A Bayesian Approach to Determination of F, D, and Z Values Used in Steam Sterilization Validation

PDA J Pharm Sci Technol. 2017 Mar-Apr;71(2):88-98. doi: 10.5731/pdajpst.2016.006981. Epub 2016 Oct 27.

Abstract

For manufacturers of sterile drug products, steam sterilization is a common method used to provide assurance of the sterility of manufacturing equipment and products. The validation of sterilization processes is a regulatory requirement and relies upon the estimation of key resistance parameters of microorganisms. Traditional methods have relied upon point estimates for the resistance parameters. In this paper, we propose a Bayesian method for estimation of the well-known DT , z, and Fo values that are used in the development and validation of sterilization processes. A Bayesian approach allows the uncertainty about these values to be modeled using probability distributions, thereby providing a fully risk-based approach to measures of sterility assurance. An example is given using the survivor curve and fraction negative methods for estimation of resistance parameters, and we present a means by which a probabilistic conclusion can be made regarding the ability of a process to achieve a specified sterility criterion.LAY ABSTRACT: For manufacturers of sterile drug products, steam sterilization is a common method used to provide assurance of the sterility of manufacturing equipment and products. The validation of sterilization processes is a regulatory requirement and relies upon the estimation of key resistance parameters of microorganisms. Traditional methods have relied upon point estimates for the resistance parameters. In this paper, we propose a Bayesian method for estimation of the critical process parameters that are evaluated in the development and validation of sterilization processes. A Bayesian approach allows the uncertainty about these parameters to be modeled using probability distributions, thereby providing a fully risk-based approach to measures of sterility assurance. An example is given using the survivor curve and fraction negative methods for estimation of resistance parameters, and we present a means by which a probabilistic conclusion can be made regarding the ability of a process to achieve a specified sterility criterion.

Keywords: Bayesian; Moist heat; Steam; Sterility assurance; Sterilization validation.

MeSH terms

  • Bayes Theorem*
  • Drug Industry / standards*
  • Drug Industry / statistics & numerical data
  • Models, Statistical*
  • Quality Control*
  • Steam*
  • Sterilization / standards*
  • Sterilization / statistics & numerical data

Substances

  • Steam