Abstract
When approaching an ethylene oxide (EO) sterilization validation, medical device manufacturers traditionally have two choices. They can use biological indicators (BIs) to monitor each production run or establish a parametric release process in which sterile release is based on the monitoring and control of physical process parameters that ensure process specifications are met. In ISO 11135:2014, parametric release was brought to the forefront as an acceptable release method; however, a perception exists that implementing parametric release is challenging and time consuming. This article will demonstrate that the opposite is true. It presents a streamlined approach in which parametric release is addressed through the various stages of validation: product definition, process definition, performance qualification, routine release, and process control. Considerations for establishing specifications directly from validation versus "run and record" and trending critical process parameters (e.g., relative humidity, temperature, EO concentration) are discussed. In addition, the benefits of parametric release (active monitoring) over BI release (passive monitoring), including improvements to turnaround time, process control, risk mitigation, reduction of resource investment, and elimination of microbiological release testing, are highlighted. With multiple benefits, parametric release should be the gold standard for EO sterilization processes. It is not novel and has been widely accepted by regulatory agencies globally and notified bodies. The article further describes how the data collection and process capability that is central to process control and parametric release is more powerful than the information provided by a BI, which is merely a catastrophic indicator when used in routine processing.