美国FDA分析方法验证指南中英文对照

　I. INTRODUCTION This guidance provides recommendations to applicants on submitting analytical procedures, validation data, and samples to support the documentation of the identity, strength, quality, purity, and potency of drug substances and drug products. 1. 绪论 本指南旨在为申请者提供建议，以帮助其提交分析方法，方法验证资料和样品用于支持原料药和制剂的认定，剂量，质量，纯度和效力方面的文件。

　This guidance is intended to assist applicants in assembling information, submitting samples, and presenting data to support analytical methodologies. The recommendations apply to drug substances and drug products covered in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), product license applications (PLAs), and supplements to these applications. 本指南旨在帮助申请者收集资料，递交样品并资料以支持分析方法。这些建议适用于 NDA，ANDA，BLA，PLA 及其它们的补充中所涉及的原料药和制剂。

　The principles also apply to drug substances and drug products covered in Type II drug master files (DMFs). If a different approach is chosen, the applicant is encouraged to discuss the matter in advance with the center with product

　jurisdiction to prevent the expenditure of resources on preparing a submission that may later be determined to be unacceptable. 这些原则同样适用于二类 DMF 所涉及的原料药和制剂。如果使用了其它方法，鼓励申请者事先和 FDA 药品评审中心的官员进行讨论，以免出现这种情况，那就是花了人力物力所准备起来的递交资料后来发现是不可用的。

　The principles of methods validation described in this guidance apply to all types of analytical procedures. However, the specific recommendations in this guidance may not be applicable to certain unique analytical procedures for products such as biological, biotechnological, botanical, or radiopharmaceutical drugs. 本指南中所述的分析方法验证的原则适用于各种类型的分析方法。但是，本指南中特定的建议可能不适用于有些产品所用的特殊分析方法，如生物药，生物技术药，植物药或放射性药物等。

　For example, many bioassays are based on animal challenge models, 39 immunogenicity assessments, or other immunoassays that have unique features that should be considered when submitting analytical procedure and methods validation information. 比如说，许多生物分析是建立在动物挑战模式，免疫原性评估或其它有着独特特性的免疫分析基础上的，在递交分析方法和分析方法验证资料时需考虑这些独特的性质。

　Furthermore, specific recommendations for biological and immunochemical tests that may be necessary for characterization and quality control of many drug substances and drug products are beyond the scope of this guidance document. 而且，许多原料药和制剂的界定和质量控制所需的生物和免疫化学检测并不在本指南的范围之内。

　Although this guidance does not specifically address the submission of analytical procedures and validation data for raw materials, intermediates, excipients, container closure components, and other materials used in the production of drug

　substances and drug products, validated analytical procedures should be used to analyze these materials. 尽管本指南并不专门叙述原料，中间体，赋形剂，包装材料及原料药和制剂生产中所用的其它物料的分析方法及分析方法验证资料的递交，但是应该应用验证过的分析方法来分析检测这些物质。

　For questions on appropriate validation approaches for analytical procedures or submission of information not addressed in this guidance, applicants should consult with the appropriate chemistry review staff at FDA. 对于本指南中未提及的关于分析方法验证和资料提交方面的问题，请向 FDA 相关的化学评审人员咨询。

　This guidance, when finalized, will replace the FDA guidance for industry on Submitting Samples and Analytical Data for Methods Validation (February 1987). 本指南，一旦定稿，将取代 FDA 于 1987 年 2 月份发布的工业指南：分析方法验证所需提交的样品和分析资料。

　II. BACKGROUND

　Each NDA and ANDA must include the analytical procedures necessary to ensure the identity, strength, quality, purity, and potency of the drug substance and drug product, including bioavailability of the drug product (21 CFR 314.50(d)(1) and 314.94(a)(9)(i)).

　II. 背景 每个 NDA 和 ANDA 都必需包括必要的分析方法以确保原料药和制剂的认定，剂量，质量，纯度和效力，还包括制剂的生物利用度(21 CFR 314.50(d)(1) 和 314.94(a)(9)(i))。

　FDA 验证文件现场备查，可以不与 DMF 一起交。

　Data must be available to establish that the analytical procedures used in testing meet proper standards of accuracy and reliability (21 CFR 211.165(e) and 211.194(a)(2)). 必须要有资料来论证所用的分析方法是符合一定的准确度和可靠性标准的。

　Methods validation is the process of demonstrating that analytical procedures are suitable for their intended use. The methods validation process for analytical procedures begins with the planned and systematic collection by the applicant of the validation data to support the analytical procedures. 分析方法验证是论证某一分析方法适用于其用途的过程。分析方法的验证过程是从申请者有计划地系统性收集验证资料以支持分析方法开始的。

　The review chemist evaluates the analytical procedures and validation data submitted in the NDA or ANDA.

　审评化学家会对 NDA 或 ANDA 中的分析方法和验证资料进行评审。

　On request from FDA, an NDA or ANDA applicant must submit samples of drug product, drug substance, noncompendial reference standards, and blanks so that the applicant"s drug substance and drug product analytical procedures can be evaluated by FDA laboratories (21 CFR 314.50(e) and 314.94(a)(10)). 一旦 FDA 有要求，则 NDA 或 ANDA 的申请者必须提交制剂，原料药，非药典对照品和空白以使 FDA 实验室能对申请者所用分析方法进行评审(21 CFR 314.50(e) and 314.94(a)(10))。

　The FDA laboratory analysis demonstrates that the analytical procedures are reproducible by laboratory testing. The review chemists and laboratory analysts

　determine the suitability of the analytical procedures for regulatory purposes. FDA 实验室的分析会论证该分析方法在实验室内是可以重现的。审评化学家和实验室分析家会从法规的角度确定该分析方法的适用性。

　FDA investigators inspect the analytical laboratory testing sites to ensure that the analytical procedures used for release and stability testing comply with current good manufacturing practices (CGMPs) (21 CFR part 211) or good laboratory practices (GLPs) (21 CFR part 58), as appropriate. FDA 检查官会对分析实验室进行检查确保用于放行和稳定性实验的分析方法符合现行的 GMP（21CFR part 211) 和 GLP (21 CFR part 58)。

　Each BLA and PLA must include a full description of the manufacturing methods, including analytical procedures, that demonstrate that the manufactured product meets prescribed standards of safety, purity, and potency (21 CFR 601.2(a) and 601.2(c)(1)(iv)). 每个 BLA 和 PLA 都必须要有详细的生产工艺描述，包括分析方法，以说明所生产的产品是符合规定睥安全，纯充和效力标准的(21 CFR 601.2(a) and 601.2(c)(1)(iv))。

　Data must be available to establish that the analytical procedures used in testing meet proper standards of accuracy and reliability (21 CFR 81211.194(a)(2)). For BLAs, PLAs, and their supplements, the analytical procedures and their validation are submitted as part of the license application or supplement and are evaluated by the review committee. 必须要有资料证明所用的分析方法是符合一定的准确度和可靠性要求的(21 CFR 81211.194(a)(2))。对于 BLA，PLA 及它们的补充，在所提交的许可证申请中应当要有分析方法和方法验证这部分的资料，审评委员会会对这部分资料进行评审。

　Representative samples of the product must be submitted and summaries of results of tests performed on the lots represented by the submitted sample must be provided (21 CFR 601.2(a) and 601.2(c)(1)(vi)). The review committee chair may request analytical testing by CBER laboratory analysts to evaluate the applicant=s analytical procedures and verify the test results. 需 提 供 代 表 性 样 品 及 该 样 品 所 代 表 批 号 的 检 测 结 果 总 结 (21 CFR 601.2(a) and 601.2(c)(1)(vi))。评审委员会主席会要求 CBER 实验室的分析人员进行分析实验对申请者的分析方法进行评估，并确认其分析结果。

　All analytical procedures are of equal importance from a validation perspective. In general, validated analytical procedures should be used, irrespective of whether they are for in-process, release, acceptance, or stability testing. Each quantitative analytical procedure should be designed to minimize assay variation. 从验证的角度来看，所有的分析方法有着同样的重要性。一般来说，应当要应用已验证过的分析方法，而不论其是被用于过程控制，放行，合格或稳定性实验。高等每个定量分析方法时都应当要减少其分析误差。

　Analytical procedures and validation data are submitted in the sections of the application on analytical procedures and controls. Recommendations on information to be submitted are included in sections III through IX and XI of this guidance. Information on submission of the methods validation package to the NDA or ANDA and samples to the FDA laboratories is provided in section X. 分析方法和验证资料应当摆在申请的分析方法和控制章节中提交。本指南的第 III 到 IX 章

　和 XI 章给出了所需提供资料方面的建议。向 FDA 实验室提供样品和递交 NDA 和 ANDA 中的分析方法验证资料的信息见第 X 章。

　III. TYPES OF ANALYTICAL PROCEDURES

　A. Regulatory Analytical Procedure A regulatory analytical procedure is the analytical procedure used to evaluate a defined characteristic of the drug substance or drug product. The analytical procedures in the U.S. Pharmacopeia/National Formulary (USP/NF) are those legally recognized under section 501(b) of the Food, Drug, and Cosmetic Act (the Act) as the regulatory analytical procedures for compendial items. For purposes of determining compliance with the Act, the regulatory analytical procedure is used. III 分析方法的类型 A. 法定分析方法 法定分析方法是被用来评估原料药或制剂的特定性质的。USP/NF 中的分析方法是法定的用于药典项目检测的分析方法。为了确认符合法规，需使用法定分析方法。

　B. Alternative Analytical Procedure

　An alternative analytical procedure is an analytical procedure proposed by the applicant for use instead of the regulatory analytical procedure. A validated alternative analytical procedure should be submitted only if it is shown to perform equal to or better than the regulatory analytical procedure. B. 替代分析方法 替代分析方法是申请者提出用于代替法定分析方法的分析方法。只有当一替代分析方法相当于或优于法定分析方法时，才可以应用验证过的替代分析方法。

　If an alternative analytical procedure is submitted, the applicant should provide a rationale for its inclusion and identify its use (e.g., release, stability testing), validation data, and comparative data to the regulatory analytical procedure. 如果提交了替代分析方法，申请者还应当提供其理由，并标明其用途（如，放行，稳定性实验），验证资料及其与法定分析方法的对比资料。

　C. Stability-Indicating Assay

　A stability-indicating assay is a validated quantitative analytical procedure that can detect the changes with time in the pertinent properties of the drug substance and drug product.

　C. 稳定性指示分析 稳定性指示分析是能检测出原料药或制剂的某些性质随着时间的延长而出现的变化的定量分析方法。

　A stability-indicating assay accurately measures the active ingredients, without interference from degradation products, process impurities, excipients, or other potential impurities。

　稳定性指示分析能不受降解产物，工艺杂质，赋形剂或其它潜在杂质的影响而准确测定其中的活性成分。

　If an applicant submits a non-stability-indicating analytical procedure for release testing, then an analytical procedure capable of qualitatively and quantitatively monitoring the impurities, including degradation products, should complement it. Assay analytical procedures for stability studies should be stability-indicating, unless scientifically justified.

　如果申请者递交了用于放行检测的非稳定性指示分析方法，则应当要有能定性和定量地监测杂质，包括降解产物，的分析方法对其进行补充。稳定性试验中所用的含量分析方法应当要有稳定性指示能力，除非有科学的理由能证明其合理性。

　IV. REFERENCE STANDARDS

　A. Types of Standards A reference standard (i.e., primary standard) may be obtained from the USP/NF or other official sources (e.g., CBER, 21 CFR 610.20). If there are questions on whether a source of a standard would be considered by FDA to be an official source, applicants should contact the appropriate chemistry review staff. When there is no official source, a reference standard should be of the highest possible purity and be fully characterized. IV 标准品 A．标准品的类型 可以从 USP/NF 处或其它官方(比如说，CBER，21CFR 610.20)获得标准品 (也就是一级对照品)。如果不能确定一标准品的来源是否会被 FDA 认为是官方来源，申请者应当要向适当的化学评审人员咨询。如果没有官方来源，则被用来作标准品的物质应当要有尽可能高的纯度，并得到充分界定。

　A working standard (i.e., in-house or secondary standard) is a standard that is qualified against and used instead of the reference standard. 工作对照品 (也就是内部标准品或二级标准品)是根据一级对照品标定的，并用来代替一级对照品的。

　B. Certificate of Analysis

　A certificate of analysis (COA) for reference standards from non-official sources should be submitted in the section of the application on analytical procedures and controls. For standards from official sources, the user should ensure the suitability of the reference standard. The standard should be stored correctly and used within the established use interval. B．分析报告单 对于非官方标准品，在申请的分析方法和控制章节中应当要提供该标准品的分析报告单。对于从官方获得的标准品，用户应当要确保标准品的适用性。应当正确储存标准品并在已确定的时间段内使用该标准品。

　C. Characterization of a Reference Standard

　Reference standards from USP/NF and other official sources do not require further characterization. A reference standard that is not obtained from an official source should be of the highest purity that can be obtained by reasonable effort, and it should be thoroughly characterized to ensure its identity, strength, quality, purity, and potency. C．标准品的界定 从 USP/NF 及其它官方来源获得的标准品是不需要进一步界定的。非官方对照品要有尽可能高的纯度，并进行充分地界定以确保其结构，剂量，质量，纯度和效力。

　The qualitative and quantitative analytical procedures used to characterize a reference standard are expected to be different from, and more extensive than, those used to control the identity, strength, quality, purity, and potency of the drug substance or the drug product. Analytical procedures used to Draft — Not for Implementation characterize a reference standard should not rely solely on

　comparison testing to a previously designated reference standard. 用于界定标准品的定性和定量分析方法应当要不同于用于控制原料药或制剂的结构，剂量，质量，纯度和效力的分析方法，要比它们更深入。用于标准品界定的分析方法不应仅仅是和先前的指定标准品进行比较实验。

　Generally, this characterization information should include:

　 A brief description of the manufacture of the reference standard, if the manufacturing process differs from that of the drug substance. Any additional purification procedures used in the preparation of the reference standard should be described. 一般来说，界定资料应当要包括：

　标准品的简单工艺描述，如果其生产工艺是否于其相应的原料药的话。应当要叙述制备标准品时所用的补充精制过程。

　Legible reproductions of the relevant spectra, chromatograms, thin-layer chromatogram (TLC) photographs or reproductions, and other appropriate instrumental recordings.

　Data establishing purity. The data should be obtained by using appropriate tests, such as TLC, gas chromatography (GC), high-pressure liquid chromatography (HPLC), phase solubility analysis, appropriate thermometric analytical procedures, and others as necessary. 相关光谱图，色谱图，TLC 照片及其它仪器输出的清晰复印件。建立纯度的资料。应当要应用适当的检测方法来获得这些资料，比如说 TLC，GC，HPLC，相溶解分析，适当的热分析方法及其它必要的分析方法。

　Appropriate chemical attribute information, such as structural formula, empirical formula, and molecular weight. Information to substantiate the proof of structure should include appropriate analytical tests, such as elemental analysis, infrared spectrophotometry (IR), ultraviolet spectrophotometry (UV), nuclear magnetic resonance spectroscopy (NMR), and mass spectrometry (MS), as well as applicable functional group analysis. Detailed interpretation of the test data in support of the claimed structure should be provided. 适当的化学性质资料，比如结构式，经验式和分子量等。结构确证资料应当要包括适当的分析测试，比如元素分析，IR，UV,NMR 和 MS，及适用的官能团分析。还应当要提供具体的结构解析资料。

　A physical description of the material, including its color and physical form.

　Appropriate physical constants such as melting range, boiling range, refractive index, dissociation constants (pK values), and optical rotation.

　A detailed description of the analytical procedures used to characterize the reference standard. 物理性质的描述，包括颜色和物理形态。

　适当的物理常数，比如说熔程，沸程，折射率，离解常数(pK 值)和旋光度。用于界定标准品的分析程序的详细叙述。

　For biotechnological/biological product reference standards, the recommendations on characterization information above may apply and should be considered. However, additional and/or different tests would be important to assess physicochemical characteristics, structural characteristics, biological activity, and/or immunochemical activity. 至于生物技术/生物产品的标准品，应当要考虑上述建议，可能可以应用。然而，其它确定

　物理化学性质，结构特性，生物活性和/或免疫化学活性的补充检测和/或其它检测将是非常重要的。

　Physicochemical determinations may include isoform, electrophoretic, and liquid chromatographic patterns, as well as spectroscopic profiles. Structural characterization may include a determination of amino acid sequence, amino acid composition, peptide map, and carbohydrate structure. Biological and/or immunochemical activity should be assessed using the same analytical procedures used to determine product potency. 物理化学性质包括异构体，电泳和液相色谱行为及光谱性质等。结构界定可能包括氨基酸序列，氨基酸组成，缩氨酸图和碳水结构。确定生物和/或免疫化学活性的分析方法应当要和用来确定产品效力的分析方法一样。

　These can include animal-based, cell culture-based, biochemical, or ligand/receptor-binding assays. While these tests may be needed for complete characterization of certain reference standards, specific recommendations for validation of biological and immunochemical tests are not contained in this guidance document. 这些分析方法可以包括基于动物的，细胞培养的，生物化学的或配位体/接受体螯合的分析方法。如果这些检测需用于某些标准品的界定，生物和免疫化学检测的分析方法验证方面的特殊建议并不在本指南的范围之内。

　V. METHODS VALIDATION FOR INDs

　For an investigational new drug, sufficient information is required in each phase of an investigation to ensure proper identification, quality, purity, strength, and/or potency. The amount of information on analytical procedures and methods validation necessary will vary with the phase of the investigation (21 CFR 312.23(a)(7)). V．IND 中的分析方法验证

　对于 IND 而言，每个阶段的研究都需要有足够的资料以确保合适的认定，质量，纯度，剂量和/或效力。所需的分析方法和方法验证方面的资料会随着研究的阶段变化而变化(21 CFR 312.23(a)(7))。

　For general guidance on analytical procedures and methods validation information to be submitted for phase 1 studies, sponsors should refer to the FDA guidance for industry on Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well- Characterized, Therapeutic, Biotechnology-Derived Products (November 1995). 关于在第 1 阶段研究所需提交的分析方法和方法验证资料方面的指南，发起人可以参考 FDA的指南：药品（包括结构确定的，有疗效的，生物技术产品）第 1 阶段研究的 IND 申请的内容和格式（1995 年 11 月）。

　General guidance regarding analytical procedures and methods validation information to be submitted for phase 2 or phase 3 studies will be provided in the FDA guidance for industry INDs for Phase 2 and 3 Studies of Drugs, Including Specified Therapeutic Biotechnology-Derived Products, Chemistry, Manufacturing, and Controls Content and Format, when finalized (draft guidance published April 1999). 第 2 和第 3 阶段研究所需提交的分析方法和方法验证资料方面的指南，发起人将可以参考FDA 的指南：药品（包括结构确定的，有疗效的，生物技术产品）第 1 阶段研究的 IND 申请

　的 CMC 内容和格式（草案，1999 年 4 月）。

　All analytical procedures should be fully developed and validation completed when the NDA, ANDA, BLA, or PLA is submitted. 在递交 NDA，ANDA，BLA 或 PLA 时，所有的分析方法都应当要开发出来，并得到验证。

　VI. CONTENT AND FORMAT OF ANALYTICAL PROCEDURES FOR NDAs, 230ANDAs, BLAs, AND PLAs

　Any analytical procedure submitted in an NDA, ANDA, BLA, or PLA should be described in sufficient detail to allow a competent analyst to reproduce the necessary conditions and obtain results comparable to the applicant=s. Aspects of the analytical procedure that require special attention should be described. VI． NDA，ANDA，BLA 和 PLA 中分析方法的内容和格式 NDA，ANDA，BLA 和 PLA 中所提交的任一分析方法都应当要有详细的描述，以使合格的分析人员能重现出所需的实验条件并获得和申请者相当的实验结果。应当要叙述分析方法中需要特殊注意的地方。

　If the analytical procedure used is in the current revision of the USP/NF or other FDA recognized standard references (e.g., AOAC International Book Of Methods) and the referenced analytical procedure is not modified, a statement indicating the analytical procedure and reference may be provided rather than a description of the method (21 CFR 211.194). 如果所用的分析方法是 USP/NF 或其它 FDA 认可参考文献（如，<<AOAC 国际方法汇编>>）中且所参考的分析方法未经过修改的话，则需提供该分析方法的参引，而不用提供该分析方法的描述（21 CFR 211.194）。

　A description of analytical procedures from any other published sources should be provided, because the referenced sources may not be readily accessible to the reviewer. 对于从其它公开发表的文献上获得的分析方法，应当要对其进行叙述，因为评审官可能并不能很方便的获得这些文献。

　分析方法描述中需要包括的典型内容如下所示：

　A. Principle

　A statement of the principle of the analytical procedure should be included. For example, separation is based on isocratic reversed phase HPLC with detection by UV.

　B. Sampling

　The number of samples (e.g., vials, tablets) selected, how they are used (i.e., as individual or composite samples), and the number of replicate analyses per sample should be described. A．基本方法 HPLC 进行分离的，检测器为 UV 检测器。

　B．取样 需要叙述的有：所选样品的数目（比如，瓶，片等），它们是如何使用的（也就是，单独的或是混合样品），每个样品分析的重复次数。

　C. Equipment and Equipment Parameters

　A listing of all equipment (e.g., instrument type, detector, column type, dimensions) should be included, as well as a list of equipment parameters (e.g., flow rate, temperatures, run time, wavelength settings). A drawing representing the experimental configuration (e.g., illustrating positions for a spray pattern analytical procedure) should be provided, when appropriate.

　C．仪器和仪器参数 需要叙述的有：仪器列表（比如，仪器类型，检测器，柱子类型，尺寸等）和仪器参数（比如，流速，温度，运行时间和设定波长等）。如果必要的话，还要提供实验结构示意图（比如，阐述喷洒式分析方法的位置）。

　D. Reagents

　A list of reagents and their grades (e.g., USP/NF, American Chemical Society (ACS) Analytical Reagent) should be included. If in-house or modified commercial reagents are used, directions for their preparation should be included. Unstable or potentially hazardous reagents should be identified, and storage conditions, directions for safe use, and usable shelf life for these reagents should be specified. D．试剂 需要叙述的有：试剂列表及其相应的规格（比如：USP/NF，美国化学社（ACS）分析试剂）。如果使用的是自制试剂或更改过的商业试剂，则应当要有其制备方法。对于不稳定的或有潜在危险的试剂，应标明其储存条件，安全使用说明和使用周期。

　E. System Suitability Testing

　System suitability test parameters and acceptance criteria are based on the concept that the equipment, electronics, analytical operations, and samples to be analyzed constitute an integrated system. System suitability testing ensures that the system is working properly at the time of analysis. Appropriate system suitability criteria should be defined and included in the analytical procedure. E．系统适应性实验 系统适应性实验参数和合格标准是建立基础是：仪器，电子元件，分析操作和待测样品是个不可分割的整体。系统适应性实验确保系统在样品分析的时候能很好地运行。在分析方法中应当要包括适当的系统适应性合格标准。

　All chromatographic analytical procedures should include system suitability testing and criteria. Parameters typically used in system suitability evaluations are defined and discussed in the CDER reviewer guidance on Validation of Chromatographic Methods (November 1994). 所有的色谱分析方法都应当要有系统适应性实验及相应的合格标准。CDER 评审官指南<<色谱分析方法的验证>>（1994 年 11 月）对用于评估系统适应性的典型参数进行了定义和讨论。

　System suitability testing is recommended as a component of any analytical procedure, not just those that involve chromatographic techniques. Regardless of the type of analytical procedure, testing should be used to confirm that the system will function correctly independent of the environmental conditions. For example, titration analytical procedures should always include the evaluation of a blank (commonly referred to as a blank titration). 建议系统适应性实验应成为所有分析方法的一部分，而不仅仅是色谱分析方法。无论是哪类分析方法，都要采用实验来证实该系统能不受环境条件的影响而正确地运行。比如说，滴定法一般来说需要进行空白实验。

　F. Preparation of Standards Procedures for the preparation of all standard solutions (e.g., stock, working standard solutions, internal standards) should be included. F．标准品的制备 要有所有标准品溶液（比如，储备液，工作对照品溶液，内部对照品溶液）的配制方法。

　G. Preparation of Samples

　Sample preparation for individual tests should be clearly described. Specific details should be provided for unusual sample preparations (e.g., solid-phase extraction, derivatization). G.操作过程 应当要按操作步骤对操作过程进行逐步叙述。叙述应当要适当包括如下信息：平衡时间，样品进样顺序和系统适应性或启动参数。需标明不常见的危险。

　I. Calculations

　Representative calculations, with a tabulation defining all symbols and numerical factors, and specific instructions for the calculation of degradation products and impurities should be included. Any mathematical transformations or formulas used in data analysis should be described in detail. These may include logarithmic transformations used to obtain a linear relationship from exponential data, or the use of multiple order regression analyses. I．计算 应当要提供代表性计算公式，并要列表说明所有符号和数字系数，及计算降解产物和杂质的特殊使用说明。所有用于数据分析的数学转换或公式应详细描述。这些包括对数转换以获得指数数据的线性关系，或多元回归分析的使用。

　J.Reporting of Results J.结果报告 1. General

　The format used to report results (e.g., percent label claim, weight/weight, weight/volume, parts per million (ppm)) including the specific number of significant figures to be reported should be provided. 1．通则 应该规定关键计算步骤中的数字单位（例如，‘标签’标示量的百分比，W/W，W/L，ppm 等）

　2. Impurities Analytical Procedures

　The name and location/identifier (e.g., retention time (RT), relative retention time (RRT)) of impurities and the type of impurity (e.g., process, degradant, excipient degradant) should be included in the analytical procedures for impurities in the drug substance and drug product. The detection limit (DL) or quantitation limit (QL) should be stated, as appropriate. The DL or QL can be set using the drug substance"s detection response.

　2．杂质分析规程 在有关原料药和产品的杂质检测规程中，应当包括杂质的名称和检测位/标志（例如，保留时间 RT，相对保留时间 RRT），以及杂质的种类（比如工艺降解产物，赋形剂降解产物），如有可能，还应当指明检测限 DL 或定量限 QL。也可以在原料药检测中设置 DL 和 QL。

　Reporting of organic impurities should cover (1) specified identified impurities by name, (2) specified unidentified impurities by location/identifier, (3) any unspecified impurities, and (4) total impurities. The total organic impurities for the drug product or drug substance is the sum of all impurities equal to or greater than their individual QL. See recommendations regarding appropriate QLs in FDA impurities guidances (see references). Inorganic impurities and residual solvents should also be addressed.

　有机杂质的报告中，应当包括：1、有记载的已经过确认的杂质的名称；2、有记载但未经过确认杂质的（检测）位/标志；3、所有的没有记载的杂质，以及；4、总杂质。总有机杂质是指所有达到或超过其自身定量限度的杂质的总量。在这里可以参考 FDA 杂质指南文章中有关判定定量限度的内容（看后面的参考）。无机杂质和溶剂的残留，也应该被提到。

　For the drug product, drug substance process impurities may be excluded from reporting if an acceptable rationale is provided in the sections on analytical procedures and controls. Drug product impurities from the drug product manufacturing process, packaging, and labeling should be addressed.

　对于产品以及原料药的工艺杂质也可以不包括在报告中，除非分析规程和控制环节中描叙了一个可以被接受的原则，那么，在产品制造和包装过程中（包括贴签）产生的杂质就要被提到。

　The above reporting information may not be strictly applicable to all products (e.g., biological, biotechnological, botanical, radiopharmaceutical drugs), but any significant process and product-related impurities should be determined and reported.

　并不是所有产品（比如，生物制剂、生物工艺制剂、植物制剂、放射制剂）的报告都必须严格按照以上谈到的内容来写，但是所有关键的工序以及产品相关的杂质都要有检测和报告。

　VII. METHODS VALIDATION FOR NDAs, ANDAs, BLAs, AND PLAs

　A. Noncompendial Analytical Procedures

　In an NDA, ANDA, BLA, or PLA, data must be submitted to establish that the analytical procedures used in testing meet proper standards of accuracy and reliability (21 CFR 211.194(a)(2)). Methods validation is the process of demonstrating that analytical procedures are suitable for their intended use. At the time of submission, the NDA, ANDA,

　BLA, or PLA should contain methods validation information to support the adequacy of the analytical procedures. VII．NDA，ANDA，BLA 和 PLA 中的分析方法验证 A．非药典分析方法 在 NDA，ANDA，BLA 或 PLA 中，应当要递交资料以说明检测中所用的分析方法是满足适当的准确度和可靠性要求(21 CFR 211.194(a)92))。分析方法验证是个论述分析方法是适用于其拟定用途的过程。在递交资料时，NDA，ANDA，BLA 或 PLA 中应当要包含分析方法验证资料以支持分析方法的准确度。

　The International Conference on Harmonisation (ICH) guidance Q2A Text on Validation of Analytical Procedures (March 1995) and Q2B Validation of Analytical Procedures: Methodology (November 1996) provide recommendations on validation of analytical procedures. Analytical procedures outside the scope of the ICH guidances should still be validated. ICH 指导原则 Q2A：分析方法验证（1995 年 3 月）和 Q2B：分析方法验证：方法学（1996 年11 月）给出了分析方法验证的建议。对于超出 ICH 指导原则范围的分析方法也是需要验证的。

　1. Validation Characteristics Applicants should submit information on the validation characteristics of their proposed analytical procedures (see ICH Q2A and ICH Q2B). Although not all of the validation characteristics are needed for all types of tests (see section VII.A.3),

　typical validation characteristics are: 1.验证项目 申请者应当要送交其所拟定分析方法的验证项目方面的信息（见 ICH Q2A 和 ICH Q2B）。尽管不是对于所有类型的分析方法都需要进行所有的验证项目（见第 VII.A.3 章），但还是有典型的验证项目，如：

　Accuracy

　Precision (repeatability and intermediate precision)

　Specificity

　Detection limit

　Quantitation limit

　Linearity

　Range

　Robustnes 准确度 精密度（重复性和中间精密度）

　专属性 检测限 定量限 线性 范围 耐用性 2. Other Methods Validation Information

　Methods validation information should also include:

　Data to demonstrate the stability of all analytical sample preparations through the time required to complete the analysis. 2.其它验证资料 分析方法验证资料还应当要包括：

　说明所有分析制备样品在完成分析所需的时间内的稳定性的资料。

　Legible reproductions of representative instrument output or recordings (e.g., chromatograms) and raw data output (e.g., integrated areas), as appropriate. Instrument output for placebo, standard, and sample should also be provided (see section VII.A.2.c). 清晰可读的仪器代表性输出和记录资料（如色谱图）和原始资料输出（积分面积）。安慰剂，对照品和样品的仪器输出也都是需要提供的（见第 VII.A.2.c 章）。

　Representative calculations using submitted raw data, to show how the impurities in drug substance are calculated. Information from stress studies (see section VII.A.2.b). Impurities labeled with their names and location identifiers (e.g., RRT for chromatographic data) for the impurity analytical procedure. 代表性计算公式，以表明原料药中的杂质是如何计算的。(见 VII.A.2.b 章）。对于杂质分析方法，要标明杂质的名称和位置标识符（如，色谱中的相对保留时间 RRT）。

　For drug substances:

　 A discussion of the possible formation and control of polymorphic and enantiomeric substances.

　Identification and characterization of each organic impurity, as appropriate. This

　information may not be needed for all products (e.g., botanicals). Other impurities (e.g., inorganics, residual solvents) should be addressed and quantitated. 对于原料药：

　1. 讨论可能会形成的异构体并讨论异构体的控制。

　对每个有机杂质进行适当的标识和界定。不是所有的产品（如，植物药）都需要这些资料的。对于其它杂质（如无机杂质，残留溶剂），应当要进行说明并定量分析。

　Recommendations on submitting information on i...

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