发布时间 : 星期二 文章中英对照-APIC 原料药厂清洁验证指南：8.0残留量检测更新完毕开始阅读
— 表示该特性一般不需要评估。 + 表示该特性一般要进行评估。 说明 2 如果一个方法缺乏专属性，则可以用另一个支持性分析方法进行补偿。 3 有时需要。
The requirements for ‘Testing for Impurities’ are typically employed for the validation of analytical methods specific to cleaning validation. 在清洁验证专用分析方法验证中，一般应用“杂质检测”的要求。
The requirements for ‘Quantitative Testing for Impurities’ can apply, for example, in cases where a method should be suitable for several possible acceptance limits and therefore quantitation of the residue over a certain range may be necessary e.g. the measured amount of residue M must be compared with acceptance limits between 5 and 750 g/equipment. This is possible when the method will be used for several changeovers. 有时可以应用“杂质定量检测”要求，例如，如果一个方法适用于几个可能的可接受限度，因此可能需要对一定水平范围内的残留物进行定量检测，例如，残留物M的测得量必须与可接受标准5-750g/设备相比较。如果方法要用于几个产品更换情况下的检测，则可以使用上述方法。
The requirements for ‘Limit Testing for Impurities’ can apply, for example, in cases where the method should be suitable for one specific acceptance limit e.g. the measured M must be compared with Mper ≤ 105 g/equipment.
有时可以应用“杂质限度检测”要求，例如，如果方法需要符合一个特定的可接受限度，例如，对M的测量必须与Mper ≤ 105 g/设备进行比较。
1 如果做了重复性测试，则不需要做中间精密度。 8.2.2 Analytical Method Validation for Cleaning Validation 清洁验证所用分析方法验证
In the following sections, aspects of analytical method validation specific to cleaning validation are emphasised. For further details refer to ICH Q2 (R1).
在以下部分强调了清洁验证专用的分析方法要点。更详细的要求参见ICH Q2(R1)。
Specificity is a basic requirement for all analytical methods (see Table 1), however, in the case of cleaning validation it may occur, that not all potential impurities are clearly specified. It is important to note that in such a situation a specific method may not always detect all impurities. Studies should be performed to characterise the unknown impurities, develop and validate suitable analytical methods. However, this can be an unacceptably time consuming task. In this case a method that detects all potential impurities together can be suitable, even when it is not specific for each of the impurities. For example, in a situation where only non-volatile impurities occur, a dry residue determination method that is specific for the sum of non-volatile impurities could be used, provided that the validation requirements according to Table 1 are satisfied. In order to consider the equipment acceptable for use it must be assumed that the dry residue consists of the worst case impurity (most toxic, most active etc.). In some cases a combination of several methods can achieve the necessary specificity.
专属性是所有分析方法（见表1）都适用的基本要求，但是，在清洁验证中，可能并不是所有潜在杂质都能被明确，在这种情况下要重点注意即使是专属的方法，也并不一定能检测出所有杂质。可以研究未知杂质的特性，建立适当的检验方法并验证，但这样做所耗费的时间可能是无法接受的。这时，可能会适当的办法是采用一个能检出所有潜在杂质的方法，即使该方法对有些杂质不具有专属
性。例如，如果只有不挥发性杂质产生，只要验证结果符合表1的要求，可以使用非专属性方法蒸发残渣来检测所有不挥发性杂质的总和。考虑到要使设备清洁程度可以接受，必须假定蒸发残渣结果中会包括最差情形的杂质（毒性最强、活性最强等）。有时，可以联合使用几个方法来达到必需的专属性要求。 After the completion of a cleaning validation study an unspecific method (e.g. dry residue) may be used for the routine verification of equipment cleaned by the validated cleaning procedure provided that it is shown that the unspecific method is suitable for the intended purpose. If possible, the sensitivity of impurity detection for cleaning validation should be determined for both the sampling and analytical methods together (see Section 7.2.4).
在清洁验证完成后，可以使用非专属性方法（例如，蒸发残渣）对按验证过的清洁程序清洁后的设备进行日常检测，只要该方法适合其既定用途。可能的情况下，清洁验证所用检验方法对杂质检测的灵敏度应与取样方法和分析方法一起测试（参见7.2.4部分）。
8.2.3 Detection and Quantitation Limits 定量限和检测限
Measured values below limit of quantification (LOQ) should be reported as the LOQ value (worst case approach). For example if the LOQ is 10 mg/l, the measured blank is 7 mg/l and the measured residue amount is 3 mg/l, the reported value for the sample should be equal to the LOQ i.e. 10 mg/l. 低于定量限（LOQ）应报告为定量限值（最差情况法）。例如，如果LOQ为10mg/L，测得空白结果为7mg/L，测得残留值为3mg/L，则该样品的残留值应报告为LOQ，即10mg/L。
Usually it can be assumed that, for quantitative impurity determination, the LOQ should approximately be 0.5 of the specification i.e. for cleaning validation 0.5 of the acceptance limit or lower. LOQ should never be higher
than the acceptance limit. In the following sections three methods of LOQ/LOD determination are outlined:
一般可以假定，在杂质定量检测时，LOQ应为质量标准的约0.5倍，即对于清洁验证来说，可接受限度的0.5或更低。LOD不得高于可接受限度。在以下部分，列出了三种确定LOQ/LOD的方法： ? Based on Visual Evaluation 目视评估
Visual evaluation may be used for non-instrumental methods but may also be used with instrumental methods. Frequently this approach is used for TLC.
目视评估可以用于非仪器方法，但也可用于仪器分析方法。这种方法经常用于TLC。
? Based on Signal-to-Noise Approach 信噪比方法
This approach can only be applied to analytical procedures which exhibit baseline noise (e.g. GC, HPLC). A signal-to-noise ratio (S/N) between 3 or 2:1 is generally considered acceptable for estimating the detection limit (LOD) and a typical ratio for acceptable quantitation limit is 10:1 (LOQ). The value for S/N can be calculated according to Equation 1 and Figure 1:
本方法只能用于产生基线噪声的分析方法（例如，GC、HPLC）。信噪比（S/N）为2-3：1时，一般可以作为估计的检测限（LOD），10：1可以作为定量限（LOQ）。信噪比值可以根据公式1和图1计算：
where: H is the height of the peak from the mean baseline.