关键工艺参数的定义指南(中英对照)

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：

•t he 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）

•t he ability to technically control the parameter (technical limitations)

参数控制的技术能力（技术限制）

•t he 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 narrower than ± six standard deviations.

测量的不确定性是探头或检测器的校验，监测器本身的变化和从探头到DCS的信号传输的变化的不确定因素的综合。如果测量结果是正态分布的，3.4PPM（百万分之一）将在+/-4.5标准偏差的范围之外。这是六西格玛理论的基础。4.5和6之间1.5的差异是一个经验值基于观察实际工艺趋势相对时间数值的漂移。基于六西格玛概念当一个参数的可接受的范围比+/-六个标准偏差窄时，我们定义这个参数为关键参数。

figure 1: critical parameter figure 2: non-critical parameter

set point set point

lower/upper edge of failure

lower/upper edge of failure

Whereas a proven acceptable range depends only on the process, the variance of a control system is equipment-specific. The variance of a control system for the same process parameter might be different in another operational environment, which could result in a different criticality assessment (e.g. a critical process parameter in one plant may be judged to be non-critical in another plant which has a control system with a lower variance).

如果一个可接受的参数范围仅仅依赖于工艺，控制系统的变异是设备属性。对同样的工艺参数的控制系统的变异可能在另一个操作环境下不同，这个可能导致一个不同的关键性评估（比如在一个工厂的一个关键参数在另一个有较低变异的控制系统的工厂就可能被判定为不关键）

The following table can be used for guidance to assess the criticality of a process parameter

以下列表在指南中用于评定一个工艺参数的关键性

1) The pH is typically much more difficult to be controlled than to be measured. Unless a system is in place which significantly reduces the control uncertainties (local pH, re-adjustment, etc.) a PAR of +/-1.0 pH units is recommended.