山东2008年验证总计划山东瑞博德制药有限公司

1、SHANDONG TRIPARDUS PHARMACEUTICALS CO., LTD.山东瑞博德制药有限公司VALIDATION DOCUMENT验证文件Validation Master Plan for the First Phase2008年验证总计划Docume nt No./ 文件编号：VD01001Issue No.版本号： 1Issue Date颁发日期：2007年12月28日Written by/起草人：To ny Liu/刘福堂Validation Man ager / 验证经理Sig ned签名：Date/日 期：年月日Authorized by/授权人:Ray Yu/于

2、 瑞清Technical Director/ 技术总监Sig ned签名：Date/日 期：年月日Document check/审核Audited by审核人Title职位Signature 签名Date日期Jane Cha ng常鸿雁Production Director/ 生产总监Production Ma nager/ 生产经理Tony Liu/刘福堂QA Manager/QA 经理Rocky Zhao/ 赵岩Equipme nt Man ager/ 设备经理Anna Song/宋晓燕QC Manager /QC 经理Engin eeri ng Man ager/ 维修经理Storage

3、 Man ager/仓库经理Long Bao/ 包龙Commercial Director/ 商务总监DistributionCommercial Man ager (Copy)商务经理(复印件)Producti on Director (Copy)生产总监(复印件)QA Validati on archive (Completed origi nal)Tech ni cal Director (Copy)QA验证档案（完整的原件）技术总监（复印件）Engin eeri ng Man ager (Copy)QC Man ager (Copy)维修经理（复印件）QC经理（复印件）Producti

4、o n Man ager (Copy)QA Man ager (Copy)生产经理（复印件）QA经理（复印件）Pack ing Man ager (Copy)Validati on Man ager (Copy)包装经理（复印件）验证经理（复印件）Table of Content/ 目 录1 Purpose/ 目的 62 Summary/ 概述 62.1 Company introduction and summary of fist stage project / 公司及一期工程项目概述 622 Scope/验证范围62.3 Validation Policy / 验证方针 63 Valid

5、ation Organizational Chart and Personnel Responsibilities/ 验证组织结构及人员职责 73.1 Organizational Chart/ 组织结构图 73.2 Validation Committee/ 验证委员会 73.3 Validation/Qualification Team/ 验证小组 73.4 Responsibilities/ 职责： 73.4.1 Responsibilities of Validation Committee/ 验证委员会职责 73.4.2 Responsibilities of Validation

6、Team/ 验证小组职责： 83.4.3 All Departmental Managers/ 所有部门经理职责 93.5 Training / 验证培训 94 The Writing and Approval of Validation Plan, Protocol and Report/ 验证计划、方案、报告的起草审批程序 95 Documentation/ 文件 95.1 Content/文件范围95.1.1 ValidationPlan/ 验证计戈U 95.1.2 ValidationProtocol/ 验证方案 95.1.3 ValidationReport/ 验证报告 105.1.

7、4 ValidationCertificate/ 验证证书 105.2 Format/文件格式105.3 Validation Document numbering/验证文件的编号 115.4 Validation/Qualification Archiving验证 /确认归档 126 Validation Implementation/ 验证实施 126.1 Safety and Health/ 安全与健康 126.2 Validation Classification and Applicable Scope / 本次验证所用到的验证分类与适用范围 .126.2.1 Prospective

8、 Validation / 前验证 126.2.2 Concurrent Validation/ 同步验证 126.2.3 Revalidation/再验证136.3 Validation Implementation/ 验证的实施 136.4 Validation Project Collection/ 本次验证的项目汇总 136.4.1 Analytical Methods Validation/ 分析方法学 136.4.2 Facilities/ 设施 136.4.3 Instruments and equipments/仪器设备 146.4.4 Process工艺156.4.5 Equ

9、ipment Cleaning/ 设备清洁 156.4.6 Computerized system/计算机化系统166.5 Schedule/本次验证的时间计划安排 166.5.1 First Phase/第一阶段176.5.2 Second phase第二阶段176.5.3 Third phase/第三阶段186.5.4 Fourth phase 第四阶段197 Validation Method and Acceptance Criteria/ 验证方法和可接受标准 197.1 URS/用户需求标准197.2 Analytical methods validation/ 分析方法学验证 2

10、07.3 Facilities Validation/ 厂房设施、仓库设施的验证 207.3.1 Design Qualification/ 设计确认 207.3.2 Installation Qualification/ 安装确认 217.3.3 Operational Qualification/ 运行确认 217.4 Validation of Clean Rooms and Air-conditioning System/ 洁净车间、空调系统的验证 217.4.1 Design Qualification/ 设计确认 217.4.2 Installation Qualification

11、/ 安装确认 227.4.3 Operational Qualification 运行确认 237.4.4 Performance Qualification/ 性能确认 237.5 Purified water system validation/ 纯化水系统验证 247.5.1 Design Qualification/ 设计确认 247.5.2 Installation Qualification/ 安装确认 247.5.3 Operational Qualification/ 运行确认: 257.5.4 Performance Qualification/ 性能确认 267.6 Com

12、pressed air system validati on/压缩空气系统验证 267.6.1 Design Qualification/ 设计确认 267.6.2 Installation Qualification/ 安装确认 267.6.3 Operational Qualification/ 运行确认 277.6.4 Performance Qualification/ 性能确认 277.7 Instruments and equipments validations/ 仪器设备验证 277.7.1 Design Qualification/ 设计确认 277.7.2 Installa

13、tion Qualification/ 安装确认 287.7.3 Operational Qualification/ 运行确认 287.7.4 Performance Qualification/ 性能确认 297.8 Equipment cleaning validation/ 设备清洁验证 297.8.1 Establishment of cleaning procedure/ 建立清洁规程 307.8.3 Validation of sampling method/ 验证取样方法 307.8.4 Confirmation of Chemical Residue/ 确定化学残留量 307

14、.8.5 Confirmation of microbes residue/ 确定微生物残留量 317.8.6 Expiry Date of Cleaned Equipment/ 确定清洁设备的存放有效期 317.9 Process Validation/生产工艺验证317.9.1 Precon diti ons/验证先决条件317.9.2 Validation Method/ 验证方法 317.10 Validation of Computerized System/ 计算机化系统验证 317.10.1 Hardware/ 硬件 327.10.2 Operational System/ 操作

15、系统 327.10.3Firmware/ 生产或支持设备使用的固件 327.10.4Commercial system/ 商业化系统 327.10.5Configurable software package/ 可配置软件包 328 Deviations and change control/ 偏差处理及变更控制 329 History of Change / 文件变更及历史 3310 References/参弓丨 3311 Annex/附录331 Purpose/ 目的This Validation Master Plan (VMP) describes the Validation and

16、 Qualification activities that will be undertaken at Tripardus Pharmaceuticals Ltd. at first phase before start-up. It summarizes the company ' s Validation intentions, philosoph,ypolicy, project, plan, and approach and acceptance criteria.本验证总计划 (VMP )描述了瑞博德制药有限公司新建的一期工程在启用前应该进行的验证和确 认活动，概括地阐述验

17、证目的、原则、方针、项目、计划、方法和可接受标准等。2 Summary/ 概述2.1 Company introduction and summary of fist stage project / 公司及一期工程项目概述Shandong Tripardus Pharmaceutical Co., Ltd. is located in Jinan Export Processing Zone, and the construction start in 2006. Tripardus undertakes manufacturing of products and Nutritional/Vi

18、tamin products on a contractual basis. The annual output of tablet will be * after completion. The warehouse is * m2 and the granulation plant is * m2 瑞博德制药有限公司一期工程位于山东济南出口贸易加工区，于2006年开始建设，本工厂根据与客户的合同，从事药品及营养维生素产品的加工。项目建成后，将达到年产量*的片剂生产量，有仓储系统*平方米，制粒生产车间* ,。2.2 Scope/验证范围This plan is to be followed f

19、or the validation of plant, purified project, facilities, HV AC, purified water system, compressed air system, production equipment, computerized system, process, cleaning procedures, etc. The validation will prove that the plant meets GMP requirements and is suitable for medicine production.验证包括本次建

20、设的厂房、净化工程、仓储设施、HVAC系统、纯化水系统、压缩空气系统、生产设备、计算机化系统、加工工艺、清洁程序等，本次验证后，本次建设的项目应符合 GMP要求可以生产药品。2.3 Validation Policy / 验证方针In order to produce the product of right quality, safety and efficacy and ultimately protection of patients, the validation must conform to cGMP and customer requirements. .A planned ap

21、proach is therefore required in order to progress the work in a structured and controlled manner. Ensure the validation is based on the risk assessment and cGMP-related critical equipment, process, cleaning, facilities, computerized system and supportive system have been validated. The risk assessme

22、nt is carried out with protocol establishment simultaneously by Validation Team. The scope and extent of Validation activities for an individual project, based on the conclusions and recommendations in the GMP Risk Analysis, and approved by Validation Committee as well as QA Manager.为使瑞博德能生产出合格、 安全和

23、有效的产品， 最终能保证用户的健康。 验证应符合 cGMP 和客户的验证要求，验证工作应有计划、有组织、有控制的进行，确保验证建立在风险评 估的基础上，确保与 cGMP 相关的、有主要作用的关键设备、工艺、清洗、设施、计算机 系统和支持系统都进行验证。 风险分析由验证小组成员负责在制定验证方案时进行，根据 GMP 风险分析的结果和建议确定的单个项目的验证内容和范围，由包括QA 经理在内的验证委员会在审核验证方案时批准。3 Validation Organizational Chart and Personnel Responsibilities/ 验证组织结构及人员职责3.1 Orga ni

24、zatio nal Chart/ 组织结构图3.2 Validation Committee/ 验证委员会Technical Director is responsible for the whole validation activities; Validation Manager is resp on sible for co-coord in at ing. The Validatio n Committee is compromised of Tech ni cal Director, Validation Manager, Production Director, EHS Manag

25、er, Commercial Manager, QA Manager, QC Man ager, Product ion Man ager, Warehouse Man ager, Equipme nt Man ager, Engin eeri ng Man ager, and Maintenance Man ager.瑞博德的验证总负责人为技术总监，组织协调人为验证经理，由技术总监、验证经理、生 产总监、环境安全健康总监、商务总监、QA经理、QC经理、生产经理、仓库经理、设备经理、维修经理组成验证委员会。3.3 Validation/Qualification Team/ 验证小组A Val

26、idati on/Qualificati on team is assembled to guide the in dividual projects through to completion. The team should be multidisciplinary and will be comprised of personnel with skills to assist the satisfactory completion of Validation and Qualification activities, and the Team Leader should be the p

27、eople who is familiar with the validati on project and is appo in ted by Validati on Man ager. The team members are appo in ted by Team Leader at the time of protocol draft.验证小组是为完成每个项目验证工作而成立的工作小组，该小组应是多学科的，组长由熟 悉本项目验证要求的人员担任，小组成员掌握的技术能协助验证和确认工作的圆满完成。组长一般由验证经理根据实际情况指定，小组成员由验证组长在起草验证方案时根据要求 指定。3.4 R

28、espo nsibilities/ 职责：3.4.1 Responsibilities of Validation Committee/ 验证委员会职责Personnel 人员Responsible for:职责Tripardus Pharmaceuticals SeniorEnsuring that sufficient commitment and resources are available to releva nt departme nts to achieve the aims of the projects set out inMan ageme nt瑞博德咼层the VMP a

29、nd in complia nee with cGMP.确保为相关部门提供足够的义务和资源，以达到VMP中规定的验证目标，并符合GMP要求。Validati on Man ager验证经理To co-ord in ate validati on and qualificati on projects, draft the VMP, ensure the Validation Team completing the validation, and establish validati on archive.协调验证和确认工作，起草验证总计划，督促各验证小组按照计划和方案完成验证，建立验证档案。T

30、ech ni cal Director技术总监To approve the Validati on Pla n, Validati on Protocol and Validati on Report批准验证计划、验证方案、验证报告。Other members in theValidati on Committee验证委员会其他成员En suri ng that products are manu factured using Validated Equipme nt. Facilities, Processes, Test Method and SystemsTo check the Val

31、idati on Pla n, Protocol and Report.确保正式生产使用的设施、设备、工艺、检验方法和系统经过验 证。审核验证计划、方案和报告。QA Man agerQA经理Ensuring that all Validation & Qualification activities are completed and authorized according to QA acceptable standards and in complia nee with cGMP.To issue the Validation Certificate for the qualif

32、ied validation project by referri ng to the approved Validati on Report.Check the Validatio n Pla n, Protocol and Report.确保按照QA合格标准及GMP要求完成所有的验证和确认。根据批准的验证报告发放验证合格证书。审核验证计划、方案和报告。342 Responsibilities of Validation Team/ 验证小组职责:Personnel/人员Responsibilities职责Team Leader验证组长To draft the Validati on Pro

33、tocol and Report, orga nize the in dividual validation activities, arrange the validation archive, organize the training and ensure the Team Member can keep the record in detail accord ing to the protocol requireme nts.起草验证方案、组织项目的具体验证、督促验证小组成员按照验证 方案的要求做好验证记录、起草验证报告、整理验证档案，组织相 关的验证培训。MembersofValid

34、ati on TeamTo carry out the validati on activities, make record, report the in cide nt, and assist drafting the validation protocol and report.按照方案实施验证、并做好记录、例外情况及时汇报和记录、协助验证小组成员起草验证方案和报告。343 All Departmental Managers/ 所有部门经理职责Completio n of Validati on/Qualificati on projects relat ing to their are

35、as.完成与其区域相关的验证/确认工作。3.5 Trai ning /验证培训Appropriate training must be give n to facilitate the satisfactory performa nee of Validati on and Qualification activities, including the Validation Plan, Validation Protocol and required skills. The training should follow the requirements specified in Trainin

36、g Management ”验证过程中，验证计划、验证方案以及验证中应该掌握的技能应该进行培训，培训应 遵循培训管理办法。4 The Writing and Approval of Validation Plan, Protocol and Report/验证计划、方案、报告的起草审批程序4.1 The Validation Plan is written by Validation Manager, Validation Protocol and Validation Report are writte n by Validati on Team Member.验证计划由验证经理起草，验证方

37、案和报告由验证小组组织起草。4.2 The docume nts are checked by all members of Validati on Committee.以上文件的审核由验证委员会全体成员审核。4.3 The Validati on Pla n. Protocol and Report are approved by Tech ni cal Director.所有验证计划、方案、报告均由技术总监批准。4.4 The Validati on Certificate is issued by QA Man ager by referri ng to the Validatio n

38、Report which will state the approved project.验证报告显示验证符合要求的验证项目由QA经理发放验证证书。5 Documentation/文件5.1 Con te nt/文件范围The documentation is compromised of Validation Plan, Validation Protocol, Validation Report and Validation Certificate文件包括验证计划、方案、报告、证书5.1.1 Validation Plan/ 验证计划It con sists of Validati on

39、Master Pla n, In dividual Validati on Pla n and Annual Validati on Plan, which describe the pla n and requireme nts for in dividual or ann ual validati on activities. A Validati on Pla n gen erally in cludes the project summary, validati on scope, regulatory and statutory requirements, validated pro

40、ject, validation organizational chart, acceptance criteria, docume ntati on requireme nts and schedule, etc.包括验证总计划、分项的或年度的验证计划，是对某个项目或者某个年度的验证工作 的规划和要求。一般包括：项目概述、验证的范围、所遵循的法规标准，被验证的厂 房设施、系统、生产工艺，验证的组织机构，验证合格的标准，验证文件管理要求， 验证大体进度计划等内容。5.1.2 Validation Protocol/ 验证方案It is a written protocol stating ho

41、w to validate and specifying the acceptance criteria. The Validati on Protocol gen erally in cludes three main parts: the validati on project summary which describes the specific contents to be checked calibrated and tested; the acceptanee criteria and validation method for critical points; and reco

42、rd, i.e. check and test results and evaluati on.一个阐述如何进行验证并确定验证合格标准的书面方案。通常由三大部份组成：一是 验证项目概述，阐述需要检查、校正及试验的具体内容；二是对需要验证的关键点设 定可接受标准和验证方法，即检查及试验达到什么要求以及如何检查的方法；三是记 录格式，即检查及试验应记录的内容、结果及评估意见。5.1.3 Validation Report/ 验证报告It is a written document for review and evaluation of validation results, miss out a

43、nd deviati ons. The contents that are ide ntical with that in the protocol may not be repeated but must be referred to.对验证方案及已完成验证试验的结果、漏项及发生的偏差等进行回顾、审核并做出评 估的说明文件，与方案的内容一致的可以不重复方案内容，仅写明与对应的方案相同 即可。5.1.4 Validation Certificate/ 验证证书The Validation Certificate is issued by QA proving the validated pro

44、ject is qualified and maintained in Validation File. The Certificate should indicate the numbers of validation protocol and report, and the applicable scope.由QA部门颁发一个证书，以证明对某个项目通过验证，存放于项目的档案中。验证证书应包括验证方案和验证报告的编号，以及可以该项目可以使用的范围。5.2 Format/文件格式5.2.1 The protocol and report shall typically in clude, bu

45、t not be limited to, the follow ing:-方案和报告一般应包括，但不限于以下内容：1Document title, reference and version number, the protocol number should be in cluded in the report文件题目、文件编号及版本号，报告中应有对应的方案编号2Table of Contents, number of document pages, e.g.,“ Page X of Y目录、文件页码，如：第 X页共Y页3Docume nt pers onnel en dorseme nt

46、for writi ng, review and authorizati on.文件签字，包括起草、审核和授权4Docume nt distributio n文件分发的对象5Summary of validati on project验证项目的基本情况概述6Summary of in dividual critical validati on project, accepta nee criteria and validati on method.每个关键验证项目的简述，确认及合格标准，验证方法7Schedule验证实施的时间计划安排8Refere nces to other releva n

47、t docume nts applicable to the project (e.g., SOP s, guida nee docume nts etc.)适用于本项目的其它相关文件的参引(如SOP、指导文件等)9Deviations from the protocol, including the treatment and record. 偏差的处理方案，报告中应有每个偏差的处理情况总结与记录。10Validationreport, the summary of each validation project including theconclusions, confirmation

48、and suggestions.报告是对每一个验证关键点的总结，包括结论、确认和建议。11Docume nt cha nge history/Reas on for update文件变更历史/修订原因12Attachme nts or appe ndices, e.g. containing raw data and other supportive in formati on, etc. Adequate cross-refere nee shall be made in the docume ntati on to in formati on that is not possible to

49、 store in the docume nt appe ndices附录，如包括的原始数据及其它支持性信息等。无法存放在文件附录中的文 件，要有足够的参引。5.2.2 A pro-forma protocol/report may be used for the simple project. For this format, the test data is filled directly onto the protocol, whereupon the completed protocol becomes the report.This VMP may be used as a mode

50、l template docume nt on which to base Validati on Protocols and Reports.对一些特别简单的验证项目，可使用一个形式方案/报告。对此，直接将检测数据填在方案中，填写完整的方案，由此形成报告。本VMP可以作为一个模版文件，建立验证方案和报告。5.2.3 Validation Record / 验证记录：It is used for recording the results of experiment, calibration and test during the validation process. The format

51、can copy from daily used record or be specifically designed in the protocol. The record can be put in the appe ndix or in the protocol accord ing to 5.2.2.验证记录是在验证过程中的实验、校验以及检查的记录，格式可以是日常的记录格式，也可以是在方案中为了此验证而专门设计的记录格式，具体的记录格式可以在附录 中，也可以按照5.2.2在方案。5.2.4 Validation Certificate/ 验证证书：The Certificate is

52、in A4 size and includes the validation project name, validation protocol nu mber, validati on report nu mber, authorizer sig nature, etc.验证证书的格式为一张 A4纸制作的证书，应该有验证项目的名称、验证方案编号、验 证报告编号、授权人签字等。5.3 Validation Document numbering/ 验证文件的编号Docume ntThe docume nt nu mber is assig ned by Validati on Man ager

53、in accorda nee with SOP Classification and Numbering ”.验证文件的编号按照SOP文件的分类和编号由验证经理指定。5.4 Validation/Qualification Archiving 验证 /确认归档All documentation should be managed by Validation Team Leader after the completion and shall be stored in a secure location by QA Document Controller and available for au

54、dit review. The Protocol & Validation/Qualification Report should be archived for a minimum of 15 years. Validation Manager is responsible for establishing the validation documentation index.The record should be maintained with validation report as the appendix. 所有文件都应该在验证结束后，由验证小组组长负责整理，将所有验证文件

55、的原件交负责 存档的 QA 存放在一个安全的地方，可随时进行审核，方案和验证/确认报告必须至少存放15年，验证经理应建立并保存所有验证档案的索引。验证过程的记录作为验证报告的附属档案与验证报告一起保存。6 Validation Implementation/ 验证实施6.1 Safety and Health/ 安全与健康No Validation or Qualification activities should be carried out prior to safety checks on equipment being carried out. These checks must b

56、e documented and satisfactory. All appropriate Company Health & Safety precautions and policies must be followed when carrying out Validation or Qualification work.对设备安全检查之前，不能进行验证或确认。这些检查必须归档，并且检查合格。验证或 确认时，必须遵循相应的公司安全和健康预防措施及原则。6.2 Validation Classification and Applicable Scope / 本次验证所用到的验证分类与

57、适用范围6.2.1 Prospective Validation / 前验证Validation conducted prior to the formal use of process, procedure, system, equipment or materials, etc. in accordance with the pre-established protocol. The purpose of prospective validation is to testify and confirm the reproducibility and reliability of a process or procedure, which will require comparatively ade