EUGMP-中英文对照1资料

精品文档精品文档精品文档精品文档EUGMPANNEX1MANUFACTUREOFSTERILEMEDICINALPRODUCTS（中英文对照）Principle原则Themanufactureofsterileproductsissubjecttospecialrequirementsinordertominimizerisksofmicrobiologicalcontamination,andofparticulateandpyrogencontamination.Muchdependsontheskill,trainingandattitudesofthepersonnelinvoIved.QualityAssuraneeisparticularlyimportant,andthistypeofmanufacturemuststrictlyfollowcarefullyestablishedandvalidatedmethodsofpreparationandprocedure.Solerelianceforsterilityorotherqualityaspectsmustnotbeplacedonanyterminalprocessorfinishedproducttest.无菌药品的生产，必须符合一些特殊的要求，以防止微生物、微粒和热源的污染。这很大程度上要取决于相关人员的技术水平、培训和工作态度。在这方面质量保证显得特别重要，这种类型的生产，必须严格按照元善的和经过验证的生产方法和工作程序。仅基于产品的最终火菌或产品检验结果来相信其无菌性和其他质量指,标是不可靠的。Note:Thisguidancedoesnotlaydowndetailedmethodsfordeterminingthemicrobiologicalandparticulatecleanlinessofair,surfacesetc.ReferenceshouldbemadetootherdocumentssuchastheEN/ISOStandards.注：本指南没有详述测定洁净区内微生物和尘埃粒子、 表 关于同志近三年现实表现材料材料类招标技术评分表图表与交易pdf视力表打印pdf用图表说话 pdf 面的详细方法，请参阅EN/ISO中相关 标准 excel标准偏差excel标准偏差函数exl标准差函数国标检验抽样标准表免费下载红头文件格式标准下载 。General总则1.Themanufactureofsterileproductsshouldbecarriedoutincleanareasentrytowhichshouldbethroughairlocksforpersonneland/orforequipmentandmaterials.Cleanareasshouldbemaintainedtoanappropriatecleanlinessstandardandsuppliedwithairwhichhaspassedthroughfiltersofanappropriateefficiency.无菌产品的生产要在洁净区域内进行，进入这些区域内的人员、设备或物料，必须通过气闸室。洁净区必须保持一定的洁净级别，空气必须通过适宜效率的过滤器2.Thevariousoperationsofcomponentpreparation,productpreparationandfillingshouldbecarriedoutinseparateareaswithinthecleanarea.Manufacturingoperationsaredividedintotwocategories;firstlythose各种成分的制备、产品的制备和灌装，必须在洁净区的不同区域进行。生产操作分为两类，一是产品最终灭菌型，二是部分过程或全过程的无菌wheretheproductisterminallysterilised,andsecondlythosewhichareconductedasepticallyatsomeorallstages.操作3.Cleanareasforthemanufactureofsterileproductsareclassifiedaccordingtotherequiredcharacteristicsoftheenvironment.Eachmanufacturingoperationrequiresanappropriateenvironmentalcleanlinessleveintheoperationalstateinordertominimizetherisksofparticulateormicrobialcontaminationoftheproductormaterialsbeinghandled.Inordertomeet“inoperation”conditionstheseareasshouldbedesignedtoreachcertainspecifiedair-cleanlinesslevelsinthe“atrest”occupancysee.Thestateistheconditionwheretheinstallationisinstalledandoperating,completewithproductionequipmentbutwithnooperatingpersonnelpresent.Theoperationstateistheconditionwheretheinstallationisfunctioninginthedefinedoperatingmodewiththespecifiednumberofpersonnelworking.The“inoperation”and“atrest”statesshouldbedeachcleanroomorsuiteofcleanrooms.Forthemanufactureofsterilemedicinalproducts4gradescarbedistinguished.无菌生产的洁净区，按照产品对环境的要求分级，每一步生产操作，在操作状态，对环境有相应的洁净级别的l要求，以防止对所处理的物料或产品造成的粉尘或微生物污染最小。为满足操作的要求，这些区域在 设计 领导形象设计圆作业设计ao工艺污水处理厂设计附属工程施工组织设计清扫机器人结构设计 上要达到“静态”的洁净标准。“静态”指设备已经安装并运行，生产设备就位但是没有操作人员在场。“动态”是指在设备正常运转状态下和有规定数量的工作人员在场的情况下。每个或每套房间都要分别确定“静态”和“动态””。无菌药品的生产有4个环境级那efinedforGradeA:Thelocalzoneforhighriskoperations,e.g.fillingzone,stopperbowls,openampoulesandvials,makingasepticconnections.Normallysuchconditionsareprovidedbyalaminarairflowworkstation.Laminarairflowsystemsshouldprovideahomogeneousairspeedinarangeof0.3—0.54m/s(guidaneevalue)attheworkingpositioninopencleanroomapplications.Themaintenanceoflaminarityshouldbedemonstratedandvalidated.Auni-directionalairflowandlowervelocitiesmaybeusedinclosedisolatorsandgloveboxes.A级：用于高风险的生产操作，如灌装区、加盖区、安瓿与瓶开口区、和进行无菌连接的地方。通常这种情况是带有层流罩的工作点。在开放的洁净区内的工作点上，层流罩应该能产生风速为0.36-0.54米/秒的均匀气流。层流罩的维护，必须有充分的证明和经过验证。密封隔离箱和手套箱内，可米用单向低速气流。GradeB:Forasepticpreparationandfilling,thisisthebackgroundenvironmentforthegradeAzone.B级：对于无菌制备和灌装，B级区域是A级区域的背景环境。GradeCandD:Cleanareasforcarryingoutlesscriticalstagesinthemanufactureofsterileproducts.C级和D级：无菌产品非关键生产 步骤 新产品开发流程的步骤课题研究的五个步骤成本核算步骤微型课题研究步骤数控铣床操作步骤 的洁净区。Cleanroomandcleanairdeviceclassification洁净室及洁净空气装置分类4.Cleanroomsandcleanairdevicesshouldbe洁净室及洁净空气装置应符合ENISO14644-1。应根据生产操作环境监测明确地加以区分。最大允许尘埃classifiedinaccordaneewithENISO14644-1.粒子浓度应符合下表要求。|Classificationshouldbeclearlydifferentiatedfromoperationalprocessenvironmentalmonitoring.Themaximumpermittedairborneparticleconcentrationforeachgradeisgiveninthefollowingtable.MaximumpermittednumberofparticlespermequaltoorgreaterthanthetabulatedsizeAtrestInoperationGrade5.0m0.5m5.0mA3.520m35203520203520002000C35200029900[352000029000D352000029000NotdefinedNotdefined大于等于表中尺寸尘埃粒子最大允许数/m3静态动态Grade0.5m5.0m0.5m5.0mA352020352020B3520293520002900C3520002900r352000029000D352000029000NotdefinedNotdefined精品文档精品文档精品文档5.ForclassificationpurposesinGradeAzones,a3minimumsamplevolumeof1mshouldbetakenpersamplelocation.ForGradeAtheairborneparticleclassificationisISO4.8dictatedbythelimitforparticles>5.0卩m.ForGradeB(atrest)tairborneparticleclassificationisISO5forbothconsideredparticlesizes..ForGradeC(atrest&inoperation)theairborneparticleclassificationisISO7andISO8respectively.ForGradeD(atrest)theairborneparticleclassificationisISO8.For在A级区，每个采样点取样量应不小于1m3。A级尘埃粒子分类是根据ISO4.8粒子》5.0卩的数量定义的。B级（静态）尘埃粒子分类根据ISO5要考虑两种大C级（静态&动态）粒子分类分别根据ISO7和ISO8。D级（静态）粒子分类是ISO8。分类是根据EN/ISO14644-1方法论，既明确了最少的取样点数，也规定了取样量和相适应的级别的最大允许颗粒大小和采集数据评价方法。classificationpurposesEN/ISO14644-1methodologydefinesboththeminimumnumberofsamplelocationsandthesamplesizebasedontheclasslimitofthelargestconsideredparticlesizeandthemethodofevaluationofthedatacollected.6.Portableparticlecounterswithashortlengthofsampletubingshouldbeusedfoclassificationpurposesbecauseoftherelativelyhigherrateofprecipitationofparticles>5.0卩minremotesamplingsystemswithlonglengthsoftubing.Isokineticsampleheadsshallbeusedinunidirectionalairflow洁净分级应使用一个带有短取样管的便携式颗粒计数器，因为使用长距离的取样管会采集到远距离猛然落下>5.0卩的粒子的几率相对较高。单向气流系统应使用等动力采样头。systems.7.“Inoperation”classificationmaybedemonstr动态t是在正常生产条件下定义的，模拟duringnormaloperations,simulatedoperationsorduringmediafillsasworst-casesimulationisrequiredforthis.ENISO14644-2providesinformationontestingtodemonstratecontinued操作或在无菌分装的情况下，需要这方面的规定。ENISO14644-2提供了相关测试资料，以证明连续的符合洁净区的分类。complianeewiththeassignedcleanlinessclassifications.Cleanroomandcleanairdevicemonitoring8.Cleanroomsandcleanairdevicesshouldberoutinelymonitoredinoperationandthemonitoringlocationsbasedonaformalriskanalysisstudyandtheresultsobtainedduringtheclassificationofroomsand/orcleanairdevices.9.ForGradeAzones,particlemonitoringshouldbeundertakenforthefulldurationofcriticalprocessing,includingequipmentassembly,exceptwherejustifiedbycontaminantsintheprocessthatwoulddamagetheparticlecounterorpresentahazard,e.g.liveorganismsandradiologicalhazards.Insuchcasesmonitoringduringroutineequipmentsetup洁净室及洁净空气监测装置洁净室及洁净空气装置应动态条件下定期监测，监测的位置应基于正式的风险评估和日常监测结果。A级区，粒子监测应覆盖全部的关键操作，包括设备装配，除非有正当理由证明污染物这个进程将损害粒子计数器或具有危险性，例如：活生物体和辐射危害。在这类情况下，日常设定操作的监测应该在暴露之前评估风险，模拟操作期间也应该监测。应该监测A级区域以一定的频精品文档精品文档精品文档精品文档率和适当采样量，所有干预、瞬变事件和任何系统恶化都能被捕获，并且如果超出报警限能报警。分装操作过程中，＞5.0微粒可能不总是符合较低的标准要求的，只要证明微粒或小滴是从产品产生的就可以了。推荐B级区也使用和A级区类似的系统。虽然取样频率可能会减少，重要的是粒子监测系统应取决于有效的毗邻A级和B级区的隔离间。B级区也应以一定的频率和合适的取样量监测，污染程度变化的和任何系统恶化都能被捕获，并且如果超出报警限能警报。尘埃粒子监测系统，可以是独立的颗粒计数器；也可以是以单个粒子计数器采样点相连的网络，或者两者兼而有之。该系统的选定一定要适合粒子大小。而使用远程取样系统，应考虑取样管的长度及延伸的半径，必须考虑采样管中的粒子损失。选用何种监测系统应考虑当前药品存在的风险，例如那些涉及活生物体或放射性药品。使用自动化系统的采样量通常会和采用速率有一个函数关系。这样就没有必要采用和正常的洁净室分类及洁净空气装置相同的监测频率。在A级和B区，监测的＞5.0卩的粒子浓度计数问题就显得特别重要的意义，因为这是一个重要的诊断工具，以便及早发operationsshouldbeundertakenpriortoexposuretotherisk.Monitoringduringsimulatedoperationsshouldalsobeperformed.TheGradeAzoneshouldbemonitoredatsuchafrequencyandwithsuitablesamplesizethatallinterventions,transienteventsandanysystemdeteriorationwouldbecapturedandalarmstriggeredifalertlimitsareexceeded.Itisacceptedthatitmaynotalwaysbepossibletodemonstratelowlevelsof>5.0卩mparticlesatthepointoffillwhenfillingisinprogress,duetothegenerationofparticlesordropletsfromtheproductitself.ItisrecommendedthatasimilarsystembeusedforGradeBzonesalthoughthesamplefrequencymaybedecreased.TheimportaneeoftheparticlemonitoringsystemshouldbedeterminedbytheeffectivenessofthesegregationbetweentheadjacentGradeAandBzones.TheGradeBzoneshouldbemonitoredatsuchafrequencyandwithsuitablesamplesizethatchangesinlevelsofcontaminationandanysystemdeteriorationwouldbecapturedandalarmstriggeredifalertlimitsareexceeded.Airborneparticlemonitoringsystemsmayconsistofindependentparticlecounters;anetworkofsequentiallyaccessedsamplingpointsconnectedbymanifoldtoasingleparticlecounter;oracombinationofthetwo.Thesystemselectedmustbeappropriatefortheparticlesizeconsidered.Whereremotesamplingsystemsareused,thelengthoftubingandtheradiiofanybendsinthetubingmustbeconsideredinthecontextofparticlelossesinthetubing.Theselectionofthemonitoringsystemshouldtakeaccountofanyriskpresentedbythematerialsusedinthemanufacturingoperation,forexamplethoseinvolvingliveorganismsorradiopharmaceuticals.Thesamplesizestakenformonitoringpurposesusingautomatedsystemswillusuallybeafunctionofthesamplingrateofthesystemused.Itisnotnecessaryforthesamplevolumetobethesameasthatusedforformalclassificationofcleanroomsandcleanairdevices.InGradeAandBzones,themonitoringofthe>5.0卩mparticleconcentrationcdakfesonaparticularsignificanceasitisanimportantdiagnostic现失败的。偶尔显示>5.0（1r的粒子计数se能是虚假的计数因电子噪声，杂散光，巧合等，但连续或规则的失败可能是污染事件，应该进行调查。这类事件可能表明，早期失效的暖通空调系统，灌装设备故障或可能因为乏味的操作，设备安装和日常运作。toolforearlydetectionoffailure.Theoccasionalindicationof>5.01mparticlecountsmaybecountsduetoelectronicnoise,straylight,coincidenee,etc.Howeverconsecutiveorregularcountingoflowlevelsisanindicatorofapossiblecontaminationeventandshouldbeinvestigated.SucheventsmayindicateearlyfailureoftheHVACsystem,fillingequipmentfailureormayalsobediagnosticofpoorpracticesduringmachineset-upandroutineoperation.Theparticlelimitsgiveninthetableforthe在无人状态，“a-20分钟(指导值)自净periodof15-20minutes(guidaneevalue)inanunmannedstateaftercompletionofoperations.ThemonitoringofGradeCandDareasinoperationshouldbeperformedinaccordaneewiththeprinciplesofqualityriskmanagement.Therequirementsandalert/actionlimitswilldependonthenatureoftheoperationscarriedout,buttherecommended“cleanupperiodhoulbbeattained.Othercharacteristicssuchastemperatureandrelativehumiditydependontheproductandnatureoftheoperationscarriedout.Theseparametersshouldnotinterferewiththedefinedcleanlinessstandard.ExamplesofoperationstobecarriedoutinthevariousgradesaregiveninthetablebelowC级和D区的监察应根据质量风险管理的原则动态进行。标准和报警/行动限应根据日常监测制定，还应制定“自净周期”其他特点，如温度和相对湿度在很大程度上依赖于产品和业务活动的性质进行的。这些参数不应该干涉与界定洁净标准。不同级别的操作实例参看下面内容（亦见第28至35位）rest”stateshouldbeachievedaftshort“cleanup期间，粒子应符合列表中的静态标准。菌准备型操作分级举例：A、无菌准备与灌装B、准备即将过滤的溶液C、在清洗后处理部件如无菌操作应频繁进行沉降菌，浮游菌和表面微生物（擦拭和接触）的监测。取样的方法不应干涉区域的保护。产品放行审(seealsoparagraphs28to35):AFillingofproducts,whenunusuallyatriskCPreparationofsolutions,whenunusuallyatrisk.FillingofproductsDPreparationofsolutionsandcomponentsforsubsequentfillingGradeExamplesofoperationsforasepticpreparations.(seeparagraphs.31-35)AAsepticpreparationandfilling.CPreparationofsolutionstobefiltered.DHandlingofcomponentsafterwashing.Whereasepticoperationsareperformedmonitoringshouldbefrequentusingmethodssuchassettleplates,volumetricairandsurfacesampling查批记录时应考虑监测的结果。关键操作后，应对表面和人员应当进行监测，在生产操作之外如验证后，清洁和消毒后进行微生物监测。(e.g.swabsandcontactplates).Samplingmethodsusedinoperationshouldnotinterferewithzoneprotection.Resultsfrommonitoringshouldbeconsideredwhenreviewingbatchdocumentationforfinishedproductrelease.Surfacesandpersonnelshouldbemonitoredaftercriticaloperations.Additionalmicrobiologicalmonitoringisalsorequiredoutsideproductionoperations,e.g.aftervalidationofsystems,cleaningandsanitisation.Recommendedlimitsformicrobiological建议上限微生物监测的清洁区操作:monitoringofcleanareasduringoperation:Recommendedlimitsformicrobialcontamination(a)Gradeairsamplecfu/msettleplates(diameter90mm)cfu/4hours(b)contactplates(diameter55mm)cfu/plategloveprint5fingerscfu/glovA<1<1<1<1B10555C1005025-D20010050-Theseareaveragevalues.Individualsettleplatesmaybeexposedforlessthan4hours.Appropriatealertandactionlimitsshouldbesetfortheresultsofparticulateandmicrobiologicalmonitoring.Iftheselimitsareexceededoperatingproceduresshouldprescribecorrectiveaction。Isolatortechnology（一）这些都是平均值。（二）单个沉降皿放置的时间可以少于4小时。对尘埃粒子和微生物的监控结果，要设置适当的警戒限度和行动限度。当超出这些限度时，操作规程应说明需要采取的措施。隔离技术在生产区采用人员方面的隔离技术，在无菌产品的生产中，会显著降低周围环境微生物污染的风险。有很多隔离和传递设施可供选择，隔离和背景环境的设计，必须保证各区域相应的空气质量要求。隔离设施的建造材料，多少有些易于穿孔和泄漏。传递设施可以是单门、双门或结合无菌机制的全封闭系统。Theutilisationofisolatortechnologytominimizehumaninterventionsinprocessingareasmayresultinasignificantdecreaseintheriskofmicrobiologicalcontaminationofasepticallymanufacturedproductsfromtheenvironment.Therearemanypossibledesignsofisolatorsandtransferdevices.Theisolatorandthebackgroundenvironmentshouldbedesignedsothattherequiredairqualityfortherespectivezonescanberealised.Isolatorsareconstructedofvariousmaterialsmoreorlesspronetopunctureandleakage.Transferdevicesmayvaryfromasingledoortodoubledoordesignstofullysealedsystems精品文档精品文档精品文档incorporatingsterilizationmechanisms.22.Thetransferofmaterialsintoandoutoftheunitisoneofthegreatestpotentialsourcesofcontamination.Ingeneraltheareainsidetheisolatoristhelocalzoneforhighriskmanipulations,althoughitisrecognisedthatlaminarairflowmaynotexistintheworkingzoneofallsuchdevices.原材料的进出是污染的最大来源之一。尽管人们已经认可，层流罩不可能存在于所有隔离设施的工作区内，但是，通常隔离区内是高风险操作的局部区域。Theairclassificationrequiredforthebackgroundenvironmentdependsonthedesignoftheisolatoranditsapplication.ItshouldbecontrolledandforasepticprocessingitshouldbeatleastgradeD.Isolatorsshouldbeintroducedonlyafterappropriatevalidation.Validationshouldtakeintoaccountallcriticalfactorsofisolatortechnology,forexamplethequalityoftheairinsideandoutside(background)theisolator,sanitisationoftheisolator,thetransferprocessandisolatorintegrity.Monitoringshouldbecarriedoutroutinelyandshouldincludefrequentleaktestingoftheisolatorandglove/sleevesystem背景环境的洁净级别，视隔离区的设计和应用而定。要控制无菌生产的背景环境，并且最低为D级在经过适当的验证之后，隔离器才能使用。验证必须将隔离技术的所有关键因素考虑在内，如：隔离器的内外部空气质量、隔离器的消毒，传递过程和隔离器的完整性。必须进行常规监控，包括隔离室和手套/袖系统的泄漏检查。Blow/fill/sealtechnoIogym.(26-27)吹/灌佳寸技术Terminallysterilisedproducts(28-30)最终灭菌产品AsepticpreparationComponentsafterwashingshouldbehandledinatleastagradeDenvironment.Handlingofsterilestartingmaterialsandcomponents,uniesssubjectedtosterilisationorfiltrationthroughamicro-organism-retainingfilterlaterintheprocess,shouldbedoneinagradeAenvironmentwithgradeBbackground.PreparationofsolutionswhicharetobesterilefilteredduringtheprocessshouldbedoneinagradeCenvironment;ifnotfiltered,thepreparationofmaterialsandproductsshouldbedoneinagradeAenvironmentwithagradeBbackground.Handlingandfillingofasepticallyprepared无菌制备清洗后的材料要在最低D级环境下处理。无菌产品的原料和辅料，除非将在生产过程中进行灭菌或采用微生物滞留过滤器过滤除菌，要在B级环境下的A级区处理。采用过滤除菌的溶液的制备，要在C级环境下进行，如果不过滤，要在B级环境下的A级区处理。通过无菌方法生产的产品，要在B级环境下精品文档精品文档精品文档精品文档的A级区处理和灌装。在完成加盖前，半密封容器的传递，如在冻干中使用的，要在B级环境下的A级区进行，或在B级环境中的密封的转移盘中进行。只有工作需要的最低人数可以进入洁净区，这对无菌生产过程特别重要。检查和控制都要尽可能在洁净区外面进行。所有在这些区域工作的人员（包括清洁和维护人员）都要定期进行与无菌药品生产有关的纪律培训。这些培训要包括卫生和微生物学的基本知识。当外来的没有接受培训的人员（如建造或维修人员）需要进入时，要特别注意给予指导和监督。从事动物组织加工处理或微生物培养的人员，不包括生产在用的材料，除非遵照严格明确的进入程序，不可进入洁净区。高标准的人员卫生和清洁是非常关键的。要指导涉及生产的人员，及时 报告 软件系统测试报告下载sgs报告如何下载关于路面塌陷情况报告535n,sgs报告怎么下载竣工报告下载 可能产生异常污染的任何情况；要对人员定期进行健康检查。对可能带来微生物污染的人的处理措施，要由指定的合格的人员作出决定。productsshouldbedoneinagradeAenvironmentwithagradeBbackground.Priortothecompletionofstoppering,transferofpartiallyclosedcontainers,asusedinfreezedryingshouldbedoneeitherinagradeAenvironmentwithgradeBbackgroundorinsealedtransfertraysinagradeBenvironment.Preparationandfillingofsterileointments,如果产品有暴露和不再进行灭菌，软膏、霜creams,suspensionsandemulsionsshouldbedone剂、混悬齐V、栓齐U和乳齐U的制备和灌装，要inagradeAenvironment,withagradeB在B级环境下的A级区处理。background,whentheproductisexposedandisnotsubsequentlyfiltered.Personnel人员Onlytheminimumnumberofpersonnelrequiredshouldbepresentincleanareas;thisisparticularlyimportantduringasepticprocessing.Inspectionsandcontrolsshouldbeconductedoutsidethecleanareasasfaraspossible.Allpersonnel(includingthoseconcernedwithcleaningandmaintenance)employedinsuchareasshouldreceiveregulartrainingindisciplinesrelevanttothecorrectmanufactureofsterileproducts.Thistrainingshouldincluderefereneetohygieneandtothebasicelementsofmicrobiology.Whenoutsidestaffwhohavenotreceivedsuchtraining(e.g.buildingormaintenancecontractors)needtobebroughtin,particularcareshouldbetakenovertheirinstructionandsupervision.Staffwhohavebeenengagedintheprocessingofanimaltissuematerialsorofculturesofmicro-organismsotherthanthoseusedinthecurrentmanufacturingprocessshouldnotentersterile-productareasuniessrigorousandclearlydefinedentryprocedureshavebeenfollowed.Highstandardsofpersonalhygieneandcleanlinessareessential.PersonnelinvoIvedinthemanufactureofsterilepreparationsshouldbeinstructedtoreportanyconditionwhichmaycausethesheddingofabnormalnumbersortypesofcontaminants;periodichealthchecksforsuchconditionsaredesirable.Actionstobetakenaboutpersonnelwhocouldbeintroducingunduemicrobiologicalhazardshouldbedecidedbyadesignatedcompetentperson.Wristwatches,make-upandjewelleryshouldnotbewornincleanareas.Changingandwashingshouldfollowawrittenproceduredesignedtominimizecontaminationofcleanareaclothingorcarry-throughofcontaminantstothecleanareas.Theclothinganditsqualityshouldbeappropriatefortheprocessandthegradeoftheworkingarea.Itshouldbeworninsuchawayastoprotecttheproductfromcontamination.Thedescriptionofclothingrequiredforeachgradeisgivenbelow:GradeD:Hairand,whererelevant,beardshouldbecovered.Ageneralprotectivesuitandappropriateshoesorovershoesshouldbeworn.Appropriatemeasuresshouldbetakentoavoidanycontaminationcomingfromoutsidethecleanarea.GradeC:Hairandwhererelevantbeardandmoustacheshouldbecovered.Asingleortwo-piecetrousersuit,gatheredatthewristsandwithhighneckandappropriateshoesorovershoesshouldbeworn.Theyshouldshedvirtuallynofibresorparticulatematter.GradeA/B:Headgearshouldtotallyenclosehairand,whererelevant,beardandmoustache;itshouldbetuckedintotheneckofthesuit;afacemaskshouldbeworntopreventthesheddingofdroplets.Appropriatesterilised,non-powderedrubberorplasticglovesandsterilisedordisinfectedfootwearshouldbeworn.Trouser-legsshouldbetuckedinsidethefootwearandgarmentsleevesintothegloves.Theprotectiveclothingshouldshedvirtuallynofibresorparticulatematterandretainparticlesshedbythebody.OutdoorclothingshouldnotbebroughtintochangingroomsleadingtogradeBandCrooms.ForeveryworkerinagradeA/Barea,cleansterile(sterilisedoradequatelysanitised)protectivegarmentsshouldbeprovidedateachworksession.在洁净区内不准戴手表、首饰和化装。要按照书面的更换和清洗程序，尽可能降低对洁净区工作服的污染或将污染物带进洁净区。工作服及其质量必须适应所从事的工作和工作场所的洁净级别。要正确穿戴，防止对产品产生污染。下面对各个级别洁净区的工作服的要求进行说明：D级：头发和胡须要覆盖，要穿戴一般工作服和合适的工作鞋或鞋套。要采取适当措施防止污染物从外界进入洁净区。C级要覆盖头发和所有胡须，要穿戴一件或两件套裤式、袖口收拢、高领的工作服，穿合适的工作鞋或鞋套。这些工作服都不得脱落纤维或颗粒。A/B级：头套要覆盖所有的头发和胡须并要收紧在工作服领子内；要带口罩以防止液体飞沫的喷射。要穿戴正确消毒后的、不脱落粉尘的橡胶或塑料手套、灭菌或消毒的鞋子。袖口要塞进手套内，裤腿要塞进鞋子里。保护工作服要不脱落任何纤维或颗粒，并阻隔身体产生的颗粒。外界的衣服不得带进通向B级和C级的更衣室。在A/B级区域工作的各个岗位工作的人员，要穿戴洁净服（灭菌的或充分消毒的）在生产操作中要对手套定期消毒。每班都要更换口罩和手套。Glovesshouldberegularlydisinfectedduringoperations.Masksandglovesshouldbechangedatleastforeveryworkingsession.45.Cleanareaclothingshouldbecleanedandhandiedinsuchawaythatitdoesnotgatheradditionalcontaminantswhichcanlaterbeshed.Theseoperationsshouldfollowwrittenprocedures.Separatelaundryfacilitiesforsuchclothingaredesirable.Inappropriatetreatmentofclothingwilldamagefibresandmayincreasetheriskofsheddingofparticles.洁净区工作服的清洁和处理的方法，要保证不吸附或携带随后又会脱落的污染物。这些操作要按照书面规程。这些工作服最好分开洗涤。对工作服不适当的处理方法会损害纤维、增加颗粒脱落的风险。PremisesIncleanareas,allexposedsurfacesshouldbesmooth,imperviousandunbrokeninordertominimizethesheddingoraccumulationofparticlesormicro-organismsandtopermittherepeatedapplicationofcleaningagents,anddisinfectantswhereused.Toreduceaccumulationofdustandtofacilitatecleaningthereshouldbenouncleanablerecessesandaminimumofprojectingledges,shelves,cupboardsandequipment.Doorsshouldbedesignedtoavoidthoseuncleanablerecesses;slidingdoorsmaybeundesirableforthisreason.Falseceilingsshouldbesealedtopreventcontaminationfromthespaceabovethem.Pipesandductsandotherutilitiesshouldbeinstalledsothattheydonotcreaterecesses,unsealedopeningsandsurfaceswhicharedifficulttoclean.SinksanddrainsshouldbeprohibitedingradeA/Bareasusedforasepticmanufacture.Inotherareasairbreaksshouldbefittedbetweenthemachineorsinkandthedrains.Floordrainsinlowergradecleanroomsshouldbefittedwithtrapsorwatersealstopreventback-flow.Changingroomsshouldbedesignedasairlocksandusedtoprovidephysicalseparationofthedifferentstagesofchangingandsominimizemicrobialandparticulatecontaminationofprotectiveclothing.Theyshouldbeflushedeffectivelywithfilteredair.Thefinalstageofthechangingroomshould,intheat-rest