Advertisement

Pharmaceutisch Weekblad

, Volume 6, Issue 5, pp 209–215 | Cite as

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
  • F. A. Boom
  • A. C. A. Paalman
  • A. Stout-Zonneveld
Original Articles

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.

Keywords

Process Time Membrane Filtration Heat Resistance Safety Margin Maximum Heat 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Nederlandse Farmacopee, Ed. VIII. 's-Gravenhage: Staatsuitgeverij, 1978:344–5.Google Scholar
  2. 2.
    British Pharmacopoeia. Cambridge: University Press, 1980:A196.Google Scholar
  3. 3.
    United States Pharmacopeia, Ed. XX. Easton: Mack Publishing Company, 1980:1037.Google Scholar
  4. 4.
    Food and Drug Administration. Current Good Manufacturing Practice in Manufacturing Processing, Packing or Holding of Large Volume Parenterals. Federal Register 1976:41(no. 106):22208.Google Scholar
  5. 5.
    Parenteral Drug Association. Technical Monograph no. I: Validation of steam sterilization cycles, 1978:1–36.Google Scholar
  6. 6.
    Van Asten J, Dorpema JW. A new approach to sterilization conditions. The IMO concept. Pharm Weekbl [Sci] 1982;4:49–56.Google Scholar
  7. 7.
    Boom FA, Paalman ACA. Microbiologische aspecten van het steriliseren van geneesmiddelen door middel van hitte. 1. Het afsterven van micro-organismen onder invloed van vochtige hitte. Pharm Weekbl 1979;114:157–65.Google Scholar
  8. 8.
    Wallhäusser KH. Sterilization-Desinfektion-Konservierung. 2nd ed. Stuttgart: Georg Thieme Verlag, 1978:204.Google Scholar
  9. 9.
    Caputo RA, Odlang TE, Wilkinson RL, Mascoli CC. Biological validation of a sterilization process for a parenteral product-fraction exposure method. J Parenter Drug Assoc 1979;33:214–21.PubMedGoogle Scholar
  10. 10.
    Tromp ThFJ. Autoclavering, microbiologische aspecten. Pharm Weekbl 1980;115:142–9.Google Scholar
  11. 11.
    Russel AD. The Destruction of Bacterial Spores. In: Hugo WB, ed. Inhibition and Destruction of the Microbial Cell. London-New York: Academic Press, 1971:451–612.Google Scholar
  12. 12.
    Gould GW. Methods for studying Bacterial Spores. In: Norris JR, Ribbons DW, eds. Methods in Microbiology. Part VIA. London-New York: Academic Press, 1971:327–81.Google Scholar
  13. 13.
    Briggs A. The resistance of spores of the genusBacillus in phenol, heat and radiation. J Appl Bacteriol 1966;29:490–504.PubMedGoogle Scholar
  14. 14.
    Jones AT, Pflug IJ.Bacillus coagulans, FRR B666, as a potential biological indicator organism. J Parenter Sci Technol 1981:35:82–7.PubMedGoogle Scholar
  15. 15.
    Reich RR.Bacillus stearothermophilus spores suspensions: effect of storage conditions and time on viability and moist heat resistance. J Parenter Sci Technol 1981;35:74–7.PubMedGoogle Scholar
  16. 16.
    Friesen WT, Anderson RA. Effects of sporulation conditions and cation-exchange treatment on the thermal resistance ofBacillus stearothermophilus spores. Can J Pharm Sci 1974;9:50–3.Google Scholar
  17. 17.
    Holcomb RG, Pflug IJ. The Spearman-Karber Method of analyzing quantal assay microbial destruction data. In: Pflug IJ, ed. Microbiology and engineering of sterilization processes. Philadelphia: Parenteral Drug Association Inc., 1978:75–92.Google Scholar
  18. 18.
    Pflug IJ. Heat Sterilization. In: Philips GB, Miller WS, eds. Industrial Sterilization. Durham NC: Duke University Press, 1973:239–82.Google Scholar
  19. 19.
    Strumbo CR, Murphey JR, Cohren J. Nature of thermal death time curves for P.A. 3679 andClostridium botulinum. Food Technol 1950;9:321–6.Google Scholar
  20. 20.
    Boom FA. Microbiologische contaminatie tijdens de bereiding van parenteralia. Pharm Weekbl 1980;115:170–81.Google Scholar
  21. 21.
    Boom FA, Graatsma BH, Oremus EThHGJ. Bereiding van parenteralia in ziekenhuisapotheken. III. Toetsing aan de hand van het produkt. Pharm Weekbl 1981:116:724–30.Google Scholar
  22. 22.
    Kooiman WJ, Geers JM. Simple and accurate technique for the determination of heat resistance of bacterial spores. J Appl Bacteriol 1975;38:185–9.PubMedGoogle Scholar
  23. 23.
    Brown MRW, Gilbert P. Increasing the probability of sterility of medical products. J Pharm Pharmacol 1977:29:517–23.PubMedGoogle Scholar
  24. 24.
    Whyte W, Baily PV, Tinkler J. An evaluation of the routes of bacterial contamination occurring during aseptic pharmaceutical manufacturing. J Parenter Sci Technol 1982:36:102–8.PubMedGoogle Scholar
  25. 25.
    Buchanon RE, et al., eds. Bergey's Manual of Determinate Bacteriology. 8th ed. Baltimore: The Williams & Wilkens Company, 1974:529–50.Google Scholar
  26. 26.
    Pflug IJ, Smith GM. Survivor Curves of Bacterial Spores heated in Parenteral Solutions. In: Pflug IJ, ed. Micro biology and engineering of sterilization processes. Philadelphia: Parenteral Drug Association Inc., 1978:17–57.Google Scholar
  27. 27.
    Anderson RA, Friesen WT. The thermal resistance ofBacillus stearothermophilus spores. The effects of temperature and pH of the heating medium. Pharm Acta Helv 1974:49:295–8.PubMedGoogle Scholar
  28. 28.
    Pflug IJ, Smith GM, Scheyer M, Chapman PA. Thermal resistance ofBacillus stearothermophilus spores suspended in parenteral solutions. Bull Parenter Drug Assoc 1976;30:128–38.PubMedGoogle Scholar
  29. 29.
    Härnulv BG, Snygg BG. Heat resistance ofBacillus subtilis spores at various water activities. J Appl Bacteriol 1972;35:615–24.PubMedGoogle Scholar
  30. 30.
    Gautier CA, Smith GM, Pflug IJ. Effect of fosfate buffer concentration on the heat resistance ofBacillus stearothermophilus spores suspended in parenteral solutions. Appl Environmental Microbiol 1978;36:457–64.Google Scholar
  31. 31.
    Reich RR, Whitbourne JE, McDaniel AW. Effect of storage conditions on the performance ofBacillus stearothermophilus biological indicators. J Parenter Drug Assoc 1979;33:228–34.PubMedGoogle Scholar
  32. 32.
    Heintz MT, Urban S, Schiller J, Gay M, Bühlmann X. The production of spores ofBacillus stearothermophilus with constant resistance to heat and their use as biological indicators during the development of aqueous solution for injection. Pharm Acta Helv 1976;51:137–43.PubMedGoogle Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1984

Authors and Affiliations

  • F. A. Boom
    • 1
  • A. C. A. Paalman
    • 1
  • A. Stout-Zonneveld
    • 2
  1. 1.Department of PharmacySlotervaart HospitalEC AmsterdamThe Netherlands
  2. 2.Department of Medical MicrobiologySlotervaart HospitalEC AmsterdamThe Netherlands

Personalised recommendations