EU GMP指南 第1部分第4章：文件

EUROPEANCOMMISSION

HEALTH ANDCONSUMERS DIRECTORATE-GENERAL

Public Healthand Risk Assessment

Pharmaceuticals

Brussels,SANCO/C8/AM/sl/ares(2010)1064587

EudraLex

TheRules Governing Medicinal Products in the European Union

Volume4

GoodManufacturing Practice

MedicinalProducts for Human and Veterinary Use

Chapter4: Documentation

第四章：文件

Legal basisfor publishing the detailed guidelines: Article47 of Directive 2001/83/EC on the Community code relating to medicinal productsfor human use and Article 51 of Directive 2001/82/EC on the Community coderelating to veterinary medicinal products. This document provides guidance forthe interpretation of the principles and guidelines of good manufacturingpractice (GMP) for medicinal products as laid down in Directive 2003/94/EC formedicinal products for human use and Directive 91/412/EEC for veterinary use.

立法基础：2001/83/EC法令第47款对人用药品的相关要求，2001/82/EC法令第51款兽用药相关的欧共体法规。本文件主要是2003/94/EC法令对人用药和91/412/EEC对兽用药品的GMP原则和指南的解释。

Status of thedocument: revision 1

文件状态：第一次修订

Reasons forchanges: the sections on "generationand control of documentation" and "retention of documents" havebeen revised, in the light of the increasing use of electronic documents withinthe GMP environment.变更理由：鉴于GMP环境下电子文档的增加，对“文件的生成和控制”和“文件和保存”进行修订。

Deadline forcoming into operation: 30 June 2011

实施时间：2011年6月30日

Tableof Contents目录

Principle原则

Required GMPDocumentation要求的GMP文件

Generation andControl of Documentation文件生成和控制

GoodDocumentation Practices优良

Retention ofDocuments记录保存

Specifications质量标准

ManufacturingFormula and Processing Instructions生产处方和工艺规程

Procedures andrecords程序和记录

Principle原则

Gooddocumentation constitutes an essential part of the quality assurance system andis key to operating in compliance with GMP requirements. The various types ofdocuments and media used should be fully defined in the manufacturer's QualityManagement System.好的文件管理，是质量保证系统的一个关键部分，对于GMP符合性操作至关重要。在生产商的质量管理体系中应对所使用的各种文件和媒质的类型进行全面界定。

Documentationmay exist in a variety of forms, including paper-based, electronic orphotographic media. The main objective of the system of documentation utilizedmust be to establish, control, monitor and record all activities which directlyor indirectly impact on all aspects of the quality of medicinal products. TheQuality Management System should include sufficient instructional detail tofacilitate a common understanding of the requirements, in addition to providingfor sufficient recording of the various processes and evaluation of anyobservations, so that ongoing application of the requirements may bedemonstrated.文件可以各种形式存在，包括纸质、电子的或图像，公司应建立、控制、监督文件记录系统所采用的主要方法，并记录下所有会对药品质量各方面产生直接或间接影响的活动。质量管理系统应对记录方式有足够的细致操作说明，这样除了对各工艺有充分记录，对各缺陷有评价外，还方便对记录要求有一般性了解，才可以达到应用目的。

Thereare two primary types of documentation used to manage and record GMPcompliance: instructions (directions, requirements) and records/reports.Appropriate good documentation practice should be applied with respect to thetype of document.这里有两种基本记录方式应用于GMP符合性管理和记录中：操作说明（指令、要求）和记录/报告，公司应根据不同文件类型，采用相应的优良文件规范。

Suitablecontrols should be implemented to ensure the accuracy, integrity, availabilityand legibility of documents. Instruction documents should be free from errorsand available in writing. The term ‘written’ means recorded, or documented onmedia from which data may be rendered in a human readable form.应对文件进行适当的控制以保证文件的准确、完整、有效及清晰易读。操作说明类文件应没有错误并有书面版本发行。术语“书面”意思是在某种介质上记录或记载，以使数据形式可以被人们读出。

Required GMPdocumentation (by type):所需要的GMP文件（按类型）

Site MasterFile: A document describing the GMPrelated activities of the manufacturer.

工厂主文件：描述生产商与GMP相关活动的文件。

Instructions(directions, or requirements) type:规程（指令，或要求）类型

SpecificationsDescribe in detail the requirements withwhich the products or materials used or obtained during manufacture have toconform. They serve as a basis for quality evaluation.

质量标准：是对产品或所用原料或中间产品所必须符合的要求的详细说明。这是质量评价的一个基础。

ManufacturingFormulae, Processing, Packaging and Testing Instructions: 生产处方，生产、包装和检测说明，

Providedetail all the starting materials, equipment and computerised systems (if any)to be used and specify all processing, packaging, sampling and testinginstructions. Inprocess controls and process analytical technologies to beemployed should be specified where relevant, together with acceptance criteria.

规定所有使用的起始物料、设备和计算机系统（如有）的详细要求，并说明所有工艺、包装、取样和检测规程，还需要说明相关的中控和所使用的过程分析技术及可接受标准。

Procedures:(Otherwise known as Standard Operating Procedures, or SOPs 也称为标准操作规程，或SOPs),give directions for performing certain operations.

规程：是对某一项工作的说明。

Protocols:Give instructions for performing and recording certain discreet operations.

记录：是形成每一批产品的历史，包括发送给客户，也包括其他相关的可能会影响最终产品质量的因素。

TechnicalAgreements: Are agreed between contractgivers and acceptors for outsourced activities.

技术协议：外包活动中，外包方和承包方达成的协议。

Record/Reporttype:记录/报告类型

Records: Provideevidence of various actions taken to demonstrate compliance with instructions,e.g. activities, events, investigations, and in the case of manufacturedbatches a history of each batch of product, including its distribution. Recordsinclude the raw data which is used to generate other records. For electronicrecords regulated users should define which data are to be used as raw data. Atleast, all data on which quality decisions are based should be defined as rawdata.

记录：提供各种按照操作要求实施行动的证据，例如，活动、事件、调查、已生产产品的各批次历史，包括销售。记录包括用于产生其它记录的原始数据。对于采用电子记录的用户，应界定该电子记录为原始数据，至少所有用于作出质量决定的数据应界定为原始数据。

Certificatesof Analysis: Provide a summary of testingresults on samples of products or materials[1] together with the evaluation forcompliance to a stated specification.

分析报告：给产品或原料样品提供一个检测结果的总结，以及是否符合指定标准的评价。

Reports: Documentthe conduct of particular exercises, projects or investigations, together withresults, conclusions and recommendations.

报告：记录实施特定活动、项目或调查及结果、结论和建议的文件。

Generationand Control of Documentation文件生成和控制

4.1     All types of document should be definedand adhered to. The requirements apply equally to all forms of document mediatypes. Complex systems need to be understood, well documented, validated, andadequate controls should be in place. Many documents (instructions and/orrecords) may exist in hybrid forms, i.e. some elements as electronic and othersas paper based. Relationships and control measures for master documents,official copies, data handling and records need to be stated for both hybridand homogenous systems. Appropriate controls for electronic documents such astemplates, forms, and master documents should be implemented. Appropriatecontrols should be in place to ensure the integrity of the record throughoutthe retention period.所有类型文件均应定义并执行，对所有以文件形式制定的表格也一样。复杂的系统应能被理解、记录、验证，并进行充分控制。许多文件（指令和/或记录）可能以混合方式存在，即一些为电子的，而另一些为纸质的。不管是混合方式还是同一方式，母版本文件、正式复印件、数据处理和记录之间的关系及控制方式均应明确说明。对于电子文件应进行适当控制，如文件模板、表格、需要实施的母版本文件。必须有适当的控制以保证记录在整个保存期间均完整。

4.2     Documents should be designed, prepared,reviewed, and distributed with care. They should comply with the relevant partsof Product Specification Files, Manufacturing and Marketing Authorisationdossiers, as appropriate. The reproduction of working documents from masterdocuments should not allow any error to be introduced through the reproductionprocess.文件应仔细设计、起草、审核、发放，其内容应符合产品质量标准文件、生产文件和上市许可文件的相关部分要求。需要执行填写的文件记录母版在复制时不允许有差错。

4.3     Documents containing instructions shouldbe approved, signed and dated by appropriate and authorised persons. Documentsshould have unambiguous contents and be uniquely identifiable. The effectivedate should be defined.

包含指令的文件应经过适当的有授权的人批准、签字、签署日期。文件内容应清楚、唯一、可识别，生效日期应明确。

4.4     Documents containing instructions shouldbe laid out in an orderly fashion and be easy to check. The style and languageof documents should fit with their intended use. Standard Operating Procedures,Work Instructions and Methods should be written in an imperative mandatorystyle.包含指令的文件应有序编制，易于检查。文件的形式和用词应与其用途相适应。标准操作规程、工作指令和方法应形成强制实施的书面文件。

4.5     Documents within the Quality ManagementSystem should be regularly reviewed and kept up-to-date. 文件管理体系内的文件应定期进行审核并保持更新。

4.6     Documents should not be hand-written;although, where documents require the entry of data, sufficient space should beprovided for such entries. 文件不应手写，如果有些地方需要手动填写，应保留足够的空间以便填入。

GoodDocumentation Practices 优良文件规范

4.7     Handwritten entries should be made inclear, legible, indelible way. 所有书写应清晰、易读且不易擦除。

4.8     Records should be made or completed at thetime each action is taken and in such a way that all significant activitiesconcerning the manufacture of medicinal products are traceable. 所有操作完成后应即进行记录，以保证与药品生产有关的重大活动均可追踪。

4.9     Any alteration made to the entry on adocument should be signed and dated; the alteration should permit the readingof the original information. Where appropriate, the reason for the alterationshould be recorded. 任何修改必须有签名和日期，修改后原内容必须清楚可读。必要时要对修改原因进行说明和记录。

Retention ofDocuments文件保留

4.10   It should be clearly defined which record isrelated to each manufacturing activity and where this record is located. Securecontrols must be in place to ensure the integrity of the record throughout theretention period and validated where appropriate.必须明确定义哪些记录与某一生产活动相关，记录放置在什么地方。对放置文件的区域应有安保控制，以保证记录在整个保留期间的完整性，必要时应进行验证。

4.11   Specific requirements apply to batchdocumentation which must be kept for one year after expiry of the batch towhich it relates or at least five years after certification of the batch by theQualified Person, whichever is the longer. For investigational medicinalproducts, the batch documentation must be kept for at least five years afterthe completion or formal discontinuation of the last clinical trial in whichthe batch was used. Other requirements for retention of documentation may bedescribed in legislation in relation to specific types of product (e.g.Advanced Therapy Medicinal Products) and specify that longer retention periodsbe applied to certain documents.批记录必须保留至该批有效期后一年，或在QP放行该产品后至少5年，选其中更长者。对于临床研究药品，批生产记录应保留至少临床试验完成后5年，或该批次所用于的最迟的临床试验正式结束时。如有相关法规对特殊类型的产品（例如先进的治疗用药品）的文件保留时间有特殊规定，则应符合这些法规要求。

4.12   For other types of documentation, theretention period will depend on the business activity which the documentationsupports. Critical documentation, including raw data (for example relating tovalidation or stability), which supports information in the MarketingAuthorisation should be retained whilst the authorization remains in force. Itmay be considered acceptable to retire certain documentation (e.g. raw datasupporting validation reports or stability reports) where the data has beensuperseded by a full set of new data. Justification for this should bedocumented and should take into account the requirements for retention of batchdocumentation; for example, in the case of process validation data, theaccompanying raw data should be retained for a period at least as long as therecords for all batches whose release has been supported on the basis of thatvalidation exercise.对于其它类型的文件，保存期限根据文件所支持的商业活动而定。关键文件，包括原始数据（例如与验证和稳定性有关），支持上市批准信息，则应在上市批准有效期间均保留。如果有些数据已被新的全套数据替代，则可以考虑对这些数据进行销毁（例如支持验证报告或稳定性报告的原始数据）。对此的判定应记录，并考虑批文件的保留要求。例如，如果是工艺验证数据，原始数据至少应保留至其验证所支持的所有放行批次的记录一样长。

Thefollowing section gives some examples of required documents. The qualitymanagement system should describe all documents required to ensure productquality and patient safety. 下列部分对于要求的文件给出了一些例子，质量管理体系应描述所有要求的文件，以保证产品质量和患者安全

Specifications质量标准

4.13   There should be appropriately authorised anddated specifications for starting and packaging materials, and finishedproducts. 起始原料、包装物料和成品应有适当批准并标明日期的质量标准

Specificationsfor starting and packaging materials 起始物料和包装材料的质量标准

4.14   Specifications for starting and primary orprinted packaging materials should include or provide reference to, ifapplicable:起始物料、内包材料、印字包材应对包括或对以下项目提供参考（适用时）

a)         A description of the materials,including:对物料的描述，包括

—       The designated name and the internalcode reference;给定名称和内部参考代码

—       The reference, if any, to apharmacopoeial monograph;参照物，如有时，

—       The approved suppliers and, ifreasonable, the original producer of the material;批准的供应商，合理情况下，原料的生产商

—       A specimen of printed materials; 印刷包材的样本

b)        Directions for sampling and testing; 取样和检测要求

c)        Qualitative and quantitativerequirements with acceptance limits;定量和定性要求及可接受标准

d)        Storage conditions and precautions;贮存条件和警示

e)         The maximum period of storage beforere-examination.可以不需复测的最长存贮期

Specificationsfor intermediate and bulk products中间体和原料药产品的质量标准

4.15   Specifications for intermediate and bulkproducts should be available for critical steps or if these are purchased ordispatched. The specifications should be similar to specifications for startingmaterials or for finished products, as appropriate.

关键步骤，或采购及销售的中间体和原料药产品的质量标准，适用时，该质量标准应与起始原料或成品质量标准类似。

Specificationsfor finished products成品质量标准

4.16   Specifications for finished products shouldinclude or provide reference to:成品质量标准应包括或提供以下项目的参照物

a)        The designated name of the product andthe code reference where applicable; 产品名称和索引代码（适用时）

b)        The formula; 分子式

c)         A description of the pharmaceuticalform and package details; 药品形态和包装细节描述

d)        Directions for sampling and testing 取样和检测要求

e)        The qualitative and quantitativerequirements, with the acceptance limits; 定性和定要求及可接受限度

f)         The storage conditions and any specialhandling precautions, where applicable; 存贮条件及特殊处理警示（需要时）

g)        The shelf-life.有效期

ManufacturingFormula and Processing Instructions生产配方和工艺规程

Approved,written Manufacturing Formula and Processing Instructions should exist for eachproduct and batch size to be manufactured. 每一产品和批量应有经批准的书面生产配和工艺规程

4.17  The Manufacturing Formula should include:生产配方应包括

a)         The name of the product, with aproduct reference code relating to its specification; 产品名称，包括与其质量标准相关的产品索引代码

b)        A description of the pharmaceuticalform, strength of the product and batch size; 药品形态描述、产品剂量和批量

c)        A list of all starting materials to beused, with the amount of each, described; mention should be made of anysubstance that may disappear in the course of processing; 所有使用的起始物料，包括各物料投料量的描述；任何在工艺过程中会消失的物料也应提及

d)        A statement of the expected final yieldwith the acceptable limits, and of relevant intermediate yields, whereapplicable 最终产品期望收率的可接受限度说明，以及相关的中间体收率（适用时）

4.18   The Processing Instructions should include:工艺规程应包括

a)         A statement of the processing locationand the principal equipment to be used; 将要使用的生产场所和主要设备的说明

b)        The methods, or reference to themethods, to be used for preparing the critical equipment (e.g. cleaning,assembling, calibrating, sterilising); 将要用于关键设备处理的方法或方法引用的文件（如清洁、装配、校正、消毒）

c)        Checks that the equipment and workstation are clear of previous products, documents or materials not required forthe planned process, and that equipment is clean and suitable for use; 对设备和工作场所的检查，包括本次生产不需要的前批产品、文件或物料清除，设备清洁并适宜使用

d)        Detailed stepwise processinginstructions [e.g. checks on materials, pre-treatments, sequence for addingmaterials, critical process parameters (time, temp etc)]; 详细的逐步操作指令【例如，物料检查、前处理、加料顺序、关键工艺参数（时间、温度等）】。

e)         The instructions for any in-processcontrols with their limits; 所有中控指令及其限度

f)         Where necessary, the requirements forbulk storage of the products; including the container, labeling and specialstorage conditions where applicable; 必要时，未包装产品的贮存要求，包括容器、标签和特殊的贮存条件（适用时）

g)        Any special precautions to be observed.其它特殊注意事项

PackagingInstructions包装指令

4.19   Approved Packaging Instructions for eachproduct, pack size and type should exist. These should include, or have areference to, the following: 每个产品、包装规格和类型应有批准的包装指导，应包括以下项目，或有一份样品进行对照

a)         Name of the product; including thebatch number of bulk and finished product 产品名称，包括未包装产品和成品的批号

b)        Description of its pharmaceutical form,and strength where applicable; 其成品剂型、剂量（适用时）的描述

c)        The pack size expressed in terms of thenumber, weight or volume of the product in the final container; 最小包装容器上注明以数字形式表达的包装规格，产品重量或体积

d)        A complete list of all the packagingmaterials required, including quantities, sizes and types, with the code orreference number relating to the specifications of each packaging material; 需要的完整包材清单，包括数量、尺寸和类型，以及与每一包材质量标准对应的代码或索引号

e)         Where appropriate, an example orreproduction of the relevant printed packaging materials, and specimensindicating where to apply batch number references, and shelf life of theproduct; 适用时，应提供一个相关印刷包材的样品或复制品，以及样本来显示在何处标示产品批号和有效期

f)         Checks that the equipment and workstation are clear of previous products, documents or materials not required forthe planned packaging operations (line clearance), and that equipment is cleanand suitable for use. 对设备和工作场所的检查，包括本次将要进行的包装操作（包装线清场）不需要的前批产品、文件或物料清除，设备清洁并适宜使用

g)        Special precautions to be observed,including a careful examination of the area and equipment in order to ascertainthe line clearance before operations begin; 需要注意的特殊注意事项，包括对生产区域和设备的仔细检查以确保在操作开始前生产线已清场

h)        A description of the packagingoperation, including any significant subsidiary operations, and equipment to beused; 包装操作的说明，包括任何重要的辅助操作，以及需要用到的设备

i)          Details of in-process controls withinstructions for sampling and acceptance limits. 中控取样和可接受标准的详细操作说明

BatchProcessing Record批生产记录

4.20   A Batch Processing Record should be kept foreach batch processed. It should be based on the relevant parts of the currentlyapproved Manufacturing Formula and Processing Instructions, and should containthe following information:

每一批号的生产均应保留批生产记录，批记录应根据现行批准的生产配方和工艺规程相关部分制订，应包括以下信息

a)         The name and batch number of theproduct; 产品名称和批号

b)        Dates and times of commencement, ofsignificant intermediate stages and of completion of production; 重要中间体生产步骤开始和结束的日期时间

c)        Identification (initials) of theoperator(s) who performed each significant step of the process and, whereappropriate, the name of any person who checked these operations; 工艺每个重要步骤操作人员签名，必要时对复核人员的签名

d)        The batch number and/or analyticalcontrol number as well as the quantities of each starting material actuallyweighed (including the batch number and amount of any recovered or reprocessedmaterial added); 每一实际投料的起始物料的批号、和/或分析控制号以及数量（包括加入的回收或返工物料的批号和数量）

e)         Any relevant processing operation or eventand major equipment used;所有相关工艺操作或事件，以及使用的主要设备

f)         A record of the in-process controlsand the initials of the person(s) carrying them out, and the results obtained; 中控操作记录、中控人员签名、中控结果

g)        The product yield obtained at differentand pertinent stages of manufacture; 各生产步骤的收率

h)        Notes on special problems includingdetails, with signed authorisation for any deviation from the ManufacturingFormula and Processing Instructions; 特殊问题的详细说明，任何不符合生产配方、工艺规程的偏差应有责任人员的签名批准

i)          Approval by the person responsiblefor the processing operations. 工艺操作负责人的批准

Note:Where a validated process is continuously monitored and controlled, thenautomatically generated reports may be limited to compliance summaries andexception/ out-of specification (OOS) data reports. 如果一个验证过的工艺进行持续的监测和控制，由系统自动生成的报告应仅限于符合性总结和例外/超标数据报告

BatchPackaging Record批包装记录

4.21       A Batch Packaging Record should be keptfor each batch or part batch processed. It should be based on the relevantparts of the Packaging Instructions. 每一批或一个分批次均应有批包装记录保留，批包装记录应基于包装操作规程的相关部分。

Thebatch packaging record should contain the following information:批包装记录应包括以下信息

a)    The name and batch number of the product, 产品名称和批号

b)    The date(s) and times of the packagingoperations; 包装操作日期时间

c)    Identification (initials) of the operator(s)who performed each significant step of the process and, where appropriate, thename of any person who checked these operations; 工艺任一重要步骤的操作人员的签名，以及检查这些操作的人员的姓名（适用时）

d)    Records of checks for identity andconformity with the packaging instructions, including the results of in-processcontrols; 对包装进行检查，确认是否正确及符合包装操作规程的记录，包括中控结果

e)    Details of the packaging operations carriedout, including references to equipment and the packaging lines used; 实施的包装操作细节，包括所用的设备和包装线的参照物

f)    Whenever possible, samples of printedpackaging materials used, including specimens of the batch coding, expiry datingand any additional overprinting; 可能时，印刷包材的样品，包括印有批代码、有效期和其它套印内容的样本

g)    Notes on any special problems or unusualevents including details, with signed authorisation for any deviation from thePackaging Instructions; 对特别问题或异常情况的详细说明，任何与包装要求有偏离时要有授权人的签名

h)    The quantities and reference number oridentification of all printed packaging materials and bulk product issued,used, destroyed or returned to stock and the quantities of obtained product, inorder to provide for an adequate reconciliation. Where there are there arerobust electronic controls in place during packaging there may be justificationfor not including this information 所有发放、使用、销毁或退回库存的印刷包材和待包装产品的数量、索引号或识别号，及包装后成品数量，以对上述物料进行衡算。如果包装过程采用电子控制，可以不需要这些信息。

i)     Approval by the person responsible for thepackaging operations 包装操作负责人的批准

Procedures andrecords程序和记录

Receipt接收

4.22       There should be written procedures andrecords for the receipt of each delivery of each starting material, (includingbulk, intermediate or finished goods), primary, secondary and printed packagingmaterials. 每一起始物料（包括散装货、中间体或成品）、内包材和印刷包材，每一次收货均应有书面程序和记录

4.23       The records of the receipts shouldinclude: 接收记录应包括

a)    The name of the material on the deliverynote and the containers; 送货单上和容器上的物料名称

b)    The "in-house" name and/or code ofmaterial (if different from a); 内部名称和/或物料代码（与a项不同时）

c)    Date of receipt; 接收日期

d)    Supplier’s name and, manufacturer’s name; 供应商名称，生产商名称

e)    Manufacturer’s batch or reference number; 生产批号或索引号

f)    Total quantity and number of containersreceived; 收到总数量及件数

g)    The batch number assigned after receipt; 接收后给定的批号

h)    Any relevant comment. 其它相关说明

4.24      There should be written procedures for theinternal labeling, quarantine and storage of starting materials, packagingmaterials and other materials, as appropriate. 应有书面程序规定起始物料、包装材料和其它物料（适用时）的内标签、待验和存贮

Sampling取样

4.25       There should be written procedures forsampling, which include the methods and equipment to be used, the amounts to betaken and any precautions to be observed to avoid contamination of the materialor any deterioration in its quality. 应有书面程序规定取样操作，包括使用的取样方法和工具、取样量，避免物料污染和对样品质量产生影响的注意事项

Testing检测

4.26       There should be written procedures fortesting materials and products at different stages of manufacture, describingthe methods and equipment to be used. The tests performed should be recorded.

应有书面程序规定物料和产品在不同生产工序的检测程序，描述需要采用的方法和仪器，并记录检测过程。

Other其它

4.27       Written release and rejection proceduresshould be available for materials and products, and in particular for thecertification for sale of the finished product by the Qualified Person(s). Allrecords should be available to the Qualified Person. A system should be inplace to indicate special observations and any changes to critical data.

应有书面程序规定物料和产品的放行和拒收程序，尤其是质量受权人批准的成品的销售许可。质量受权人应可以得到所有记录，应有一个体系显示特定的缺陷和对关键数据的所有变更。

4.28       Records should be maintained for thedistribution of each batch of a product in order to facilitate recall of anybatch, if necessary.

每一产品每一批次的销售记录均应保留，以便必要时对任何批次进行召回

4.29       There should be written policies,procedures, protocols, reports and the associated records of actions taken orconclusions reached, where appropriate, for the following examples: 应有书面方针、程序、方案、报告及相关记录来记下采取的措施或形成的结论（适用时），例如

—   Validation and qualification of processes,equipment and systems;       工艺、设备和系统验证和确认

—   Equipment assembly and calibration;设备安装和校正

—   Technology transfer;技术转移

—   Maintenance, cleaning and sanitation;维护保养、清洁和消毒

—   Personnel matters including signature lists,training in GMP and technical matters, clothing and hygiene and verification ofthe effectiveness of training. 人员情况包括签名清单、GMP和技术培训、着装和卫生、培训有效性的确认

—   Environmental monitoring;环境监控

—   Pest control; 虫鼠控制

—   Complaints;客诉

—   Recalls;召回

—   Returns;退货

—   Change control;变更控制

—   Investigations into deviations andnon-conformances;偏差和不符合调查

—   Internal quality/GMP compliance audits;内部质量/GMP审计

—   Summaries of records where appropriate (e.g.product quality review);适用时的记录摘要（例如产品质量回顾）

—   Supplier audits.供应商审计

4.30       Clear operating procedures should beavailable for major items of manufacturing and test equipment. 主要生产设备和检测仪器应有清楚的操作程序

4.31       Logbooks should be kept for major orcritical analytical testing, production equipment, and areas where product hasbeen processed. They should be used to record in chronological order, asappropriate, any use of the area, equipment/method, calibrations, maintenance,cleaning or repair operations, including the dates and identity of people whocarried these operations out. 主要或关键分析检测仪器、产品生产所用的设备和区域应有日志，用于按时间顺序记录（适用时）使用的区域、设备/方法、校正、维护、清洁或维修，包括时间和操作人员的签名

4.32       An inventory of documents within theQuality Management System should be maintained. 应有一个质量管理体系的文件清单

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[1]Alternatively the certification may bebased, in-whole or in-part, on the assessment of real time data (summaries andexception reports) from batch related process analytical technology (PAT),parameters or metrics as per the approved marketing authorisation dossier. 可以根据上市批准文件的内容，完全或部分，基于对批相关工艺分析技术（PAT）实时数据（总结和摘要报告）、参数或计量的评估，取代分析报告。

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