原料药生产质量管理手册

文件内容：INDEX：1、质量方针………….………...4QualityPolicy………….……...42、质量管理原则…...……………….……………4PrinciplesforQualityAssurance…………...…….…………..43、定义….………...……………….6Definitions…………….……….……………….64、人员管理………....……………………..…….10PersonnelandOrganization…………………....…………...105、培训……...…….……………….…….……………….………15Training………………...…….……………….…….……….….….…………156、厂房……………………...……16Premises…………..………......167、消毒与卫生……………………..………..…21SanitationandHygiene……….………………..……….……..2127MaterialsSupply…………….………………..………………2730Manufacturing-DocumentationandRecords…….………………..………3010、原料药生产………………….………………..…………….39ManufactureOfAPI…………….………………..…………….3911、质量文件与记录………………….………………..………52.DocumentationandRecords…….………………..……………..………5212、质控处文件与记录………………….………………..…………….………63QualityControl…………….………………..…………..…...…6313、检验报告单………………….………………..…….………84CertificateofAnalysis…………….………………..……..……8414、有效期和复检期………………….………………..………………..………84ExpiryandRetestDating……………….……………..….……8415、留样……………….…….…………..…….…85ReserveSamples………….…….…………..….…8516/Retention仓、储………………….………………..………………….…86Warehousingand8617、委托生产/委托检验….………………..……96ContractAnalysis…….………………..……………...…9618证……………….………………..…………………..…99Manufactureand验、Validations……………….………………..…………………9919回…….………………..…………………..106CustomerComplaintsRecalls…….………………..…………………106、客户投诉与召and……108SelfInspection………….………………..………………….10821、产品质量回Quality控顾…….………………..…….109ProductReview……………….………………..……10922、变更制…….………………..……………110ChangeControl….………………..…………110发放范围：全厂文件复审：复审人复审日期复审意见编审批过程：部门签名日期1、质量方针QualityPolicy：“质量”的定义是指为符合预定用途所具有的一系列固有特性的程度。质量体系是基于一定的设备、人员基础上通过设计、文件化、执行及控制来实现预期质量、纯度、安全性及稳定性等目标的系统。根据质量系统分工，各部门包括研发、生产、技术、仓储、销售、质量和质检等部门分工合作，共同实现质量方针。质量管理体系主要包括验证、GMP、文件、内审、培训及客户投诉。质量目标的最终实现是基于全员范围质量方针、质量通则贯彻落实基础上实现的。Our‘QUALITY’philosophyisasynthesisorworldguidelines,lawsregulationsandbesthumanrequirements,whichenableustocatertothebestneedsofourcustomers.The‘QUALITY’systemisdesigned,documented,implementedandcontrolledwhichisbasedoninstrumentation,manpowerandmanagementdesiresoastogiveaassurancethattheproductsmanufacturedbythecompanywillbeconsistentintheirintendedusewithrespectivetoquality,purity,safety,efficacyandstability.Itismonitoredbyateamresponsibleforvalidation,GMP,documentation,self-audits,trainingandmarketcomplaints.Theultimate‘QUALITY’goalisachievedbyeveryoneadheringtoqualitypolicyandprinciple.2、质量管理原则PRINCIPLESFORQUALITYASSURANCE我公司保证产品质量安全可靠，我厂质量管理能够实现质量目标。Wepledgedtoassurethatitsproductsandservicesareofhighqualitywithregardtosafety,propertiesofuseandmanagementofShenyangAntibioticManufactureisfullycommittedtosupportingallnecessarymeasures.质量目标基于下列要求的制定：QualityAssurancecomprisesthetotalityofallmeasuresdesiredtoachievethisaimtakingintoaccount（1）客户的需求Theneedsofourcustomers（2）相关法规要求Therelevantlegalrequirements（3）工艺要求Thestateoftheart（4）内控质量标准。Theinhousestandards产品质量的保证是研发、供应、生产、仓储、销售等部门必须各自制定并完成相应质量目标从而实现的。Thequalityassuranceofproductsandservicesisthereforeacompanyobligation,whichmustbesharedbythedepartmentsfordevelopment,purchasing,manufacturing,distribution,marketingandbyallothermembers.质量部的职责：TheQualityAssuranceDepartment’sDuty：（1）质量标准的建立及更新；Ensuresthatappropriatequalitystandardsareset,maintainedandkeptuptodate.（2）生产过程质量监督管理；Supervisestheimplementationofallnecessarymeasuresthroughtheline/manufacturingfunctions.（3）提高全员质量意识。Playsaleadingroleinpromotingqualityawarenessthroughoutthecompany.质量部的工作：ThetasksoftheQualityAssuranceDepartmentinclude:（1）生产及委托生产生产过程监督指导；Technicalguidanceandsupervisiontodifferentmanufacturingunitsownedbythecompanyandthirdparties.（2）协调相关部门建立各项标准；Settingstandardsinco-operationwithalldepartmentsconcerned.（3）生产储存及发运的全过程实施质量管理；Implementingqualityassurancemeasuresatalllevelsofmanufacture,storageanddistribution.（4）组织应对突发事件及产品召回；Organizingemergencyandrecallprocedures.质量部长直接向厂长汇报工作，独立于销售、生产、供应及研发部门。QualityAssuranceDepartmentministerreportstoDirectorofthecompanysoastoensureindependencefrommarketing,manufacturing,purchasingandR&Ddepartments.遵守有关部门各项法律法规要求。Promisetoobservealltherelevantauthoritiesonqualityassurancematters.3、定义DEFINITIONS批Batch在连续生产中，批量可以定义为一定数量或一段时间内生产的产品的集合。Aspecificquantityofmaterialproducedinaprocessorseriesofprocessessothatitisexpectedtobehomogeneouswithinspecifiedlimits.Inthecaseofcontinuousproduction,abatchmaycorrespondtoadefinedfractionoftheproduction.Thebatchsizecanbedefinedeitherbyafixedquantityofbytheamountproducedinafixedtimeinterval.批号BatchNumber一组唯一对应、用于区分不同产品或物料从进厂到交付出厂过程，便于追溯生产全过程的数字、字母和/或符号的组合。Auniquecombinationofnumbers,letters,and/orsymbolsthatidentifiesabatch(orlot)andfromwhichtheproductionanddistributionhistorycanbedetermined.批生产和控制记录Batchproductionandcontrolrecord基于技术转移文件根据生产工艺流程编写的、用于描述给定批次产品其原料及生产过程的文件。Adocumentstatingthematerialsusedandtheoperationscarriedoutduringtheprocessingofagivenbatch.ItshouldbebasedonthetechnologytransferdocumentandMethodandbecompiledasthemanufacturingoperationproceeds.批包装记录BatchPackagingRecord基于技术转移文件并按照包装操作过程编写的用于描述指定批次成品、包材及包装过程的文件。如需分步骤包装，每步分别记录。Adocument(ordocuments)statingthefinishedproductandpackagingmaterialsused,andtheprocessescarriedoutduringthepackagingofagivenbatch.Itshouldbebasedonthetechnologytransferdocumentandbecompiledduringthepackagingoperation.Abatchmaybepackagedinseveralparts,eachwithitsowncompletesetofpackagingdocumentation/records.校验Calibration体现仪器设备经检定符合相关标准限度要求的材料。Thedemonstrationthataparticularinstrumentordeviceproducesresultswithinspecifiedlimitsbycomparisonwiththoseproducedbyareferenceortraceablestandardoveranappropriaterangeofmeasurements.控制程序ControlProcedure规定原料、包装材料、过程产品、成品质量标准和检测方法的文件。Adocumentgivingspecificationsandtestproceduresforstartingmaterials,packagingmaterials,Inprocess,finishedproducts.原料药Activepharmaceuticalingredient(Drugsubstance)治疗、预防，影响机体的结构与功能的物质或混合物。Anysubstanceormixtureofsubstancesintendedtobeusedinthemanufactureofadrug(medicinal)productandthat,whenusedintheproductionofadrug,becomesanactiveingredientofthedrugproduct.Suchsubstancesareintendedtofurnishpharmacologicalactivityorotherdirecteffectinthediagnosis,cure,mitigation,treatment,orpreventionofdiseaseortoaffectthestructureandfunctionofthebody.药品生产质量管理规范GoodManufacturePractice（GMP）药品生产质量管理规范（GMP）是定义并有效组织生产操作以确保持续稳定地生产出符合预定用途和注册要求的药品的操作规范。GoodManufacturingPracticeisthedefinitionandorganizationofmanufacturingoperationstoensurethatproductsareconsistentlyproduced,tested,andcontrolledtothequalitystandardsappropriatetotheirintendeduseandinaccordancewiththeregisteredrequirements.过程控制In-processControl在生产过程中监管并调整工艺以确保原料药符合质量标准的行为。Checksperformedduringproductioninordertomonitorand,ifappropriate,toadjusttheprocessand/ortoensurethattheAPIconformstoitsspecification.主生产和管理记录Masterproductionandcontrolrecord描述药品生产的起始物料及其数量、生产操作过程控制细节（一般除包装外）的文件。Adocumentstatingthestartingmaterials,withtheirquantities,tobeusedinthemanufactureofamedicinalproduct,togetherwithadescriptionofthemanufacturingoperationsincludingdetailsofspecificin-processcontrols,butnormallyexcludingpackaginginformation主包装指令MasterPackagingInstruction用于描述物料包装过程使用的包材、包装方式、包装过程控制细节的文件。包括贴标签或唛头等的操作。Adocumentlistingthecomponentstobeusedforastatedcontainerorpackagetogetherwithadescriptionofthemethodofpackagingandwithdetailsofspecificin-processcontrols.Theinstructionsmayincludethemethodofassemblingthecomponentparts.包装材料PackagingMaterial用于产品包装的物料，一般不包括苫布、集装箱等。Anymaterialusedinthepackagingofaproduct.Thetermisnotnormallyextendedtocovertheouterpackagingordeliverycasesusedforthetransportationorshipmentoforders.包材分类：TheClassificationforpackingmaterial：（1）直接接触产品的包装材料，即内包材；Packagingmaterialswhichcomeincontactwiththeproduct(oftencalled`PrimaryPackagingMaterials')（2）中级包装材料，外包材；Secondarypackagingmaterials（3）其他包装材料。Otherpackagingmaterials确认Qualification验证设备或辅助设施正确安装、正常运转、能够实现预期效果的操作。确认是验证的一部分，但仅有确认验证并不是完整的工艺验证。Actionofprovinganddocumentingthatequipmentorancillarysystemsareproperlyinstalled,workcorrectly,andactuallyleadtotheexpectedresults.Qualificationispartofvalidation,buttheindividualqualificationstepsalonedonotconstituteprocessvalidation.质量保证QualityAssurance质量保证是以保证产品质量达到预期要求为目的，组织和管理活动的总和。质量保证协调GMP与其他外在因素如原始设计和实际发展等的资源配置。QualityAssuranceisthesumtotaloftheorganizedarrangementsmadewiththeobjectofensuringthatproductswillbeofthequalityrequiredfortheirintendeduse.QualityAssurancethereforeincorporatesGoodManufacturingPracticeplusotherfactorsoutsidethescopeoftheserules,.originaldesignanddevelopment.隔离Quarantine在未决定物料批准或拒收之前，物料应单独存放或其他有效措施隔离的状态。Thestatusofmaterialsisolatedphysicallyorbyothereffectivemeanspendingadecisionontheirsubsequentapprovalorrejection.半成品Semi-finishedProduct完成所有生产步骤准备包装产品（即散装产品）Aproduct,whichhascompletedallstagesofproduction,andisreadyforpackaging(Alsoknownasbulkproduct).标准操作规程StandardOperatingProcedure(SOP)经审批、可作为批生产文件补充规定的通用操作标准（如设备操作、维护与清洁、区域清Awrittenauthorizedprocedure,whichgivesinstructionsforperformingoperationsnotnecessarilyspecifictoagivenproductormaterial,butofamoregeneralnature.equipmentoperation,maintenanceandcleaning,cleaningofpremisesandenvironmentalcontrol,samplingandinspection,etc).CertainStandardOperatingProceduresmaybeusedtosupplementtheproduct-specificBatchproductiondocumentation.原料StartingMaterial除包材外用于生产药物的原料、辅料、中间体等物料。Anysubstanceusedinthemanufactureofamedicinalproduct,butexcludingpackagingmaterials.Astartingmaterialissometimesknownasarawmaterialoraningredient,althoughnotallstartingmaterialsnecessarilyremainasingredientsofthefinalproduct.验证Validation有效保证某一工艺、方法或系统可持续产生符合既定标准的文件程序。Adocumentedprogramthatprovidesahighdegreeofassurancethataspecificprocess,method,orsystemwillconsistentlyproducearesultmeetingpre-determinedacceptancecriteria.4、人员管理PERSONNELORGANISATION通则GeneralRequirements人事处应为各部门配备足够数量的胜任相应工作能力、培训、经验、专业技术资格和管理技能方面要求的员工。Thereshouldbesufficientnumberofpersonnelatalllevelswiththeability,training,experienceandwhatevernecessaryprofessional/technicalqualificationsandmanagerialskillsappropriatetothetasksassignedtothem.建立组织机构图，明确各负责人职责权限。质量相关的工作职责不应存在空缺或重叠。Thereshouldbeanorganizationchartandallresponsiblepersonsshouldhavetheirdutiesclarifiedandadequateauthoritytocarryouttheirresponsibilities.ThereshouldnotbegapsorunexplainedoverlapsintheresponsibilitiesofpersonnelconcernedwithGMPapplications.负责生产、质保、销售、产品出厂环节的工作人员为关键人员。负责生产和质保的人员不能兼任，但均有责任实现质量要求。Keypersonnelincludepersonresponsibleforproduction,personresponsibleforqualityassuranceandpersonresponsibleforsales/distribution.Differentpersonsshouldberesponsibleforproductionandqualityassurance,neitherofwhoshouldberesponsibleforother,butwhobothhaveaachievingtherequisitequality.responsibilityfor负责监督生产和质量的关键人员应具备化学、药剂学、化学工艺、微生物等学科工艺培训经历及法规要求的操作经验等资质。从事新工作项时应遵循专业人员指导。Thekeypersonnelresponsibleforsupervisingtheproductionandqualityassuranceshouldpossessthequalificationofscientificeducationandpracticalexperiencerequiredfornationallegislation.ThisincludesstudyofChemistry,Pharmacy,ChemicalTechnology,Microbiologyorotherrelatedgainingthepracticalexperience,theyshouldexercisetheirdutiesunderprofessionalguidance.上述关键人员除生产关系外禁止利益往来或冲突以便执行指定的职责。Suchkeypersonnelshouldnothave,preferably,anyinterestsoutsidethemanufacturer'sorganizationsoastopreventorrestricttheirdevotingthenecessarytimetotheirassigneddutiesand/orresultintoconflictoffinancialinterest.兼职人员或顾问禁止从事关键岗位操作。Personsengagedpart-timeorinconsultativecapacityshouldnotbeappointedtokeypositions.关键岗位职能可以委托，但是职责不能委托。Thedutiesofthekeypersonnelmaybedelegatedtothedesignateddeputieswithasatisfactoryqualification.However,theresponsibilitycannotbedelegated.主要职责KeyResponsibilities明确定义关键人员职责并依据指导方针和相关法律法规进行委派。Responsibilitiesofkeypersonnelshouldbeclearlydefinedandallocatedinaccordancewiththeseguidelinesandnationallegislation.生产部门职责：Theproductiondepartmenthasthefollowingresponsibilities:（1）根据书面程序起草、审核、批准并下发原料药生产指令单，根据预先批准的指令生产原料药或中间体。Preparing,reviewing,approvinganddistributingtheinstructionsfortheproductionofAPIsaccordingtowrittenAPIsand,whenappropriate,intermediatesaccordingtopre-approvedinstructions.（2）审核所有批次产品记录，确保已完成并签字。Reviewingallproductionbatchrecordsandensuringthatthesearecompletedandsigned.（3）确保产品偏差的及时上报及评估，调查关键偏差并记录结论。Makingsurethatallproductiondeviationsarereportedandevaluatedandthatcriticaldeviationsareinvestigatedandtheconclusionsarerecorded.（4）确保生产设施清洁和定期消毒。Makingsurethatproductionfacilitiesarecleanandwhenappropriatedisinfected.（5）确保校验的执行及记录存档。Makingsurethatthenecessarycalibrationsareperformedandrecordskept.（6）确保厂房和设备的维护保养及相关记录存档。Makingsurethatthepremisesandequipmentaremaintainedandrecordskept.（7）确保验证方案及报告经审核并获得批准。Makingsurethatvalidationprotocolsandreportsarereviewedandapproved.（8）提出产品、工艺或设备变更。Evaluatingproposedchangesinproduct,processorequipment.（9）确保设备设施改造或新增符合要求。Makingsurethatnewand,whenappropriate,modifiedfacilitiesandequipmentarequalified.其他职责见本手册相关章节要求。Otherdutiesaregivenintherelevantsectionofthismanual.质量部门有权参与质量相关全部事宜，其主要职责不予委派且包括但不仅限以下项：Thequalityunitsshouldbeinvolvedinallqualityrelatedmatters.Themainresponsibilitiesoftheindependentqualityunit(s)shouldnotbedelegated.Theseresponsibilitiesshouldbedescribedinwritingandshouldincludebutnotnecessarilybelimitedto（1）原料药放行或拒收。ReleasingorrejectingallAPIs.（2）建立原料、中间体、包材及标签的放行或拒收系统。Establishingasystemtoreleaseorrejectrawmaterials,intermediates,packagingandalllabelingmaterials.（3）原料药放行前审核完成的批产品生产和关键步骤检测记录。ReviewingcompletedbatchproductionandlaboratorycontrolrecordsofcriticalprocessstepsbeforereleaseoftheAPIfordistribution.（4）确保重大偏差的调查及关闭。Makingsurethatcriticaldeviationsareinvestigatedandresolved.（5）审批质量标准和生产指令。Approvingallspecificationsandproductioninstructions.更。Approvingallproceduresimpactingthequalityofmakingsurethatareperformed.（7）审核和批准验证方案及报告。Reviewingandapprovingvalidationprotocolsandreports.（8）确保质量相关投诉经调查解决。Makingsurethatqualityrelatedcomplaintsareinvestigatedandresolved.（10）确保关键设备维护、校正有效运行。Makingsurethateffectivesystemsareusedformaintainingandcalibratingcriticalequipment.（11）确保原辅料正确检测并出具报告。Makingsurethatmaterialsareappropriatelytestedandtheresultsarereported.（12）确保原料药有效期和仓储条件有稳定性数据支持。MakingsurethatthereisstabilitydatatosupportretestorexpirydatesandstorageconditionsonAPIswhereappropriate,and（13）执行产品质量回顾。Performingproductqualityreviews.其他职责参见本手册相关章节。OtherdutiesaregivenintherelevantsectionsofthisManual.厂长同样对质量负责，在遵守相关法规要求条件下具备下列职责：TheHeadsofPlantandQAhassomesharedorjointlyexercisedresponsibilitiesrelatedtoquality.Thesemayinclude,withrespecttonationalregulations;（1）文件及文件修正的批准。Theauthorizationofwrittenproceduresandotherdocumentsincludingamendments（2）生产环境的监督和控制。Themonitoringandcontrolofthemanufacturingenvironment（2）厂区卫生Planthygiene（3）工艺验证Processvalidation（4）培训Training（5）物料供应商、委托生产的批准和监管。TheapprovalandmonitoringofsuppliersofmaterialsTheapprovalandmonitoringofcontractmanufacturers（6）监管物料和成品的贮存条件。Themonitoringofstorageconditionsformaterialsandproducts（7）GMP执行情况监管。ThemonitoringofcompliancewiththerequirementsofGMP（8）记录保存。Theretentionofrecords（9）通过巡视、调查及取样监控可能影响产品质量的因素。Theinspection,investigationandtakingsamplesinordertomonitorfactorswhichmayaffectproductquality5、培训TRAINING应依照培训计划对生产、储存、检测相关人员进行培训（包括工艺员、机修人员、保洁人Trainingshouldbeprovidedinaccordancewithawrittenprogrammeforallpersonnelwhoareinvolvedinproductionactivities,storagefunctions,andcontrollaboratories(Includingtechnical,maintenanceandcleaningpersonnel).应定期培训GMP相关知识并对培训效果进行评估。TrainingonGoodManufacturingPracticesshouldberepeatedperiodicallyanditspracticaleffectivenessshouldbeassessed.应对新进员工进行适应岗位要求的岗前培训。经评估岗位技能合格后方予以独立上岗操作。评估记录应存档。Newlyrecruitedpersonnelshouldbegiventrainingappropriatetothetasksassignedtothem.Theirabilityandknowledgetoperformtheassignedoperationsshouldbetestedandevaluatedbeforeputtingthemtoworkindependently.Therecordsofevaluationshouldbekeptindetail.高风险操作区（如：高活性、高毒性、传染性、高致敏性物料的生产区）的工作人员应接受专门培训。Personnelworkinginareaswherecontaminationishazardous,.areaswherehighlyactive,toxicorsensitizingmaterialsarehandled(shouldbegivenspecifictrainingappropriatetotheseactivities.质量保证的理念和质量过程控制方法应全员重点培训以提高质量管理工作理解和执行能力。Theconceptofqualityassuranceandallthemeasurescapableofimprovingitsunderstandingandimplementationshouldbewidelydiscussedduringthetrainingsessions.培训管理制度由质量部长和总工程师审核批准后，执行相关培训记录存档。WrittentrainingprogrammersshouldbeavailableapprovedbyQualityAssuranceManagerandProductionManagerasdeemedappropriate.Trainingrecordsshouldbekeptindetail.定期评估培训效果。Atdefiniteintervals,assessmentoftrainingprogramme’seffectivenessshouldbedone.6、厂房PREMISES一般要求GeneralRequirements厂房选址、设计、布局、建造、改造和维护必须符合药品生产需求，应当能够最大限度避免影响产品质量的污染和混淆，便于清洁、操作和维护。Premisesmustbelocated,designed,constructed,adaptedandmaintainedtosuittheoperationstobecarriedoutandaimedtominimizetheriskoferrorsandpermiteffectivecleaningandmaintenanceinordertoavoidbulk-upofdustordirtandingeneral,anyadverseeffectonqualityoftheproduct.药品生产厂房应根据厂房及生产防护措施综合考虑选址。厂房所处的环境应当能够最大限度地降低物料或产品遭受污染的风险。Pharmaceuticalmanufacturingpremisesshouldbesituatedinanenvironment,whichwhenconsideredtogetherwithmeasurestoprotectmanufactureandstorage,presentminimalriskofcausingcontaminationofmaterialsandproducts.Pharmaceuticalmanufactureshouldalsopresentminimalriskofenvironmentalcontaminationviaemissions,waste,etc.应定期对厂房进行维护，确保厂房维护保养操作不危害人员和产品质量。根据清洁、消毒规程进行清洁、消毒。Premisesshouldbecarefullymaintained,ensuringthatrepairandmaintenanceoperationsdonotpresentanyhazardstothepersonnelandqualityoftheproduct.Theyshouldbecleanedandwhereapplicable,disinfectedaccordingtothedetailedwrittenprocedures.生产、储存过程应配备相应照明、温度、湿度和通风设施并确保其不会直接或间接影响产品质量、仪器设备精度。Lighting,temperature,humidityandventilationshouldbeappropriateandsuchthattheydonotaffectdirectlyorindirectlyeithertheproductduringtheirmanufactureandstorageortheaccuratefunctioningoftheequipment.厂房应设计、建造、装配预防昆虫和其他动物的进入的设施，并定期维护。设置门禁设施禁止非生产人员进入。Premisesshouldbedesigned,constructed,equippedandmaintainedtoprevententryofinsectsandotheranimals.Stepsshouldbetakeninordertoprevententryofunauthorizedpersons.生产区、库房及实验室禁止其他部门工作人员穿行。Manufacturing,storageandqualitycontrolareasshouldnotbeusedasameansofaccesstootherareasbypersonnelwhodonotworkinthem.工作区域、走廊等不用于储存目的。Workingareas,corridors,etc.shouldnotbeusedforstoragepurposes.减少灰尘容易堆积的突出的臂架、架子、壁橱和设备或难以清洁的角落等清洁死角。Toreducetheaccumulationofdustandtofacilitatecleaningthereshouldbenouncleanablerecessesandaminimumofprojectingledges,shelves,cupboardsandequipment.Doorsshouldbecarefullydesignedtoavoiduncleanablerecesses.气锁间的门禁止同时敞开。Airlockdoorsshouldnotbeopenedsimultaneously.仓储区域Storageareas仓储区域应具备足够的空间储存各类产品和物料，如原辅料、包装材料、半成品、成品。放行、拒收、退货及召回的产品单独存放。Storageareasshouldbeofsufficientcapacitytostorevariouscategoriesofproductsandmaterials:startingmaterialsandpackagingmaterials,bulkandfinishedproducts,productsinquarantine,released,rejected,returnedandrecalled.仓储区域设计和使用应确保良好的储存条件，定期清洁并维持在物料或产品保存所需温湿度范围内。Storageareasshouldbedesignedandadoptedtoensuregoodstorageconditions.Theyshouldbecleanedperiodicallyandmaintainedwithinacceptabletemperatureandhumiditylimitssuitableformaterialsorproductsbeingstored.接、发货区应保证物料和产品免受外界天气的影响，接货区应允许物料入库前清洁。Acceptanceanddispatchbaysshouldprotectmaterialsandproductsfromtheweather.Receivingbayshouldbedesignedandequippedtoallowincomingmaterialstobecleanedbeforestorage.明确标示隔离区仅授权人员进入。Quarantineareasmustbeclearlymarkedandtheiraccessrestrictedtoauthorizedpersonnel.原料和内包材应配备单独的取样区域。Thereshouldbeseparatesamplingareaforstartingmaterialsandprimarypackagingmaterials.拒收、召回、退货的物料或产品离存放，仅授权人员可以进入。Separatesegregatedareasshouldbeprovidedforstorageofrejected,recalledorreturnedmaterialsorproducts.Theaccesstotheseareasshouldberestrictedtoauthorizedpersonsonly.易燃或其他有害物料适宜条件下单独存放以确保储存、取样和处理的安全。Highlyflammableorotherwisehazardousmaterialsshouldbeseparatelystoredunderappropriateconditionstoensuresafetyinstorage,samplingandhandling.印字包材（如标签等）应该在安全条件下储存于独立密闭包装内，仅授权人员进入。Printedtextcomponents.labelsetc.)shouldbestoredundersecuredconditions,inseparateclosedbundlesorcontainerswithaccessrestrictedtoauthorizedpersonnel.生产区域ManufacturingAreas对特定药品采用专用密闭设施预防交叉污染的风险。Inordertoeliminatetheriskofaseriousmedicalhazardduetocross-contamination,dedicatedandself-containedfacilitiesshouldbeavailablefortheproductionofparticulardrugs.厂房使用应确保按照生产操作流程分布，清晰界定洁净级别划分洁净区，确保厂房符合洁净级别要求。Premisesshouldpreferablybelaidoutinsuchawayastoallowtheproductiontotakeplaceininalogicalordercorrespondingtothesequenceofoperationsandtotherequisitecleanlinesslevels,whichshouldbeclearlyidentifiedandseparatedintocleanlinesszones.生产区过程控制检查应定期执行以预防产品生产出现风险。Certainin-processcontrolchecksmaybeperformedwithintheproductionareaprovidedthattheydonotpresentanyrisktotheproductsbeingmanufactured.工作区域与转存区域应允许设备及物料合理定位避免批不同产品或不同批次产品混淆或交叉污染。Workingspaceandin-processstoragespaceshouldbeadequatefororderlyandlogicalpositioningofequipmentandmaterialstominimizetheriskofconfusionbetweendifferentproductsortheircomponentsandofcross-contamination.原料、内包材接触的环境其内表面（墙体、地面或天花板）应该光滑，无裂缝和接头，无堆积尘埃，应能够简单有效地清洁和消毒。窗、门、阀门、管线等应充分密封。棚顶通风口密封。Wherestartingmaterials,primarypackingmaterialsareexposedtotheenvironment,interiorsurfaces(ofwalls,floors,andceilings)shouldbesmooth,freefromcracksandopenjoints,shouldnotshredparticles,shouldpermiteasyandeffectivecleaningand,doors,entryofducts,pipes,etc,shouldbeadequatelysealed.Intheareaswheredustisgenerated,voidsabovesuspendedceilingsshouldbesealed.管线、照明设施、通风换气口等设施设计安装应尽量避免清洁死角及维护保养难以进入的部位。Pipework,lightfittings,ventilationpointsandotherservicesshouldbedesignedandsitedtoavoidthecreationofrecesseswhicharedifficulttocleanandasfaraspossible,theyshouldbeaccessiblefromoutsideformaintenancepurpose.排水设施应当大小适宜，并安装防止倒灌的装置。应当尽可能避免使用明渠排水；不可避免时，明沟宜浅，以便清洁和消毒。Drainsshouldbeofadequatesizeandfittedwithtraps.Openchannelsshouldbeavoided.Ifnecessary,theyshouldbeshallowtofacilitatecleaninganddisinfecting.Whennotinuse,theyshouldbemaintaineddry.生产区域配备空调净化系统确保空气高效流通（包括温度、压力、湿度和空气净化过滤）以保证药品的生产环境符合要求。空气循环回风系统应充分过滤以避免产生交叉污染。Productionareasshouldbeeffectivelyventilatedwithaircontrolfacilities(includingtemperature,pressure,ifnecessary,humidityandfiltration)appropriatetoproductshandled,operationsundertakenwithinthemandtotheexternalenvironment.Anyrecycledairshouldbeadequatelyfilteredtopreventcross-contamination.产尘操作间（如称重、混合操作间）应采取专门的吸尘措施。Localdustextractionsystemshouldbeprovidedwheredustisgenerated.weighing,mixingandprocessingoperations).通风和吸尘系统应经过确认并定期清洁和维护，过滤器更换的周期应明确规定，确认和维护保养（包括滤芯更换）应在文件明确规定并且记录，记录存档。Ventilationanddustextractionsystemshouldbequalifiedandregularlycleanedandmaintained.Filterchangeintervalsshouldbeclearlyspecified.Qualificationandmaintenance(includingfilterchange)shouldbedocumentedandtherecordsaremaintained.车间分析室LaboratoryAreas实验室应与生产区分开。微生物实验室应与其他实验室分开。Laboratoriesshouldbeseparatedfromproductionareas.Laboratoriesshouldbeseparatedfromotherlaboratories.Microbiological实验室的设计应当确保其适用预定的用途，应提供足够的区域避免混淆和交叉污染。Laboratoriesshouldbedesignedtosuitoperationstobecarriedoutinthem.Sufficientspaceshouldbeprovidedtoavoidmix-upsandcross-contamination.设备、玻璃器皿、化学试剂、样品、留样和记录储存应设有足够的空间。Thereshouldbeadequatestoragespaceforspareequipment,glassware,chemicals,samples,retainedsamplesandrecords.必要时应当设置专门的仪器室，保证灵敏度高的仪器免受震动、静电、潮湿或其他外界因素的干扰。Separateprovisionmaybenecessarytoprotectsensitiveinstrumentsfromvibrations,electricalinterference,humidity,etc.以下物质单独存放：Provisionshouldbemadeforseparatestorageof(1)待销毁的废料；Wastematerialawaitingdisposal(2)成瘾性药物或精神麻醉类药物；Controlleddrugsornarcotics(3)剧毒物质；Highlytoxicsubstances(4)易燃溶剂与非易燃溶剂分离；Flammablesolventsseparatefromnon-flammablesolvents应该提供专门的空气流通和烟雾抽取设施；Separateventilationandfumeextractionfacilitiesshouldbeprovided.每个实验室正确配备灭火器及其他安全防火设备。Appropriatefirefightingandothersafetyequipmentshouldbeavailableineachlaboratory.实验室日常使用应建立清洁/消毒规程。Thereshouldbewrittencleaning/sanitationprogrammeforalllaboratories,appropriatefortheworkundertaken.辅助区域AncillaryAreas食堂与休息区域应该与其他区域分开。Canteenandrestareasshouldbeseparatefromotherareas.用于更衣、盥洗、如厕目的的设施应适用使用者数量配备，便于使用。卫生间不应该直接与生产区域相通，并提供水、肥皂、清洁剂和手烘干器或一次性毛巾。Facilitiesforchangingclothesandforwashingandtoiletpurposesshouldbeeasilyaccessibleandappropriateforthenumberofshouldnotdirectlycommunicatewithproduction,soapordetergentandairdryersorsingleusetowelsshouldbeprovidedinwashingfacilities.车间应该与成品区分离。在生产区存放的部件或工具，应该根据其用途保存在房间或上锁的柜子里。Workshopsshouldbeseparatedfromproductionareas.Wheneverpartsandtoolsarestoredintheproductionarea,theyshouldbekeptinroomsorlockersreservedforthispurpose.7、消毒与卫生SANITATIONANDHYGIENE清洁和消毒流程CleaningandSanitationProgrammes生产厂房保持清洁避免垃圾堆积和虫鼠害孳生。Manufacturingpremisesshouldbemaintainedinacleanedcondition,freefromaccumulatedwaste,orderly,andfreefrominsectsandvermin.以下内容需要文件规定：Awrittensanitationprogrammeshouldbeavailableforthepremises,indicating:（1）应定期清洁保持干净的区域及清洁频次；areastobecleanedandcleaningintervals（2）具体清洁流程和清洁使用的工具；detailedcleaningprocedurestobefollowedandequipmenttobeusedforcleaning.（3）清洁剂、消毒剂的选择、使用方法及定期更换避免产生抗性的规定；cleaningagentsanddisinfectantstobeusedincludinginstructionsforuse,