中英对照-APIC 原料药厂清洁验证指南：8.0残留量检测(3)

Where: M: True value for the amount of residue remaining in the equipment after cleaning;

Mres: The measured amount of residue (sampling and then analytical measurement);

R Recovery in % divided by 100 (e.g. for 75%, 75/100 = 0.75). 公式4：

其中M：清洁后设备上残留物的数量真值 Mres：测得残留量（取样后分析测量）

R：回收率除以100（例如，对于75%即为75/100=0.75）

APIC 201405原料药厂清洁验证指南：8.0残留量检测（下）（中英文）

2014-07-11 julia翻译 蒲公英

接上部分。

8.2.5 Validation Requirements for Quantitative Testing of Impurities 杂质定量测试的验证要求

The requirements for the validation of quantitative testing of impurities according to ICH Q2 (R1) are shown in Table 2, including proposed

acceptance criteria (as an example only). Alternative acceptance criteria may be established based on sound scientific rationale.

根据ICH Q2(R1)，杂质定量检测方法的验证要求在表2中列出，包括制订的可接受标准（只是举例）。可以根据科学合理的原则制订适当的可接受标准。 It is important to note, that the summarised requirements should be used for the validation of quantitative testing for impurities during cleaning validation studies. Validation of quantitative testing for impurities is usually applied when the analytical method will be used for several specifications of the residue amount in the equipment.

重点要注意的是，在清洁验证研究中，定量检测方法验证应满足所有要求。如果分析方法将用于设备中残留量有不同的几个质量标准，则一般采用杂质定量方法验证要求。

The lowest foreseen acceptance limit is referred to as MperMin and the highest limit as MperMax in Table 2. For only one specific acceptance limit normally limit testing for impurities and the corresponding validation of the analytical method is sufficient. If the validation of quantitative testing for impurities will be used for one specific acceptance limit, then MperMin = MperMax = Mper.

最低预期可接受限度，在表2中称为MperMin，和最高限度，称为MperMax。对于只有一个特定的可接受限度，一般可以使用杂质限度测试方法，对方法只要做相应的验证即可。如果要将杂质定量方法的验证用于单一可接受限度，则MperMin = MperMax = Mper。

For the experimental work described in Table 2, the samples can be spiked with appropriate levels of the impurities (when standards are available) or compared with another well-characterised procedure (when standards are not available) to obtain the true value of the analyte concentration.

表2中试验里，可以采用杂质（如果可以获得标准品的话）加入样品中至适当的浓度水平，或与另一个经过确认的检验方法进行对比（如果不能得到标准品的话），以得到被分析物的真实浓度值。

TABLE 2 Validation Requirements

Experiments Possible Acceptance Criteria Accuracy: Perform a minimum of 9 determinations over a minimum of 3 concentration levels covering the specific range (e.g. 3 concentrations/3 replicates each of the total analytical procedure). Determine analyte with respect to the total amount of residue in the sample (e.g. weight/weight). Report: □ Accuracy as percent recovery or □ Difference between the mean and the accepted true value. □ Confidence intervals. 90.00-110.00% ≤10.00% (P=95%) Precision: Investigate using homogenous, authentic samples or (if not possible) artificially prepared sample. Perform a minimum of 9 determinations covering the specified range for the procedure (e.g. 3 concentrations/3 replicates each) or a minimum of 6 determinations at 100% of the test concentration. Repeatability (intra-assay precision): Establish precision under the same operating conditions over a short interval of time. Report: □ Standard deviation (interdependent with S) See S □ Overall relative standard deviation over the whole range of the method □ Relative standard deviation within one con≤20.00% ≤10.00% centration level □ Confidence interval Intermediate Precision (may include robustness, ruggedness): establish precision on different days, for different analysts, on different equipment and after variation of method parameters (= robustness, e.g. stability of solutions, variations of pH, of mobile phase composition, of flow rate, of temperature, of columns etc.). It is not necessary to study these effects individually. Experimental design (matrix) may be applied. Report: □ Standard deviation (interdependent with relative standard deviation) □ Relative standard deviation 3×S from repeatability or 10% whichever is greater See S □ Confidence interval Specificity: Demonstrate the discrimination of analyte in the presence of the other impurities: □ Test samples containing the analyte and other impurities. Obtain positive and correct results for the analyte. □ Test samples without the analyte. □ For chromatographic procedures use representative chromatograms to document specificity. Label individual components appropriately. Linearity: Measure a minimum of 5 concentrations across the range of the proceduNegative results Specify acceptable resolution of peaks Specify acceptable deviation re (dilute standard stock solution or prepared synthetic mixtures). Plot the signals as function of concentration. Evaluate the plot: □ Visually □ Statistically (e.g. regression line by the method of least squares) Correlation coefficient y-intercept ≥0.99000 Confidence band (P = 95%) contains 0 Linear Slope of the regression line Residual sum of squares Range: Confirm that the analytical procedure provides an acceptable degree of linearity, accuracy and precision within or at the extremes of the specified range. Minimum specified ranges: □ From the reporting level to 120% of MperMax. The reporting level for cleaning validation reasonably will be the LOQ. However, the reporting level must be below MperMin and should be below or at 80% of MperMin.

表2 验证要求 测试项目 准确度 在指定的浓度范围内对3个浓度进行至少9次检测（例如，3个浓度各按完整的分析方法检测3次）。测试残留物在样品中的总量（例如重量/重量）。 报告： 可能的可接受标准 From LOQ or 80% of MperMin to 120% of MperMax.

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