工艺验证方案计划 Process Validation VPP

1、Validation Project Plan验证验证方案计划方案计划验证/确认分计划Sub-VMP and Sub-QMPNumber / version:版号：06.01.02-001-00Document name:文档名称Process Validation Project Plan工艺验证方案计划工艺验证方案计划文件题目文件题目Document TitleProcess Validation Project Plan工艺验证方案计划工艺验证方案计划文件编号文件编号Document Code07-01-02-001-00文件版本号文件版本号Version Code00文件种类文件种类C

2、ategory of Document主计划主计划Master plan发放部门发放部门Department of IssueQA 人员人员 Person类别类别 Category姓名姓名/职位职位Name /Position签名签名Signature日期日期Date编写人编写人Compiled by审核人审核人Check by批准人批准人Approved by生效日期生效日期Valid from文件分发部门：（文件分发部门：（ ）Department of document distributed:序号序号Serial No.部门名称部门名称Department Name房间号房间号Room

3、 No.负责人负责人Manager123456文件变更历史：文件变更历史：History of document changing:版本号版本号Version Code变更日期变更日期Changing Date变更内容摘要变更内容摘要Abstract of Changing Contents00建立文件 File foundationDocument name:文档名称：Process Validation Project Plan工艺验证方案计划工艺验证方案计划Number / version:编号/版本号：06.01.02-001-00Jialin Pharmaceutical This

4、document is uncontrolled if printed outPage 2 of 19工艺验证方案计划工艺验证方案计划PROCESS VALIDATION PROJECT PLAN Document name:文档名称：Process Validation Project Plan工艺验证方案计划工艺验证方案计划Number / version:编号/版本号：06.01.02-001-00Jialin Pharmaceutical This document is uncontrolled if printed outPage 3 of 19TABLE OF CONTENT 目

5、录表目录表1Introduction 介绍介绍. 41.1Project Background 方案背景 . 41.2Objectives of this Validation Project Plan 验证方案计划目标 . 41.3Regulatory Requirements 法规要求 . 42Scope of the validation 验证范围验证范围 . 52.1Physical Boundaries 区域界定 . 52.2Manufacturing processes to be validated 待验证工艺. 53Validation Personnel 验证人员验证人员 .

6、 53.1Validation Project Group 项目验证组 . 63.2Validation Team 验证小组 . 74Planning and Scheduling 计划和进度计划和进度. 75Validation Methodology 验证方法验证方法. 85.1Validation Activities 验证活动. 85.2Pre-Qualification 准备工作 . 105.3Planning 制定计划. 105.4Process Validation 工艺验证. 115.5Reporting 报告. 125.6Ongoing Operation 验证跟进 . 13

7、6Document Management 文件管理文件管理. 136.1Document Writing and Approval 文件起草与批准 . 136.2Testing and Result Approval 文件起草与批准 . 136.3Deviations Management 偏差管理. 146.4Reference Documents 参考文件 . 157Standard Operating Procedures Required for Validation 验证所需要的标准操作规程验证所需要的标准操作规程 .158Abbreviations 缩写词缩写词 . 15APPEN

8、DIX 1 Validation Project Group 附录附录 1 验证项目组验证项目组. 16APPENDIX 2 List of Validation Projects 附录附录 2 验证项目清单验证项目清单 . 1Document name:文档名称：Process Validation Project Plan工艺验证方案计划工艺验证方案计划Number / version:编号/版本号：06.01.02-001-00Jialin Pharmaceutical This document is uncontrolled if printed outPage 4 of 191 I

9、NTRODUCTION 介绍介绍The Quality Board has nominated responsible individuals for the Validation Project Group (VPG) as defined in Section 3 of this document, to write and maintain this Validation Project Plan.质量部任命 “项目验证组（VPG）”人员起草和主持验证方案计划。项目验证组（VPG）在本文第三节做了详细说明。The relevant Policy and General Procedure

10、 for this Validation Project Plan are 06.01.03-001-00 on Validation and 06.01.03-004-00on Process Validation.与验证方案计划有关的政策和常规程序，验证、工艺验证分别见文件“06.01.03-001-00”和“06.01.03-004-00”。The Validation Project Plan will be revised at least every three years or more often if required. The appendices to this Vali

11、dation Project Plan will be updated and approved independently from the main document. 验证方案计划至少每三年修订一次或如有需要时经常地被修订。主文件的验证方案计划中的附录将会独立更新和批准。1.1Project Background 方案背景方案背景Enter relevant site and discipline information here.从这里输入相关的地方和科目信息。1.2Objectives of this Validation Project Plan 验证方案计划的目标验证方案计划的目

12、标The purpose of this Validation Project Plan is to:验证方案计划的目的是：Define the scope of work for this project plan.定义该方案计划的工作范围。Identify the principal members of the VPG and their responsibilities.确定 VPG 的负责人员及其职责。Identify the program of activities for the project. 确定方案实施程序。Describe the methodology which

13、will be followed. 描述要从事的方法步骤。Describe the documentation management. 描述文件的管理。Describe the Standard Operating Procedures (SOPs) which are required for validation. 描述验证所需的标准操作规程。By signing this document, the approvers of this document are delegating the authority to the Validation Project Group to exec

14、ute the work as described. 文件的签署、文件的批准者委托有资历人士到验证方案组执行所描述的工作。This document describes the authority which the Validation Project Group will have to modify and develop this Validation Project Plan, form Validation Teams and delegate authority to members of those teams to perform specific validation ac

15、tivities. 文件中所描述的项目验证组的权威人士将必须修订验证方案计划，成立验证小组和授予职权给小组的成员去执行验证活动细节。1.3Regulatory Requirements 法规要求法规要求It is a requirement of Good Manufacturing Practice (GMP) that each pharmaceutical company identifies what qualification and validation work is needed to prove control of the critical aspects of their

16、 operation. Any aspect of, including significant changes to, the premises, facilities, equipment or processes, which may affect the quality of the product, directly or indirectly, should be qualified and validated. GMP 规定每一个制药公司都要确定哪些类型的资格认证和验证是必须的，以便用来控制他们运行中的关键因素。如果设备，仪器和生产流程有任何的改变，并且直接或间接地对产品质量造成

17、影响，都应该进行再评定或验证。All systems and processes will be assessed for their potential impact on GMP compliance and product quality. Systems or processes identified as having such an impact are classified as “critical” and will undergo a suitable level of validation to confirm that their operation is consist

18、ent, repeatable and to specification. 所有系统和生产流程都要进行评估，防止他们对 GMP 和产品质量存在潜在影响。系统或流程验证有如此重大的影响被列为危急级别，而且将在适当的验证水平确认他们的操作是可连续的，可重现的和符合法规要求的。The European Directive 2003/94/EC constitutes a requirement to validate all critical equipment, Document name:文档名称：Process Validation Project Plan工艺验证方案计划工艺验证方案计划Nu

19、mber / version:编号/版本号：06.01.02-001-00Jialin Pharmaceutical This document is uncontrolled if printed outPage 5 of 19processes and methods as part of compliance with GMP. The validation activities will largely be concerned with determining that the critical systems and processes within the site can be

20、 operated repeatedly and reliably according to agreed specifications and in accordance with GMP principles. 欧洲委员会 2003/94/EC 对所有的设备、生产工序和方式要求验证以符合 GMP 规定。验证活动将大大地涉及决定到的重要系统和程序都要求具有可重现性和可靠性.，并符合相关法规和 GMP 准则。Enter the relevant local authority regulations here. 在这里输入地方法规Appropriate and complete documen

21、tation must be in place to enable effective change control. In order to maintain the GMP status of the facility effective change control procedures are necessary and a revalidation strategy must be in place. 合适和完整的文件必须有效地控制变更。为了维持 GMP现状，设施需要有效变更程序，同时再验证的策略必须到位。2SCOPE OF THE VALIDATION 验证范围验证范围2.1Man

22、ufacturing processes to be validated 待验证工艺待验证工艺Only those manufacturing processes which could affect the quality of products. Listed below are the types of manufacturing processes that will be validated.仅有影响产品质量的工艺才会验证。下面是待验证的工艺类型Manufacture of tablets片剂Manufacture of capsules胶囊剂Manufacture of Enter

23、 pharmaceutical dosage form here 其他剂型3VALIDATION PERSONNEL 验证人员验证人员Manufacturing process validation will involve two main groups. The Validation Project Group which is responsible for planning and overview of all validation activities, and the Validation Team which is responsible for documentation a

24、nd execution of specific validation projects.工艺验证包括两个主要团队：项目验证组负责策划和阐述所有的验证活动；每个验证小组负责具体项目的执行和文件的整理。3.1Validation Project Group 项目验证组项目验证组The Validation Project Group is responsible for the planning, control and implementation of this Validation Project Plan. 项目验证组负责验证方案计划的编制、控制和执行。The objectives an

25、d responsibilities of the Validation Project Group are to: 项目验证组的目标和职责Manage and progress this Validation Project Plan and the associated validation projects identified in the appendices of this Validation Project Plan. 管理和推进验证项目方案并在验证项目计划附录里列上关联验证项目。Define the scope of each validation project.说明验证方

26、案的范围。Identify which processes are to be validated and what validation activities must be performed.确定被验证的工艺和必须执行的验证活动。Ensure that the results of each validation project are reported and any recommended actions arising are followed up. 确保每个认证项目的结果反馈报告和任何建议得到跟踪。Ensure that persons involved in validati

27、on activities are adequately resourced and that individuals are competent, adequately trained and briefed to perform the tasks allocated to them.确保在验证活动中有足够智慧和胜任的人员，接受过充分的培训，能完成指派的任务。Delegate authority to perform specific tasks to appropriate members of the Validation Team. 委派验证执行小组合适成员代表公司执行具体的任务。E

28、nsure that the systems are in place to generate and control the documentation required as part of each validation project.确保系统能形成和控制每个验证方案中各部份所需的文件。Ensure that a mechanism for revalidation and on-going system evaluation is in place. 确保机械装置再验证和在运行设备评估。Report back to the Quality Board on a regular bas

29、is. 在法规基础上定期进行信息反馈给质量委员Document name:文档名称：Process Validation Project Plan工艺验证方案计划工艺验证方案计划Number / version:编号/版本号：06.01.02-001-00Jialin Pharmaceutical This document is uncontrolled if printed outPage 6 of 19会。The Validation Project Group will delegate the authority to produce documents, perform quali

30、fications and report test work to individuals involved with specific validation activities. In the case of people who are not members of Jialin Pharmaceutical staff, details of their affiliation, a contact address and their professional training and experience will be recorded. 项目验证组会授权制定文件，执行认证并报告测

31、试工作给具体执行验证活动的人员。如果认证小组人员不是嘉林药业的员工，应记录他们的联系地址、专业培训背景与经历等详细联系资料。The individual members of the Validation Project Group are identified in Appendix 1 and acknowledge by their signature their responsibilities as described in this Validation Project Plan. 项目验证组关于验证的成员记录在附录 1 表中，他们在项目认证方案中的职责由他们的亲笔签名来确认生效。

32、The members of the Validation Project Group will have the following specific responsibilities: 项目认证组成员的具体职责：3.1.1Operations Representative/Production managers representative操作工代表/生产经理代表To ensure that GMP critical equipment and systems are validated. 确保 GMP 关键的设备和系统已经验证。To ensure that all appropriate

33、 operations procedures are in place to support validation activities. 确保所有正确的操作规程适当的支持验证活动。To arrange access to the production facility for the Validation Team.为验证小组安排使用生产设施To ensure that appropriate test materials required for validation are available. 确保验证所需的原料是经检测可用的。To ensure that production per

34、sonnel and resources are available for validation activities if required.确保验证活动所需要的生产人员和资源是可用的。Quality Representative 质量代表To ensure that all appropriate quality procedures are in place to support validation activities.确保所有正确的质量程序在恰当的支持验证活动。To ensure that all validation activities are carried out in

35、accordance with approved procedures. 确保所有的验证活动按照批准的程序执行。Overall management responsibility for the execution of the VPP.全部的管理职责都是为了验证方案计划的执行。Liaison with Regulatory Authorities if required.如果必要联络主管当局。To arrange Validation Project Group meetings.安排项目验证组会议。To ensure the scientific integrity of the vali

36、dation study.确保验证计划的科学完整性。3.1.2Validation Representative验证方面To ensure that all appropriate validation procedures are in place. 确保所有合适的验证程序可行性。To monitor the progress of the various validation projects and identify resource requirements for each validation project. 监控各种验证项目的进程并确认每个验证项目的资源需要。To ensure

37、 that validation plans, protocols and reports are approved before commencing the subsequent stages of validation. 确保验证方案、草案和报告全通过后才能开始验证工作。To arrange periodic review meetings to review progress against the Validation Project Plan and to resolve any resource and technical issues that may arise. 安排定期会

38、议回顾项目与验证计划的程序不符并解决任何可能出现的资源和技术问题。To identify which members of the Validation Project Group should attend meetings on specific issues and suggest people to be co-opted for each separate Validation Project. 针对不同具体问题确定不同的项目验证组成员来出席会议，要求每个验证项目中人员互相合作。To monitor and progress the approval status of valida

39、tion documents. 监控和跟进验证文档的批准情况。Document name:文档名称：Process Validation Project Plan工艺验证方案计划工艺验证方案计划Number / version:编号/版本号：06.01.02-001-00Jialin Pharmaceutical This document is uncontrolled if printed outPage 7 of 193.2Validation Team 验证小组验证小组For each individual validation study a Validation Team will

40、 be appointed. The members of the Validation Team and their responsibilities for each individual study will be identified in the project specific validation documents.对于每个验证课题会派一个验证小组负责。验证小组的成员和他们关于每个单独课题的职责会被记录在具体的项目验证文档中。4PLANNING AND SCHEDULING 计划和进度计划和进度In Appendix 2 of this Validation Project P

41、lan is a validation programme which will be used to plan, monitor and control the validation activities described in this document. The appendices will be revised and updated as the validation studies progress.附录 2 里验证项目方案将用来计划、监督和控制文档里描述的验证活动。根据最新研究进展修订和更新这些附录。To commence this validation programme

42、all of the existing systems will be given a priority rating related to their requirement for validation.验证前，所有现有的系统都要根据验证的要求拟定好优先等级。Priority 1优先等级 1Manufacturing processes for new pharmaceutical products.新产品工艺。New manufacturing processes with no validation history will be validated at the pilot scal

43、e for products that are in development. If the product has been transferred to the manufacturing facility the first commercial scale batches will be validated.在研究中未验证的中试规模产品的新工艺需要的验证。第一次大生产时的工艺需要的验证。Priority 2优先等级 2Manufacturing processes for existing products 现有产品的工艺。Manufacturing processes which a

44、re under control through Change Control programs in accordance with GMP. 按照 GMP 变更控制程序变更的工艺。Manufacturing processes which have had some previous validation work will be reviewed and a validation review report generated.已经完成验证工作的工艺进行验证回顾，并形成验证回顾报告。This program will be revised by members of the Valida

45、tion Project Group using appropriate documented and traceable Quality Assurance Systems.此项目将由项目验证组进行修改，并使用适当的记录和跟踪质量保证体系。5VALIDATION METHODOLOGY 验证方法验证方法5.1Validation Activities 验证活动验证活动5.1.1Strategy and Risk Assessment: 策略和风险评估Risk Assessment is used to assess the GMP risks associated the processes

46、 in order to evaluate the validation strategy i.e. the need, scope, extent, type of validation and number of validation batches. This has taken into account such aspects as: 用风险评估评定与工艺有关联的 GMP 风险，以评价验证策略也就是验证要求、范围、程度、类型和验证批次。风险评估应包括下列内容：Complexity/difficulty of the process. 工艺的复杂/困难性。Previous experi

47、ence with the product or equipment.产品或设备的原有经验。The toxicity/bioavailability of the active ingredient. 活性成份的毒性/生物利用度。The nature of the dosage form.剂型特性。Whether there are pro-rata strengths.是否有成比例的浓度。In the case of revalidation, the nature of the change.再验证时，变更的情况Product history.产品的历史。For prospective a

48、nd concurrent validation, normally three consecutive batches/runs are manufactured and tested for validation of the process. For retrospective validation of an Document name:文档名称：Process Validation Project Plan工艺验证方案计划工艺验证方案计划Number / version:编号/版本号：06.01.02-001-00Jialin Pharmaceutical This document

49、 is uncontrolled if printed outPage 8 of 19established process, normally 25-30 batches are reviewed. 对于预验证和同步验证，工艺验证要正常连续三批/运转生产和检测。对于已确定工艺的回顾性验证，通常要回顾 25-30 批。The type of validation used for each product is found in the List of Validation Projects Appendix 2.每个产品使用的验证类型在验证方案附录 2 中的列表中被创建。All prospe

50、ctive and concurrent validation activities will be performed according to previously approved protocols. All retrospective validation activities will comprise a review and collation of existing data to demonstrate conformance to predetermined acceptance criteria. 所有的预验证和同步验证将按照先前批准的草案执行。所有的回顾性验证应包含验

51、证回顾和现有数据的整理，以证明其与预设的可接受标准相一致。Details of the specific tests and methodology which will be used to determine validation compliance will be found in the validation protocols for each item.每个项目的验证草案中应建立用于确定验证依从性的特殊检验和方法的详细资料。The following flowchart outlines the validation activities during a validation

52、study:下列流程图概要了在验证课题中的验证过程。SpecificationsPlanningValidationOngoing OperationPre-QualificationValidation PlanProcess ValidationReportingValidation ReportChange ControlApproved Manufacturing InstructionsProcess optimisationAnnual Product ReviewRevalidationQuality SpecificationValidation CriteriaApprove

53、d Manufacturing FormulaRisk AnalysisDocument name:文档名称：Process Validation Project Plan工艺验证方案计划工艺验证方案计划Number / version:编号/版本号：06.01.02-001-00Jialin Pharmaceutical This document is uncontrolled if printed outPage 9 of 19质量标准验证验证跟进 工艺优化批准的生产指令批准的生产处方验证计划风险评估质量标准的验证标准条件准备工艺验证验证报告变更控制再验证产品年度回顾计划报告Docume

54、nt name:文档名称：Process Validation Project Plan工艺验证方案计划工艺验证方案计划Number / version:编号/版本号：06.01.02-001-00Jialin Pharmaceutical This document is uncontrolled if printed outPage 10 of 195.1.2Specifications 质量指标:Detailed requirements that the finished product must meet in order to be released for sale and pa

55、ss the validation study requirements.成品必须符合质量指标的详细要求，使其为销售和达到验证课题要求而获放行。5.1.3Product Quality Specification:产品质量标准A list of tests, references to analytical procedures, and appropriate acceptance criteria which are numerical limits, ranges, or other criteria for the tests described that are specified

56、for a product as in-house limits for release validation criteria:测试列表，分析过程的参考书，数字限度、范围表示的适用可接受标准，或为检测某个特定产品而作为验证放行内控限度的其它标准。5.1.4Validation Criteria:验证标准In-house criteria for validation tests. The validation criteria may be tighter than the requirements set in the registration dossier or quality spe

57、cifications to ensure that the finished product, manufactured with the validated manufacturing process, will comply with specifications set in the registration dossier, technical agreements for the product in question and any applicable regulatory requirements.验证检测的内控标准：验证标准可以比注册档案或者确保成品的质量标准中所设定的要求

58、更加严格，因验证生产工艺设定的标准，必须符合注册档案标准、可疑产品的技术协议及某些有关法规所设定的要求。5.2Pre-Qualification 准备工作准备工作Pre-Qualification consists of work that must be finished prior to the planning of the validation study.准备工作包括在验证课题计划前所必须完成所有的工作。5.2.1Process optimisation: 工艺优化Production of one or more batches to identify critical param

59、eters and determine that the proposed manufacturing instructions and manufacturing formula for the commercial batches will result in the manufacture of a finished product that will meet specifications.通过生产一批或多批的成品确定关键参数，按生产指令及处方进行大批量生产的产品应符合质量标准。5.2.2Approved manufacturing instructions and approved

60、manufacturing formula: 经批准的生产指令及处方：The manufacturing documents that will be used for the production of the validation lots, in the case of commercial scale manufacture these would be manufacturing instructions for commercial scale batches.用于验证批的生产文件，大批量生产时是指生产指令。5.3Planning 制定计划制定计划5.3.1Risk Analysi