APIC 201405原料药厂清洁验证指南：8.0残留量检测（上）（中英文）
8.0 Determination of the Amount of Residue 残留量的检测 8.1 Introduction 介绍
This section provides a practical guidance for the determination of the amount of residue in cleaned equipment based on the requirements from regulatory authorities[1] and current guidelines on analytical validation.[2] Specific requirements for the validation of analytical and sampling methods for cleaning validation purposes are provided in this section, in addition to examples of sampling methods and the appropriate use of analytical methods.
本部分根据药监当局的要求和现行分析方法验证指南，提供了检测已清洁设备中残留物数量的实用指南。在本部分中给出了清洁验证中所用分析方法和取样方法的验证要求，以及取样方法和适当使用分析方法的例子。
The carryover acceptance limit (Mper) is a calculated figure that represents the specification limit for the equipment cleanliness (see Section 4.0, Acceptance Limits), however, the determination of the actual amount of residue (M) remaining in the equipment following cleaning must be achieved using appropriate methods i.e. for both the sampling method and the quantitation of the contaminant in the sample.
允许残留限度（Mper）是一个计算出的数值，代表设备清洁程度的质量标准限度（参见4.0部分，可接受限度），但是，对清洁后设备中残留物（M）实际数量的检测必须使用适当的方法来获得，即，针对取样方法和样品中污染物的定量。 Since the decision on the acceptable cleanliness of the equipment bears a potential risk to product quality, the method(s) used for the
determination of M must be validated1 and the specificity, sensitivity and recovery of the method(s) should be determined as a minimum. 由于对设备可接受清洁度的决定会对产品质量有潜在风险，因此用于M检测的方法必须进行验证，必须至少验证方法的专属性、灵敏度和回收率。 8.2 Validation Requirements 验证要求 8.2.1 General 通则
The requirements for analytical method validation are defined in ICH Q2(R1), Validation of Analytical Procedures: Text and Methodology, November 2005. There are four types of analytical methods with principally different validation requirements; these are identification tests, tests for impurities (both quantitative and limit tests) and assay tests. The validation requirements for each method type are shown Table 1. 分析方法验证的要求在ICH Q2(R1)“分析方法验证：检验和方法学，2005年11月”中已给出。其中列出了四种不同类型的分析方法，各适用不同的验证要求，它们分别是：鉴别测试、杂质检验（定量和限度测试）和含量测试。每种类型方法的验证要求在表1中列出。
The list should be considered typical for the aforementioned analytical procedures, however, exceptions should be dealt with on a case-by-case basis. It should be noted that robustness is not listed in the table and should be considered at an appropriate stage in the development of the analytical procedure.
在上述的分析方法中必须考虑该清单，但是，要根据各案处理例外情况。要注意耐用性在表中并未列出，但在方法的研发过程中适当阶段需要进行考虑。 In practice, it is usually possible to design the experimental work such that the appropriate validation characteristics can be considered simultaneously to provide a sound, overall knowledge of the capabilities
of the analytical procedure, for instance; specificity, linearity, range, accuracy and precision.
在实际应用中，通常可以设计一个试验性工作，使得在方法设计时可以同步考虑方法的验证特性，例如，专属性、线性、范围、准确度和精密度。
The validation of an analytical method should occur in compliance with pre-established acceptance criteria that should be documented in a written general policy or Validation Plan. However, there should be one validation report per validated method that summarises the specific results.
分析方法验证必须符合预定的可接受限度。可接受限度应记录在书面的通用方针或验证中。但是，对每个验证过的方法必须有一个验证报告，总结验证结果。 TABLE 1 Requirement List for Analytical Validation
Type of Analytical Procedure Characteristic Accuracy Precision Repeatability Intermediate— Precision Specificity2 + Detection Limit Quantitation Limit — + — — — —3 + + + + + +1 — + + — + Identification — Testing for Impurities Assay Quantitative Limit + — + Linearity Range — — + + — — + + — Signifies that this characteristic is not normally evaluated. + Signifies that this characteristic is normally evaluated. Key termediate precision is not needed. 2 Lack of specificity of one analytical procedure could be compensated by other supporting analytical procedure(s). 3 May be needed in some cases.
表1 方法验证需求清单
分析方法类型 特性 鉴别 定量测试 准确度 精密度 重复性 中间精密度 专属性2 检测限 定量限 线性 范围 — — + — — — — + + +1 + —3 + + + 限度测试 — — — + + — — — + + + + + — + + 杂质检测 含量 1 In cases where reproducibility has been performed, in— 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。