关键工艺参数的定义指南(中英对照).docVIP

PAGE PAGE 3 Guidance in defining critical process parameters 关键参数的定义指南 The criticality of a process parameter is an assessment of the probability that it can be consistently and reproducibly controlled within the proven acceptable range (PAR) during routine manufacturing. 工艺参数的关键性是指在生产中对可接受范围的持续重复控制的可能性的评估， This probability depends on 可能性主要取决于： the robustness of the process parameter (the width of the PAR) 工艺参数的稳定性（可接受范围的宽度） the ability to technically control the parameter (technical limitations) 参数控制的技术能力（技术限制） the uncertainty of the measurement of the parameter (reflected by the standard deviation σ) 参数测量的不确定性（用标准偏差来反映） The robustness of a process parameter is reflected by the width of the proven acceptable range. The wider the range within which a parameter could be varied during process qualification without impacting product quality, the more robust it is. 可接受的参数范围反映工艺参数的稳定性。在参数确认中不影响产品质量的可改变的参数的范围越宽，工艺越稳定。 The ability to technically control a parameter is a function of a combination of process properties and equipment capabilities. For example, a highly exothermic reaction might be well controlled in a small stainless steel vessel, but could prove impossible to control in a larger glass-lined vessel. 参数的技术控制能力是工艺特性和设备能力的综合功能。例如，一个高放热的反应可能在一个小的不锈钢反应釜内能够很好的被控制，但是在一个大的塘玻璃反应釜内证明是不可能控制的。 The uncertainty of a measurement (σ) is the combined uncertainty of the calibration of the probe, the variance of the probe itself, and the variance of the signal transmission from the probe to the distributed control system (DCS). If the measurement is normally distributed, 3.4 out of a million data points will be outside a range of +/- 4.5 standard deviations. This is the basis of the ‘six sigma’ theory. The difference of 1.5 between 4.5 and 6 is an empirical value chosen based on the observation that the mean of real processes tends to drift by this value over time. Based on the ‘6σ’-concept we define a parameter as ‘critical’ when the proven acceptable range is narrow