关键工艺参数的定义指引中英对照

.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 andreproducibly 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：he robustness of the process parameter (the width of the PAR) t?工艺参数的稳定性（可接受范围的宽度）he ability to technically control the parameter (technical limitations) t?参数控制的技术能力（技术限制）deviation σ) he uncertainty of the measurement of the parameter (reflected by the standard t?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 widerimpacting without be varied during process qualification the range within which a parameter couldproduct quality, the more robust it is.在参数确认中不影响产品质量的可改变的参数的范围越可接受的参数范围反映工艺参数的稳定性。

宽，工艺越稳定。

and control a parameter is a function of a combination of process properties The ability to technicallysmall well controlled in a For equipment capabilities. example, a highly exothermic reaction might bestainless 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 the probe, calibration is the combined uncertainty of the of σThe uncertainty of a measurement ()variance of the probe itself, and the variance of the signal transmission from the probe to the distributedcontrol system (DCS). If the measurement is normally distributed, 3.4 out of a million data points will be4.5 standard deviations. This is the basis of the ‘six sigma' theory. The difference of outside a range of +/-real of on the observation that the mean empirical 1.5 between 4.5 and 6 is an value chosen based-concept we define a parameter as 'processes tends to drift by this valueover time. Based on the ‘6σ ‘critical' when the proven acceptable range is narrower than ± six standard deviations. 的信号传输的变化的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 标准偏差的范不确定因素的综合。

如果测量结果是正态分布的，3.4PPM （百万分之一）将在+/-4.5的差异是一个经验值基于观察实际工艺趋势和6之间1.5围之外。

这是六西格玛理论的基础。

4.5六个标准偏差窄时，我+/-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 们定义这个参数为关键参数。

figure 2: non -critical parameterfigure 1: critical parameterpointsetsetpoint 0°0°5° 5 6 55° 6 5° 7 6 50° 7 65°0° 4 45°0°0° 5 40°40°5°6σ6σ6σ6σproven acceptable rangeproven acceptablerangelower/upper edge of failurelower/upper edge of failure. .Whereas a proven acceptable range depends only on the process, the variance of a control system isequipment -specific. The variance of a control system for the same process parameter might be different inanother operational environment, which could result in a different criticality assessment (e.g. a criticalprocess parameter in one plant may be judged to be non -critical in another plant which has a controlsystem 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 parameter1) The pH is typically much more difficult to be controlled than to be measured. Unless a system is inplace which significantly reduces the control uncertainties (local pH, re-adjustment, etc.) a PAR of +/-1.0pH units is recommended...pH是典型的控制比检测要难得多。

如果一个适当的系统能够显著的降低控制的不确定性（在线pH，重新校正等）推荐使用+/-1.0pH的可接受的范围。

2) Taking into account the difficulties of controlling a pressure under changing process conditions asobserved during e.g. drying, distillation operation and reactions under pressure, a PAR of +/-20% isrecommended.考虑到在干燥、蒸馏操作和压力下反应中观察到的工艺条件改变时压力控制的难度。

推荐使用+/-20%的可接受的参数范围Examples:例子：1）A reaction temperature is likely to be not critical if the proven acceptable range (PAR) for a set point of50°C is determined as 42°- 58°C for a calibrated temperature range of 200°C (e.g. -20°C to +180°C).如果一个可接受参数范围是温度范围是42~58°C，设定点是50°C，而校验过的温度为200°C（比如-20°C~180°C）,那么一个反应温度或许就是不关键的。

2）A pH has to be adjusted to 5.0 (PAR: 4.4 –5.6) by charging acid. The final pH is relevant; anovercharge of acid can be corrected by charging base. This parameter is well controlled and not critical.一个pH必须通过加酸调节至5.0（范围：4.4~5.6），最终pH是相应的。

加过量的酸可以通过加碱来校正。

那么这个参数可以被很好的控制并不关键。

3）During a reaction an acid is released and the pH has to be controlled between 6.4 and 7.6 by chargingbase. This parameter is likely to be critical as the local pH might differ significantly from the valuemeasured and as the charge of base has to be controlled.在一个反应中酸已经加了，pH必须通过加碱控制在6.4~7.6，因为现场的pH与检测的值可能有显著不同，碱的加入必须控制，所以这个参数可能是关键的。