CTD质量部分中英文指南

1、精选优质文档-倾情为你奉上INTERNATIONAL CONFERENCE ON HARMONISATION OF TECHNICAL REQUIREMENTS FOR REGISTRATION OF PHARMACEUTICALS FOR HUMAN USE人用药物注册技术要求国际协调会议ICH Harmonised Tripartite GuidelineICH 三方协调指南The Common Technical Document for theRegistration of Pharmaceuticals for Human Use:人用药物注册通用技术文件Quality质量Quali

2、ty Overall Summary of Module 2Module 3 : Quality模块2：质量概要模块3：质量Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 9 November 2000, this guideline is recommended for adoption to the three regulatory parties to ICHICH指导委员会会议ICH进程第4步2000年11月9日该指南建议三方法规处采用ICH(Numbering and

3、Section Headers have been edited for consistency and use in e-CTD as agreed at the Washington DC Meeting, September 11-12, 2002)2002年9月11-12日华盛顿会议一致通过采用统一编号和标题并在e-CTD中使用This Guideline has been developed by the appropriate ICH Expert Working Group and has been subject to consultation by the regulator

4、y parties, in accordance with the ICH Process. At Step 4 of the Process the final draft is recommended for adoption to the regulatory bodies of the European Union, Japan and USA.该指南已经合格的专家工作组研究并按照ICH程序经法规部协商。进程第4步最终草案已被欧盟、日本和美国采纳专心-专注-专业The Common Technical Document for theRegistration of Pharmaceut

5、icals for Human Use:人用药物注册通用技术文件Quality质量Quality Overall Summary of Module 2Module 3 : Quality模块2：质量概要模块3：质量ICH Harmonised Tripartite GuidelineICH三方协调指南Having reached Step 4 of the ICH Process at the ICH Steering Committee meeting on 9 November 2000, this guideline is recommended for adoption to the

6、 three regulatory parties to ICH(Numbering and Section Headers have been edited for consistency and use in e-CTD as agreed at the Washington DC Meeting, September 11-12, 2002)ICH指导委员会会议ICH进程第4步2000年11月9日该指南建议三方法规处采用ICH2002年9月11-12日华盛顿会议一致通过采用统一编号和标题并在e-CTD中使用TABLE OF CONTENTS目录MODULE 2 : COMMON TECH

7、NICAL DOCUMENT SUMMARIES模块2：通用技术文件概要2.3 : QUALITY OVERALL SUMMARY (QOS)2.3: 质量概要（QOS）The Quality Overall Summary (QOS) is a summary that follows the scope and the outline of the Body of Data in Module 3. The QOS should not include information, data or justification that was not already included in M

8、odule 3 or in other parts of the CTD.质量概要是对模块3中的主要数据和范围的小结。质量概要不能包括那些已经不在模块3或CTD其它任何部分中的信息、数据或证明。The QOS should include sufficient information from each section to provide the Quality reviewer with an overview of Module 3. The QOS should also emphasise critical key parameters of the product and prov

9、ide, for instance, justification in cases where guidelines were not followed. The QOS should include a discussion of key issues that integrates information from sections in the Quality Module and supporting information from other Modules (e.g. qualification of impurities via toxicological studies di

10、scussed under the CTD-S module), including cross-referencing to volume and page number in other Modules.质量概要应包括每部分的充足信息，给质量审核者提供模块3的概况。质量概要还应重点强调产品的关键参数并提供，如，没有按照指南进行时的说明。质量概要应包括对来自于质量模块和其它模块的支持信息（如，在CTD-S模块中通过毒理学研究对杂质定量等）关键问题的讨论，包括交叉引用的其它模块的卷号和页码。This QOS normally should not exceed 40 pages of text

11、, excluding tables and figures. For biotech products and products manufactured using more complex processes, the document could be longer but normally should not exceed 80 pages of text (excluding tables and figures). 质量概要通常不超过40页，除表格和数字外。对于生物制品和用更复杂的工艺生产的产品，文件可以长一些但通常不超过80页（除表格和数据外）。The italicised

12、text below indicates where tables, figures, or other items can be imported directly from Module 3.模块3中说明表格、数字或其它项目的斜体文字可直接引用。INTRODUCTION引言The introduction should include proprietary name, non-proprietary name or common name of the drug substance, company name, dosage form(s), strength(s), route of

13、administration, and proposed indication(s).引言中应包括原料药的专利商品名、非专利商品名，公司名称、剂型、浓度、用药途径，说明。2.3.SDRUG SUBSTANCE (NAME, MANUFACTURER)2.3.s原料药（名称、厂商）2.3.S.1General Information (name, manufacturer)2.3.S.1概要（名称，厂商）Information from 3.2.S.1 should be included.应包括3.2.S.1中的信息。2.3.S.2Manufacture (name, manufacturer

14、)2.3.S.2生产（名称，厂商）Information from 3.2.S.2 should be included:应包括3.2.S.2中的信息：· Information on the manufacturer;· 厂商信息；· A brief description of the manufacturing process (including, for example, reference to starting materials, critical steps, and reprocessing) and the controls that are

15、 intended to result in the routine and consistent production of material(s) of appropriate quality;· 简述生产工艺（包括，如，起始原料、关键步骤和返工等）和可生产出具有优良品质产品的生产控制。· A flow diagram, as provided in 3.2.S.2.2;· 流程图，如3.2.S.2.2中所述；· A description of the Source and Starting Material and raw materials o

16、f biological origin used in the manufacture of the drug substance, as described in 3.2.S.2.3;· 简要描述原料药生产用的起始原料以及生物来源的原材料及其来源，如3.2.S.2.3中所述；· A discussion of the selection and justification of critical manufacturing steps, process controls, and acceptance criteria. Highlight critical proces

17、s intermediates, as described in 3.2.S.2.4;· 讨论关键生产步骤、工艺控制和接受标准的选择和论证，突出关键工艺中间体，如3.2.S.2.4中所述；· A description of process validation and/or evaluation, as described in 3.2.S.2.5.· 工艺验证和/或评估的描述，如3.2.S.2.5中所述；· A brief summary of major manufacturing changes made throughout developme

18、nt and conclusions from the assessment used to evaluate product consistency, as described in 3.2.S.2.6. The QOS should also cross-refer to the non-clinical and clinical studies that used batches affected by these manufacturing changes, as provided in the CTD-S and CTD-E modules of the dossier.·

19、 从对产品的评价到评估产品的一致性得到结论的过程中的重大生产变更的总结，如3.2.S.2.6中所述。质量概要还应参照使用受这些生产变更影响的批次进行的非临床临床研究，如文件CTD-S和CTD-E模块中所述；2.3.S.3Characterisation (name, manufacturer)2.3.S.3性质（名称，厂商）For NCE:注意：A summary of the interpretation of evidence of structure and isomerism, as described in 3.2.S.3.1, should be included.应包括结构和异构

20、化的证据的简要解说，如3.2.S.3.1所述。When a drug substance is chiral, it should be specified whether specific stereoisomers or a mixture of stereoisomers have been used in the nonclinical and clinical studies, and information should be given as to the stereoisomer of the drug substance that is to be used in the f

21、inal product intended for marketing. 当原料药为手性药时，应说明特定的立体异构体或立体异构体混合物是否已被用于非临床和临床研究，还应给出将用于市场的成品原料药的立体异构体信息。For Biotech:生物制品：A description of the desired product and product-related substances and a summary of general properties, characteristic features and characterisation data (for example, primary

22、and higher order structure and biological activity), as described in 3.2.S.3.1, should be included.应包括对产品及产品有关物质的描述，及对一般性质、特征和特征数据（例如，初级和高级结构和生物活性）的小结，如3.2.S.1中所述;For NCE and Biotech:注意及生物制品：The QOS should summarise the data on potential and actual impurities arising from the synthesis, manufacture

23、and/or degradation, and should summarise the basis for setting the acceptance criteria for individual and total impurities. The QOS should also summarise the impurity levels in batches of the drug substance used in the non-clinical studies, in the clinical trials, and in typical batches manufactured

24、 by the proposed commercial process. The QOS should state how the proposed impurity limits are qualified.质量概要应总结合成、生产和/或降解过程中产生的潜在的和实际的杂质，应说明设置的单个杂质和总杂质的接受标准的依据。质量概要还应概括用于非临床研究、临庆试验和用既定的商业化工艺生产的典型批次的原料药中的杂质水平。质量概要应叙述既定的杂质限度是如何达标的。A tabulated summary of the data provided in 3.2.S.3.2, with graphical

25、representation, where appropriate should be included.应包括3.2.S.3.2中提供的数据一览表，必要时用图形表示。2.3.S.4Control of Drug Substance (name, manufacturer)2.3.S.4原料药的控制（名称，厂商）A brief summary of the justification of the specification(s), the analytical procedures, and validation should be included. 应包括对质量标准、分析程序和验证的说明

26、的简单小结。Specification from 3.2.S.4.1 should be provided.应提供3.2.S.4.1中的质量标准。A tabulated summary of the batch analyses from 3.2.S.4.4, with graphical representation where appropriate, should be provided.应提供3.2.S.4.4中的批分析小结表，必要时应用图形表示。2.3.S.5Reference Standards or Materials (name, manufacturer)2.3.S.5对照标

27、准品或物料（名称，厂商）Information from 3.2.S.5 (tabulated presentation, where appropriate) should be included.应包括3.2.S.5中的信息（必要时用表格表示）。2.3.S.6Container Closure System (name, manufacturer)2.3.S.6容器密封系统（名称，厂商）A brief description and discussion of the information, from 3.2.S.6 should be included.应包括对3.2.S.6的信息的简

28、要描述和讨论。2.3.S.7Stability (name, manufacturer)2.3.S.7稳定性（名称，厂商）This section should include a summary of the studies undertaken (conditions, batches, analytical procedures) and a brief discussion of the results and conclusions, the proposed storage conditions, retest date or shelf-life, where relevant,

29、 as described in 3.2.S.7.1.该项应包括对已进行的研究的小结（条件、批次和分析方法）及对结果、结论、预定的贮存条件、复验日期或有效期等相关信息的简单讨论，如3.2.S.7.1中所述。The post-approval stability protocol, as described in 3.2.S.7.2, should be included.应包括批准后的稳定性方案，如3.2.S.7.1中所述。A tabulated summary of the stability results from 3.2.S.7.3, with graphical representa

30、tion where appropriate, should be provided.应提供3.2.S.7.3中的稳定性结果的数据表，必要时应用图形表示。2.3.PDRUG PRODUCT (NAME, DOSAGE FORM)2.3.P制剂（名称，厂商）2.3.P.1Description and Composition of the Drug Product (name, dosage form)2.3.P.1制剂描述和组份（名称，厂商）Information from 3.2.P.1 should be provided.应提供3.2.P.1中的信息。Composition from 3

31、.2.P.1 should be provided.应提供3.2.P.1中的组份。2.3.P.2Pharmaceutical Development (name, dosage form)2.3.P.2药学研究（名称，厂商）A discussion of the information and data from 3.2.P.2 should be presented.应有对3.2.P.2中的信息和数据的讨论。A tabulated summary of the composition of the formulations used in clinical trials and a pres

32、entation of dissolution profiles should be provided, where relevant. 应提供用于临床试验的处方组成的表格总结。2.3.P.3Manufacture (name, dosage form)2.3.P.3生产（名称，剂型）Information from 3.2.P.3 should include:应包括3.2.P.3中的信息：· Information on the manufacturer. · 厂商信息。· A brief description of the manufacturing pr

33、ocess and the controls that are intended to result in the routine and consistent production of product of appropriate quality.· 简述生产工艺和对优良品质产品的常规稳定生产的控制。· A flow diagram, as provided under 3.2.P.3.3.· 流程图，如3.2.P.3.3· A brief description of the process validation and/or evaluation

34、, as described in 3.2.P.3.5.· 简述工艺验证和/或评估，如3.2.P.3.5中所述。2.3.P.4Control of Excipients (name, dosage form)2.3.P.4辅料控制（名称，剂型）A brief summary on the quality of excipients, as described in 3.2.P.4, should be included.应包括辅料质量的简单小结，如在3.2.P.4中所述。2.3.P.5Control of Drug Product (name, dosage form)2.3.P.5

35、制剂控制（名称，剂型）A brief summary of the justification of the specification(s), a summary of the analytical procedures and validation, and characterisation of impurities should be provided.应提供对质量标准说明、分析方法和验证的小结以及杂质特征的简单总结。Specification(s) from 3.2.P.5.1 should be provided.应提供3.2.P.5.1中的质量标准。A tabulated sum

36、mary of the batch analyses provided under 3.2.P.5.4, with graphical representation where appropriate should be included.应包括3.2.P.5.4项下批分析小结，适当时采用图形表示。2.3.P.6Reference Standards or Materials (name, dosage form)2.3.P.6参照标准品和物料（名称，剂型）Information from 3.2.P.6 (tabulated presentation, where appropriate)

37、should be included.应包括3.2.P.6中信息（适当时采用表格形式）。2.3.P.7Container Closure System (name, dosage form)2.3.P.1容器密封系统（名称，剂型）A brief description and discussion of the information in 3.2.P.7 should be included.应包括对3.2.P.7中信息的简述和讨论。2.3.P.8Stability (name, dosage form)2.3.P.8稳定性（名称，剂型）A summary of the studies un

38、dertaken (conditions, batches, analytical procedures) and a brief discussion of the results and conclusions of the stability studies and analysis of data should be included. Conclusions with respect to storage conditions and shelf-life and, if applicable, in-use storage conditions and shelf-life sho

39、uld be given.应给出已进行的研究（条伯、批次和分析方法）的小结，以及对稳定性研究、数据分析的结果和结论的简单讨论。如适用，应给出结论相关的贮存条件和效期。A tabulated summary of the stability results from 3.2.P.8.3, with graphical representation where appropriate, should be included.应包括3.2.P.8.3中稳定性结果的表格总结，适当时采用图形表示。The post-approval stability protocol, as described in

40、3.2.P.8.2, should be provided.应提供3.2.P.8.2中所述的经批准后的稳定性方案。2.3.AAPPENDICES2.3.A附件2.3.A.1Facilities and Equipment (name, manufacturer)2.3.A.1设施和设备（名称，厂商）Biotech:生物制品A summary of facility information described under 3.2.A.1 should be included.应包括3.2.A.1项下所述的设施信息总结。2.3.A.2Adventitious Agents Safety Evalu

41、ation (name, dosage form, manufacturer)2.3.A.2外源性试剂安全性评估（名称、剂型）A discussion on measures implemented to control endogenous and adventitious agents in production should be included.应包括对控制生产中内源性和外源性试剂所采取措施的讨论。A tabulated summary of the reduction factors for viral clearance from 3.2.A.2, should be provi

42、ded.应提供3.2.A.2项下病毒清除的还原因子的总结。2.3.A.3Excipients2.3.A.3辅料2.3.RREGIONAL INFORMATION 2.3.R区域信息A brief description of the information specific for the region, as provided under “3.2.R” should be included, where appropriate.适当时应包括3.2.R项下所述的区域特定信息的简单描述。Module 3 : Quality模块3：质量SCOPE OF THE GUIDELINE指南的范围Thi

43、s document is intended to provide guidance on the format of a registration application for drug substances and their corresponding drug products as defined in the scope of the ICH Guidelines Q 6 A ("NCE") and ICH Guideline Q 6 B ("Biotech"). This format may also be appropriate fo

44、r certain other categories of products. To determine the applicability of this format for a particular type of product, applicants should consult with the appropriate regulatory authorities. 本文旨在提供ICH指南Q6A（NCE）和ICH指南Q6B（Biotech）中定义的原料药及其制剂注册申请格式指南。为了确定该格式对于特定类型产品的适用性，申请者应咨询适当的法规机构。The text following

45、 the section titles is intended to be explanatory and illustrative only. The content of these sections should include relevant information described in existing ICH guidelines, but harmonised content is not available for all sections. The "Body of Data" in this guideline merely indicates w

46、here the information should be located. Neither the type nor extent of specific supporting data has been addressed in this guideline, and both may depend upon regional guidance. 章节标题后的文本仅用于解释和说明。这些章节的内容应包括现行ICH指南中描述的相关信息，但协调的内容不适用于所有章节。该指南中“数据正文”仅指出这些信息应该位于什么地方。该指南既没有确定特定支撑数据的类型也没有确定其范围，这两项的内容均可依据区域

47、指南。The section titles of Part 3.2.R (Regional Information) represent examples of typical topics of information that are not common to all ICH regions. Hence, the information to be provided in these sections should be based on the relevant regional guidelines.章节标题3.2.R部分（区域信息）代表了不通用于所有ICH区域的信息的典型实例。因

48、此，在这些章节要提供的信息应依据相关区域指南。3.1. TABLE OF CONTENTS OF MODULE 33.1. 模块3的目录A Table of Contents for the filed application should be provided.应提供申请文件的目录。3.2. BODY OF DATA3.2. 数据正文3.2.SDRUG SUBSTANCE1For a drug product containing more than one drug substance, the information requested for part “S” should be p

49、rovided in its entirety for each drug substance (NAME, MANUFACTURER)3.2.S原料药（名称，厂商）3.2.S.1General Information (name, manufacturer)3.2.S.1一般信息（名称，厂商）3.2.S.1.1Nomenclature (name, manufacturer)3.2.S.1.1命名（名称，厂商）Information on the nomenclature of the drug substance should be provided. For example:应提供原料药

50、的命名信息。例如：· Recommended International Nonproprietary Name (INN); · 推荐的国际非专利名称；· Compendial name if relevant; · 相关药典中的名称；· Chemical name(s);· 化学名称；· Company or laboratory code; · 公司或实验室编码；· Other non-proprietary name(s), e.g., national name, United States A

51、dopted Name (USAN), Japanese Accepted Name (JAN); British Approved Name (BAN), and· 其它非专利名称，如，国家名称，美国采用名称，日本接受名称；英国批准名称，和· Chemical Abstracts Service (CAS) registry number.· 化学文摘注册号。3.2.S.1.2Structure (name, manufacturer)3.2.S.1.2结构（名称，厂商）NCE: NCE：The structural formula, including rel

52、ative and absolute stereochemistry, the molecular formula, and the relative molecular mass should be provided.应提供结构式，包括相对的和绝对的立体化学结构式、分子式以及相对分子量。Biotech: 生物制品：The schematic amino acid sequence indicating glycosylation sites or other post-translational modifications and relative molecular mass should

53、 be provided, as appropriate. 适当时应提供氨基酸序列图，指出糖基化位置或其它翻译后的修钸和相对分子量。3.2.S.1.3General Properties (name, manufacturer)3.2.S.1.3一般性质（名称，厂商）A list should be provided of physicochemical and other relevant properties of the drug substance, including biological activity for Biotech.应提供原料药的物理化学或其它相关性质，包括生物制品的

54、生物活性。Reference ICH Guidelines: Q6A and Q6B参照ICH指南：Q6A和Q6B3.2.S.2Manufacture (name, manufacturer)3.2.S.2生产（名称，厂商）3.2.S.2.1Manufacturer(s) (name, manufacturer)3.2.S.2.1厂商（名称、厂商）The name, address, and responsibility of each manufacturer, including contractors, and each proposed production site or facil

55、ity involved in manufacturing and testing should be provided.应提供每个厂商的名称、地址和职责，包括签约人、涉及生产和检验的每个预定的生产厂址或厂房。3.2.S.2.2 Description of Manufacturing Process and Process Controls (name, manufacturer)3.2.S.2.2生产工艺和工艺控制的描述（名称、厂商）The description of the drug substance manufacturing process represents the appl

56、icants commitment for the manufacture of the drug substance. Information should be provided to adequately describe the manufacturing process and process controls. For example:表明申请者承诺生产原料药的生产工艺的描述。提供的信息应能够充分描述生产工艺和工艺控制。例如：NCE:NCE：A flow diagram of the synthetic process(es) should be provided that inc

57、ludes molecular formulae, weights, yield ranges, chemical structures of starting materials, intermediates, reagents and drug substance reflecting stereochemistry, and identifies operating conditions and solvents.应提供合成工艺的流程图，包括分子式、重量、产量范围，起始原料、中间体、试剂和反映立体化学的原料药的化学结构式，指出操作条件和溶剂。 A sequential procedural narrative of the manufacturing process should be submitted. The narrative should include, for example, quantities of raw materials, solvents, catalysts and reagents reflecting the representative batch scale for commercial manufacture, identification of critical steps, process cont