title: A Bayesian Approach to Determination ofF, D, andZValues Used in Steam Sterilization Validation.
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-knownDT,z, andFovalues 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.
authors: Allergan Inc., Waco, TX, psfaya@gmail.com; and psfaya@gmail.com.
authors: Paul
authors: P
authors: Faya
authors: Department of Statistical Science, Baylor University, Waco, TX, USA.
authors: James D
authors: JD
authors: Stamey
authors: Department of Statistical Science, Baylor University, Waco, TX, USA.
authors: John W
authors: JW
authors: Seaman
mesh_terms: D001499:Bayes Theorem; D004345:Drug Industry / Q000592:standards* / Q000706:statistics & numerical data; D015233:Models, Statistical; D011786:Quality Control; D013227:Steam; D013242:Sterilization / Q000592:standards* / Q000706:statistics & numerical data
chemical_list: D013227:Steam
keywords: Bayesian; Moist heat; Steam; Sterility assurance; Sterilization validation