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随着计算机化系统在制药企业的广泛应用，尤其是GMP附录《计算机化系统》的颁布和实施，制药企业的计算机化系统的验证被提上日程，日益受到重视。然而，制药企业的计算机化系统验证既需要制药和计算机专业知识，又需要IT知识，由于大部分企业没有专门从事验证的人员，因此大家对计算机化系统的验证保持神秘，不停的参加各种培训，却越培训越糊涂，越培训越觉得神秘。面对计算机化系统验证，仍然不知所措，GXP计算机化系统验证为了帮助大家更好的进行计算机化系统验证，特推出一系列验证相关的文档和知识，以飨读者。 Computerised System Validation SOP 计算机系统验证SOP 1 | Objective 目的 |
| Test and assessment should be taken for URS, design, purchase, installation, function, as well as process adaptability of computerized and PLC control system related to GMP in compliance with this SOP so as to ensure that computerized and PLC are fit for design requirement and stated technical criteria and are able to work stably for a long time. 测试、评估采取的URS、设计、采购、安装、功能以及计算机控制和PLC控制系统符合GMP，以确保计算机和PLC符合设计要求和工艺要求并且能够稳定工作很长时间。 | 2 | Scope范围 |
| This SOP is fit for the validation management of computerized and PLC control system related to GMP, which apply to material control and management, laboratory equipment control and communication management, manufacturing process control, and utilities control. 本SOP适用于电脑,PLC控制系统的管理是否符合GMP,物料控制和管理,实验设备控制和通信管理、生产过程控制、公用设施的控制的验证。 | 3 | Responsibilities 职责 |
| QA is responsible for drafting, revising, reviewing, training, implementing and supervising this SOP. QA负责起草、修订、审核、培训、实施和监督本SOP。 |
| The quality director is responsible for approving this SOP. 质量副总负责批准本SOP。 |
| Relevant departments are responsible for reviewing and implementing this SOP。 相关部门负责审核和实施本SOP。 | 4 | Definitions定义 |
| Computerized or PLC control system: It composed of hardware, system software, applications, and relevant peripheral devices is a system that can implement a function and a set of functions. 无论是计算机化还是PLC控制系统:都是由硬件、系统软件、应用、及相关的周边设备组成的一个系统,可以实现某一功能和一套功能。 Source code: It is source program of computer whose format( program language) can be read by operator, before computer execution, it should be translate to machine language whose format can be executed by computer. 源代码:它是计算机的源程序(程序语言),可以在电脑执行前被计算机识别,它应该被翻译成可以被计算机识别的机器语言。 | 5 | Procedures 程序 | 5.1 5.1.1 5.1.2 | Organization of Validation team and responsibility 验证机构及责任 Validation team is composed of supplier, QA, Equipment Department, use department. 验证团队由供应商,QA、工程设备部和使用部门组成。 Implementation department responsibility of system validation 系统验证实施部门的职责 l Use department: Responsible for providing written URS, preparing validation protocol and report, implementing approved IQ and OQ protocol, completing final report and participating validation deviation investigation and alteration review. l 使用部门:负责提供书面的URS,准备验证方案和报告、实施批准IQ,OQ协议,完成最终报告偏差并参与调查及变更验证审核。 l Equipment Department: Responsible for cooperating with use department to prepare URS and validation protocol, receiving system, installing system and implementing IQ, guiding use department on IQ and OQ process and participating validation deviation investigation and alteration review. l 设备部门:负责准备使用部门的合作协议,并确认你接收系统,安装系统,实施IQ,指导使用部门关于IQ和OQ的验证过程和参与验证偏差调查和变更回顾。 l QA: Responsible for reviewing validation draft and final report, implementing validation protocol, participating validation deviation investigation and alteration approval and archiving validation protocol and report. QA:负责审查验证,也是最后一项报告草案、实施验证方案,参与调查及变更验证偏差的批准验证方案和归档,并做好报告。 | 5.2 | System classification 系统分级 | 5.2.1 | Before validation, evaluation and classification should be carried out for system so as to insure that different grade validation should be provided for different type computerized and PLC control system. Classification as follows: 在验证之前,评估和分级应当进行系统分类,以确保不同等级验证需提供不同类型的计算机化的,PLC控制系统,分类如下: |
| Classification 分类 | Description 描述 | Validation method 验证方法 | Operating system, network 网络操作系统, | Established network and operating system for commerce. E.g. DOS\Windows 95/98NT. 已做好网络和操作系统例如:DOS\ Windows 95/98NT. | Validate name and edition number 确认名称及版本号 | Standard device, microcontroller, sensitive equipment 标准配置,微控制器,灵敏的电气设备 | These system is designed by non-consumer for driving firmware which can be installed in special integrate circuit (IC) for application, read only memory (ROM), random access memory (RAM), PLC sometimes, such as bar code modem, single-cycle controller, filling device, Checkweigher, temperature controller etc. 这些系统是根据用户可以安装在特殊的集成电路(IC)的驱动固件,只读存储器(ROM)、随机存取存储器(RAM)、PLC,例如条形码调制解调器,single-cycle控制器、灌装设备,重量控制、温度控制器等来设计的。 | Validate construction and configuration 确认构造及配置 | Standard package 标准程序包 | Ready-made package for commerce, such as multiplan software, standard chemical analysis software etc. 现成的软件包,例如多计划软件,标准化学分析软件等。 | Validate application process 验证应用过程 | Configurable package 可配置的程序包 | Users develop their own application through pre-definite software modules and developing application modules can be carried out in this system, such as man-machine dialogue port, management control, data acquisition system, adaptive control system for laboratory, information management system for laboratory, material requirement planning system, data processing system for system/ application and product, part PLC etc. 用户自己开发应用可通过pre-definite软件模块和发展应用模块都可以在这个系统中运行,采用人机对话端口,管理控制,数据采集系统,自适应控制系统,信息管理系统,原材料需求计划系统、数据处理系统和产品、系统应用部分可编程序控制器(PLC)等。 | Audit supplier and validate application process and some pre-established code | System developed within firm 公司内部系统开发 | Modifying or developing system in compliance with requirement of himself 修改或开发符合自己要求的系统 | Implement all validation processes of computerized and PLC control system 实施计算机及PLC控制系统验证的全过程 |
| 5.2.2 | Some computerized and PLC control system with complex construction should be classified in accordance with developing degree of each module. 一些计算机化的和PLC控制系统复杂程度应当跟各分类模块的开发程度相一致。 | 5.2.3 | Validation of computerized and PLC control system should be carried out not only for use process of system, e.g. validation of new system should be carried out not only for initial definition and designing phase but also whole life cycle of system development. 计算机验证,PLC控制系统不仅体现在系统使用过程,如新系统的验证不仅在初始定义和设计阶段进行,而且贯穿于全部生命周期体系的发展。 | 5.3 | Validation implementation 验证实施 | 5.3.1 | URS |
| URS should be prepared by system user and project expert detailed with fundamental requirement, expectation and performance index of new/changed computerized and PLC control system, which will be use to determine system designing criteria. Content as follow: URS应该为系统用户和项目专家准备基本要求详细的,预期和新的性能指标、更改计算机化和PLC控制系统,可以用来决定系统设计标准。内容如下: |
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| 5.3.1.1 | System description: what to do about system, how connection and interaction between different module, control methods (e.g. logic control, separation control, interlock control, alarm control, location control, temperature control, pressure control, time control, counting and other multipolar control), implementing process, ports and safety requirement for operator. 系统描述:系统做到什么程度,如何关联不同模块、控制方法(例如:逻辑控制、分离控制,连锁控制、报警控制、位置控制,温度控制,压力控制、时间控制、计数和其他多级控制)、实施流程、操作员的端口和安全标准。 | 5.3.1.2 | Physical requirement: include sufficient space, location, peripheral environment, etc. 物理要求:包括有足够的空间,位置,周边环境等。 | 5.3.1.3 | Document criteria for hardware: include chart paper, schematic chart, hand book, spare parts list etc. 硬件的文件标准:包括:图纸,原理图,操作指南,备件清单等。 | 5.3.1.4 | Document criteria for software: include program number and revising number, output program and detailed explanation, reproduction of software provision and retention condition, system block drawing and configuration list. 软件的文件标准:包括程序编号和修改编号,输出接口程序和详细说明、软件的追加和保留条件、系统分程序图纸和配置清单。 | 5.3.1.5 | Test requirement: test items and record required to be carried out on system developing process, including module separated test and integrated test. 测试要求:测试项目和记录必须在系统的发展过程中进行,包括模块测试和集成分离测试。 | 5.3.1.6 | Other requirement to supplier: such as finished system validation, quality control and change control on developing process, etc. 对供应商的其他要求:如在发展进程中完成系统验证、质量控制和变更控制等。 | 5.3.2 | System design 系统设计 | 5.3.2.1 | System design should compose of system configurable chart design, hardware design, and software design. After document of system design reviewed and approved by consumer which should be prepared by supplier, system configurable chart design should be carried out, including system PID (process and instrument), I/O (input/output) connection diagram, control element pareto diagram. 系统设计应该由系统配置图、硬件设计和软件设计组成。在供应商准备的系统设计被用户评估和检验后，可配置的系统图纸设计应该完成,包括系统PID, I/O (输入/输出)连接图、连接原理帕累托图。 | 5.3.2.2 | Hardware design: include all I/O (input/output) connection template and type, CPU selection, communication template, man-machine Interface controller, screen viewer selection, medium relay, memory, printer, auxiliary power unit, electronic element/wire/cable, other elements etc. 硬件设计:包括所有I/O (输入/输出)连接模板和类型,CPU选型,通信模板、人机界面控制器,屏幕查看选择、中继电器、记忆存储器、打印机、辅助动力装置,电子部件/电线/电缆、其他元件等。 | 5.3.2.3 | Software: include system software, application, and data. 软件:包括系统软件、应用和数据。 | 5.3..3 | IQ |
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| IQ should be carried out to ensure that system installation is fit for design criteria and needed technical data should be completely provided. Special content as follow: IQ应该确保该系统安装符合设计标准和工艺需求，数据完全提供。特殊内容如下: | 5.3.3.1 | Document qualification should consist of consumer technical guide, SOP, training plan, post-sale service agreement, equipment inventory, security program, hardware qualification, software qualification, source code, instrument list, instrument calibration procedure, PID, control loop diagram, I/O (input/output) device list and connection diagram, spare parts list, and maintenance procedure. 文件确认应该由用户工艺要求、SOP,培训计划,售后服务协议、设备库存,安全程序、硬件说明,软件说明,源代码、仪器清单、仪器校准程序、PID、控制回路图,I/O(输入/输出设备清单和连接图,备件清单和维护规程。 | 5.3.3.2 | Installation process qualification: qualify that installation is fit for requirement PID and operating manual. 安装过程说明:安装符合PID和操作手册的要求。 | 5.3.3.3 | Circumstance and utilities qualification 事件和实用程序说明 |
| (1) Qualify and record circumstance of system installation, such as clean level, radiofrequency/electromagnetic interference, physical protection, temperature, humility, sound, lighting, etc. 系统安装环境的检验和记录:例如洁净水平、射频/电磁干扰、物理保护、温度、湿度、声音、照明等。 |
| (2) Record condition of critical utilities and qualify that critical nature of utilities should be fit for instruction including fire alarm announcement/prevention, cooling system, electric power and its adjustment, continuous power supply, wide area network connection, local area network connection, disaster recovery, telephone figure/ analog, etc. 记录关键设施以及条件, 鉴定的公共设施应该跟说明一致:包括消防报警公告/预防系统、冷却系统、电力及调整,持续供电、大面积网络连接,本地区域网络连接,灾难恢复、电话图形/模拟等 |
| (3) Qualify that record system is fit for requirement of man-machine engineer. 条件和记录系统符合人控机工程师的要求。 | 5.3.3.4 | System test and qualification 系统测试、条件 |
| (1) The first step to do is to qualify that report items of FAT (factory acceptance test) should be completely supplied by supplier and fit for design criteria. 第一步要做的是,报告项目FAT的验收测试应该完全由供应商提供,适用于设计标准。 |
| (2) Necessary test should be carried out for system on operational circumstance. Essential content as follow: 应该对系统运行情况开展必要的测试。基本内容如下: | 5.3.4 | l All instruments and meters should be calibrated and on expire day of calibration. Calibration should be fit for definite criteria and corresponding certification should be provided. 所有仪器仪表应该被校准和标注过期日，校准应该有明确的标准及应提供相应的检查证件。 l I/O (input/output) signal test should be carried out so as to ensure that single can transmit from control system to device and return. I/O (输入/输出)信号试验应确保信号可以在控制系统设备间进行传输和反馈。 l Data acquisition and transmission and signal memory test 数据采集,传送和信号记忆测试 l Other tests l其他测试 |
| OQ (operation qualification) 运行确认 |
| The purpose of OQ is that all function tests should be carried out on operational circumstance so as to ensure that system and operation should be fit for design criteria. Content as follow; OQ的目的是进行所有功能运行情况方面的测试以确保系统和运行符合设计标准，内容如下： | 5.3.4.1 |
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| Test for system security: “worst case” of all logic systems should be tested, e.g. use authority of different persons should be tested so as to identify that operation unauthorized should be forbidden. 测试系统安全:“最坏情况”的系统逻辑应该进行测试,如使用不同权限以便确认未经授权运行是否被禁止。 | 5.3.4.2 |
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| Various processes control function tests required by system request: “ worst case “ ( e.g. maximum communication load, process of considerable data document, etc.) test for all function of system and decision routines should be carried out in accordance with various requirements and criteria supplied by system definition. (It is important that a functional diagram including all branch routines should be provided. ) 根据系统要求进行的各种各样的过程控制功能的测试:“最坏情况”(例如最大通信承载、过程相当大的数据文件等)试验检查系统和决策程序的功能,应根据系统不同的要求和标准提供的定义。(提供功能图表包括所有出现的偏差是非常重要的。) | 5.3.4.3 |
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| Test for alarm and interlock: efficacy of corresponding program should be tested on the condition of alarm and interlock for system in accordance with system operation manual. 检测报警及连锁:程序连锁应根据报警条件及系统连锁操作手册进行测试。 | 5.3.4.4 |
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| Test for timer and sequencer: establish time and program of system generating corresponding function according to system operation manual so as to validate efficacy of system timing or ordering program. 定时器和定序器测试: 根据系统的操作手册设置时间和系统产生相应的功能以确认系统有效时间或程序命令 | 5.3.4.5 |
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| Test for data disposal and memory 测试数据处理和记忆 |
| (1) Qualify correct data memory, collection and search of system’s own. 正确的数据记忆,准确的数据采集和系统的自我搜索的确认。 |
| (2) Qualify disposal of data output length, carry and empty 数据处理的输出长度、承载和空载的确认 |
| (3) Qualify the function of saving data to corresponding folder. 数据保存到相应文件夹的功能确认。 |
| Test for shutdown/ recovery 关机/恢复测试 | 5.3.4.6 | (1) Check condition of the data acquisition before and after shutdown so as to ensure that data have not been damaged or lost. 在系统关闭之前和之后检查数据采集的情况,确保数据没有损坏或丢失。 |
| (2)Check the function of backup power supply, uninterruptible power supply, power adjuster and power generator. 检查备用电源的供应、不间断电源供应器、电力调节器和电力发电机。 |
| (3)System breakdowns or failures should be made in accordance with system operation manual so as to ensure that back-up system should be provided. 系统故障和失败的时候,能够根据系统的操作手册提供系统备份。 |
| Other function test 其他功能测试 | 5.3.4.7 | Performance qualification (PQ) 性能确认 |
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| 5.3.5 | The purpose of PQ is that qualify the efficacy and stability of running process on operational circumstance. Test items should be established in accordance with achieving desired result and duplicate qualification should be also carried out. PQ的目的是确认系统运行过程中的有效性和稳定性方面的情况。测试项目应确定跟期望达到的结果相一致、二次确认也应该执行。 |
| If system is part of production, laboratory or utilities, PQ of system should be completed conformity with PQ of equipment (utilities). 如果系统是生产,实验室或公共设施系统的一部分,系统的PQ必须根据设备的PQ进行完整性测试。 | 5.3.5.1 | If a manual system is being replaced by computerized and PLC control system, the two should be run in parallel. 当一个人工系统被电脑,PLC控制系统取代时,两者需要平行运行。 | 5.3.5.2 | Regarding to production equipment, the test for product specification, such as assay, test for packaging specification, etc, should be carried out so as to ensure that the all process control functions are effective. Tests should be carried out for at least 3 consecutive batches on the some production condition. 对于生产设备,要进行产品规格测试,如化验、包装规格测试等等,确保所有的过程控制功能都是有效的，应当在相同的生产的条件下进行至少3个连续批次的测试。 |
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| 5.3.5.3 | Monitoring for equipment of consecutive process disposal should be carried out, e.g. index of clean-air system, such as dust particle, microorganism, temperature, humidity, air flow, pressure difference, air exchange frequency, etc, should be monitored during a period. 对设备的连续过程进行监控应当进行,如空气净化体系的指标,例如尘埃粒子、微生物、温度、湿度、风量、压差、换气频率等,应在一个周期内被监控。 |
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| 5.3.5.4 | Validation deviation 偏差验证 |
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| 5.3.6 | The disposal of system validation deviation can refer to < validation="" organization="" and="" implementation="">. 处置系统偏差验证可参阅验证组织和实施>。 |
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| Change control 变更控制 |
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| 5.3.7 | Change classification: change is composed of hardware change, software change and change of critical parameters in database. 变更的分类:变更是由硬件变更、软件变更，和数据库的临界参数变更组成。 |
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| 5.3.7.1 | If change occurring, change control should be carried out so as to ensure that system should be on validated status. 若发生改变,变更控制应确保系统处在已验证状态 |
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| 5.3.7.2 | (1) Written application should be prepared by use department, including change reason, evidence, and content and implementation protocol. 使用部门应该准备好书面申请,包括变更原因,证据,内容和实施方案。 (2)Professional technologist, the head of relevant department and QA are responsible for assessing, reviewing and approving. 工艺主管,相关部门经理和QA负责评估、审查和批准。 (3) Whether revalidation should be taken or not should be on the basis of impacting range. E.g. validation should be carried out for the parts of change which impacting the validated statues of computerized and PLC control system; sometimes revalidation should not be carried out after assessment if sufficient evidence can be provided. 是否再验证应该在影响范围的基础上，如当改变的部分影响计算机,PLC控制系统的验证状态时，改变的各个部分应当进行验证; 有时如果在评估之后可以提供充分的证据表明没有影响，那么就不需要再验证,。 (4) The implementation should be carried out after change approved by relevant personnel and altering content of approved change should be forbidden . 变更实施后,经有关人员、改变批准的变更内容是被禁止的。(不会翻译) (5) Influence of change to other relevant system should be taken into consideration, and assessment of influenced systems should be carried out, where necessary, revalidation should also be carried out for relevant systems. 对于变更对其他有关系统的影响，应当进行考核和系统评估,必要时, 相关系统还要进行再验证。 (6) The records should be made or completed at the time each action is taken, such as change application, assessment, approval and revalidation, and in such a way that all changes are traceable. 记录在每时每刻都要进行,如变更申请、评估、审批和再验证,用这样一种方式保证所有的变化可追踪。 |
| Annex附录 None 无 |
| Related Documents相关文件 | 6 | SOP01801 Validation Organization and Implementation | 7 | 验证的组织和实施 |
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