第二模块-CTD

Module 2 Common Technical Document Summaries 通用技术文件总结

NTA, Volume 2B, CTD-Module 2

Edition July 2003

Module 2.1 Common Technical Document Table of Contents (Module 2 – 5) 通用技术文件目录（模块2-5）Module 2.2 Introduction 简介

Module 2.3 Quality Overall Summary 质量综述

Module 2.4 Nonclinical Overview 非临床概述

Module 2.5 Clinical Overview 临床概述

Module 2.6 Nonclinical Summary 非临床摘要

Module 2.7 Clinical Summary 临床总结

Module 2.1 Common Technical Document Table of Contents

(Modules 2 – 5) 通用技术文件目录（模块2-5）Module 2: Common Technical Document Summaries 通用技术文件摘要2.1 CTD Table of Contents (Module 2 – 5) CTD文件目录

2.2 CTD Introduction CTD简介

2.3 Quality Overall Summary 质量摘要

2.4 Nonclinical Overview 非临床概述

2.5 Clinical Overview 临床概述

2.6 Nonclinical Written and Tabulated Summary 书面临床摘要和列表的摘要

Pharmacology 药理学

Pharmacokinetics 药物代谢学

Toxicology 毒理学

2.7 Clinical Summary 临床摘要

Biopharmaceutics and Associated Analytical Methods 生物制药学和相关检测方法Clinical Pharmacology Studies 临床药理学

Clinical Efficacy 临床效用

Clinical Safety 临床安全性

Synopses of Individual Studies 个体性状研究

Module 3: Quality 质量

3.1 Module 3 Table of Contents 模块三内容

3.2 Body of Data 具体数据

3.3 Key Literature References 关键参考文献

Module 4: Nonclinical Study Reports 非临床研究报告

4.1 Module 4 Table of Contents 模块四内容

4.2 Study Reports 研究报告

4.3 Literature References 参考文献

Module 5: Clinical Study Reports 临床研究报告

5.1 Module 5 Table of Contents 模块五内容

5.2 Tabular Listing of All Clinical Studies 所有临床研究数据列表

5.3 Clinical Study Reports 临床研究报告

5.4 Literature References 参考文献

Module 2.2 Introduction 简介

The general introduction to the medicinal product should include its pharmacological class, mode of action and the proposed clinical use. In general the introduction should not exceed one page.

关于药品的简要介绍包括：药理级别，服用方法，建议中临床效果，建议此部分不超过一页

Module 2.3 Quality Overall Summary 质量综述

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 Module 3 or in other parts of the CTD. 质量综述（QOS）是根据第三模块的数据做的总结。质量综述不应该包括第三模块没有准备好的数据和CTD中其余的数据。

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 provide, for instance, justification in cases where guidelines were not followed.

质量综述应该包括含每部分详细的信息，以方便第三模块的质量模块回顾。此部分应该强调产品关键的工艺参数。

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 discussed under the CTD-S module), including cross-referencing to volume and page number in other Modules.

质量综述应该包括关键问题的讨论，融合了质量模块部分的相关信心，以及其它模块相关信息（举例：CTD-S模块下，杂质质量与毒理研究的对比研究）

This QOS normally should not exceed 40 pages of text, 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). The italicised text below indicates where tables, figures, or other items can be imported directly from Module 3.

质量综述正常情况下不可以超过40页（不包括表格和数据）。对于生物产品可能使用更复杂的过程，，文件可以稍长一些但不要超过80页（不包括表格和数据）。数据，图表和其他的相关项目可以写在第三模块中

INTRODUCTION 简介

The introduction should include proprietary name, non-proprietary name, European Pharmacopoeia name or common name of the drug substance, company name, dosage form(s), strength(s), route of administration according to the current version of the Standard Terms of the European Pharmacopoeia and proposed indication(s)

简介部分应当包括专利药品的名称，非专利药品的名称，欧盟药典名称或者是原料药的通用名臣，公司名称，剂型，药效，行政信息，上述信息必须根据是欧盟药典现行条款的标准版本。

2.3.S DRUG SUBSTANCE (NAME, MANUFACTURER) 原料药（名称，生产商）2.3.S.1 General Information (name, manufacturer) 简明信息（名称，生产商）Information from 3.2.S.1 should be included. 相见3.2S1的相关部分

2.3.S.2 Manufacture (name, manufacturer) 生产信息（名称，生产商）Information from 3.2.S.2 should be included: 3.2S.2的相关信息

?Information on the manufacturer; 关于制造商的相关信息

?A brief description of the manufacturing process (including, for example, reference to starting materials, critical steps, and reprocessing) and the controls that are intended to result in the routine and consistent production of material(s) of appropriate quality;

关于生产过程的简要描述（举例：起始材料，关键材料和再加工）。控制连续生产的过程质量

?A flow diagram, as provided in 3.2.S.2.2; 流程图3.2.S.2.2;

?A description of the Source and Starting Material and raw materials of biological origin used in the manufacture of the drug substance, as described in 3.2.S.2.3;

对于起始物料的生物起源的相关描述，在原料药生产单位，详情参见3.2.S.2.3; ? A discussion of the selection and justification of critical manufacturing steps, process controls, and acceptance criteria. Highlight critical process intermediates, as described in 3.2.S.2.4;

需要列出关键工艺控制点的选择和验证，工艺控制和验证准则。强调关键控制点的中间产品3.2.S.2.4;

?A description of process validation and/or evaluation, as described in 3.2.S.2.5.

过程验证描述或者评估，3.2.S.2.5.

?A brief summary of major manufacturing changes made throughout development 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.

对于生产变更的简要描述和相关评估的发展和总结来评估生产过程的连续性，3.2.S.2.6.质量系统综述指的是生产变更对临床研究和非临床研究数据的影响。在CTD-S和CTD-E的文件的模块中由描述。

2.3.S.3 Characterisation (name, manufacturer)

For NCE:标准等效曲线

A summary of the interpretation of evidence of structure and isomerism, as described in

3.2.S.3.1, should be included. When a drug substance is chiral, it should be specified whether specific stereoisomers or a mixture of stereoisomer 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 final product intended for marketing.

对于结构和异性的总结，正如3.2.S.3.1中包括的内容。当原料药的由手性特征的时候，它的立体异购术的混合应用于临床和非临床研究，在原料药产品销售的时候应该提供相关信息。

For Biotech: A description of the desired product and product-related substances and a summary of general properties, characteristic features and characterisation data (for example, primary and higher order structure and biological activity), as described in

3.2.S.3.1, should be included. For NCE and Biotech:

对于生物技术：对于期望中的产品和与产品相关的原料药，需要总结其相关性质，特点和数据特点（举例：初级和高级结构，生物活动）。正如NCE和生物技术特点中所描述的那样。

The QOS should summarise the data on potential and actual impurities arising from the synthesis, manufacture and/or degradation, and should summarise the basis for setting the acceptance criteria for individual and total impurities.

质量综述系统要总结潜在的和实际生产中存在的杂志问题。应该对杂质问题建立哟个系统。

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 by the proposed commercial process. The QOS should state how the proposed impurity limits are qualified. A tabulated summary of the data provided in 3.2.S.3.2, with graphical representation, where appropriate should be included.

无论是在临床还是非临床研究中，质量综述系统应该总结每批原料药中的杂质程度。在此系统中还应该明确杂质的限度问题。在3.2.S.3.2.记录表中所提供的数据，并且以表格的形式。

2.3.S.4 Control of Drug Substance (name, manufacturer) 原料药的控制（名称，生产商）

A brief summary of the justification of the specification(s), the analytical procedures, and validation should be included. Specification from 3.2.S.4.1 should be provided.

A tabulated summary of the batch analyses from 3.2.S.4.4, with graphical representation where appropriate, should be provided.

关于评价的标准，分析过程的判断和验证问题应当在3.2.S.4.1表格中提供出来。

2.3.S.5 Reference Standards or Materials (name, manufacturer) 物料的参考标准（名称，生产商）

Information from 3.2.S.5 (tabulated presentation, where appropriate) should be included. 应该包括3.2.S.5的信息（数据表格）

2.3.S.6 Container Closure System (name, manufacturer) 容器的密闭性（名称，生产商）

A brief description and discussion of the information, from 3.2.S.6 should be included.

3.2.S.简要叙述相关信息

2.3.S.7 Stability (name, manufacturer) 稳定性（名称，生产商）

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, as described in 3.2.S.7.1.

此部门应当包括相关研究的摘要（条件，批次，分析程序），以及相关结果的简要描述。建议使用的储存条件，复测的日期或者是保存限期。相关程序在3.2.S.7.1.描述

The post-approval stability protocol, as described in 3.2.S.7.2, should be included.

A tabulated summary of the stability results from 3.2.S.7.3, with graphical representation where appropriate, should be provided.

在3.2.S.7.2中描述稳定性计划。在3.2.S.7.3,中应该描述用数据表描述稳定性。

2.3.P DRUG PRODUCT (NAME, DOSAGE FORM) 药品（名称、剂型）

2.3.P.1 Description and Composition of the Drug Product (name, dosage form)

药品的成分描述（名称、剂型）

Information from 3.2.P.1 should be provided. 在3.2.P.1中提供相关信息

Composition from 3.2.P.1 should be provided.在3.2.P.1中的组成成分

2.3.P.2 Pharmaceutical Development (name, dosage form)药物的研发（名称、剂型）

A discussion of the information and data from 3.2.P.2 should be presented.

在3.2.P.2中提供相关的信息和数据

A tabulated summary of the composition of the formulations used in clinical trials and a presentation of dissolution profiles should be provided, where relevant.

需要提供关于临床细节和溶解的剖面图的新数据摘要

2.3.P.3 Manufacture (name, dosage form) 生产（名称，剂型）

Information from 3.2.P.3 should include: 在3.2.P.3部分应包含如下信息

?Information on the manufacturer. 生产商的相关信息

?A brief description of the manufacturing process and the controls that are intended to result in the routine and consistent production of product of appropriate quality.

生产过程及控制的简要概括，连续生产的质量总结。

?A flow diagram, as provided under 3.2.P.3.3.

在 3.2.P.3.3中流程图，

?A brief description of the process validation and/or evaluation, as described in 3.2.P.3.5. 在3.2.P.3.5.部分提到生产过程验证

2.3.P.4 Control of Excipients (name, dosage form) 赋形剂的控制（名称，剂型）

A brief summary on the quality of excipients, as described in 3.2.P.4, should be included. 在3.2.P.4部分中应当对赋形剂的质量简单描述

2.3.P.5 Control of Drug Product (name, dosage form) 药品控制（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.

应该提供评价的标准，分析过程的判断和验证过程。

Specification(s) from 3.2.P.5.1 should be provided. 在3.2.P.5.1部分提出。

A tabulated summary of the batch analyses provided under 3.2.P.5.4, with graphical representation where appropriate should be included.

在3.2.P.5.4，需要提供关于临床细节和溶解的剖面图的新数据摘要

2.3.P.6 Reference Standards or Materials (name, dosage form)

原料的参考标准（名称，剂型）

Information from 3.2.P.6 (tabulated presentation, where appropriate) should be included. 在3.2.P.6提供相关信息（数据提供）

2.3.P.7 Container Closure System (name, dosage form) 容器的密闭性（名称，剂型）

A brief description and discussion of the information in 3.2.P.7 should be included.

在3.2.P.7中包括简单的信息和讨论结果。

2.3.P.8 Stability (name, dosage form) 稳定性（名称，剂型）

A summary of the studies undertaken (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 should be given.

对于研究的摘要（条件，批次，分析程序），产品的稳定性数据的研究和分析结果应该给出总结。应在结论中给出存储条件，保质期。如果可以的话，应该给出现有的储存条件和保质期。

A tabulated summary of the stability results from 3.2.P.8.3, with graphical representation where appropriate, should be included. The post-approval stability protocol, as described in 3.2.P.8.2, should be provided.

在3.2.P.8.3,中，以图表的形式给出稳定性数据。在3.2.P.8.2中给出稳定性计划。2.3.A APPENDICES 附录

2.3.A.1 Facilities and Equipment (name, manufacturer) 厂房和设备（名称和生产商）

Biotech: 生物技术

A summary of facility information described under 3.2.A.1 should be included.

在3.2.A.1中给出厂房的简明信息

2.3.A.2 Adventitious Agents Safety Evaluation (name, dosage form, manufacturer)

异常情况下的安全评价（名称，剂型和生产商）

A discussion on measures implemented to control endogenous and adventitious agents in production should be included. A tabulated summary of the reduction factors for viral clearance from 3.2.A.2, should be provided.

关于控制异常情况生产药品的安全性的方法。3.2.A.2列出对残留因素的清洁数据。

2.3.A.3 Excipients 赋形剂

2.3.R REGIONAL INFORMATION 区域信息

A brief description of the information specific for the reg ion, as provided under “3.2.R” should be included, where appropriate.

对于地区的简要信息可以在“3.2.R”中进行描述

Module 2.4 Nonclinical Overview 非临床概述

NONCLINICAL OVERVIEW 非临床概述

The Nonclinical Overview should provide an integrated overall analysis of the information in the Common Technical Document. In general, the Nonclinical Overview should not exceed about 30 pages.

非临床概述对通用技术文件信息分析的总结。一般来说，非临床概述部应超过30页。General Aspects 通常情况

The Nonclinical Overview should present an integrated and critical assessment of the pharmacologic, pharmacokinetic, and toxicologic evaluation of the pharmaceutical. Where relevant guidelines on the conduct of studies exist, these should be taken into consideration, and any deviation from these guidelines should be discussed and justified. The nonclinical testing strategy should be discussed and justified.

非临床概述英爱包括对于药理学，药物代谢动力学和毒理学进行关键的评估和总结。对于现有研究的相关方针，也应该考虑进去。这些条款中存在的偏差问题可以列出。非临床的测试方法应该讨论和证实。

There should be comment on the GLP status of the studies submitted. Any association between nonclinical findings and the quality characteristics of the human pharmaceutical, the results of clinical trials, or effects seen with related products should be indicated, as appropriate.

应该递交GLP状态的相关评价，介于非临床研究和人用药品质量的相关联系，临床试验的相关结果，或者是相关产品的药效等都应列出。

Except for biotechnology-derived products, an assessment of the impurities and degradants present in the drug substance and product should be included along with what is known of their potential pharmacologic and toxicologic effects. This assessment should form part of the justification for proposed impurity limits in the drug substance and product, and be appropriately cross-referenced to the quality documentation.

除了生物技术技术产品，杂质和崩解物的评估都会作为对潜在药理或者毒理作用的影响。对于原料药和成品中杂质限度的检测，应该参照相关的质量文件。

The implications of any differences in the chirality, chemical form, and impurity profile between the compound used in the nonclinical studies and the product to be marketed should be discussed. For biotechnology-derived products, comparability of material used in nonclinical studies, clinical studies, and proposed for marketing should be assessed. If a drug product includes a novel excipient, an assessment of the information regarding its safety should be provided.

关于非临床研究中，非临床研究的混合物和市场上销售的产品中关于手型特征的不同，化学形式，或者是杂质的检测是应该被列出来的。对于生物技术演化的产品，非临床研究和临床研究的的相似性评估应该列出。如果药品生产中包括赋形剂，关于此类药物的安全性应该被评估。

Relevant scientific literature and the properties of related products should be taken into account. If detailed references to published scientific literature are to be used in place of studies conducted by the applicant, this should be supported by an appropriate justification that reviews ，the design of the studies and any deviations from available guidelines.

相关的科学文献和相关的产品特性都应该考虑进去。如果文献的相关细节作为证明，不是用相关研究做的证明，研究的设计和相关的偏差。

In addition, the availability of information on the quality of batches of drug substance used in these referenced studies should be discussed. The Nonclinical Overview should contain appropriate reference citations to the Tabulated Summaries, in the following format: (Table X.X, Study/Report Number).

另外，在这些参考文献中，原料药质量信息和批生产信息应该被列出来。非临床综述包括在数据总结中饮用的参考标准，格式如下（X.X表，研究报告的编号）Content and Structural Format 内容和结构格式

The Nonclinical Overview should be presented in the following sequence:

根据下列顺序累出非临床研究综述

Overview of the nonclinical testing strategy 非临床研究政策的概述

Pharmacology 药理学

Pharmacokinetics 药物动力学

Toxicology 毒理学

Integrated overview and conclusions 整体概述和结论

List of literature references 参考文献清单

Studies conducted to establish the pharmacodynamic effects, the mode of action, and potential side effects should be evaluated and consideration should be given to the significance of any issues that arise.

根据研究建立药物动力学效用，检测方法和潜在的影响都应该被评估并且考虑到其中

The assessment of the pharmacokinetic, toxicokinetic, and metabolism data should address the relevance of the analytical methods used, the pharmacokinetic models, and the derived parameters. It might be appropriate to cross-refer to more detailed consideration of certain issues within the pharmacology or toxicology studies (e.g. impact of the disease states, changes in physiology, anti-product antibodies, cross-species consideration of toxicokinetic data).

对于药物代谢动力学，毒理学和新陈代谢数据的评估必需协商其质量方法进行评估。对于药理学或者毒理学研究的相关信息应该给出更多的细节。（如：对于疾病的影响，生理的改变，抗生素产品，跨品种交叉数据的分析）

Inconsistencies in the data should be discussed. Inter-species comparisons of metabolism and systemic exposure comparisons in animals and humans (AUC, Cmax, and other appropriate parameters) should be discussed and the limitations and utility of the nonclinical studies for prediction of potential adverse effects in humans highlighted.

应该讨论数据中存在的不一致性。在动物与人类的暴露性上进行内在暴露的对比(AUC, Cmax, and other appropriate parameters)。关于人类潜在的不良反应的预测都应该包含记录。

The onset, severity, and duration of the toxic effects, their dose-dependency and degree of reversibility (or irreversibility), and species- or gender-related differences should be evaluated and important features discussed, particularly with regard to:

从发病，加重到毒效，他们剂型的独立性和可逆性；应该评估与类型和性别相关的特点。考虑到如下几方面：

?pharmacodynamics 药物动力学

?toxic signs 毒性标记

?causes of death 死亡原因

?pathologic findings 病理发现

?genotoxic activity - the chemical structure of the compound, its mode of action, and its relationship to known genotoxic compounds

遗传毒性问题-化合物中的化学结构，临床效果，与遗传毒性的关系。?carcinogenic potential in the context of the chemical structure of the compound, its relationship to known carcinogens, its genotoxic potential, and the exposure data

化合物的化学成分中致癌物质，与现有致癌物质的关系，与潜在遗传毒性的关系，以及暴露数据。

?the carcinogenic risk to humans - if epidemiologic data are available, they should be taken into account对人类致癌性物质-如果流行病的数据有效，考虑到其中?fertility, embryofetal development, pre-and post-natal toxicity

毒性的繁殖能力，

?studies in juvenile animals 幼崽研究

?the consequences of use before and during pregnancy, during lactation, and during pediatric development妊娠期，哺乳期，儿科使用后的效果

?local tolerance 地域性的耐受力

?other toxicity studies/ studies to clarify special problems 其他的毒性研究

The evaluation of toxicology studies should be arranged in a logical order so that all relevant data elucidating a certain effect / phenomenon are brought together. Extrapolation of the data from animals to humans should be considered in relation to:

相关的毒理研究评价应该以合理的方式评估。以便相关的数据可以集中到一起分析。从动物到人用药的分析可以考虑一下几方面：

?animal species used 动物种类

?numbers of animals used 动物的数量

?routes of administration employed 相关的行政信心

?dosages used 剂型

?duration of treatment or of the study 治疗的耐受性

?systemic exposures in the toxicology species at no observed adverse effect levels and at toxic doses, in relation to the exposures in humans at the maximum recommended human dose. Tables or figures summarising this information are recommended.

在动物毒理测试中，没有观测到不良反应的程度以及限制人类使用的最大剂量。此类信息应该被列入其中。

?the effect of the drug substance observed in nonclinical studies in relation to that expected or observed in humans。If alternatives to whole-animal experiments are employed, their scientific validity should be discussed.

在非临床药物中，应该观察药物的作用。以便观察其在人体中的药效。如果这对动物实验由任何的替代物，需要进行科学验证

The Integrated Overview and Conclusions should clearly define the characteristics of the human pharmaceutical as demonstrated by the nonclinical studies and arrive at logical, well-argued conclusions supporting the safety of the product for the intended clinical use. Taking the pharmacology, pharmacokinetics, and toxicology results into account, the implications of the nonclinical findings for the safe human use of the pharmaceutical should be discussed (i.e., as applicable to labeling)

最后的结论和综述应该准确的描述出人用的特点，并且此药品已经在非临床研究中得到验证并且由临床使用安全性的研究数据。综合考虑到药理学，药物动力学和毒理学，非临床研究结果对于人用药品的安全性还是需要探讨的。（适用于标签）

Module 2.5 Clinical Overview 临床综述

Preamble 前言

The Clinical Overview is intended to provide a critical analysis of the clinical data in the Common Technical Document. The Clinical Overview will necessarily refer to application data provided in the comprehensive Clinical Summary, the individual clinical study reports (ICH E3),and other relevant reports; but it should primarily present the conclusions and implications of those data, and should not recapitulate them.

临床综述用以提供通用技术文件临床关键分析数据，临床综述必须要提供全面的临床总结，个性研究（ICH E3）以及相关的研究报告的，但是首先应该考虑到数据和结论，不可以对此部分进行概述。

Specifically, the Clinical Summary should provide a detailed factual summarisation of the clinical information in the CTD, and the Clinical 。Overview should provide a succinct discussion and interpretation of these findings together with any other relevant information (e.g., pertinent animal data or product quality issues that mayhave clinical implications).

值得一提的是，临床摘要应该在CTD格式中提供真实的临床数据总结。总结必须提供相关结果简明过程，并提供相关信息。（举例：真实的动物实验数据和产品质量数据）

The Clinical Overview is primarily intended for use by regulatory agencies in the review of the clinical section of a marketing application. It should also be a useful reference to the overall clinical findings for regulatory agency staff involved in the review of other sections of the marketing application.

临床总结首先要对营销申请中的临床部分做一个总结，其中应该包括营销申请中包括的临床结果。

The Clinical Overview should present the strengths and limitations of the development program and study results, analyse the benefits and risks of the medicinal product in its intended use, and describe how the study results support critical parts of the prescribing information.

临床总结中应该明确药品研发的程序和研究的结果，分析产品的药效和风险，评估研究结果如何能支持所陈述的信息。

In order to achieve these objectives the Clinical Overview should:

为了获取上述客观事实，临床总结应该包括：

?describe and explain the overall approach to the clinical development of a medicinal product, including critical study design decisions;

描述一下药品的临床科研过程，其中包括关键工艺控制点的研发和设计?assess the quality of the design and performance of the studies, and include a statement regarding GCP compliance;

评估设计的质量和研究的表现，其中包括符合药品临床试验质量管理规范。

?provide a brief overview of the clinical findings, including important limitations (e.g., lack of comparisons with an especially relevant active comparator, or absence of information on some patient populations, ; pertinent endpoints, or on use in combination therapy).对于临床结果进行简单描述，其中包括重要的限度（举例：缺乏相关的对比仪器，或者是缺少相关患者的信息：相关的端点，或者化合物的使用）

?provide an evaluation of benefits and risks based upon the conclusions of the relevant clinical studies, including interpretation of how the efficacy and safety findings support the proposed dose and target indication and an evaluation of how prescribing information and other approaches will optimise benefits and manage risks;

为相关的临床研究提供风险评估，其中包括药效和安全性的研究结果，主要是用来证明相关的伎俩，目标。评估描述的信息和相关的风险管理。

?address particular efficacy or safety issues encountered in development, and how they have been evaluated and resolved;

明确写出药品发展过程中的药效和安全性，以及如何对他们进行评估的过程?explore unresolved issues, explain why they should not be considered as barriers to approval, and describe plans to resolve them;

发现一些尚待解决的问题，解释没有获得批准的原因，并且为此做出相应的计划。?explain the basis for important or unusual aspects of the prescribing information.

The Clinical Overview should generally be a relatively short document (about 30 pages). The length, however, will depend on the complexity of the application. The use of graphs and concise tables in the body of the text is encouraged for brevity and to facilitate understanding. It is not intended that material presented fully elsewhere be repeated in the Clinical Overview; crossreferencing to more detailed presentations provided in the Clinical Summary or in Module 5 is encouraged.

解释一下以前信息重要的方面。临床研究总结应该是相对较短的一个文件（大致30页）。其长度主要取决于申请的复杂性。主体文件中图表的使用和数据的链接。要求相对简洁便于理解。在临床总结中不要有重复的地方，相关细节的描述应该在第五模块中提供。

Table of Contents 目录

2.5.1 Product Development Rationale 产品研发的基本原理

2.5.2 Overview of Biopharmaceutics 生物制药学的总结

2.5.3 Overview of Clinical Pharmacology 临床药理学的总结

2.5.4 Overview of Efficacy 药效的总结

2.5.5 Overview of Safety 安全性的总结

2.5.6 Benefits and Risks Conclusions 药效和风险总结

2.5.7 Literature References 参考文献

Detailed Discussion of Content of the Clinical Overview Sections

关于临床信息目录的具体内容

2.5.1 Product Development Rationale 产品研发的基本原理

The discussion of the rationale for the development of the medicinal product should:

药品研发原理的讨论

?identify the pharmacological class of the medicinal product.

药品的药理学级别

?describe the particular clinical/pathophysiological condition that the medicinal product is intended to treat, prevent, or diagnose (the targeted indication).

详细描述药品的临床条件，是治疗，预防或者是诊断

?briefly summarise the scientific background that supported the investigation of the medicinal product for the indication(s) that was (were) studied.

对于药品调研，其支持的科学背景给出简要的总结。

?briefly describe the clinical development programme of the medicinal product, including ongoing and planned clinical studies and the basis for the decision to submit the application at this point in the programme. Briefly describe plans for the use of foreign clinical data (ICH E5).

对于药品的临床发展给出简要的描述，其中包括正在进行和计划中的临床研究，以及对相关手续的申请表都需要提交上来。简单介绍一下外用的临床数据(ICH

E5)。

?note and explain concordance or lack of concordance with current standard research approaches regarding the design, conduct and analysis of the studies. Pertinent published literature should be referenced. Regulatory guidance and advice (at least from the region(s) where the Clinical Overview is being submitted) should be identified, with discussion of how that advice was implemented. Formal advice documents (e.g., official meeting minutes, official guidance, letters from regulatory authorities) should be referenced, with copies included in the references section of Module 5.

注意并解释一下现有的科研方法是否与设计，分析检验方法存在的一致性与不一致性。其中相关的参考文献。需要明确相关的指导方针和建议（至少递交区域性的临床总结），以及建议是如何完成的。正式的建议文件（如：官方会议时间，官方的指导方针，权威部门的来信）都应该在模块中详细列出。

2.5.2 Overview of Biopharmaceutics 生物制药学的概况

The purpose of this section is to present a critical analysis of any important issues related to bioavailability that might affect efficacy and/or safety of the to-be-marketed formulation(s) (e.g., dosage form/strength proportionality, differences between the

to-be-marketed formulation and the formulation(s) used in clinical trials, and influence of food on exposure).

此部分的主要目的是针对生物等效性累出总要的分析方法，其很有可能影响市场形成。（如：剂型药效，临床的相关细节，对于食物的影响）

2.5.3 Overview of Clinical Pharmacology 临床药理学的总结

The purpose of this section is to present a critical analysis of the pharmacokinetic (PK), pharmacodynamic (PD), and related in vitro data in the CTD. The analysis should consider all relevant data and explain why and how the data support the conclusions drawn. It should emphasise unusual results and known or potential problems, or note the lack thereof. This section should address:

此本分的主要目的是对药物代谢动力学给出关键性的分析（PK），药效学（(PD），以及在CTD文件中的相关数据。应该强调的是其中潜在的问题，或者是缺少的数据等。这部分应该包括：

?pharmacokinetics, e.g., comparative PK in healthy subjects, patients, and special populations; PK related to intrinsic factors (e.g., age, sex, race, renal and hepatic impairment) and to extrinsic factors (e.g., smoking, concomitant drugs, diet); rate and extent of absorption; distribution, including binding with plasma proteins; specific metabolic pathways, including effects of possible genetic polymorphism and the formation of active and inactive metabolites; excretion; time-dependent changes in pharmacokinetics; stereochemistry issues; clinically relevant PK interactions with other medicinal products or other substances.

药物代谢动力学，举个例子，健康问题中相对的药物代谢动力学，患者以及特定的人群，以及内在的因素（如：年龄，性别，民族，肾脏损害等），外部因素（如：吸烟，伴随药物，节食），吸收程度；物流包括等离子蛋白质，特殊的代谢途径，包括基因蛋白，活性和非活性的药物代谢；排泄；药物动力学的时间改变性；立体化学；制剂或者原料药之间的相互联系。

?pharmacodynamics, e.g., information on mechanism of action, such as receptor binding; onset and/or offset of action; relationship of favorable and unfavorable pharmacodynamic effects to dose or plasma concentration (i.e., PK/PD relationships); PD support for the proposed dose and dosing interval; clinically relevant PD interactions with other medicinal products or substances; and possible genetic differences in response.

药效学，如：关于行为方便的信息，患者接受混合物的程度，药物动力学对血浆离子的利弊。（如：PK和PD之间的联系）；药效学可以作为使用剂型的证据，与药效学相关的产品或者原料药，但是在药效上可能有所不同

?interpretation of the results and implications of immunogenicity studies, clinical microbiology studies, or other drug class specific PD studies summarised in section

2.7.2.4 of the Clinical Summary.

免疫原性结果和结果的研究主要是根据微生物研究或者其他的药物级别的研究。此部分的总结可以站在2.7.2.4得出。

2.5.4 Overview of Efficacy 药效概述

The purpose of this section is to present a critical analysis of the clinical data pertinent to the efficacy of the medicinal product in the intended population. The analysis should consider all relevant data, whether positive or negative, and should explain why and how the data support the proposed indication and prescribing information.

此部分的主要是为了患者所属的特定人群提供临床关键数据的分析。此部分分析要求包括所有的相关数据，无论是成阳性还是阴性，还需要解释为什么此部分的数据可以证明说明书上的内容。

Those studies deemed relevant for evaluation of efficacy should be identified, and reasons that any apparently adequate and well-controlled studies are not considered relevant should be provided. Prematurely terminated studies should be noted and their impact considered.

此部分的研究主要是明确对药品药效的分析，并且阐述原因为什么不提供不相关的研究报告。要考虑过早的研究对其影响。

The following issues should generally be considered: 需要考虑以下问题：

?relevant features of the patient populations, including demographic features, disease stage, any other potentially important covariates, any important patient populations excluded from critical studies, and participation of children and elderly (ICH E11 and

E7). Differences between the studied population(s) and the population that would be expected to receive the medicinal product after marketing should be discussed

关于患者所属人群的相关特点，包括数据特点，疾病所属的程度，任何潜在的变量，除了关键点研究的重要患者，及其所属人群，包括年长者和年幼者（ICH E11 and

E7）。在销售之后，被研究患者所在的人群与患者的人群用药后应对比其不同?implications of the study design(s), including selection of patients, duration of studies and choice of endpoints and control group(s). Particular attention should be given to endpoints for which there is limited experience. Use of surrogate endpoints should be justified. Validation of any scales used should be discussed.

设计研究的完成，其中包括画着的选择，中断的选择和耐受力，控制的人群。应该给终端研究以特殊的关注。代理终端的使用需要进行验证。

?for non-inferiority trials used to demonstrate efficacy, the evidence supporting a determination that the trial had assay sensitivity and justifying the choice of noninferiority margin (ICH E10).

为了证明药效的非劣性，对比致命性的分析的证明和其它的非劣性的可能。?statistical methods and any issues that could affect the interpretation of the study results 数据方法和其它研究结果的分析

(e.g., important modifications to the study design, including endpoint assessments and planned analyses, as they were specified in the original protocol; support for any unplanned analyses; procedures for handling missing data; and corrections for multiple endpoints).如：科研设计的修改，其中包括终端评估和计划分析，如在原始的规章制度，计划外的分析，丢失数据的处理，对于多终端的修改）

?similarities and differences in results among studies, or in different patient sub-groups within studies, and their effect upon the interpretation of the efficacy data.

研究结果的相似性和区别或者是不同组别的研究，药效的分析

?observed relationships between efficacy, dose, and dosage regimen for each indication, in both the overall population and in the different patient subgroups (ICH E4).

观察每种药物不同剂型药效之间的关系，包括所有人群和不同患者所属的人群(ICH E4).

?support for the applicability to the new region of data generated in another region, where appropriate (ICH E5).

在另一个区域中的数据的适用性

?for products intended for long-term use, efficacy findings pertinent to the maintenance of long-term efficacy and the establishment of long-term dosage. Development of tolerance should be considered.

药品长期使用的，长期使用的药效和长期使用的剂型。耐受力的研究也需要考虑到其中。

?data suggesting that treatment results can be improved through plasma concentration monitoring, if any, and documentation for an optimal plasma concentration range.

治疗结果的相关数据，如血浆浓度的检测，血浆浓度的测量范围等。

?the clinical relevance of the magnitude of the observed effects.

临床意义观测到的效果

?if surrogate endpoints are relied upon, the nature and magnitude of expected clinical benefit and the basis for these expectations.

如果进行终端代理，预期的临床效果的本质以及基础。

?efficacy in special populations. If efficacy is claimed with inadequate clinical data in the population, support should be provided for extrapolating efficacy from effects in the general population.

特殊人群中的药效问题。如果特定的人群中，临床数据充足，其药效是可以声明的，并且此数据也可以作为药效的证据。

2.5.5 Overview of Safety 安全综述

The purpose of this section is to provide a concise critical analysis of the safety data, noting how results support and justify proposed prescribing information. A critical analysis of safety should consider:

此部分的目的是提供精密的安全数据，以及支持相关信息。关键性的安全数据应该包括如下内容：

?adverse effects characteristic of the pharmacological class. Approaches taken to monitor for similar effects should be described.

药理学级别的不良反应。采取相关方法检测相关的不良反应。

?special approaches to monitoring for particular adverse events (e.g., ophthalmic, QT interval prolongation). 采用特殊方法监测其不良反应（如：眼药，合格试验的间隔性）?relevant animal toxicology and product quality information. Findings that affect or could affect the evaluation of safety in clinical use should be considered.

相关的动物毒性试验和产品质量信息。其临床使用的安全性需要进行评估。?the nature of the patient population and the extent of exposure, both for test drug and control treatments. Limitations of the safety database, e.g., related to inclusion/exclusion criteria and study subject demographics, should be considered, and the implications of such limitations with respect to predicting the safety of the product in the marketplace should be explicitly discussed.

患者人口自然属性，针对测试药物和控制治疗。安全数据的限制：举例：相关的安全性研究图表，药品安全性的预期图应该被讨论。

?common and non-serious adverse events, with reference to the tabular presentations of events with the test drug and with control agents in the Clinical Summary. The discussion should be brief, focusing on events of relatively high frequency, those with an incidence higher than placebo, and those that are known to occur in active controls or other members of the therapeutic class. Events that are substantially more or less common or problematic (considering the duration and degree of the observed events) with the test drug than with active controls are of particular interest.

常见的和不严重的不良反应，可以参考相关控制机构的临床总结。此讨论应该简洁明了。主要是应该针对高发生率的不良反应上。应该以积极的分类和药理控制分类作为其影响的范围。药物测试无论是普通型或者是由问题的（考虑到观测结果和耐受力），应该以积极地形式控制。

?serious adverse events (relevant tabulations should be cross-referenced from the Clinical Summary). This section should discuss the absolute number and frequency of serious adverse events, including deaths, and other significant adverse events (e.g., events leading to discontinuation or dose modification), and should discuss the results obtained for test drug versus control treatments. Any conclusions regarding causal relationship (or lack of this) to the product should be provided. Laboratory findings reflecting actual or possible serious medical effects should be considered.

严重的不良反应（相关的数据应该从临床总结中参考）。此部分应该考虑到严重不良反应的数据或者频率，其中包括死亡的案例，其他的典型的不良反应（举例：数据的非连续性或者剂型的更改），应当考虑药物或者治疗控制的结果。任何与结论相关突发案例应该提供。应该考虑到实验室结果对实际不良反应的影响。?similarities and differences in results among studies, and their effect upon the interpretation of the safety data.

研究结果中的相似性与差异性的结果，以及安全数据的解释。

?any differences in rates of adverse events in population subgroups, such as those defined by demographic factors, weight, concomitant illness, concomitant therapy, or polymorphic metabolism.

在不同人群中药品不良反应的差异性，如数据信心，重量，不良反应病症，不良反应的治疗方法或者多形态的新陈代谢。

?relation of adverse events to dose, dose regimen, and treatment duration.

相关的剂型，服用发放，治疗的持续方法之间的关系。

?long-term safety (E1a). 长期服用的安全性

?methods to prevent, mitigate, or manage adverse events.

预防，减缓或者管理不良反应的方法

?reactions due to overdose; the potential for dependence, rebound phenomena and abuse, or lack of data on these issues. 过量服用的反应：潜在的毒性，反作用的现象或者药物滥用，缺少此问题的相关数据

?world-wide marketing experience. The following should be briefly discussed:

全球营销经验，以下问题需要讨论：

- the extent of the world-wide experience, 全球的营销经验

- any new or different safety issues identified, 明确新的或者不同的安全观点

- any regulatory actions related to safety. 与安全性相关的控制