ICH Q7 API FDA inspection training.ppt

Conferencesdefinedchemicalpropertiesandstructure!,1.介绍,1.2药政适应性当一种物料被一个地区或国家列为原料药，在该地区制造或在某种药物产品中使用，必须根据本指南遵循GMP要求。1.3范围本指南应用于由化学合成，提取，细胞培养/发酵，自然原料提取的原料药制造。原料药起始物料是原料，中间体，或一种原料药，它具有所要生产的原料药的有效结构部分；明确的化学属性和结构,ApplicationoftheGuidetoAPIManufacturing,Chemicalsynthesis:productionofAPIstartingmaterial-introductionofAPIstartingmaterialintoprocessproductionofintermediate(s)isolationandpurification-physicalprocessingandpackagingDerivedfromanimalsources:collectionoforgan,fluid,ortissuecutting,mixing,initialprocessingintroductionoftheAPIstartingmaterialintoprocessisolation.Extractedfromplantsources:collectionofplantscuttingandinitialextractionfurtherextractionphysicalprocessingAPIconsistingofcomminutedorpowderedherbs:collectioncutting/comminutingphysicalprocessingandpackagingBiotechnology-Fermentation/cellculture:establishmentofmasterandworkingcellbankmaintenanceofworkingcellbankcellculture/fermentationisolationandpurificationphysicalprocessingandpackagingClassical“fermentationtoproduceanAPI:Establishmentandmaintenanceofthecellbankintroductionofthecellsintofermentation,.,本指南在原料药制造的运用,化学合成：原料药起始物料的生产在工艺中加入原料药起始物料中间体生产分离和提纯物理加工和包装源于动物原料的：采集器官，液体，或组织切割，混和，初步加工在工艺中加入原料药起始物料分离从植物原料中提取的：采集植物切割和初步提取进一步提取物理加工原料药由粉末或粉末状草药组成：采集切割/粉末化物理加工和包装生物技术发酵/细胞培养：建立主细胞库和工作细胞库工作细胞库的维护细胞培养/发酵分离和提纯物理加工和包装生产一个原料药标准的发酵：细胞库的建立和维护在发酵中加入细胞,1.3Scope,ThecompanyshoulddesignateanddocumenttherationaleforthepointatwhichproiductionoftheAPIbegins.(available?,inspectorsaidememoire!(AM)Fromthispointon,appropriateGMPasdefinedintheGuideshouldbeappliedtotheseintermediateand/orAPImanufacturingsteps.ThisincludesvalidationofcriticalprocessstepsdeterminedtoimpactthequalityoftheAPI.(AMcriticalstepsidentified?)ThestringencyofGMPinAPImanufacturingshouldincreaseastheprocessproceedsfromearlyAPIstepstofinalsteps,purificationandpackaging.Physicalprocessingsuchasgranulating,coating,blendingwithexcipients/subbatches,millingrequirefullGMP!,1.3范围,工厂应确定并把原料药是从哪个点开始的制成文件（可能？检查官帮助备忘录！（AM)从这个确定的点起：本指南中相应的GMP规则应该被应用于这些中间体和/或原料药的制造步骤这包括对决定原料药质量的关键工艺步骤的验证（AM关键步骤的确认？）随着工艺从最初的原料药步骤到最终步骤，纯化和包装，原料药制造的GMP规则逐步严格。物理过程，例如造粒，包衣，和赋形剂/零头的混和，粉碎，满足GMP的要求,APIStartingMaterials(API-SM),ResponsibilityofcompaniestoproposetheAPIStartingMaterial(s);technical,quality,regulatorygroupshavetodefinethesignificantstructuralfragment!WithStartingMaterialGMPhastobeapplied!IfonlyoneortwosyntheticstepsexistbetweenanAPI-SMandtheAPIoriftheSMisanAPIitselfregulatoryauthoritieswillrequirefurtherinformationonAPI-SM!(manufactureraudited,qualitymanagementsystemestablished,documentation,changecontrol,etc.)Ingeneral,thesourceoftheAPI-SMisnotamajorfactor.EPcertificationsubmissionsrequireastatementtheproductismanufacturedaccordingtoGMP“(nottheAPI-SM!)Commerciallyavailablesubstances(latestageAPI-SM)like6-APAforsemi-syntheticpenicillinsacceptedbyFDAasAPI-SM!Authoritiesmayrequirefurtherdetails!,原料药起始物料(API-SM),工厂提出起始物料的责任：技术，质量，药政部门必须确定其重要的结构特征！必须应用起始物料的GMP规则。在原料药起始物料与原料药之间只存在一或两个合成步骤，或者如果这种起始物料本身便是一种原料药，药政官方部门将要求原料药的起始物料有更详细的资料！（受审计的制造商，已建立的质量管理系统，文件，变更控制，等）总之，原料药的起始物料的来源不是一个重要因素。EP证书的递交需要一个申明，说明产品是符合GMP的（不是原料药的起始物料）适用于商业的物质（原料药起始物料的后阶段），如用于半合成青霉素的6-APA是被FDA所接受的原料药起始物料。官方部门可能要求更详细的材料！,API-SM,WheretheproposedAPI-SMisclosetotheAPIensurethatdetailsonthesyntheticprocessandanalyticalcontrolsusedareavailableincasethesewouldberequiredbytheregulatoryauthorities!Includeinthecommercialcontractthataconfidentialparthastobeprovideddirectlytoauthoritiesifrequested!DefinealsoChangeControlRequirementsinthecontractforsupplyofAPI-SM!,Anychangeinsyntheticroute,analyticalcontrolsorspecification,needsnotificationtoandacceptancebytheAPImanufacturer,ManufacturersofIntermediates,API-SMs,APIsshouldhaveasystemforevaluatingthesuppliersofcriticalmaterials,API-SM,那些与原料药很接近的起始物料若能确定其详细的合成工艺并且有检验控制，这样做也是可以满足官方药监部门要求的！包括商业合同，如果需要，其中的保密部分必须直接提供给官方部门。对于起始物料的合同也要明确变更控制的要求,任何在合成路线，检验控制或规格中的变更，都需要告知并得到原料药制造商的接受,中间体，起始物料，原料药制造商应该对关键物料供应商进行评估。,API-SM,Syntheticorsemi-syntheticAPIsAPI-SMisanalyticallyfullycontrolledintermsofidentity,assayandimpurities!APIproducedbydirectfermentationDescribemicro-organismandmediacomponentsplustheirspecifications.Nospecificstartingmaterialtobedefined,unlessonecomponentisstructurallycloselyrelatedtotheAPI.APIextractedfromnaturalsourcesormanufacturedfromminedoreDescribethepurificationprocessand/ordefineAPI-SMbasedonascientificrationalewhichmayincluderiskassessment.,原料药起始物料,合成或半合成原料药起始物料按照鉴别，含量，杂质等全检控制由直接发酵产生的原料药在规格里加入微生物和培养基的描述如果一个要素的结构与原料药非常接近，则无须确定起始物料原料药从自然原料中提取或由矿石制造描述精制工艺并且/或根据科学原理，其中可能包括风险评估，来确定原料药的起始物料,2.QualityManagement,PrinciplesResponsibilitiesofQU(s)ResponsibilitiesofProductionInternalAuditsProductQualityReview,2.质量管理,原则质量部门职责生产部门职责内部审计产品质量审核,2.QualityManagement-Glossary,QualityAssurance(QA),QualityManagement(QM)ThesumtotaloftheorganisedarrangementsmadewiththeobjectofensuringthatallAPIsareofthequalityrequiredfortheirintendeduseandthatqualitysystemsaremaintained.QualityUnit(s)AnorganizationalunitindependentofproductionwhichfulfillsbothQAandQualityControl(QC)responsibilities.ThiscanbeintheformofseparateQAandQCunitsorasingleindividualorgroup,dependinguponthesizeandstructureoftheorganization.QualityControl(QC)Checkingortestingthatthespecificationsaremet.QualityAttribute:Anyproductcharacteristicwhichmayreflectquality,ormayaffectsafetyorpurityoftheproductduringitsexpectedshelflife.Quality:Totalityoffeaturesandcharacteristicsofaproductorserviceanditsabilitytosatisfystatedorimpliedneeds.Thisis,meetingagreedrequirementsinacosteffectivemanner.,2.质量管理词汇表,质量保证(QA),质量管理(QM)以确保所有原料药达到其应用所要求的质量，并以维持质量体系为目的的全部组织安排的总和。质量部门（QU）独立于生产部门的履行质量保证和质量控制职责的组织机构。按照组织机构的大小和结构，可以是单独的QA和QC部门,或个人,或小组。质量控制(QC)是否符合质量规格的检查或测试。质量属性:在预期的架上时间内任何可能影响产品质量，安全或纯度的产品特性。质量:产品或服务，满足规定或潜有需要的特征和特性的总和。即，采取有效的措施符合要求,Coordinatedactivitiestodirectandcontrolanorganizationthroughoutallareasandprocesseswithregardtoquality.,Glossary:QualityManagement,QualityManagementSystem-QMS,SystemneededtoimplementQualityManagementefficiently.,指导和控制一个组织的协调活动贯穿所有与质量有关的区域和工艺,词汇表：质量管理,质量管理系统QMS,需要有效的实施质量管理的系统.,TheQualityAssuranceSystem-QMSystem.recognizesanddescribesinterfaces,responsibilities,competences,Interactions.,.ensuresclearInputsfortasks,质量保证系统QM系统职责的识别和描述,管辖相互作用,确定明确的职责分配,InterfacesMilestonesInformationflow/InteractionsTasksCompetencesResponsibilities,QMSisthearrangementof,管辖分界信息流动/相互作用任务权限职责,质量管理系统,QMS,DocumentationSystem,GMP,Describessystemrelatedquality,Describesproductrelatedquality,QMS,文件系统,GMP,描述与质量相关的系统,描述与质量相关的产品,GMP+Processes=QMS,GMP,ProductrelatedQualityDocumentedevidence,Process,Asetofinterrelatedorinteractingactivitieswhichtransformsinputsintooutputs.,QMS,Includingtime-axisIncludinginterconnections,GMP+工艺=QMS,GMP,与质量相关的产品文件化的证据,工艺,一系列相关的或相互作用的，把输入转化为产出的活动,QMS,包括时间轴包括相互联络,GeneralConsiderations,PICGMPChapter1:QualityManagement“.ToachievethequalityobjectivereliablytheremustbeacomprehensivelydesignedandcorrectlyimplementedsystemofQualityAssuranceincorporatingGoodManufacturingPracticeandthusQualityControl.Itshouldbefullydocumentedanditseffectivenessmonitored.”,QMS,概论,PICGMP第1章:质量管理“要达到质量目标必须有广泛设计的和正确实施的质量保证系统，加之以GMP规范并如此质量控制。应该完全文件化并有效监督。”,QMS,GeneralConsiderations,IntroductionISO9001:“ItisemphasizedthatthequalitysystemrequirementsspecifiedinthisInternationalStandardarecomplementary-notalternative-tothetechnical(product)specifiedrequirements.”,GMP,概论,ISO9001介绍:“它被强调,质量系统要求被指定在这国际标准是补全的-不能选择-对技术(产品)规格的要求。”,GMP,ComparisonQMS/GMP,GMP,high,low,DegreeofDetail,Validitywithinthecompany,QMS,GLP,GCP,比较QMS/GMP,GMP,高,低,程度详述,公司内部的有效性,QMS,GLP,GCP,CEFICActivities,DocumentcombiningISOandGMPRequirements,December1997,CEFIC活动,ISO和GMP要求的文件的组合,December1997,2.1Principles,Qualityshouldbetheresponsibilityofallinvolvedinmanuf.Eachmanufacturershouldestablish,document,andimplementaneffectiveQMSystemreflectingtheQualityPolicysupportedbyuppermanagement.QMSshouldcoverorganisationalstructure,procedures,processesandresources,activitiestoensurefulfillmentofspecificationsofAPIs.Thereshouldbeaqualityunit(QU)independentofproductionthatfulfillsQAandQCresponsibilities.PersonsauthorisedtoreleaseintermediatesandAPIsshouldbespecified.Allqualityrelatedactivitiestoberecordedatthetimetheyareperformed.,2.1原则,质量，应当成为所有涉及制造过程的职责每个生产商应当建立，成文，执行有效的QMS，来体现对上级管理层的质量方针QMS应该覆盖组织结构、流程、工艺和资源,活动来保证APIs的规格的履行应该有独立的质量部门来履行QA和QC的职责应该指定人员批准中间体和原料药的放行所有与质量相关的活动要在他们实施时及时记录,2.1Principles,Anydeviationfromestablishedproceduresshouldbedocumentedandexplained,criticaldeviationsshouldbeinvestigated,andtheinvestigationanditsconclusionsshouldbedocumented.Proceduresshouldexistfornotifyingresponsiblemanagementinatimelymannerofregulatoryinspections,seriousGMPdeficiencies,productdefectsandrelatedactions(complaints,recalls,regulatoryactions,etc.)NomaterialsshouldbereleasedorusedbeforecompletionofevaluationbyQU,butexeptionspossibleunderquarantine“(SOP!).OfficialinspectorswillchecktheseissuesaccordingtoAM!,2.1原则,任何与已建立程序的偏差应当形成文档，作出解释，关键的偏差应当被调查，形成调查和结论的文档应该存在这样的规程，能及时地通知负责的管理层来规范：检查、严重的GMP不足、产品缺陷和相关行动(投诉、招回、规范行动,等。)在质量部门的评估没有完成前，不得对物料放行和使用，但可能的留验例外(SOP!).官方的检查员将依据AM检查这些签发文件!,QualityManagementSystem,Elementsacc.toDINISO9001ResponsibilityofSeniorManagementQualityManagementSystemControllingofContractsSteeringofDesignSteeringofDocumentsandDataMaterialsManagementSteeringofProductssuppliedbyaCustomerIdentificationandTraceabilityofProductsSteeringofProcessesTestingControlofTestingAgentsStatusofTestingSteeringofdeficientProductsCorrectionandPreventionMeasuresHandling,Storage,Packaging,PreservationandDistributionSteeringofQualityRecordsandDocumentsInternalQualityAudits(SelfInspection)TrainingMaintenanceStatisticalMethods,质量管理系统,根据DINISO9001的原理高级管理层的责任质量管理系统合同控制设计操控文件和数据的控制物料管理对客户提供产品的操控产品的识别和追踪工艺操控检测委托检测的控制检测状态缺陷产品的操控纠正与预防措施操作，储存，包装，保存和分发质量记录和文件的操控内部质量审计（自检）培训维护统计方法,RequirementsaccordingtoDINENISO90019001/4.10TestingFinalTestingaccordingtoQMprotocolorwrittentestingprocedurepreviouscheckswithresultswithinacceptancecriteriaperformednodistributionbeforehavingconductedalldefinedtestsandapprovalofdataanddocumentsTestingRecordsEvidencethatqualitytestingaccordingtodefinedacceptancecriteriaexistsSign/signatureReleased“ofresponsibleperson/unit,依据DINENISO9001的要求9001/4.10检测最终检测根据质量管理方案或书面的程序用符合标准的结果预先检查在进行全部规定的检测，数据获批准并记录前，不可销售产品检测记录根据规定的接受标准进行质量检测的证据负责人员/部门签名放行,ECGMPGuidelineQualityManagementSystemPrincipleTheholderofamanufacturingauthorizationmustensurethatmedicinalproducts-fitfortheirintendeduse(effectiveness,safety,purity)-complywiththerequirementsofthemarketingauthorization-arenoriskforpatientsduetoinadequatesafety,qualityorefficacy.Theattainmentofthisqualityobjectiveistheresponsibilityofseniormanagementandrequirestheparticipationandcommitmentby-staffindifferentdepartmentsatalllevels-thecompanyssuppliers-thedistributorsToachievethequalityobjectivereliablytheremustbeacomprehensivelydesignedandcorrectlyimplementedsystemofQualityAssuranceincorporatingGMPandthusQualityControl.QAshouldbe-fullydocumentedanditseffectivenessmonitored-adequatelyresourcedwithcompetentpersonnel,sufficientpremises,equipmentandfacilities.,ECGMP指南QMS原理制造许可证的持有人必须保证医药产品-符合既定的使用(效用，安全，纯度)-遵守市场许可证的要求-对病人没有风险，由于不充分的安全，质量或效用质量宗旨的达到是高级管理层的责任并要求以下的参与和承诺：-不同部门，不同层次的职员-公司的供应商-分销商为了可靠的达到质量宗旨，必须要有一个混和了GMP和质量控制的广泛设计和正确实施的质量保证系统。QA应当-有充分的文件和有效的监督-有足够的可以胜任的人员，办公室，设备和设施,QualityManagementSystem,CostAccountingnachBritishStandard,质量管理系统,费用单nachBritishStandard,ECGMPGuidelineDocumentationPrincipleGooddocumentationconstitutesanessentialpartoftheQASystem.Clearlywrittendocumentationpreventserrorsfromspokencommunication-permitstracingofbatchhistory-facilitatesthesearchforanymistakesincaseofcomplaints-handsoverexperience-facilitatestrainingofnewlyrecruitedemployeesanddeputiesofemployees-verifiestheknowledgeofemployees-ensuresthatcompliancewithmarketingauthorizationdossiercanbecontrolledeasily-ensuresunchangedconstantquality.Specifications,ManufacturingFormulaeandInstructions,Procedures,andRecordsmustbefreefromerrorsandavailableinwriting.Thelegibilityofdocumentsisofparamountimportance.,ECGMP指南文件原理好的文件构成了QA系统的一个要点部分.清晰的书面文件预防了口头交流的错误-可以进行批历史的追踪-帮助在投诉事件中查找错误-移交经验-帮助培训新员工和新代表-检验员工知识-确保遵照市场许可证的卷宗能容易的控制-确保一成不变的质量规格，制造的规则和指令，程序和记录必须允许错误并书面提供.文件的易识别是最重要的,2.2ResponsibilitiesoftheQU(s),QUshouldbeinvolvedinallquality-relatedmattersQUshouldreviewandapproveallquality-rel.DocumentsThemainresponsibilitiesoftheQUshouldnotbedelegated.Theseresponsibilitiesshouldbedescribedinwriting.,ResponsibleTobedonebytheQ-Unit,2.2质量部门（QU）的责任,QU应当包括所有与质量相关的因素QU应当审核，批准所有与质量相关的文件QU的职责不应当是委任的，应当有书面描述,职责由QU完成,2.22MainResponsibilitiesofQU,ReleasingorrejectingAPIs,intermediates.Establishingasystemtoreleaseorrejectrawmaterials.Reviewingbatchproduction,labcontrolrecords,.validationprotocolsandreportsMakingsurethatcriticaldeviations/OOSareinvestigated,internalauditsareperformed,complaintsareinvestigatedandresolved,effectivesystemsareusedformaintainingandcalibratingcriticalequipment,stabilitydatatosupportretest,expirydates,storageconditionsareavailable.Approvingspecifications,masterproductioninstructions,proceduresimpactingqualityofintermediates/APIs,contractmanufacturer/labs,changeswithimpacttoquality.Performingproductqualityreviews.,2.22QU的主要职责,放行或退回原料药，中间体.建立放行或退回原料制度.审核批产品,实验室控制记录,.验证方案和报告确认关键偏差/OOS的调查，内审的实施，投诉的调查和解决，有效的用于设备维护和校验的系统，提供支持复测，有效期，贮存条件的稳定性数据批准规格，主生产指令，影响中间体/原料药的程序，合同生产商/实验室，影响质量的变化实施产品质量回顾,2.3ResponsibilityforProductionActivities,Preparing,reviewing,approvinganddistributingmanufacturinginstructions(accordingtoSOP).Producingintermediates/APIsacc.topreapprovedinstructions.Reviewingallbatchrecords;complete,signed?Makingsurethatproductiondeviationsarereported,evaluated,criticalinvestigated,conclusionsrecorded!.productionfacilitiesareclean,calibrationsareperformedandrecordskept,validationprotocolsandreportsarereviewedandapproved,.new/modifiedfacilitiesandequipmentarequalified.Overseechangecontrolprocedure!,2.3生产活动的职责,（根据SOP）准备，检查，批准和分发制造指令根据预先批准的指令生产中间体/原料药检查所有的批记录；完全了，签字了？确认产品的偏差被报告，被评价，关键点被调查，结论被记录!.生产设施清洁，校验实施并留存记录，验证方案和报告被审核批准.新的/更改的设施和设备被确认监督变化控制程序!,2.4InternalAudits(SelfInspection),CompliancewiththeprinciplesofGMPforAPIsRegularinternalauditstobeperformed(schedule!)Findingsandcorrectiveactionslisted,recorded,followed-upDocumentationAttentionofmanagementAgreedactionscompletedtimely(responsibility+timeschedule)InspectorswillcheckaccordingtoAideMemoire!,2.4内审(自检),按照GMP对原料药的原则实施定期内审(计划表!)发现和纠正表，记录，追查文件管理的注意同意行为及时完成(职责+时间表)检查员将根据备忘录检查!,2.5AnnualProductQualityReview,.tobeconductedtoshowconsisitencyoftheprocess.Criticalin-processcontrolandAPItestresultsCriticalreactionparameterstobeevaluated(Dev.Report!)BatchesthatfailedtomeetspecificationsCriticaldeviations,investigations,conclusions(impact?)Anychangestotheprocesses,analyticalmethods,specs,equipment,.Qualityrelatedreturns,complaintsandrecallsAdequacyofcorrectiveactions(permanentchange?)Resultsofthereviewshouldbeevaluated,corrections,changes,revalidation,approvalsneeded?ForinspectorsitisveryeasytocheckyourQMSandproductquality!,2.5年度产品质量回顾,.被指导来表明工艺的一贯性关键的工序间控制和原料药检测结果评估关键的反应参数(设计报告!)不合格的批号关键的偏差，调查，结论（影响？）任何变化：工艺，分析方法，规格，设备质量相关的反馈，投诉，召回适当的纠正措施(一成不变?)回顾的结果应当被评估，校正，更换，再验证，需要批准？检查员们能非常容易地检查你们的QMS（质量管理系统）和产品质量!,Andwhatabouttraining?,培训是什么?,3Personnel3.1PersonnelQualificationThereshouldbeanadequatenumberofpersonnelqualifiedbyappropriateeducation,trainingand/orexperiencetoperformandsupervisethemanufactureofintermediatesandAPIs.TheresponsibilitiesofallpersonnelengagedinthemanufactureofintermediatesandAPIsshouldbespecifiedinwriting.Trainingshouldberegularlyconductedbyqualifiedindividualsandshouldcoverataminimum,theparticularoperationsthattheemployeeperformsandGMPasitrelatestotheemployeesfunctions.Recordsoftrainingshouldbemaintained.Trainingshouldbeperiodicallyassessed.,3人员3.1人员资质应该有足够数量的经过适当教育，培训和/或经验的有资质的人员来实施和监督中间体和原料药的制造所有在中间体和原料药制造中从事活动的人员的职责应当有书面的说明培训应当由有资格的个人来进行定期的指导，应当至少包含员工履行特别的操作，GMP对于员工的相关职能培训记录应当被保存培训应当被定期评定,3.1PersonnelQualificationTrainingObjectivesofGMPTrainingDefineandexplainwhatGMPmeansHowtotransferGMPintodailypracticeGenerateconsciousnessforGMPImprovequalificationofpersonnelMotivatepersonnelIncreasesafetyofAPIs/drugproducts,3.1人员资质培训GMP培训的目标定义和说明GMP意味什么如何将GMP调入日常作业产生GMP意识提高人员资质人员促动增加原料药/药物的安全,3.1PersonnelQualificationTrainingofPersonnelContentsanddefinitionsofatrainingprogramWherefore?Definetrainingissuesandobjectives!Whoshouldattend?Nameandinvite!Bywhom?Qualifiedtrainer/consultant!Howoften?Defineaprogram/yearandemployee!Howlongandwhere?WhatitemsofGMP/SOPs?Distributedocuments!,3.1人员资质人员培训一份培训纲要的规定和内容原因?规定培训的发布和目标!参加者?姓名和邀请!谁作培训?有资质的培训人/顾问!多频繁?规定一个计划/年和雇员!多长时间，哪里?GMP/SOPs的什么项目?分发文件!,3.1PersonnelQualification-TrainingofPersonnelTrainingrecordsshouldincludethefollowing:DateoftrainingAreaofproduction,qualitycontrol,etc.ObjectivesNameofteacher(s)NameofparticipantsSignaturesofparticipantsReasonfortrainingInitiator/responsiblepersonfortrainingHowtomaintaine/archivethetrainingrecord,3.1人员资质人员培训培训记录应当包括以下内容:培训日期范围：产品，质量控制，等等目标老师的名字参加人的名字参加人的签名培训原因培训的提倡人/责任人如何保存/存档培训记录,TrainingofPersonnelDocumentationofinformationgiventonewlyrecruitedpersonnelforproduction:,aus:Haffneretal.-SchulungvonMitarbeiternPharm.Ind.56,Nr.8(1994),人员培训给为生产招进的新员工的资料文件：,aus:Haffneretal.-SchulungvonMitarbeiternPharm.Ind.56,Nr.8(1994),3.1TrainingofPersonnelIntroductiontoandinformationaboutworkingplace;importantSOPstoberead,understoodandfollowed:,nach:Haffneretal.-SchulungvonMitarbeiternPharm.Ind.56,Nr.8(1994),3.1人员培训通知介绍有关工作场所；需要阅读并理解的重要SOPs：,nach:Haffneretal.-SchulungvonMitarbeiternPharm.Ind.56,Nr.8(1994),3.1TrainingofPersonnelHeardisnotyetunderstood;Understoodisnotyetagreed;Agreedisnotyetapplied;Appliedisnotyetpermanentlyfollowed.(KonradLorenz)Thebestmanagerdoesntteachhisemployeeshowtothinkbutthattheyhavetothink.(D.Goeudevert),3.1人员培训听到不等于理解;理解不等于承认;承认不等于实施；实施不等于一成不变.(KonradLorenz)最好的经理不是去教员工怎么思考而是让他们必须思考(D.Goeudevert),3.2PersonnelHygienePersonnelshouldpracticegoodsanitationandhealthhabits.Personnelshouldwearcleanclothingsuitableforthemanufacturingactivitywithwhichtheyareinvolvedandthisclothingshouldbechangedwhenappropriate.Additionalprotectiveapparel,suchashead,face,hand,andarmco