自控系统验证Validation of Automation Systems_法玛碧欧_32页.pdf

Validation of Automation Systems自控系统自控系统验证验证GAMP51Pharma Bio Solutions Ltd现代中药制药论坛首发Different Terminology不同的术语不同的术语Computerised Systems计算机系统Automation Systems自动化系统Control Systems控制系统Control Equipment控制设备Data Management systems数据管理系统Pharma Bio Solutions Ltd2Computerised System:A system including the input of data,electronic processing and the output of information to be used either for reporting or automatic control计算机系统:系统中包括数据输入，电子化处理和用于报告或自控的信息输出SFDA:Good Manufacturing Practice for pharmaceutical products药药品生产质量管理规范品生产质量管理规范现代中药制药论坛首发US FDAAutomated processes.When computers or automated data processing systems are used as part of production or the quality system,the manufacturer shall validate computer software for its intended use according to an established protocol.All software changes shall be validated before approval and issuance.These validation activities and results shall be documented.自动化过程。当计算机或自动数据处理系统做为生产或质量系统的一部分时，制造商需要验证计算机软件系统是按照预先设计使用的。所有软件变更在准许使用前是可验证的。这些验证的活动和结果应该被文档记录。PART 820 QUALITY SYSTEM REGULATION质量体系规范质量体系规范Pharma Bio Solutions Ltd3现代中药制药论坛首发EMEAValidation:The extent of validation necessary will depend on a number of factors including the use to which the system is to be put,whether the validation is to be prospective or retrospective and whether or not novel elements are incorporated.Validation should be considered as part of the complete life cycle of a computer system.This cycle includes the stages of planning,specification,programming,testing,commissioning,documentation,operation,monitoring and modifying.验证：验证的范围基于一组包含应用于系统的因素，无论验证是预见性的还是回顾性的，无论有无新元素的使用。验证应该被认为是计算机系统完整生命周期的部分。这个周期包括设计，规范，编程，测试，高度，文档，运行，监控和修改。Commission Directive 3003/94/ECAnnex 11 Computerised system计算机系统计算机系统Pharma Bio Solutions Ltd4现代中药制药论坛首发SFDAWhere automated and monitoring systems are used for these applications they should be validated to ensure that critical process requirements are met.使用自动化和监视系统的地方，应该被验证以确保满足关键过程要求Good Manufacturing Practice for pharmaceutical products,Part II Annex Chapter 12 Terminal Sterilisation:药品生产质量管理规药品生产质量管理规范范 第第2部分部分 附录附录12 Pharma Bio Solutions Ltd5现代中药制药论坛首发Functional Hierarchy,ISA-S95Pharma Bio Solutions Ltd6Business Logistics SystemsPlant Production Schedulingand Operational ManagementLevel 4Manufacturing Control SystemsArea Supervision,ProductionScheduling,Reliability AssuranceLevel 3DiscreteControlSystemsLevels 2,1,0BatchControlSystemsContinuousControlSystems现代中药制药论坛首发Process Control Systems Level 1&2Pharma Bio Solutions Ltd7Process Control systemsConfigurableControllers,AnalysersEmbeddedMachine+PLC+HMIStandalonePLC+SCADADCS现代中药制药论坛首发Examples of Process Control System工艺控制系统示例工艺控制系统示例Standard hardware,Configurable(no programming only parameterisation)标准硬件，组态（无编程，只有参数设置）HPLCControllers(Temperature Controller,pH Controller,etc.)控制器（温度控制器，pH控制器等）Embedded:Generally standard hardware,Software may include just parameterisation,partial programming or full programming 内嵌：通常标准硬件，软件可能包括参数设置，部分编程或全部编程Freeze Dryer control system,冻干机控制系统Autoclave control system,灭菌柜控制系统etc.等Standalone:Requires custom hardware,and software requires programming SCADA+PLC,DCS需要定制硬件，和需要编程的SCADA和PLC,DCS的软件BMS&EMS system楼宇管理系统和环境监测系统API Control system原料药控制系统Plant SCADA system厂房SCADA系统Pharma Bio Solutions Ltd8现代中药制药论坛首发Validation of Automation System自控系统验证自控系统验证GAMP5(Good Automated Manufacturing Practice)良好自动化生产规范A RisK Based Approach to Compliant GxPComputerised System基于风险的方法去顺从基于风险的方法去顺从GxP计算机系统计算机系统Pharma Bio Solutions Ltd9现代中药制药论坛首发GAMP5 V Model(1)Planning计划URS用户需求说明Risk Assessment风险评估Vendor Assessment&Selection供货商评估和选择Quality Plan 质量计划Specification规范Functional Specification功能规范Hardware Design Specification硬件设计规范Software Design Specification软件设计规范Software Module Specification软件模块规范Risk Assessment风险评估Design Qualification 设计确认Pharma Bio Solutions Ltd10现代中药制药论坛首发GAMP5 V Model(2)Pharma Bio Solutions Ltd11Configuration&Coding组态和编码Build system hardware构建系统硬件Configure system software配置系统软件Integrate hardware&software集成软件和硬件Verification验证Code Review代码审核FAT Protocol&Execution FAT方案和执行SAT Protocol&Execution SAT方案和执行Reporting报告Final Documentation 最终文件Final Quality Report and handover 最终质量报告和移交现代中药制药论坛首发Computerised System Life Cycle现代中药制药论坛首发What GAMP5 Is and Isnt?什么是什么是GAMP5，什么不是呢？，什么不是呢？It is not about making documents不只是编写文件GAMP5 is a Guideline which is accepted by major regulatory bodies as a methodology for the development and operation of Control Systems GAMP5是大型法规机构接受的指南，用来作为控制系统的研发和操作的方法It is about ensuring the Brain of a Machine or a Process work properly and is fit for its intended use.旨在确保机器主题或工艺工作满足预期用途It is about Building Quality onto a Control System throughout its Life Cycle.是关于在生命周期确保控制系统的质量It defines the steps to be taken at each stage of Control System Life Cycle定义了控制系统生命周期每个阶段要采取的步骤It defines Roles and Responsibilities of User and Suppliers 定义了用户和供应商和角色和责任Pharma Bio Solutions Ltd13现代中药制药论坛首发Process Owner:The person ultimately responsible for the business process or processes being managed过程所有者：为最终生产或被管理的过程而负责的人System Owner:The person ultimately responsible for the availability,support,and maintenance of a system and for the security of the data residing on that system系统所有者：为系统的可用性，支持和维护，及系统上数据安全性而负责的人Subject Matter Expert:Those individuals with specific expertise in a particular area or field.SME should take the lead role in the verification of computerised systems.SME responsibilities include planning and defining verification strategies,defining acceptance criteria,selection of appropriate test methods,execution of verification tests and reviewing results领域专家：在某一领域有某特定技术的人。SME应该引导计算机系统的验证。SME责任包括计划和定义验证策略，定义验收标准，选择合适的测试方法，执行验证测试和审核结果Key Personnel关键人关键人现代中药制药论坛首发Scalable Life Cycle ActivityLife cycle activities should be scaled according to:生命周期可根据下列分类System impact on patient safety,product quality and data integrity 系统对病人安全，产品质量和数据完整性带来的影响GxP Assessment GxP评估Impact Assessment影响评估System complexity and novelty 系统复杂性和新颖性Software category软件类别Hardware Category硬件类别Pharma Bio Solutions Ltd15现代中药制药论坛首发GxP Assessment,GxP 评定评定Pharma Bio Solutions Ltd16Does the system generate,manipulate or control data supporting regulatory safety and efficacy submissions?此系统生成，操作和控制的数据，是否支持产品安全和产出品的效力？Yes/NoDoes the system control critical parameters and data in preclinical,clinical,development,or manufacturing?此系统是否控制临床前期，临床，开发或者制造关键参数和数据？Yes/NoDoes the system control or provide data or information for product release?此系统是否控制或提供产品放行要求的数据/信息？Yes/NoDoes the system control data or information required in case of product recall?此系统是否控制用于产品召回事件的数据和信息Yes/NoDoes the system control adverse event or compliant recording or reporting?此系统是否控制不良反应事件或进行符合性记录或报告？Yes/NoDoes the system support pharmacovigilance?此系统是否支持药物警戒(药物监测)Yes/No现代中药制药论坛首发System Impact Classification系统影响分类系统影响分类Pharma Bio Solutions Ltd17Worst case impact on patient safety对患者安全的最坏影响High=potential for serious injury or deathMedium=potential for minor injuryLow=potential for little harm to patient高=潜在的致命或者严重伤害影响中=潜在的轻微伤害影响低=潜在的患者轻微伤害Worst case impact on product quality对产品质量的最坏影响High=potential for release of product which would cause serious injury to a patientMedium=potential for release of product which would cause minor injury to a patientLow=potential for poor quality product which would not be released or would not cause harm to patient高=潜在的因放行产品引起患者严重伤害中=潜在的因放行产品引起患者轻微伤害低=潜在的不允许放行的不合格产品，或者放行后不会对患者造成伤害Worst case impact on data integrity对数据完整性最坏影响High=loss of data integrity such that product recall could not be carried out or release could be made of product which would cause serious injury to a patientMedium=loss of data integrity such that release could be made of product which would cause minor injury to a patient Low=loss of data integrity such that product would need to be scrapped or data records not essential to product release or recall might be lost or impaired高=数据丢失后，无法对产品的召回进行调查，或者放行的产品或许对患者造成伤中=数据被破坏后，放行的产品或许对患者造成轻微伤害低=数据完整性被破坏后，产品需要被废除，或者数据记录对产品的放行不必要，或无法完成召回现代中药制药论坛首发Category类别类别Typical Approach典型方法典型方法1,Standard Hardware Components标准硬件部件Document manufacturer or supplier detail,serial number and version number 通过文件记录下生产厂家或供应商的详情、序列号和版本号Correct installation to be verified 确认正确的安装Configuration Management and Change control apply适用组态管理和变更控制2,Custom Built Hardware Components定制制造的硬件部件As per above plus:上述内容再加上：Design specification设计说明Acceptance testing验收测试Configuration and Change control apply 适用配置和变更过控制Pharma Bio Solutions Ltd18GAMP 5 Hardware Categories 硬件类别硬件类别现代中药制药论坛首发GAMP 5 Software Categories 软件类别软件类别Category类别类别Description说明说明Typical examples典型示例典型示例Typical Approach典型方法典型方法1,Infrastructure Software基础软件Layered software底层软件Software used to manage the operating environment用于管理操作环境的软件Operating systems操作系统Database engines数据库引擎Middleware中间件Programming languages编程语言Spreadsheets电子制表软件Version control tools版本控制工具Network monitoring tools网络监控工具Record version number,verify correct installation by following approved installation procedure记录版本号，按照所批准的安装规程验证正确的安装。3,Non-configured非配置软件Runtime parameters maybe entered and stored,but the software can not be configured to suit the business process可以输入并储存运行参数，但是并不能对软件进行配置以适合业务流程Firmware based applications 基于固件的应用程序COTs software 商用现货软件Abbreviated Life cycle approach简化的生命周期法URS 用户需求说明Risk based approach to supplier assessment基于风险的供应商评估方Record version number,verify correct installation 记录版本号，验证正确的安装方式Risk based test基于风险进行测试Procedure in place for maintaining compliance 有用于维持系统符合性的规程Pharma Bio Solutions Ltd19现代中药制药论坛首发GAMP 5 Software Categories 软件类别软件类别Category类别类别Description说明说明Typical examples典型示例典型示例Typical Approach典型方法典型方法4,configured 可配置Software,often very complex,that can be configured by the user to meet the specific needs of the users business process.Software code is not altered通常非常复杂的软件，可以由用户来进行配置以满足用户具体业务流程的特殊要求，这种软件的编码不能更改。DAQ systemsSCADADCSBMSHMILIMSERPClinical trail monitoringLife cycle approach生命周期法Risk based approach to supplier assessment基于风险的供应商评估法Supplier QMS供应商的质量管理系统Record version number,verify correct installation记录版本号，验证正确的安装方式Risk based testing in a test environment在测试环境中根据风险进行测试Risk based testing within the business process在业务流程中根据风险进行测试Procedure in place for maintaining compliance具有维持符合性的规程5,Custom定制Software custom designed and coded to suit the business process定制设计和编码以适于业务流程的软件Internally,externally developed IT applications.内部和外部开发的IT应用程序Internally,externally developed process control applications.内部和外部开发的工艺控制应用程序Custom ladder logic 定制的梯形图逻辑Custom firmware定制固件Spreadsheet(macro)电子表格(宏)Same as cat 4 plus 与第4类相同，再加上More rigorous supplier assessment,with possible supplier audit更严格的供应商评估，包括可能供应商审计Possession of full life cycle 完整的生命周期Design and source code review设计和源代码审核Pharma Bio Solutions Ltd20现代中药制药论坛首发Pharma Bio Solutions Ltd21Software Category 3 第第3类软件类软件现代中药制药论坛首发Pharma Bio Solutions Ltd22Software Category 4 第第4类软件类软件现代中药制药论坛首发Software Category 5第第5类软件类软件Pharma Bio Solutions Ltd23现代中药制药论坛首发Example of GAMP5 CategoriesItemHardware CategorySoftware CategoryConfigurable(Controllers,weigher,etc)13Embedded Standard(PLC+HMI)13Embedded Non-Standard(PLC+HMI)1 or 2 3,4,5 Standalone(DCS,SCADA+PLC)23,4,5Pharma Bio Solutions Ltd24现代中药制药论坛首发User Requirement Specification用户需求说明用户需求说明Pharma Bio Solutions Ltd25Most important document最重要的文件Describes what the system is supposed to do描述系统预期用途Normally written by the end user,maybe also be provided by supplier.通常由最终用户编写，也可以由供应商提供Controlled Document 受控文件For Cat 3 written for a specific solution 第3类针对具体解决方案编写For Cat 4&5 It is written in general 第4、5类整体编写Sufficient,Realistic,Measurable,Achievable充分、现实、可衡量、可达到Testable:Clear,Precise,basis for formal testing 可测量：清楚、简洁、正式测试的基础Traceable:Design and testing可追溯：设计和测试Define priority:Mandatory,Beneficial,Nice to have 规定优先级：必须、有益、有了更好现代中药制药论坛首发Pharma Bio Solutions Ltd26Functional Specification功能说明功能说明A Functional Specification is a key document in defining how the customer functional requirements,as defined in the user requirements specification,are to be met.功能规范是一重要的文件，定义了是如何来满足在用户需求说明中所规定的客户功能要求的。Functional Specification is the responsibility of the supplier功能规范属于供应商的责任It is written in response to URS 需要根据URS进行编写It provides the main basis for FAT 它提供了FAT的主要基础It needs to be approved by User.需要用户批准Generally may require further revision during the project life cycle.一般在项目生命周期过程中需要进行修订现代中药制药论坛首发Pharma Bio Solutions Ltd27Test Phases测试阶段测试阶段A system test phases depends on its size and complexity系统测试的阶段取决于其大小和复杂性Typical test phases include 典型的测试阶段包括Software Module testing 软件模块测试Internal integrated testing 内部集成测试Hardware硬件Software软件FAT test FAT测试Hardware硬件Software软件SAT test SAT 测试Hardware(IQ)硬件（IQ）Software (OQ)软件（OQ）现代中药制药论坛首发Test Protocols测试方案测试方案A Test protocol or specification defines the testing to be carried out to verify that the system(or its individual elements)meets pre-defined requirements.测试“方案”或“规范”规定了为了确认系统（或其单独部件）是否符合其预先规定的要求而需进行的测试A project may include Software Module Test Protocol,FAT protocol,SAT protocol一个项目中可能会包括软件模块测试方案、FAT方案和SAT方案Depending the size of the project there maybe a separate Hardware Test protocol 根据项目的大小，可能会有单独的硬件测试方案Test Protocols are the responsibility of the supplier They should be approved by User.测试方案属于供应商的责任，需要用户的批准Generally may require further revision during the FAT.一般可能需要在FAT过程中继续修订Pharma Bio Solutions Ltd28现代中药制药论坛首发Risk Management风险管理Change&Configuration Management变更和组态管理Design Review设计审核Traceability追溯性Document Management文档管理Supporting Processes支持过程支持过程现代中药制药论坛首发Pharma Bio Solutions Ltd30On-going Operation 后续后续运行运行Maintaining compliance and fitness for intended use of GxP Validted system throughout its life cycle整个生命周期中，维持已经过GxP认证的系统拟定用途的符合性和适用性Users of the system must be able to demonstrate that they have considered and reviewed maintenance requirement and supports needs for the system and decided what procedures and records should be established and maintained.系统的使用人必须能够证明他们已经仔细思考和审核系统的维护需求，并且已决定建立和维护相应的流程及记录现代中药制药论坛首发On-going Operation activities后后续运续运行活动行活动Performance Monitoring 性能监视Incident Management 事件管理Corrective and Preventive Action 纠正和预防措施Repair activity 维修工作Periodic Review 周期审查Backup&Restore 备份和恢复Security Management安全管理Archival and Retrieval归档和检索Pharma Bio Solutions Ltd31现代中药制药论坛首发Project Stages现代中药制药论坛首发