清洁验证分析方法的专属性、准确度、精密度要求！
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译自2020年8月份发布的《ISPE基准指南：清洁验证生命周期–应用，方法和控制（ISPE Baline Guide: Cleaning Validation Lifecycle: Applications, Methods, and Controls）》
8 Analytical and Biological Assay Methods
清洁验证分析和生物分析方法
Testing cleaning validation samples is critical to provide an accuratereprentation of the level of cleanliness of equipment both after cleaning(API or formulation; cleaning agent and bioburden as necessary) and before u(bioburden). API residue is typically tested, as it may be the high hazardcomponent in the formulation. Any test method ud must be validat
ed for thesample being taken [21]. The primary consideration for the test method is thatit is nsitive to levels lower than the cleaning limit for the analyte ofinterest. If the test method is not nsitive enough to test residue levels lowerthan the cleaning limit, the method nsitivity must be enhanced, a differenttest method must be employed, or themanufacturing equipment must be dedicated [17].
清洁验证样品的检测对于对于提供设备清洁(API或制剂、清洁剂、生物负荷)后和使用前（生物负荷）的清洁水平的准确表征是非常重要的。通常测试API残留，因为它可能是配方中的高危害成分。所用的任何测试方法都必须经过取样验证[21]。测试方法的主要考虑是它对低于相关分析物的清洗极限的水平敏感。如果测试方法不够灵敏，无法进行现场测试任何用于测试目标样品的方法均应被验证，检测方法首要考虑的是其灵敏度应低于被检测物的清洁限度。如果试验方法灵敏度不够，无法检测低于清洁限度的残留物水平，则方法灵敏度必须提高，或者采用其他方法，或生产设备专用。
A specific method (e.g., HPLC) ispreferred by regulatory agencies [17], but a non-specific method (e.g., TOC)can be acceptable. Bioburden testing isoften conducted by compendial methods as a general test, with individualspecies identified asnecessary.
监管机构通常首选专属性的方法（如HPLC)，但非专属性的方法（如TOC)也可能可以接受，生物负荷检测经常采用药典方法，必要时进行菌种鉴定。
The analytical performancecharacteristics, or validation parameters, should conform to tho defined byICH Q2 [107]: accuracy, precision, specificity, LOD, LOQ, linearity, range,robustness, and recovery (e Section 8.1). Definitions of the parameters areshown in Table 8.1.
分析性能特征或验证参数应符合ICHQ2（107）的要求，包括准确度、精密度、专属性、LOD、LOQ、线性、范围、耐用性和回收率（见8.1章），这些参数的定义见表8.1。
8.1 Analytical Methods
分析方法
8.1.1 Validation Parameters
验证参数
Validation parameters are describedin Table 8.1.
验证参数的描述见表8.1
Table 8.1: ICH Q2Validation Parameter Definitions [107]
表8.1 ICH Q2验证参数定义（107）
countyParameter 参数中关村留学中介 | Definition 定义 |
Accuracy uyc准确度 | “Express the cloness of agreement between the value which is accepted either as a conventional true value or an accepted reference value and the value found” 表示真实值或认可的参考值与测量值之间的相近程度。 scottrade com |
Precision 精密度 | “Express the cloness of agreement (degree of scatter) between a ries of measurements obtained from multiple sampling of the same homogeneous sample under the prescribed conditions 是指规定条件下对均质样品多次取样进行一系列检测结果的接近程度（离散程度） · Repeatability – the precision under the same operating conditions over a short interval of time. Repeatability is also termed intra-assay precision. 重复性——指在同样的操作条件下，在较短时间间隔的精密度：也称为间隙测量精密度（Intra-assay precision） · Intermediate Precision – within-laboratories variations: different days, different analysts, different equipment, etc. 中间精密度——是指实验室内部条件改变，如不同日，不同试验分析者，不同仪器等情况下的精密度。。 n是什么意思· Reproducibility – express the precision between laboratories (collaborative studies, usually applied to standardization of methodology)” 重现性是指不同试验室之间的精密度（合作研究，通常用于方法学的标准化）。 |
Specificity/Selectivity 专属性/选择性 | “Specificity is the ability to asss unequivocally the analyte in the prence of components which may be expected to be prent.” 专属性是指可能存在某些组分时，对被分析物准确可靠测定的能力。 |
Detection Limit (LOD) 检测限 | “The lowest amount of analyte in a sample which can be detected but not necessarily quantitated as an exact value” 样品中的被分析物能够被检测到的最低量，但不一定要准确定量。 |
Quantitation Limit (LOQ) 我想你日语定量限 | “The lowest amount of analyte in a sample which can be quantitatively determined with suitable precision and accuracy” 是指在合适的准确性和精密度下，能够定量测定样品中被分析物的最低量。 |
Linearity 线性 | “The ability (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample” 是指在给定的范围内检测结果与样品中被分析物的浓度（量）成比例关系的能力。 |
Range 范围 | “The interval between the upper and lower concentration (amounts) of analyte in the sample (including the concentrations) for which it has been demonstrated that the analytical procedure has a suitable level of precision, accuracy and linearity” 是指样品中被分析物的较高浓度(量)和较低浓度(量)的一个区间，并已证实在此区间内，该方法具有合适的准确性、精密度和线性。 |
heel什么意思Robustness 耐用性 | “A measure of its capacity to remain unaffected by small, but deliberate variations in method parameters and provides an indication of its reliability during normal usage” administrator是什么是指试验参数适当地发生细小改变时，测量保持不受影响的能力，可用于说明正常使用时的可靠性。 |
Ruggedness 重现性 | The degree of reproducibility of test results obtained by the analysis of the same samples under a variety of normal test conditions such as different laboratories, analysts, instruments, reagents lots, or days 是指样品在正常的测试条件下在不同试验室，分析员、分析仪器、试剂批号、日期所获得分析结果的重现程度 |
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8.1.1.1 Accuracy
准确度
Accuracy determines the cloness of test results to the true value acrossthe range [107].
准确度决定了测试结果在一定范围内与真实值的接近程度
Samples extracted into solutions aremeasured and compared to standard solutions at comparable concentrations to determine accuracy. For cleaning validation samples,accuracy is measured through recovery of samples from equipment surfaces and extraction ofthe recovered samples into a testing solution. Accuracy should be establishedusing a sufficient number of data points. One example is three recovery levelsin triplicate, for a total of nine recoveries (e Chapter 7). Accuracy isreported as % recovery of the amount of analyte in the recovered samples measured against the amount of analyte spiked onto thesample recovery surface.
测定提取溶液中的样品并与同等浓度的标准溶液进行比较，以确定准确度。对于清洁验证样品，准确度是通过从设备表面回收样品并将回收样品提取到测试溶液中进行测量，建立准确度应使用足够数量的数据。一种方式是三个回收水平，每个水平三份，总共九个回收样（见第7章）。准确度报告为回收样品中被测物相比取样表面上所涂布的量的%回收率。
Accuracy should be determined aroundthe ARL, which is the point around which accurate data is most esntial.However, for a relatively safe product, the ARL could be relatively high. Forexample:
准确度应在可接受残留限度上测定，在可接受限度附近得到准确数据是最重要的。然而，对于相对安全的产品，可接受残留限度可能相对较高。例如:
· Typical accuracy at 75%, 100%, and125% of ARL
典型的准确度在可接受残留限度的75%、100%和125%
· If ARL > 100 µg/25 cm2 swab, perform recovery around 100 µg/25 cm2
blessyou如果可接受残留限度> 100 µg/25 cm2 ,则在 100 µg/25 cm2左右进行回收测试
· Advisable to extend linearity upto ARL to understand possible method limitations
建议将线性扩展到可接受残留限度以了解可能的方法限制
· Advisable to extend accuracy downto method LOQ and one to three levels in between, which is where most data should be
建议将准确度向下延伸到检测限，采用介于两者之间的一到三个级别，大多数数据都在该区间
8.1.1.2 Precision
精密度
msPrecision determines the degree of agreement among individual test resultsapplied repeatedly to multiple samples from a homogeneous sample [107]. It is ameasure of the combined variability of the sample recovery, the sample extraction, and the samplemeasurement. Precision may be considered at three levels: repeatability, Interme
diatePrecision (IP), and reproducibility. All the parameters of the recovery process(e Chapter 7) can affect the recovery
