Process control in electron beam sterilization of medical devices and a pathway to parametric release

This paper presents a review of process control methods in electron beam sterilization of medical devices. Starting from normative requirements, the proper use of different types of control charts to demonstrate that the process is in statistical control, is discussed in depth. Special emphasis is laid on the establishment of control limits. Their performance is analyzed using data from an actual electron beam process. In addition to SPC charts for monitoring doses, the concept of a performance index based on processing parameters is proposed and its implementation in control charts is discussed. It is shown that these charts allow an extraordinary tight control of the sterilization process which is superior to standard monitoring dosimetry. Especially time-weighted control (CUSUM) charts are identified as means to control a process effectively. Subsequently, the process parameter analysis approach is extended towards assessment and decision whether product specifications have been met and a potential pathway to parametric release from electron beam sterilization is outlined. A process definition method which addresses minimum and maximum dose specifications directly and does not rely on monitoring doses is presented in an example using actual data. Terminology and the treatment of uncertainties follow closely the ISO 11137 family of standards. A discussion of potential advantages of parametric release and a roadmap and requirements for this paradigm shift in electron beam sterilization of medical devices complement the paper. •Process control in electron beam sterilization of medical devices.•SPC charts.•Parametric release.