a D value over 2 min at 105 degrees C in all three media. D values at 110 degrees C in sodium chloride 0.9% for these 2 Bacillus 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 degrees C, calculated with the experimentally determined bioburden and D 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 lower F0 values is possible.

MeSH terms

  • Bacillus / physiology
  • Drug Contamination*
  • Infusions, Parenteral
  • Solutions
  • Spores, Bacterial*
  • Sterilization*
  • Temperature

Substances

  • Solutions