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1、实验室分析仪器的验证March 2010王 旭目的和定义目的和定义分析仪器的验证是对所有用于产生GxP数据的仪器设备的要求 法规要求这里的分析仪器定义为：“直接或间接影响用于物料、产品质量评估的数据质量和有效性的测量、监控、称量、记录和控制设备”分析仪器验证提供文件证明：用于GxP目的的分析仪器将持续的符合持续的符合其预定预定的标准和质量要求法规要求法规要求EUDRALEX-Volume 4-Medicinal Products for Human and Veterinary Use:Good Manufacturing PracticeAnnex 15 Qualification and
2、Validation21 CFR Part 211,Part 11USP 30 NF 25Physical tests and determinations 621 CHROMATOGRAPHY 851 SPECTROPHOTOMETRY AND LIGHT-SCATTERING 1058 Analytical Instrument Qualification draft Jul/Aug.2005 GAMP 4GAMP Guide for Validation of Automated Systems GAMP Good Practice GuideValidation of Laborato
3、ry Computerized Systems总的指导原则总的指导原则Specification PhaseInstallation&Operational PhasesPerformance PhaseInstallation PhaseProductionValidation Plan PhaseGSOPBIO_VAL_1204_30001GSOPBIO_VAL_1205_30046GSOPBIO_VAL_1205_30047GSOPBIO_VAL_1204_30007QC007System ConfigurationSystem installedValidation Master Pl
4、anInstallation QualificationOperational QualificationPerformance QualificationURSMaintenance&Change ControlSupplier AssessmentDesign PhaseANS Validation Life CycleGSOPBIO_VAL_1201_30031ANS Validation Life CycleGSK Bio compliance with CAP45ANS Validation Life CycleNonConformity Rec.URSURS?Document de
5、scribing user specifications for equipmentNon Conformity RecordNon Conformity Record?Form for handling identification and corrective action of any incidentsTest AttachmentsTest Attachments?Any existing evidences used for entering test data(e.g.Weight print out)Test RecordsTest Records?Any automatica
6、lly generatedrecord with test data(e.g.Chromatogram)验证文件验证文件Test Instructions.QA approvalTest AnnexesTest MethodologyURS1 Specificity2 Linearity3 Precision4 Repeatability5 Accuracy6 RobustessTest Protocol/RecordTest Protocol/Record?Form for manual enteringall test resultsTest InstructionsTest Instru
7、ctions?Methodology to execute the test&acceptance criteriaTest Annexes?Form to record test resultsIQ/OQ ProtocolIQ/OQ ReportTESTRECORDTESTAttchmtsTest Annexes紫外分光光度计 标准紫外分光光度计 标准在特定背景溶液和波长条件下透光率在特定背景溶液和波长条件下透光率75%3.3.2波长准确度波长准确度(高氯酸钬溶液高氯酸钬溶液)紫外分光光度计 性能测试标准紫外分光光度计 性能测试标准药典对241nm波长精度没有检查要求：咖啡因溶液：205+/
8、-1nm汞：185+/-1nm3.3.2波长准确度波长准确度(钬玻璃钬玻璃)紫外分光光度计 性能测试标准紫外分光光度计 性能测试标准其他替代方法：铷玻璃：可见光 氘灯、汞灯吸收峰波长以供应商提供的为准吸收峰波长以供应商提供的为准3.3.3吸收值准确度吸收值准确度(重铬酸钾溶液重铬酸钾溶液)紫外分光光度计 性能测试标准紫外分光光度计 性能测试标准其他替代方法：中密度滤光片硅金片注意清洁！注意清洁！欧洲药典要求测可见光欧洲药典要求测可见光3.3.4基线稳定性基线稳定性200nm 700nm透射值透射值 100+/-2%吸收值吸收值 0+/-0.005紫外分光光度计 性能测试标准紫外分光光度计 性能
9、测试标准3.3.5离散光离散光紫外分光光度计 性能测试标准紫外分光光度计 性能测试标准1.1.0%碘化钠碘化钠/0.025%重铬酸钾重铬酸钾:220nm、370nm2.Schott WG295 glass filter：220nm3.12 g/l 氯化钾：氯化钾：198nm透光率透光率 2.03.3.6分辨率（若用于鉴别）分辨率（若用于鉴别）紫外分光光度计 性能测试标准紫外分光光度计 性能测试标准0.020%苯苯/正己烷溶液，在正己烷溶液，在269 nm和和266 nm 下的吸光率比值下的吸光率比值若光谱带宽若光谱带宽=1.5若光谱带宽若光谱带宽2nm;比值应比值应=1.5塔板数系统适应性控制
10、参数接受标准2系统适应性控制参数接受标准2系统适应性参数 公式可接受标准精确度检查系统适应性参数 公式可接受标准精确度检查保留时间重现性比较标样和样品的保留时间+/-2%标准重复性比较同一标准品不同制备液间的峰面积 RSD=2.0系统重现性比较同一标准品制备液5次连续进样的峰面积RSD=1.0注：可接受标准可能不同，参见具体实验方法和药典外标外标法：法：HPLC方法原理HPLC方法原理内标法：内标法：注：至少制备2个标样HPLC进样方法HPLC进样方法1-6,12,13,19,2026,27 的的RSD=2.0%用用12,13,19,20来计算样品来计算样品J-M分离均匀性:+/-10%=菌检
11、仪菌检仪Steritest 性能测试标准 性能测试标准培养基生长促进试验无菌试验膜完整性（泡点试验）实验室自动系统验证简介实验室自动系统验证简介GAMP 分类分类-1/2GAMP ClassCAP045ClassGAMP-identificationTranslation to GSK Biologicals laboratory environment(CAP045)Typical examples within QC Laboratories0ANot defined within GAMPSimple COTS equipment used mostly in sample prepar
12、ation or otherwise indirectly used in laboratory areas.Readings from these are not used to generate GxP data.Typically firmware-based no data storage,run-time parameters set when used.Not connected to a computerized system.Stirrers,hotplates,heating,mantles,glassware washing machines,water stills,ro
13、tary evaporators,sonicators,centrifuges(Out of scope of this procedure)BNot defined within GAMPLogistic equipments:Non-electronic COTS devices and standards not depending on electronic logic,embedded logic or external computer systems to control instrument function.They do not store data on durable
14、media or report information.All critical parameters are assured by a calibration program,maintenance program or similar.Direct impact:Rulers,non-digital thermometersIndirect impact:check weights,mechanical friability testers,analog-type chart recorders,U-tube viscometers,stiring plates,simple water
15、baths,mercury thermometer,(Non CRS;Out of scope of this procedure)(Out of scope of this procedure)1NAOperating SystemsOperating systemsWindows 95,98,NT,2000,Me,XP(Not considered to be analytical systems;Out of scope of this procedure)2CFirmwareSimple,non-programmable firmware-based COTS equipment th
16、at provides a measurement reading via a digital display and/or to an attached printer.Will be calibrated periodically.Data storage will be limited to a few simple run-time parameter settings.Not connected to an external computer.Digital thermometers,digital callipers,pH meter(with printer and/or tem
17、perature compensation),balances,conductivity meters,digital viscometers,digital chronometer3DStandard softwarepackagesFirmware based COTS systems but with additional featuressuch as the ability to store run-time configurations as methods.Could be controlled from an external computer or system via an
18、 electronic interface.Usually will not store measurement data except where data logging is the main functionality.Calibrated periodically or at run-time.No direct programmable interface.Some autotitrators,HPLC or GC hardware components such as pumps,column ovens,autosamplers,Chessel chart recorders.
19、Excel spreadsheets.GAMP-分类分类-2/2GAMP ClassCAP045ClassGAMP-identificationTranslation to GSK Biologicals laboratory environment(CAP045)Typical examples within QC Laboratories4EConfigurable Software PackagesHardware may be firmware-based or controlled by an external computer.Standard application softwa
20、re which will allow configuration of run-time parameters,instrument control,data acquisition and standard reporting functionality.Standard(non-programmable)data processing functionality,which may involve regulated records and signatures applicability.Usually stand-alone,not relying on CDS or similar
21、 separate controlling and post-acquisition data processing systems.Typically utilises a local level of access control.Stand-alone UV/Vis,FT-IR spectrophotometers,stand-alone HPLC system software i.e.not connected via CDS(Chromatography Data System).Spectrophotometer or HPLC with standard,dedicated a
22、pplication software(including custom reports,.),FMore complex systems that mostly have PC-based application software.Mostly programmable via standard method sequence lists.May utilise computer network functionality.Often these are hardware and software components used to control a variety of other s
23、tandard COTS lab equipment.Likely to involve regulated records and signatures.May acquire and utilise reference data as libraries,requiring advanced statistical or pattern recognition data processing.Typically uses operating system functionality for access control.Robotic workstation controllers e.g
24、.Zymark,some NIR systems,NMRs,Mass Spectrometers,Vitek speciation systems,HPLC connected via CDS5NACustom(bespoke)SoftwareCustom build or bespoke systems,prototypes.They can either be custom built analytical systems,or individual custom built software packages.Electrolyte System(E-Lise)Excel spreadsheets with macro(VB)电脑验证特别应注意的地方电脑验证特别应注意的地方DQ IQ OQ Generic Protocol数据保护和完整性Audit TrailsData Integrity数据备份和恢复Back-up and RestoreData ArchivingData Reconstruction/Reprocessing权限控制Physical SecurityLogical SecurityQuestions?