WHO现场主文件编写指南
WHO数据完整性指南2019.10(中英对照)
QAS/19.819GUIDELINE ON DATA INTEGRITY数据完整性指南(October 2019)2019 年10 月1. INTRODUCTION AND BACKGROUND前言与背景1.1. Data governance and data integrity (DI) are important elements in ensuring the reliability of data and information obtained in production and control of pharmaceutical products. The data and information should be complete as well as being attributable, legible, contemporaneous, original and accurate, commonly referred to as meeting “ALCOA” principles.数据管理与数据完整性（DI）是确保药品生产和检测期间所获得的数据和信息可靠性的重要要素。
这些数据和信息应完整，同时具有可追溯性、清晰、同步、原始和准确，一般称为符合“ALCOA”原则。
1.2. In recent years, the number of observations made regarding the integrity of data, documentation and record management practices during inspections of good manufacturing practice (GMP), good clinical practice (GCP) and good laboratory practice (GLP) has been increasing. Possible causes for this may include (i) too much reliance on human practices; (ii) the use of computerized systems that are not appropriately managed and validated; and (iii) failure to adequately review and manageoriginal data and records.近年，在 GMP、GCP 和 GLP 检查中，数据完整性、文件记录管理规范性方面的缺陷数量大大上升。
WHO《数据完整性指南》-2021（中英文对照版）
WHO《数据完整性指南》-2021（中英文对照版）3月29日，WHO发布了第55 届药物制剂规范专家委员会（ECSPP）技术报告TRS No.1033，其中包含新的《数据完整性指南》，翻译如下，分享给大家！Guideline on data integrity数据完整性指南1. Introduction and background介绍和背景1.1. In recent years, the number ofobservations made regarding the integrity of data, documentation and recordmanagement practices during inspections of good manufacturing practice (GMP) (2),good clinical practice (GCP), good laboratory practice (GLP) and Good Trade andDistribution Practices (GTDP) have been increasing. The possible causes forthis may include近年来，在对良好生产规范(GMP)(2)、良好临床规范(GCP)、良好实验室规范(GLP)和良好贸易和分销规范(GTDP)的检查过程中，对数据完整性、文件和记录管理规范的缺陷数量持续增加。
可能的原因包括：(ⅰ) reliance on inadequate human practices;依赖于不适当的人员操作;(ⅱ)poorly defined procedures;规定糟糕的规程(ⅲ)resource constraints;资源限制(ⅳ) the use of computerized systems that are not capable of meetingregulatory requirements or are inappropriately managed and validated (3, 4);使用不满足法规要求，或管理/验证不当的计算机系统(3,4);(ⅴ) inap propriate and inadequate control of data flow; and不适当和不充分的数据流控制;和(ⅵ)failure to adequately review and manage original data and records.未能充分审核和管理原始数据和记录。
who实验室生物安全管理手册
【如何撰写一份高质量、深度和广度兼具的《WHO实验室生物安全管理手册》】众所周知，生物安全是指人们在进行生物实验或工作时，保护自身和他人免受活体病原体或毒素的侵害的一种技术和管理措施。
而《WHO 实验室生物安全管理手册》则是一份由世界卫生组织（WHO）制定的关于实验室生物安全管理的权威指南。
1. 背景介绍WHO实验室生物安全管理手册是为了保证实验室环境的健康和安全，确保实验室工作的质量和可靠性，以及遵循国际标准和规定，防范生物风险，减少实验室意外的发生而制定的。
这份手册以其权威性和实用性而备受全球范围内生物实验室从业者的高度关注和推崇。
2. 内容深度评估手册内容包括实验室生物安全管理的一般概念、实验室设计和操作、生物安全设备和设施、生物危险物质的管理、应急响应和事故处理等多个方面。
它不仅包括了关于生物材料的安全管理和废弃物处置，还涵盖了实验室内部排放物控制和实验室防护设备的规范及维护，可以说是一本全面而翔实的指南。
3. 内容广度评估在对生物安全管理的各个方面进行深入介绍的手册还以案例分析和经验共享的形式，对实验室生物安全管理中常见的问题和挑战进行了全面归纳和总结。
这种深度和广度并茂的方式，使得手册的适用范围非常广泛，无论是从事基础研究的科研人员，还是从事临床检验的实验室技术人员，都能从中受益良多。
4. 个人观点和理解在我看来，WHO实验室生物安全管理手册不仅是一份管理手册，更是一部生物实验室安全文化的倡导者和践行者。
它的倡导理念和严谨执行标准，已经成为全球范围内生物实验室安全管理的金标准，对于提高全球生物安全水平，保障全人类的生命健康安全，都发挥着不可或缺的重要作用。
5. 总结和回顾通过对WHO实验室生物安全管理手册的全面评估和深度论述，我对实验室生物安全管理这一重要议题的认识更加全面和深入。
手册中的实用指导和案例分析，也为我今后的工作实践提供了强有力的支持和指导。
我相信，随着生物技术的不断发展和应用，这份手册的内容和精神将继续发挥着巨大的作用。
WHO现场主文件编写指南
© World Health OrganizationWHO Technical Report Series, No.961, 2011附件14Annex 14WHO现场主文件编写指南1WHO guidelines for drafting a site master file11. 介绍Introduction2. 目的Purpose3. 范围Scope4. 现场主文件的内容Content of site master file附件Appendix现场主文件的内容Content of a site master file1. 介绍Introduction1.1 现场主文件是由药品制药商编写的，应当包含下列具体的信息：生产厂区的质量管理方针及活动、在指定的生产厂区实行的对药品生产操作的生产和/或质量控制以及在与其相邻的建筑物内所进行的任何紧密的完整的操作。
如果只有一部分药品生产操作在此厂区内进行，那么在现场主文件中只需要描述这些操作，例如分析、包装等。
The site master file (SMF) is prepared by the pharmaceutical manufacturer and should contain specific information about the quality management policies and activities of the site, the production and/or quality control of pharmaceutical manufacturing operations carried out at the named site and any closely integrated operations at adjacent and nearby buildings. If only part of a pharmaceutical operation is carried out on the site, an SMF need only describe those operations, e.g. analysis, packaging, etc.1.2 当提交给监管机构时，现场主文件中应当包含对常规监督、有效计划及进行GMP检查有用的、关于制造商与GMP相关的活动的清晰信息。
世界卫生组织药品临床试验管理规范指南
世界卫生组织药品临床试验管理规范指南引言此WHO临床试验管理规范指南的目的是为在人体进行生物医学研究而建立的、供全球采用的标准。
它是以一些高度发达国家包括澳大利亚、加拿大、欧洲共同体国家、日本、北欧国家和美国已颁布的规定为基础的，不可避免地在内容和侧重点上与这些国家的临床试验管理规定有所不同，但为保证道德上和科学上的完整性，临床试验所需满足的先决条件和应用的原则是相一致的。
事实上，它已经为对此感兴趣的国家的临床数据的相互承认提供了一种正式的基础。
为了WHO成员国在更广泛一致的合作中，使用本指南作为一种实用的管理工具，本指南已尽量保证与已经存在的国家法规与其他法规相容而无抵触。
希望在进一步磋商的基础上，使WHO各成员国能正式接受本指南，为协调国际标准和促进药品国际间转移做出贡献。
但是，它并不存在向各国已有的法规或要求提出非议或侵占的问题。
它的目的只是提供一个国际上有效的补充标准。
本指南不仅论及研究者，也论及伦理审查委员会、药品制造商和其他的研究申办者以及药品管理当局。
本指南，既为涉及人体的研究在科学上和道德上的完整性，也为有效的观察和对发现做出充分的记录提供了基础，不仅为积极参与研究的各方的利益服务，也保护受试者的权利和安全，包括病人，保证研究者执行试验以公众利益为指导。
本指南特别希望被用于药物研究的各个阶段，即在产品注册之前和注册之后，它的全部或部分也可用于一般的生物医学研究。
本指南为主编们决定是否接受要发表的被报告的研究提供一种支持，尤其是对影响药物注册的任何临床研究提供支持。
更重要的是，本指南为从事生物医学研究的人和新培养的医师提供了一种教育工具，他们应该熟悉之。
术语以下为本指南中术语专用的定义。
在其他文件中它们可以有不同的涵义。
［不良事件］（Adverse event）指在接受一种药品治疗期间发生的任何不良的医疗事件，但不一定与该治疗有因果关系。
［不良反应］（Adverse reaction）指对一种药物的反应，对人体是有害的，非意求的，可能出现在用于预防、诊断、治疗疾病或改变生理功能的正常剂量时。
世界卫生组织 工厂主文件 起草 指南
Working document QAS/10.378 July 2010 RESTRICTEDWHO GUIDELINES FOR DRAFTING A SITE MASTER FILEDRAFT FOR COMMENTSThe Prequalification Programme currently uses a site master file (SMF). Your feedback would be very much appreciated as to whether this SMF needs to be revised in light of new developments, e.g. by the Pharmaceutical Inspection Co-operation Scheme (PIC/S). Please address any comments on this proposal, by 1 September 2010 to Dr A.J. van Zyl, Head of Inspections, Prequalification Programme, World Health Organization, 1211 Geneva 27, Switzerland, fax: (+41 22) 791 4730 or e-mail: vanzyla@who.int with a copy to gaspardm@who.int and to bonnyw@who.int. During the past few years we have moved more towards an electronic system for sending out our working documents for comment, for convenience and in order to speed up the process. If you do not already receive our documents electronically, please let us have your e-mail address (to bonnyw@who.int) and we will add it to our electronic mailing list.© World Health Organization 2010 All rights reserved. This draft is intended for a restricted audience only, i.e. the individuals and organizations having received this draft. The draft may not be reviewed, abstracted, quoted, reproduced, transmitted, distributed, translated or adapted, in part or in whole, in any form or by any means outside these individuals and organizations (including the organizations' concerned staff and member organizations) without the permission of the World Health Organization. The draft should not be displayed on any web site. Please send any request for permission to: Dr A.J. van Zyl, Head of Inspections, Prequalification Programme, Quality Assurance and Safety: Medicines, Department of Essential Medicines and Pharmaceutical Policies, World Health Organization, CH-1211 Geneva 27, Switzerland. Fax: (41-22) 791 4730; e-mail: vanzyla@who.int. The designations employed and the presentation of the material in this draft do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this draft. However, the printed material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. This draft does not necessarily represent the decisions or the stated policy of the World Health Organization.Working document QAS/10.378 page 2 SCHEDULE FOR THE PROPOSED ADOPTION PROCESS OF DOCUMENT QAS/10.378: Guidelines for drafting a site master fileNeed for possible revision identified by WHO Prequalification May 2010 Programme Draft mailed out for comments Collation of comments received Presentation to the WHO Expert Committee on Specifications for Pharmaceutical Preparations Further action as necessary July-August 2010 September 2010 18-22 October 2010…Working document QAS/10.378 page 3GUIDELINES FOR DRAFTING A SITE MASTER FILE (SMF)A site master file (SMF) for each manufacturing site of a finished pharmaceutical product (FPP) listed in a product dossier, should be submitted on a CD or DVD to the Inspection unit. A SMF for each manufacturing site of active pharmaceutical ingredient (API) and contract research organization (CRO), listed in a product dossier, should be submitted on request from the Inspection unit. A SMF should be succinct and, as far as possible, not exceed 25 A4 pages. A SMF is a document prepared by the manufacturer containing specific and factual good manufacturing practice (GMP) information about the production and/or control of pharmaceutical manufacturing operations carried out at the named site and any closely integrated operations at adjacent and nearby buildings. If only part of a pharmaceutical operation is carried out on the site, the SMF need describe only those operations, e.g. analysis, packaging. Layout of the SMF Front page Table of contents Contents 1. General information1.1 Brief information on the firm (including name and address), relation to other sites, and, in particular, any information relevant to understanding the manufacturing operations. 1.2 1.3 Pharmaceutical manufacturing activities as licensed by the national authority. Any other manufacturing activities carried out on the site.1.4 Name and exact address of the site, including telephone, fax and 24-hour telephone numbers. 1.5 Type of products manufactured on the site and information about any specifically toxic or hazardous substances handled, mentioning the way they are manufactured (in dedicated facilities or on a campaign basis). 1.6 Short description of the site (size, location and immediate environment and other manufacturing activities on the site).Working document QAS/10.378 page 4 1.7 Number of employees engaged in production, quality control, storage and distribution. 1.8 Use of outside scientific, analytical or other technical assistance in relation to manufacture and analysis. 1.9 Short description of the quality management system of the firm responsible for manufacture. 2. Personnel2.1 Organization chart showing the arrangements for quality assurance, including production and quality control. 2.2 Qualifications, experience and responsibilities of key personnel.2.3 Outline of arrangements for basic and in-service training and how records are maintained. 2.4 2.5 3. Health requirements for personnel engaged in production. Personnel hygiene requirements, including clothing. Premises and equipment3.1 Simple plan or description of manufacturing areas with indication of scale (architectural or engineering drawings not required). 3.2 Nature of construction and finishes.3.3 Brief description of ventilation systems. More details should be given for critical areas with potential risks of airborne contamination (schematic drawings of the systems are desirable). Classification of the rooms used for the manufacture of sterile products should be mentioned. 3.4 Special areas for the handling of highly toxic, hazardous, and sensitizing materials. 3.5 Brief description of water systems (schematic drawings of the systems are desirable), including sanitation. 3.6 Description of planned preventive maintenance programmes for premises and of the recording system. Equipment 3.7 Brief description of major equipment used in production and control laboratories (a list of equipment is not required).Working document QAS/10.378 page 5 3.8 Description of planned preventive maintenance programmes for equipment and of the recording system. 3.9 Qualification and calibration, including the recording system. Arrangements for computerized systems validation. Sanitation 3.10 Availability of written specifications and procedures for cleaning manufacturing areas and equipment. 4. Documentation4.1 Arrangements for the preparation, revision, and distribution of necessary documentation for manufacture. 4.2 Any other documentation related to product quality that is not mentioned elsewhere (e.g. microbiological controls on air and water). 5. Production5.1 Brief description of production operations using, wherever possible, flow sheets and charts specifying important parameters. 5.2 Arrangements for the handling of starting materials, packaging materials, and bulk and finished products, including sampling, quarantine, release, and storage. 5.3 5.4 6. Arrangements for the handling of rejected materials and products. Brief description of general policy for process validation. Quality control6.1 Description of the quality control system and of the activities of the quality control department. Procedures for the release of finished products. 7. Contract manufacture and analysis7.1 Description of the way in which the GMP compliance of the contract accepter is assessed. 8. 8.1 8.2 Distribution, complaints and product recall Arrangements and recording system for distribution. Arrangements for the handling of complaints and product recalls.Working document QAS/10.378 page 6 9. 9.1 Self-inspection Short description of the self-inspection system. ***。
WHO组织DMF编制指南
WHO组织DMF编制指南WHO（世界卫生组织）是全球最高级别的公共卫生组织，致力于提高全球人民的健康水平。
WHO通过制定和推动各种指南和政策，帮助各国制定和实施公共卫生策略，以应对各种疾病和健康挑战。
DMF（伤残、功能和健康分级）是一种用于评估和描述人类功能和行动能力的框架，这一概念广泛应用于医疗领域和公共卫生政策制定中。
DMF的编制指南由WHO负责制定，以确保其在全球范围内的一致性和可操作性。
编制DMF指南的目的是提供一个统一的框架，用于评估和描述人类功能和行动能力，从而更好地理解健康和伤残的影响，有助于制定和改进公共卫生政策和服务。
编制DMF指南的过程通常包括以下步骤：1.收集证据：WHO召集一组专家，收集和审查关于人类功能和行动能力的最新研究和证据。
这些证据可以包括生理测量、社会调研、临床研究等。
2.制定概念模型：根据收集到的证据，专家组织整理出一个系统的概念模型，以描述人类功能和行动能力的不同维度和因素。
3.制定指标和分类：基于概念模型，专家组织制定出一套指标和分类，用于评估和描述人类功能和行动能力的不同方面。
这些指标和分类通常包括生理功能、认知功能、社会功能等。
4.草案审查和反馈：专家组制定出初步的DMF指南草案，并征求相关利益相关者以及其他感兴趣方的意见和反馈。
根据收到的反馈，草案进行适当的修订和完善。
5.正式发布和宣传：修订后的DMF指南被正式发布，并通过各种渠道向全球公众、医疗专业人员和政策制定者宣传。
这些渠道包括WHO网站、学术期刊、会议和培训等。
需要注意的是，DMF指南的编制是一个动态的过程，会随着研究进展和社会需求的变化而进行更新和修订。
因此，WHO在制定DMF指南时，通常会考虑将来的发展趋势和需求，以确保指南的持续有效性和适用性。
编制DMF指南对于改善全球公共卫生意义重大。
通过提供一个统一的框架，DMF指南有助于促进全球各国在功能和行动能力评估和描述方面的一致性，提供可比较的数据和信息，为决策者制定和改进公共卫生策略和服务提供科学依据。
WHO报告对技术转移的详细指南（5篇）
WHO报告对技术转移的详细指南（5篇）第一篇：WHO报告对技术转移的详细指南WHO报告对技术转移的详细指南WHO技术报告（No：961，2011年）附件7（第285 – 309页)发布了关于药品生产的技术转移（WHO Guidelines on Transfer of Technology inPharmaceutical Production）。
关于这个主题，到目前为止欧美国家均没有具体指南，仅ISPE有过该主题的一些建议，因此这指南备受业界的重视。
本指南共分九个章节，1.介绍、2.范围、3.术语、4.组织与管理、5.生产转移（工艺、包装和清洁）、6.分析方法转移、7.设备与设备、8.文件、9.确认与验证。
现将一些亮点介始如下：1.技术转移包含文件转移和接受能力转移，从而有效地执行技术转移的关键要素，使得两方和监管部门均满意为宗旨。
2.在第4章的组织与管理中介绍了转移方案的详细清单等内容。
3.在第5章的生产转移中对原料药和辅料的转移信息有非常细的要求清单。
4.在第6章的质量控制的分析方法转移中，包括原材料和包装材料的检验方法，工艺验证和清洁验证的检验方法。
表1是关于《分析方法的设计与接受标准表》，包含了详细的内容。
包含了鉴别、含量、含量均匀度、溶出度、清洁验证（擦洗取样）和微生物的定性与定量、杂质、降解物、残留溶剂等。
对每一个实验方法，你均可在表中找到下列信息：⌝⌝⌝⌝方法转移需要考虑的事项；重复实验的要求清晰的比较因子接受标准(平均值与标准偏差要求)现将表中的一些要求介绍如下：⎫含量测定的方法转移：每个实验室均应需要2人进行实验，三批样品、每批做三个样品，每个实验室需要做2×3×3＝18数据。
接收标准是两个实验室的平均值应≤2%；⎫溶出度的方法转移：每个实验室均应需要2人进行实验，一批样品，接收标准是两个实验室的平均值应≤±3%；⎫含量均匀度的方法转移：每个实验室均应6片，一批样品，接收标准是两个实验室的平均值应≤±5%；⎫杂质、降解物、残留溶剂的方法转移：考虑的因子有RRT、定量限、图谱比较、准确度和中间精密度。
WHO组织DMF编制指南
15 January 2007GUIDELINE ONACTIVE PHARMACEUTICAL INGREDIENT MASTER FILE(APIMF) PROCEDURE1(The APIMF procedure guideline does not apply to biological APIs.)TABLE OF CONTENTS1 INTRODUCTION (2)2 SCOPE (2)3 MAIN GUIDELINE TEXT (2)3.1 Content of the APIMF (2)3.2 Use of APIMF Procedure (2)3.3 Content of the PD when the APIMF Procedure is Used (3)3.4 Changes and updates to the APIMF (4)ANNEX 1 - OVERVIEW APIMF CONTENTS (5)ANNEX 2 - TEMPLATE LETTER OF ACCESS (7)ANNEX 3 - PART OF COVERING LETTER (8)ANNEX 4 - LIST OF ABBREVIATIONS (9)ANNEX 5 - GLOSSARY (10)1This guideline is based on the approach described in the document CPMP/QWP/227/02 Rev 2 Consultation draft GUIDELINE ON ACTIVE SUBSTANCE MASTER FILE PROCEDURE (London, 27 April 2005) of the European Medicines Agency1 INTRODUCTIONThe main objective of the APIMF procedure is to allow valuable confidential intellectual property or "know-how" of the Manufacturer of the active pharmaceutical ingredient (API) to be protected, while at the same time allowing the Applicant or holder of Prequalification Dossier (PD) to take full responsibility for the finished pharmaceutical product (FPP) and the quality and quality control of the API. The Prequalification Team thus has access to the complete information that is necessary for an evaluation of the suitability of the use of the API in the FPP.2 SCOPEThis Guideline is intended to assist Applicants/PD holders in the compilation of the API information of their dossiers for a prequalification dossier application (PDA) or a prequalification dossier variation (VPD) of a FPP. It is also intended to help APIMF holders in the compilation of their APIMFs.3 MAIN GUIDELINE TEXT3.1 Content of the APIMFThe overall content of the APIMF should contain detailed scientific information as indicated in Section 2. ACTIVE PHARMACEUTICAL INGREDIENT(s) [API(s)] of the “Guideline on Submission of Documentation for Prequalification of Multi-source (Generic) Finished Pharmaceutical Products (FPPs) Used in the Treatment of HIV/AIDS, Malaria and Tuberculosis”.The scientific information in the APIMF should be physically divided into two separate parts, namely the Open Part (OP) and the Restricted Part (RP). The OP contains the information that the APIMF holder regards as non-confidential to the Applicant/PD holder, whereas the RP contains the information that the APIMF holder regards as confidential, see Annex 1. It is emphasized that the OP is still a confidential document that cannot be submitted by anyone to third parties without the written consent of the APIMF holder. In all cases the OP should contain sufficient information to enable the Applicant/PD holder to take full responsibility for an evaluation of the suitability of the specifications for the API to control the quality of this API for use in the manufacture of a specified FPP.The RP shall contain the remaining information, such as detailed information on the individual steps of the manufacturing method (reaction conditions, temperature, validation and evaluation data of critical steps) and the quality control during the manufacturing method of the API. Information that is relevant to the Applicant/PD holder (see notes 2 and 5 of ANNEX 1 regarding residual solvents and impurities, respectively) should be discussed in the RP but should also be submitted in the OP.In addition to the OP and RP, the APIMF should contain a table of contents, and a separate summary for the OP and the RP. Both summaries should be presented as a Pharmaceutical Quality Information Form (PQIF). The OP and RP should each have a version number. The structure of the version numbers should be unique and follow a logical order. Preferably the following structure is used: Name APIMF holder / Name active pharmaceutical ingredient/ OP or RP/ version number / date in yyyy-mm-dd.3.2 Use of APIMF ProcedureAn APIMF can only be submitted in support of a PDA or VPD. The relationship between the quality of the API and its use in the FPP needs to be justified in this PDA or VPD. Although the APIMF procedure is developed to keep intellectual property of the API confidential, it is also permissible to use the procedure when there is no confidentiality issue between the Applicant/PD holder and the API manufacturer (e.g. when the Applicant/PD holder manufactures the API itself). It is expected that the API manufacturer is also the holder of the APIMF.The APIMF procedure should be used for APIs where a professed standard is declared (namely no monograph exists in the Ph. Eur., Ph. Int. or USP), or where a monograph exists but a manufacturer’sin-house standard is declared.The APIMF procedure can also be used when APIs are included in the Ph. Eur., Ph. Int. or USP.A Drug Master File of an API (active substance, drug substance) assessed by a drug regulatory agency in the International Conference on Harmonization (ICH) regions and associated countries - including among others the EU, Japan and USA - is accepted without further evaluation as a prequalified APIMF on condition that evidence of such regulatory acceptance has been submitted. The holder of the DMF should also declare in writing that there have been no changes to the DMF content and manufacture of batches of API to be supplied for Applicants/PD holders.The APIMF holder should give permission to WHO to assess the data in the APIMF in relation to a specific PDA/VPD, in the form of a 'Letter of Access', see Annex 2. The APIMF holder should submit to the Applicant/PD holder:a copy of the latest version of the OP.a copy of the PQIF on the latest version of the OP.the Letter of Access.In addition, the APIMF holder should submit to WHO:the APIMF accompanied by a covering letter, see Annex 3.the Letter of Access.The APIMF holder should provide the APIMF to WHO only once, independently from the number of the PD holders and the number of PDAs/VPDs. The submission of the relevant documentation by the APIMF holder to WHO must be synchronised to arrive at approximately the same time as the first PDA or the first VPD is received from the FPP manufacturer that references the APIMF.Where the APIMF procedure is used, the Applicant/PD holder should submit the PDA or VPD to WHO together with the Letter of Access.WHO requires that any APIMF updates made in relation to one PD should apply to all. It is the APIMF holder's responsibility to notify the PD holders and WHO about any changes to the OP and/or RP, so that the PD holders can update all affected PDs accordingly and file the appropriate variation(s) to WHO as necessary.3.3 Content of the PD when the APIMF Procedure is UsedThe Applicant/PD holder is responsible for ensuring that he has access to all relevant information concerning the current manufacture of the API.The specifications used by the Applicant/PD holder to control the quality of the API should be laid down unambiguously in the PD. The Applicant/PD holder should quote the OP version number / date in yyyy-mm-dd , or should include a copy of the OP in the PD dossier.The version of the OP in the PD dossier should be the most recent and it should be identical to the OP as supplied by the APIMF holder to WHO as part of the APIMF.The Applicant/PD holder should include all relevant details from the OP in the PQIF of the PD dossier. Issues of the APIMF that are specifically relevant to the FPP under consideration should be highlighted in the PQIF of the PD.In the case of a single supplier and where the APIMF procedure or CEP procedure is used, the specifications of the Applicant/PD holder in the PD dossier should in principle be identical to those of the APIMF holder or the CEP holder. The Applicant/PD holder does however not need to accept redundant specifications, unnecessarily tight specification limits or outdated analytical methods. In cases where the Applicant/PD holder uses a different analytical method than that described in the APIMF, both methods should be validated. Technical specifications relevant for the FPP, which are normally not part of the specifications in the APIMF (e.g. particle size), should be part of the specifications of the Applicant/PD holder.In cases where there is more than one supplier, there should be one single compiled specification that is identical for each supplier. It is acceptable to lay down in the specification more than one acceptance criterion and/or analytical method for a single parameter with the statement “for API from supplier X”(e.g. in case of residual solvents).3.4 Changes and updates to the APIMFAs for FPPs, APIMF holders should keep the content of their APIMFs updated with respect to the actual synthesis / manufacturing process. The quality control methods should be kept in-line with the current regulatory and scientific requirements. APIMF holders shall not modify the contents of their APIMF (e.g. manufacturing process or specifications) and must inform each Applicant/PD holder and WHO when a change in an APIMF requires the filing of a VPD. Before implementation, any change to the APIMF should be reported by every PD holder to WHO by means of an appropriate variation procedure. A covering letter should be provided. In cases where the contents of the APIMF cannot be changed for a certain period of time, the APIMF holder should still provide the aforementioned data to the PD holder and WHO making reference to this reason and requesting a later date of implementation.The APIMF holders' covering letter to WHO should contain the following information (if available): A tabular list summarizing the changes carried out since the first compilation of the APIMF. An overview comparing the old and new content of the APIMF.Information as to whether the change has already been accepted, rejected or withdrawn by another drug regulatory authority in the ICH region and associated countries.The names of the relevant Applicants and PD holders. The new OP and/or RP with each new version number.An updated PQIF,if relevant.A discussion of the potential impact on the quality of the API as a result of the change(s).At the occasion of the 3-yearly renewal of a FPP, PD holders are required to declare that the quality of the product, in respect of the methods of preparation and control, has been regularly updated by variation procedure to take account of technical and scientific progress, and that the product conforms with current WHO/Prequalification quality guidelines. They will also declare that no changes have been made to the product particulars other than those approved by WHO.PD holders should therefore verify with their APIMF holders whether the above declaration can be met in respect to the API particulars. In case changes have not been notified to the PD holder and WHO, the necessary variation procedure should be initiated without delay.ANNEX 1 - OVERVIEW APIMF CONTENTSTable 1 PQIF format Open RestrictedPart PartGeneral information from literature x2.1 Nomenclature x2.2 Properties of API xStructure xX 2.3 Site(s) of manufacture xManufacturer(s) xprocess1) 2)2.4 ManufacturingControl of materials XControl of critical steps and intermediates 3) 4)Process validation and/or Evaluation XManufacturing Process Development XCharacterization xElucidation of Structure and other Characteristics xSelected physicochemical andother relevant properties xImpurities x 5)Control of API x2.5 Specifications xAnalytical procedures xValidation of analytical procedures xBatch analysis xJustification of specification x 6)Reference standards or Materials x2.6 Container Closure System x2.7 Stability xStability summary and conclusion xPost-approval Stability Protocol and Stability xCommitmentStability data x1)Flow chart and textbook-level narrative is regarded as sufficient, if detailed information ispresented in the Restricted Part. However, full validation data on the sterilization process may be requested in the Open Part (in cases where there is no further sterilization of the final product).2)Detailed information.3)In so far as the information is also relevant for the Applicant/PD holder.4)In so far as the information is related to the detailed description of the Manufacturing processand in so far as this information is not relevant for the Applicant/PD holder.5)In so far as the information is related to the detailed description of the Manufacturing processand in so far as the APIMF holder sufficiently justifies that there is no need to control these impurities in the final API.6)In so far as the information is related to the detailed description of the Manufacturing process,control of materials and process validation.ANNEX 2 - TEMPLATE LETTER OF ACCESS[Address of WHO][Date and place]LETTER OF ACCESSNumber of Active Pharmaceutical Ingredient Master File:Manufacturing site: [name and address]Active Pharmaceutical Ingredient Master File holder: [name and address]The aforementioned Active Pharmaceutical Ingredient Master File holder hereby authorizes the [WHO including all PQ Team Members and their experts] to refer to and review the above mentioned Active Pharmaceutical Ingredient Master File in support of the following Prequalification Application(s) or Prequalified Dossier Variation(s) submitted by [name / Prequalification holder / Applicant] on [planned date of submission]:[Name of product and prequalification code number, if known] [Name of Applicant or PD holder] The aforementioned Active Pharmaceutical Ingredient Master File holder commits to ensure batch-to-batch consistency and to inform [name of PD holder/Applicant] and WHO of any change in the OP or RP parts of the Active Pharmaceutical Ingredient Master File.Signature for the Active Pharmaceutical Ingredient Master File holder [Name and address] [Signature]ANNEX 3 - PART OF COVERING LETTERThis Active Pharmaceutical Ingredient Master File is submitted in relation to the PDA / VPD: [Name of product in prequalification procedure][Name of Applicant/PD holder for the application concerned]and describes <changes to> the manufacturing process and specifications of the (or one of the) active pharmaceutical ingredient(s) of this PDA or VPD.[Name active pharmaceutical ingredient]The version number of this Active Pharmaceutical Ingredient Master File isOpen part: version [version number]Restricted part: version [version number]This Active Pharmaceutical Ingredient Master File has previously been submitted for assessment in combination with a PDA / VPD for a pharmaceutical product within the prequalification project: Refer to the prequalification code and name of the FPP and the FPP manufacturer.ANNEX 4 - LIST OF ABBREVIATIONSAPI Active Pharmaceutical IngredientAPIMF Active Pharmaceutical Ingredient Master FileCEP European procedure for a certificate of suitability of monographs of the European pharmacopoeia (here on chemical purity)ICH International Conference on HarmonizationOP Open (Applicants) Part of the APIMFPD Prequalification dossierPDA Prequalification Dossier Application (including line extensions)Ph. Eur. European PharmacopoeiaPh. Int. International Pharmacopoeia of WHOPQIF Pharmaceutical Quality Information FormRP Restricted Part (of APIMF)USP United States PharmacopoeiaVPD Variation to a prequalified dossierWHO World Health Organization20, AVENUE A PPIA –CH-1211G ENEVA 27–S WITZERLAND –T EL CENTRAL +41227912111–F AX CENTRAL +41227913111– WWW.WHO.INTANNEX 5 - GLOSSARYActive pharmaceutical ingredient manufacturerA party involved in the Manufacturing chain of the active pharmaceutical ingredient, including agents, brokers, traders, distributors, repackers or relabellers.Active pharmaceutical ingredient Master File holderThis is the company that has the ultimate responsibility for the Active pharmaceutical ingredient Master File.ApplicantThis is the company requesting prequalification for a pharmaceutical product. Prequalification dossier holderThis is the company that is responsible for the pharmaceutical product on the market Manufacturing chainA clear flow chart or written text explaining the Manufacturing and distribution route of the active pharmaceutical ingredient from the first starting materialQualityAccording to ICH Q6A that is “The suitability of either a drug substance or drug product for its intended use. This term includes such attributes as the identity, strength and purity.” SpecificationAccording to ICH Q6A that is “A list of test, references to analytical procedures, and appropriate acceptance criteria which are numerical limits, ranges or other criteria to which a drug substance or drug product should conform to be considered acceptable for its intended use. Conformance to specifications means that the drug substance and/or drug product, when tested according to the listed analytical procedures will meet the listed acceptance criteria. Specifications are critical quality standards that are proposed and justified by the Manufacturer and approved by regulatory authorities.”。
who生物医学研究审查伦理委员会操作指南
生物医学研究审查伦理委员会操作指南生物医学研究审查伦理委员会操作指南，世界卫生组织（Operational Guidelines for EthicsCommittees That Review Biomedical Research, 2000, World Health Organization）前言对人体进行生物医学研究试验的伦理和科学标准已在一些国际性的指南中制定和确立，包括《赫尔辛基宣言》、国际医学科学组织委员会（CIOMS）的《人体生物医学研究国际伦理指南》及世界卫生组织（WHO）和人用药物注册技术要求国际协调会议（ICH）对药品临床试验管理规范的指南。
遵循这些指南有助于使受试者的尊严、权力、安全和福利，以及研究结果的可信性得到保证。
所有的国际指南除要求有知情同意，以及对不能同意者予以适当保护外，还要求对生物医学研究进行伦理和科学的审查，以作为保护参加研究的个人和社区的必要措施。
从这些指南的目的来看，生物医学研究包括对药品、医疗仪器、医学放射和影像、外科手术、病历和生物标本，以及流行病学、社会和心理学的研究。
WHO指南的目的在于促进和支持世界各国的伦理审查。
他们基于对国际指南已确立的伦理审查要求的严格评价，以及基于对世界各国现有的伦理审查实践的评价；但无意取代各国和各地区对生物医学研究的伦理审查要求，也无意代替国家的法律和规定。
大多数生物医学研究主要考虑的是某些特殊群体的利益。
WHO估计对医学研究和开发的90%的资源仅用于造成目前不到全球危害的10%的那些疾病上。
已颁布的国际指南有助于加强各国生物医学研究的伦理审查的能力，为纠正这种不平衡作出贡献。
一、目的指南的目的是为提高生物医学研究伦理审查的质量和一致性。
指南旨在补充现有的法律、法规与惯例，并在此基础上，各国伦理委员会能够制定其各自的书面程序，以发挥它们在生物医学研究中的作用。
在这方面，指南确立了保证伦理审查质量的国际标准。
指南应被各国和地区用来制订、评估和不断修订对生物医学研究伦理审查的标准操作程序。
WHO数据与记录管理规范指南
数据与记录管理规范指南征求意见稿文档拟议采纳流程安排QAS/15.624:在药品生产检查、生产质量管理规范和风险管理指南非正式协商会议上讨论新指南的文件拟议和需求2014年4月28-30日概念文件由第49届WHO药品制剂规范专家委员会预认证项目（PQT）检查专家检查员I. Thrussell先生提出2014年10月13-17日I. Thrussell先生与检查预认证小组的同事以及包括M.Cahilly女士和国家检查员在内的起草小组密切合作共同准备指南草案2014年10月-2015年6月在数据管理、生物等效性和药品生产质量管理规范与药品检查协商会议上讨论草案2015年6月29日-2015年7月1日作者及起草小组根据协商会议会及后续WHO数据管理研讨会反馈修改草案2015年7月-8月发布文件征求意见2015年9月意见汇总2015年11月递交第50次WHO药品制剂规范专家委员会讨论2015年12月12-16日根据需要和WHO药品制剂规范专家委员会的建议施行下一步工作背景2014年4月在日内瓦召开的由世界卫生组织（WHO）举办的关于药品生产检查、药品生产质量管理规范（GMP）和风险管理指南非正式协商会议中，讨论了关于新的良好数据管理指南的提议并建议制定该指南。
参与人员包括不同日程议题的国家检查员和专家以及预认证检查小组（PQT-Inspections）工作人员。
WHO药品制剂规范专家委员会在2014年10月举行的第49次会议中收到此次非正式协商会议的反馈意见。
由预认证检查小组提出的关于新指南文件框架结构提议的概念文件(concept paper)被详细讨论。
概念文件整合现有的规范性原则并针对规范性原则的执行情况给出一些说明性示例。
在概念文件附录中，从现有良好实践和指南文件提炼的内容相结合，用以阐明现行相关指南对数据可靠性和与其相关的GxP问题的保障。
借鉴现有的良好做法并结合指南文件就现行相关指南中关于保证数据的可靠性和相关GxP 事宜进行说明。
WHO现场主文件编写指南
© World Health OrganizationWHO Technical Report Series, No.961, 2011附件14Annex 14WHO现场主文件编写指南1WHO guidelines for drafting a site master file11. 介绍Introduction2. 目的Purpose3. 范围Scope4. 现场主文件的内容Content of site master file附件Appendix现场主文件的内容Content of a site master file1. 介绍Introduction1.1 现场主文件是由药品制药商编写的，应当包含下列具体的信息：生产厂区的质量管理方针及活动、在指定的生产厂区实行的对药品生产操作的生产和/或质量控制以及在与其相邻的建筑物内所进行的任何紧密的完整的操作。
如果只有一部分药品生产操作在此厂区内进行，那么在现场主文件中只需要描述这些操作，例如分析、包装等。
The site master file (SMF) is prepared by the pharmaceuticalmanufacturer and should contain specific information about the qualitymanagement policies and activities of the site, the production and/or qualitycontrol of pharmaceutical manufacturing operations carried out at the namedsite and any closely integrated operations at adjacent and nearby buildings.If only part of a pharmaceutical operation is carried out on the site, an SMFneed only describe those operations, e.g. analysis, packaging, etc.1.2 当提交给监管机构时，现场主文件中应当包含对常规监督、有效计划及进行GMP检查有用的、关于制造商与GMP相关的活动的清晰信息。
WHO最新指南(对照阅读)
WHO最新指南（对照阅读）12月4日，世界卫生组织（W H O）于发布《药品生产技术转移指南》(W H O g ui d e l i n e s o n t h e t r a ns f e r of t e c h n o l o g y i np h a r m a c e ut i c a l m an u f ac t u r i n g)，提供了药品技术转让期间应考虑的指导原则。
本指南主体部分分为12个章节，内容如下：背景1.简介2.范围3.术语4.尽职调查和差距评估5.组织与管理6.质量管理和质量风险管理7.文件8.设施9.设备和仪器10.确认和验证11.产品生命周期和项目管理原则12.技术转移项目阶段往期推荐（1）药品生产技术转移：概述（2）药品技术转移，40个术语（3）药品技术转移：如何评估组织？（4）药品技术转移：设施设备上有哪些考虑？（5）药品技术转移：确认和验证上有哪些考虑？（5）药品技术转移：项目阶段如何设计？以下是该指南的12章（下）内容：12. 技术转移项目阶段（下）Information on process and finished pharmaceutical product information工艺信息和成品信息Processing, packaging 工艺、包装12.15.Pr o d u c t,p r o c e s s a n d p r o c e d u r e k n o w l e d ge s h o u l d b e a ne s se n t i a l p a r t of t h e t r a n s f e r p r o c e s s f r o m S U t o R U.产品、工艺和程序知识应该是从S U到R U的转移的重要组成部分。
12.16.T h e q u a l i t y t a r g e t p r o d u c t p r o f i l e,c r i t i c a l q u a l i t y a t t r i b u t e s,c r i t i c a l p r o c e ss p a r a m e t e r s,m a t e r i a l a t t r i b u t e s,c o n t r o l s t r a t e g y a nd a n y o t he r i m p a c t i n g e l e m e n t s o n t h e q u a l i t y of t h e p r o d u c t s h o u l d b e a v a i l a b l e.(S e e a l so I C Hg u i d e l i n e s.)质量目标产品概况、关键质量属性、关键工艺参数、物料属性、控制策略、以及对产品质量有任何其它影响的要素，都应可以提供。
WHODrug 最佳实践 ：第 6.0 版说明书
WHODrug 最佳实践Practices 适用于 B3 和 C3 格式第6.0版0版WHODrug 最佳实践第6.0版目录1.介绍 (3)1.1.术语定义 (3)2.非唯一名称 (4)2.1.寻找区分符以便帮助选择记录 (5)2.2.如没有任何适合的区分符可使用 (9)3.缺少的药物记录 (11)3.1.提交变更申请 (11)3.2.等待变更申请的回复 (11)3.3.编码至“占位符” (12)3.4.修订申请的流程 (13)4.药物分类（ATC 编码） (14)4.1.介绍 (14)4.2.分类方法 (16)4.3.方法描述 (16)4.4.每种分类方法的最佳实践程序 (19)4.5.其他注意事项 (23)5.版本更新 (24)5.1.背景 (24)5.2.升级版本的原因 (24)5.3.升级版本的策略 (24)5.4.版本升级的最佳实践程序 (25)6.WHODrug 编码审查须知 (29)6.1.背景 (29)6.2.审查药物编码的目的 (29)6.3.编码惯例 (29)6.4.自动编码的数据 (29)6.5.标识需特别关注的药物，例如违禁药物 (29)6.6.审查列表的编制 (30)7.不精确逐字的编码（Umbrella coding） (32)7.1.介绍 (32)7.2.什么时候应该使用概括性记录和 NOS（未特指）记录？ (32)7.3.如何选择概括性记录和 NOS（未特指）记录？ (33)7.4.选择概括性记录还是 NOS（未特指）记录 (35)7.5.版本升级对与概括性记录匹配的逐字的影响 (35)1. 介绍Uppsala Monitoring Centre (UMC) 致力于实现药品编码在制药行业的统一实践。
本文件根据来自WHODrug 用户群体的编码专家所分享的意见编写而成，就以最佳方式处理不同的编码问题提供建议。
UMC 与软件系统供应商合作，鼓励他们在其系统中实施最佳实践。
WHO数据完整性指南良好的数据和记录规范最终稿中文
WHO数据完整性指南良好的数据和记录规范最终稿中文WHO数据完整性指南是一个组织内部的规范，它旨在确保WHO（世界卫生组织）收集、维护和发布的数据和记录具有高度的完整性和可靠性。
这一指南对于确保成员国和其他利益相关方能够信任和依赖WHO提供的数据非常重要。
在这篇文章中，我将详细介绍WHO数据完整性指南中规定的良好的数据和记录规范的最终稿。
此外，数据安全和保密性也是指南的一个重点。
它强调了保护数据的机密性和防止未经授权的访问的重要性。
数据应该在合适的安全措施下进行存储和传输，以确保数据不会被恶意利用或泄露。
指南还重视数据的可用性和可访问性。
它要求所有的数据和记录都应该以公开和透明的方式发布和共享。
数据应该以易于理解和使用的格式提供，并且应该提供适当的文档和说明，以帮助利益相关方正确地解读和使用数据。
此外，指南还建议使用先进的数据管理技术和工具来提供更便捷和可操作的数据访问。
最后，指南强调了监督和审查的重要性。
它建议建立独立的数据监督机构或委员会，负责监督数据的质量和完整性，并确保所有的数据和记录符合规范。
此外，指南还建议进行定期的数据审核和审查，以便发现和纠正任何潜在的问题或错误。
综上所述，WHO数据完整性指南中规定的良好的数据和记录规范意在确保数据的准确性、一致性、安全性和可用性。
这些规范旨在建立一个可信赖的数据基础，使利益相关方能够更好地运用和利用这些数据来支持决策和行动。
通过遵守这些规范，WHO将能够更好地履行其使命，为全球卫生事业做出更大的贡献。
WHO《计算机化系统验证指南》-2018
WHO《计算机化系统验证指南》-2018WHO今年发布了《验证指南-附录5 计算机化系统验证》（征求意见稿），相比于其他机构发布的《计算机化系统验证指南》，WHO 发布的这版要求更加严格，内容更加具体。
该指南共16章，涵盖计算机化系统验证方案和报告、供应商管理、用户需求规范、系统设计和配置规范、设计确认、构建和项目实施、安装确认、运行确认、标准操作规程和培训、性能确认、系统维护、系统退役等内容，全文翻译如下：因篇幅关系，忽略第1-3章介绍性内容。
4. COMPUTERIZED SYSTEM VALIDATION PROTOCOLS AND REPORTS计算机化系统验证方案和报告4.1. A computerized system needs to be validated according to an approved protocol and final report including results and conclusions prior to routine use.计算机化系统需要根据一份批准的方案进行验证并在日常使用前报告验证结果和结论。
Validation protocol验证方案4.2. Validation should be executed in accordance with the validation protocol and applicable written procedures.验证应根据验证方案和适当的书面规程执行。
4.3. A validation protocol should define the objectives, thevalidation strategy, including roles and responsibilities and documentation and activities to be performed. The protocol should at least cover the scope, risk management approach, the specification, testing, review and release of the computerized system for GMP use.验证方案应规定目的，验证策略，包括角色和职责以及将要执行的文件和活动。
who数据完整性指南中文版_图文
WHO数据完整性指南：良好的数据和记录规范红色文字部分为与原草案对比有变化的地方。
1.介绍1.1.世界范围的药品监管系统常常依赖于企业在开发、生产和包装、检测、销售和监控药品方面的知识。
在评估和审核过程中隐含的是监管者和被监管者之间相信注册文件中提交的和用于日常决策的信息是全面、完整和可信的。
因此基于此做出决策的数据应该在完整的同时也要是可追溯至产生数据的人的、清晰易读的、同步产生的、原始的和准确的。
通常这个被称作“ALCOA”。
1.2.这些基础的ALCOA原则和保证数据可靠性的相关良好的规范的期望都不是新的，许多高和中水平的规范性的指南已经存在了。
尽管如此，近几年，在GMP、GCP和GLP检查中出现与良好数据和记录管理规范相关的缺陷项的数量还在增加。
卫生监管机构对数据可靠性的越来越多的关注的原因毋庸置疑是多方面的并包括增加的关于行业选择和适当的现代的控制策略之间的差距的法规意识和关注。
1.3.影响因素包括企业没有实施耐用的系统来约束数据风险、没有改进对数据可靠性的丧失的状况的可检测性、和/或当失效出现时没有调查和找到根本原因。
例如，遵从药品良好规范的企业已经使用计算机化系统几十年但很多没有充分地回顾和管理原始电子记录仅仅是常常回顾和管理不完整和/或不充分的打印出来的资料。
这些缺陷强调了制药行业使历史的控制策略现代化和对当前的经验模式（比如外包和全球化）也对当前使用的技术（比如计算机化系统）应用时髦的质量风险管理和合理的科学原则的需要。
1.4.可能需要开发和强化以确保良好数据管理策略的控制的例子包括但不限于以下方面：1)质量风险管理的方法通过确保管理层的期望和实际过程能力相一致来有效保证患者安全和产品质量及数据有效性。
管理层应该对通过一开始就根据工艺、方法、环境、人员、技术和其他的当前实际的能力设定事实求是的并可实现的期望的方式来实现良好的数据管理负责。
2)工艺的持续监控和由管理层分配必要的资源来确保和根据需要加强基础设施（例如，持续改进工艺和方法；确保建筑、设施、设备和系统的充分设计和维护；确保充足可靠的电和水的供应；提供对人员必要的培训；为确保外包商和供应商充分满足质量标准分配必需资源去监管等）。
who 国家药品政策监测指标使用指南
who 国家药品政策监测指标使用指南下载温馨提示：该文档是我店铺精心编制而成，希望大家下载以后，能够帮助大家解决实际的问题。
文档下载后可定制随意修改，请根据实际需要进行相应的调整和使用，谢谢!并且，本店铺为大家提供各种各样类型的实用资料，如教育随笔、日记赏析、句子摘抄、古诗大全、经典美文、话题作文、工作总结、词语解析、文案摘录、其他资料等等，如想了解不同资料格式和写法，敬请关注!Download tips: This document is carefully compiled by the editor. I hope that after you download them, they can help yousolve practical problems. The document can be customized and modified after downloading, please adjust and use it according to actual needs, thank you!In addition, our shop provides you with various types of practical materials, such as educational essays, diary appreciation, sentence excerpts, ancient poems, classic articles, topic composition, work summary, word parsing, copy excerpts,other materials and so on, want to know different data formats and writing methods, please pay attention!国家药品监测指标使用指南是指导各级药品监管部门和相关机构科学监测药品实施效果的重要手册。
WHO现场主文件编写指南
© World Health OrganizationWHO Technical Report Series, No.961, 2011附件14Annex 14WHO现场主文件编写指南1WHO guidelines for drafting a site master file11. 介绍Introduction2. 目的Purpose3. 范围Scope4. 现场主文件的内容Content of site master file附件Appendix现场主文件的内容Content of a site master file1. 介绍Introduction1.1 现场主文件是由药品制药商编写的，应当包含下列具体的信息：生产厂区的质量管理方针及活动、在指定的生产厂区实行的对药品生产操作的生产和/或质量控制以及在与其相邻的建筑物内所进行的任何紧密的完整的操作。
如果只有一部分药品生产操作在此厂区内进行，那么在现场主文件中只需要描述这些操作，例如分析、包装等。
The site master file (SMF) is prepared by the pharmaceutical manufacturer and should contain specific information about the quality management policies and activities of the site, the production and/or quality control of pharmaceutical manufacturing operations carried out at the named site and any closely integrated operations at adjacent and nearby buildings. If only part of a pharmaceutical operation is carried out on the site, an SMF need only describe those operations, e.g. analysis, packaging, etc.1.2 当提交给监管机构时，现场主文件中应当包含对常规监督、有效计划及进行GMP检查有用的、关于制造商与GMP相关的活动的清晰信息。
WHOGACP条例
药用植物种植和采集的生产质量管理规范(GACP)指南世界卫生组织(日内瓦,2003年)关键词:世界卫生组织;药材;种植与采集;规范化中图分类号:S567文献标识码:A文章编号:100422199(2005)01200032061 引言1.1 背景在过去二十年,不论是在发达国家还是在发展中国家,人们对传统医药、特别是草药的兴趣日益浓厚。
全球范围内对草药的需求量迅速增长,并产生了巨大经济效益。
根据联合国环境计划署生物多样性公约秘书处的统计,2000年全球草药产品销售额已达600亿美元。
随之而来的草药的安全性与质量问题也越来越引起健康管理部门及公众的关注[1]。
由于服用某些草药而引起不良反应的报道使得人们去寻找各种可能的解释:误用了植物品种;在草药中掺入未经申报的其他药物和/或有效物质;草药受到有毒或有害物质的污染;超剂量使用;医疗保健人员或消费者不正确的使用;以及同其他药物发生相互作用等等。
这些都会导致药物不良反应。
很显然,在那些导致成品质量低劣的因素中,有些是由于所使用的原药材质量不高引起的。
原药材及成品药的质量及安全性取决于内在因素(基因)和外部因素(环境、采集方法、栽培、采收、采收后的加工、运输及存储方法)。
在生产过程的任何一个环节中,因疏忽而被微生物或化学物质污染均可导致药品质量的降低。
从野外采集来的野生药用植物也有可能因认为其他品种、意外污染或故意掺假而产生不安全的后果。
全球性地范围内和区域性的对野生药用植物的过度采集引起了人们对濒危物种保护工作的关注。
应该考虑到种植、采集对生态环境及当地人民生活福利的影响。
应当尊重有关原料(药用植物)的知识产权。
同时世界卫生组织已经同联合国其他专门机构和国际组织针对上述问题开展了合作。
通过制订和更新该领域的相关技术指南而使这种合作进一步加强。
为了解决上述问题,确保高品质的药用植物原料能稳定、廉价和持续地供给,应当制订相关的安全及质量保证措施。
近年来,种植的生产质量管理规范(GAP)已被认为是控制食品质量与安全的最重要的方法。
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附件14Annex 14WHO现场主文件编写指南1WHO guidelines for drafting a site master file11. 介绍Introduction2. 目的Purpose3. 范围Scope4. 现场主文件的内容Content of site master file附件Appendix现场主文件的内容Content of a site master file1. 介绍Introduction1.1 现场主文件是由药品制药商编写的，应当包含下列具体的信息：生产厂区的质量管理方针及活动、在指定的生产厂区实行的对药品生产操作的生产和/或质量控制以及在与其相邻的建筑物内所进行的任何紧密的完整的操作。
如果只有一部分药品生产操作在此厂区内进行，那么在现场主文件中只需要描述这些操作，例如分析、包装等。
The site master file (SMF) is prepared by the pharmaceutical manufacturer and should contain specific information about the quality management policies and activities of the site, the production and/or quality control of pharmaceutical manufacturing operations carried out at the named site and any closely integrated operations at adjacent and nearby buildings. If only part of a pharmaceutical operation is carried out on the site, an SMF need only describe those operations, e.g. analysis, packaging, etc.1.2 当提交给监管机构时，现场主文件中应当包含对常规监督、有效计划及进行GMP检查有用的、关于制造商与GMP相关的活动的清晰信息。
When submitted to a regulatory authority, the SMF should provide clear information on the manufacturer’s good manufacturing practices (GMP)-related activities that can be useful in general supervision and in the efficient planning and undertaking of GMP inspections.1.3 现场主文件中应当包含足够的信息，但加上附件尽量不要超过25～30页。
用简单的计划、轮廓图或示意图来替代叙述性的文字是更可取的。
当用A4纸张打印出时，现场主文件及其附件应当是可读的。
An SMF should contain adequate information but, as far as possible, not exceed 25–30 pages plus appendices. Simple plans, outline drawings or schematic layouts are preferred instead of narratives. The SMF, including appendices, should be readable when printed on A4 paper sheets.1.4 现场主文件应是制造商质量管理体系文件的一部分，且应持续更新。
现场主文件应有版本号、生效期和必须对其进行审核的日期。
应当定期对现场主文件进行回顾以保证其包含了最新的信息和代表了当前所进行的活动。
每个附件可以有单独的生效期，以便进行独立的更新。
The SMF should be a part of documentation belonging to the quality management system of the manufacturer and kept updated accordingly. The SMF should have an edition number, the date it becomes effective and the date by which it has to be reviewed. It should be subject to regular review to ensure that it is up to date and representative of current activities. Each annex can have an individual effective date, allowing for independent updating.2. 目的Purpose这些注释的目的是：在药品制造商编写现场主文件时提供指导，现场主文件在监管机构计划和进行GMP检查时有用的。
The aim of these explanatory notes is to guide the manufacturer of medicinal products in the preparation of an SMF that is useful to the regulatory authority in planning and conducting GMP inspections.3. 范围Scope这些注释适用于现场主文件的编写及内容的确定。
制造商应参照区域性的和/或国家监管要求来确定编写现场主文件是否是强制性的要求。
These explanatory notes apply to the preparation and content of the SMF.Manufacturers should refer to regional and or national regulatory requirements to establish whether it is mandatory for manufacturers of medicinal products to prepare an SMF.这些注释适用于各种制造操作，例如各种药品的生产、包装和贴签、检测、重新贴签和重新包装。
本指南中的概述也可用于指导血液和组织制品和原料药（API）制造商编写现场主文件或相应的文件。
These explanatory notes apply for all kinds of manufacturing operations such as production, packaging and labelling, testing, relabelling and repackaging of all types of medicinal products. The outlines of this guide could also be used in the preparation of an SMF or corresponding document by blood and tissue establishments and manufacturers of active pharmaceutical ingredients (APIs).4. 现场主文件的内容Content of site master file格式参照附件。
Refer to the Appendix for the format to be used.附件Appendix场主文件的内容Content of a site master file1. 制造商基本信息General information on the manufacturer1.1制造商联系信息Contact information on the manufacturer- 制造商名称及官方地址；name and official address of the manufacturer;- 生产厂地名称及街道地址，在生产厂地内的建筑物和生产单元；names and street addresses of the site, buildings and production units located on the site;- 制造商联系信息，包括在产品缺陷或召回时，相关联系人的24小时联系号码；以及contact information of the manufacturer including 24-hour telephone number of the contact personnel in the case of product defects or recalls; and- 生产厂地的识别码，例如全球地位系统（GPS）详细信息、生产厂地或其它地理系统D-U-N-S（数据通用编号系统）编号（由Dun & Bradstreet提供的识别码）。
identification number of the site as e.g. global positioning system (GPS) details, D-U-N-S (Data Universal Numbering System) number (a unique identification number provided by Dun & Bradstreet) of the site or any other geographical location system.1.2生产厂地被授权的药品生产活动Authorized pharmaceutical manufacturing activities of the site- 主管部门颁发的有效的生产许可证的复印件作为附件一；或者当适用时，索引到EudraGMP数据库。
如果主管部门不颁发生产许可证，应当进行声明。
copy of the valid manufacturing authorization issued by the relevant competent authority in Annex 1; or when applicable, reference to the EudraGMP database. If the competent authority does not issue manufacturing authorizations, this should be stated;- 如果没有涵盖在生产许可证范围时，简述由相关主管部门，包括国外监管机构授权的制造、进口、出口、分发和其他活动，授权的剂型/活动，应根据许可的剂型/活动分别叙述；brief description of manufacture, import, export, distribution and other activities asauthorized by the relevant competent authorities including foreign authorities with authorized dosage forms/activities, respectively; where not covered by the manufacturing authorization;- 在超出附件一或EudraGMP数据库范围时，将目前在生产厂地生产的所有产品类型列出（附件二）；type of products currently manufactured on-site (list in Annex 2) where not covered by Annex 1 or the EudraGMP database; and- 列出最近5年内接受的所有GMP检查，包括进行检查的监管部门名称/国家和检查日期。