When the bioburden method is employed for sterilization process, the bioburden trend of materials and products should be routinely and frequently monitored and, if more heat-resistant microorganisms are identified, then method should re-validate and the potential effect of the microorganisms on pharmaceutical products already shipped from the plant need to be evaluated to ensure patient safety.
The bioburden count in the controlled manufacturing facility is generally far lower than 10^6.
To achieve a 1-log reduction means to decrease the microbial population by a factor of 10. A sterilization cycle that provides a SAL of 10^-6 effectively means that the microorganisms that “could” be present (i.e., bioburden) are killed, and an additional 6-log reduction safety factor has been provided. The following provides an example of a cycle achieving a SAL of 10^-6.
Bioburden (worst case) = 170 CFU (colony forming unit).
To reduce the microbial population from 170 to 1 = log (170) = 2.23 (i.e., a 2.23 log reduction is required to reduce the population from 170 to 1).
• Applying an additional 6-log reduction will theoretically reduce the microbial population from 1 to 0.000001.
This provides a SAL of 10^-6 or a one in one million opportunity of a survival of single microorganism.
• Total log reduction required = 2.23 + 6 = 8.23.
Therefore, to achieve a SAL of 10^-6 with a bioburden of 170 CFU requires a sterilization cycle that should provide 8.23 log reduction.
References:
Sterilization of health care products – Moist Heat – Part 2: Guidance on the application of ANSI/AAMI/ISO 17665-1
Guidance on the Manufacture of Sterile Pharmaceutical Products Produced by Terminal Sterilization, https://www.pmda.go.jp/files/000160794.pdf, accessed on 18 Jun 2020.
Technical Report No. 1, Revised 2007, Validation of Moist heat sterilization process: cycle design, development, qualification and ongoing control
