Validation of Automation Systems www.chinapat.com 现代中药制药论坛首发 GAMP5
Different Terminology
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
www.chinapat.com systems 数据管理系统 Data Management 现代中药制药论坛首发 Computerised System: A system including the input of data, electronic processing 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: FDA: Good Manuf Manuf actur ct urin ing g Practi Practice ce for ph arma rm aceutical ceuti cal
Different Terminology
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
www.chinapat.com systems 数据管理系统 Data Management 现代中药制药论坛首发 Computerised System: A system including the input of data, electronic processing 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: FDA: Good Manuf Manuf actur ct urin ing g Practi Practice ce for ph arma rm aceutical ceuti cal
US FDA
computers or automated data Automated Automated processes processes.. When computers processing systems are used as part pa rt of production producti on or the quality qualit y system, the manufacturer manuf acturer shall validate computer software for its intended use us e according according to an established establishe d www.chinapat.com protocol. All software changes shall be validated before 现代中药制药论坛首发 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
EMEA
Validation: 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, www.chinapat.com commissioning, documentation, operation, monitoring and 现代中药制药论坛首发 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。
Comm ission Directi ve 3003/94/ECAnnex 11 Computerised system
SFDA
Where automated and monitoring systems are used for these applications they should be validated to ensure that critical process requirements are met. www.chinapat.com 现代中药制药论坛首发
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:
2
12
Functional Hierarchy, ISA-S95 Business Logistics Systems Level 4
Level 3
Plant Production Scheduling and Operational Management
www.chinapat.com Manufacturing Control Systems 现代中药制药论坛首发 Area Supervision, Production Scheduling, Reliability Assurance
Levels 2,1,0
Batch
Continuous
Discrete
Control Systems
Control Systems
Control Systems
Process Control Systems Level 1 & 2 Process Control systems
Configurable
Controllers, Analysers
www.chinapat.com 现代中药制药论坛首发 Embedded
Machine+ PLC+ HMI
Standalone
PLC+ SCADA
DCS
Examples of Process Control System
Standard hardware, Configurable (no programming only parameterisation)标准硬件，组态（无编程，只有参数设置）
Embedded: Generally standard hardware, Software may include just www.chinapat.com 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 现代中药制药论坛首发
HPLC Controllers (Temperature Controller, pH Controller, etc.)控制器（温度 控制器，pH控制器等）
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 syste 原料药控制系统
Validation of Automation System
GAMP5 (Good Automated Manufacturing Practice) 良好自动化生产规范 A RisK Basedwww.chinapat.com Approach to Compliant GxP 现代中药制药论坛首发 Computerised System GxP
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 www.chinapat.com 现代中药制药论坛首发 Functional Specification 功能规范 Hardware Design Specification
硬件设计规范
Software Design Specification 软件设
Software Module Specification
计规范
软件模块规范
Risk Assessment风险评估
GAMP5 V Model (2)
Configuration & Coding组态和编码
Build system hardware构建系统硬件 Configure system software配置系统软
Integrate hardware & software 集成软
件
件和硬件
Verification验证 www.chinapat.com 现代中药制药论坛首发 Code Review代码审核
FAT Protocol & Execution FAT方案和
SAT Protocol & Execution SAT方案
执行
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
Computerised System Life Cycle
www.chinapat.com 现代中药制药论坛首发
What GAMP5 Is and Isn’t? GAMP5
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 www.chinapat.com 艺工作满足预期用途 现代中药制药论坛首发 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
Key Personnel
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 www.chinapat.com 负责的人
现代中药制药论坛首发 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
Scalable Life Cycle Activity Life 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 www.chinapat.com 现代中药制药论坛首发 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
GxP Assessment, GxP Does the system generate, manipulate or control data supporting regulatory safety and efficacy submissions?
Yes / No
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 ？
Does the system control critical parameters and data in preclinical, clinical, development, or manufacturing?
Yes / No
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？
Does the system control orwww.chinapat.com provide data or information for product 现代中药制药论坛首发 release? 此系统是否控制或提供产品放行要求的数据/信息？ Does the system control data or information required in case of product recall?
Yes / No
Yes / No
此系统是否控制用于产品召回事件的数据和信息
Does the system control adverse event or compliant recording or reporting?
Yes / No
此系统是否控制不良反应事件或进行符合性记录或报告？
Does the system support pharmacovigilance?
Yes / No
System Impact Classification High = potential for serious injury or death Worst case Medium = potential for minor injury impact on patient safety Low = potential for little harm to patient 对患者安全的 高=潜在的致命或者严重伤害影响 中= 潜在的轻微伤害影响 最坏影响 低= 潜在的患者轻微伤害 High = potential for release of product which would cause serious injury to a patient Worst case Medium = potential for release of product which would cause minor in jury to a impact on patient product Low = potential for poor quality product which would not be released or would not quality www.chinapat.com 对产品质量的 cause harm to patient 现代中药制药论坛首发 高=潜在的因放行产品引起患者严重伤害 最坏影响 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 High = loss of data integrity such that product recall could not be carried out or Worst case release could be made of product which would cause serious injury to a patient impact on data integrity Medium = loss of data integrity such that release could be made of product which 对数据完整性 would cause minor injury to a patient Low = loss of data integrity such that product would need to be scrapped or data 最坏影响 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
GAMP 5 Hardware Categories Category
Typical Approach
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 www.chinapat.com Configuration Management and Change 现代中药制药论坛首发 •
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
•
GAMP 5 Software Categories Category
1, Infrastructure Software 基础软件
Description
Typical examples
Layered software
Operating systems操作系统
•
•
底层软件
•
Database engines数据库引擎
Software used to manage the operating environment •
用于管理操作环境的软 件
Middleware 中间件
•
Programming languages
•
Typical Approach
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。
编程语言
Spreadsheets电子制表软件
•
Version control tools
•
www.chinapat.com 版本控制工具 Network monitoring tools 现代中药制药论坛首发 •
网络监控工具
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
GAMP 5 Software Categories Category
Description
4, configured
Software, often very complex, that can be configured by the user to meet the specific needs of the user’s business process. Software code is not altered
可配置
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。
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
Typical examples
Typical Approach
Life cycle approach生命周期法
DAQ systems
•
SCADA
•
•
•
DCS
•
BMS
•
HMI
•
LIMS
•
ERP
•
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
www.chinapat.com 试环境中根据风险进行测试 Clinical trail monitoring Risk based testing within the business 现代中药制药论坛首发 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 •
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
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
Software Category 3
3
www.chinapat.com 现代中药制药论坛首发
Software Category 4
4
www.chinapat.com 现代中药制药论坛首发
Software Category 5
5
www.chinapat.com 现代中药制药论坛首发
Example of GAMP5 Categories
Item
Configurable (Controllers, weigher, etc) Embedded Standard (PLC + HMI) Embedded Non-Standard (PLC + HMI) Standalone (DCS, SCADA+PLC)
Hardware Category
Software Category
1
3
www.chinapat.com 现代中药制药论坛首发 1
3
1 or 2
3, 4 ,5
2
3, 4 ,5
User Requirement Specification
Most 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 www.chinapat.com For Cat 4 & 5 It is written in general 第4、5类整体编写
现代中药制药论坛首发 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
Functional Specification
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 www.chinapat.com
It is written in response现代中药制药论坛首发 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
Test Phases
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 www.chinapat.com 现代中药制药论坛首发 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）
Test Protocols
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 www.chinapat.com Depending the size of the project there maybe a separate Hardware Test 现代中药制药论坛首发 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
Supporting Processes
Risk Management 风险管理
Change & Configuration Management 变更和组态管理
Design
www.chinapat.com 现代中药制药论坛首发 Review
设计审核
Traceability 追溯性
Document Management 文档管理
On-going Operation
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 www.chinapat.com 现代中药制药论坛首发 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
On-going Operation activities
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 www.chinapat.com 维修工作 现代中药制药论坛首发 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
