藥品生產(chǎn)質(zhì)量管理規(guī)范2目錄1總則組織與人員廠房與設(shè)施設(shè)備成份、藥品容器和密封件的控制生產(chǎn)和加工控制5組織與人員211.22質(zhì)量控制部門的職責(zé)211.25人員資質(zhì)211.28人員職責(zé)211.34顧問6Sec.211.22Responsibilitiesofqualitycontrolunit.Thereshallbeaqualitycontrolunitthatshallhavetheresponsibilityandauthoritytoapproveorrejectallcomponents,drugproductcontainers,closures,in-processmaterials,packagingmaterial,labeling,anddrugproducts,andtheauthoritytoreviewproductionrecordstoassurethatnoerrorshaveoccurredor,iferrorshaveoccurred,thattheyhavebeenfullyinvestigated.Thequalitycontrolunitshallberesponsibleforapprovingorrejectingdrugproductsmanufactured,processed,packed,orheldundercontractbyanothercompanyAdequatelaboratoryfacilitiesforthetestingandapproval(orrejection)ofcomponents,drugproductcontainers,closures,packagingmaterials,in-processmaterials,anddrugproductsshallbeavailabletothequalitycontrolunit.Thequalitycontrolunitshallhavetheresponsibilityforapprovingorrejectingallproceduresorspecificationsimpactingontheidentity,strength,quality,andpurityofthedrugproduct.Theresponsibilitiesandproceduresapplicabletothequalitycontrolunitshallbeinwriting;suchwrittenproceduresshallbefollowed.7211.22質(zhì)量控制部門的職責(zé)批準(zhǔn)和拒收所有藥用成份、藥品包裝容器、包裝密封物、中間體、包裝材料、標(biāo)簽及藥品具有復(fù)查生產(chǎn)記錄的權(quán)力負(fù)責(zé)根據(jù)合同，批準(zhǔn)或拒收由其它公司,生產(chǎn)、加工、包裝或貯存的產(chǎn)品。適當(dāng)?shù)膶?shí)驗(yàn)室檢驗(yàn)設(shè)備、批準(zhǔn)（或拒收）的各種成份、藥品容器、密封件、包裝材料及藥品，批準(zhǔn)或駁回影響藥品的均一性、效價(jià)或含量、質(zhì)量及純度的所有程序和/或規(guī)格標(biāo)準(zhǔn)適用于本部門的職責(zé)與程序，應(yīng)成文字材料，并應(yīng)遵循。8Sec.211.25Personnelqualifications.Eachpersonengagedinthemanufacture,processing,packing,orholdingofadrugproductshallhaveeducation,training,andexperience,oranycombinationthereof,toenablethatpersontoperformtheassignedfunctions.Trainingshallbeintheparticularoperationsthattheemployeeperformsandincurrentgoodmanufacturingpractice(includingthecurrentgoodmanufacturingpracticeregulationsinthischapterandwrittenproceduresrequiredbytheseregulations)astheyrelatetotheemployee'sfunctions.TrainingincurrentgoodmanufacturingpracticeshallbeconductedbyqualifiedindividualsonacontinuingbasisandwithsufficientfrequencytoassurethatemployeesremainfamiliarwithCGMPrequirementsapplicabletothem.Eachpersonresponsibleforsupervisingthemanufacture,processing,packing,orholdingofadrugproductshallhavetheeducation,training,andexperience,oranycombinationthereof,toperformassignedfunctionsinsuchamannerastoprovideassurancethatthedrugproducthasthesafety,identity,strength,quality,andpuritythatitpurportsorisrepresentedtopossess.Thereshallbeanadequatenumberofqualifiedpersonneltoperformandsupervisethemanufacture,processing,packing,orholdingofeachdrugproduct9211.25人員資格從事藥品生產(chǎn)、加工，包裝或倉(cāng)貯工作的人員，應(yīng)接受培訓(xùn)、教育及有實(shí)踐經(jīng)驗(yàn)，具有完成委派的各項(xiàng)任務(wù)的職責(zé)。有稱職的CGMP的培訓(xùn)師,提供充分的培訓(xùn).

負(fù)責(zé)監(jiān)督藥品的生產(chǎn)、加工、包裝或倉(cāng)貯工作的每一個(gè)人員，應(yīng)受教育、培訓(xùn)及有經(jīng)驗(yàn)，具有完成委派的各項(xiàng)任務(wù)的職責(zé)。有足夠量執(zhí)行和監(jiān)督每種藥品的生產(chǎn)、加工、包裝或倉(cāng)貯的合格人員。10Sec.211.28Personnelresponsibilities.Personnelengagedinthemanufacture,processing,packing,orholdingofadrugproductshallwearcleanclothingappropriateforthedutiestheyperform.Protectiveapparel,suchashead,face,hand,andarmcoverings,shallbewornasnecessarytoprotectdrugproductsfromcontamination.Personnelshallpracticegoodsanitationandhealthhabits.Onlypersonnelauthorizedbysupervisorypersonnelshallenterthoseareasofthebuildingsandfacilitiesdesignatedaslimited-accessareas.Anypersonshownatanytime(eitherbymedicalexaminationorsupervisoryobservation)tohaveanapparentillnessoropenlesionsthatmayadverselyaffectthesafetyorqualityofdrugproductsshallbeexcludedfromdirectcontactwithcomponents,drugproductcontainers,closures,in-processmaterials,anddrugproductsuntiltheconditioniscorrectedordeterminedbycompetentmedicalpersonnelnottojeopardizethesafetyorqualityofdrugproducts.Allpersonnelshallbeinstructedtoreporttosupervisorypersonnelanyhealthconditionsthatmayhaveanadverseeffectondrugproducts.11211·28人員職責(zé)從事藥品生產(chǎn)、加工、包裝或倉(cāng)貯的人員，應(yīng)穿著適合于其履行職責(zé)的清潔衣服。人員保持良好的個(gè)人衛(wèi)生和健康。未經(jīng)監(jiān)督人員允許，其他人不能進(jìn)入限制進(jìn)入的建筑物和設(shè)施。12211·28人員職責(zé)任何人，在任何時(shí)間，明顯地表現(xiàn)出帶有影響藥品安全性和質(zhì)量的疾病或開放性損傷，應(yīng)避免接觸各種成份、藥品容器、包裝設(shè)備、密封件、中間體，直至病愈或經(jīng)醫(yī)學(xué)測(cè)定認(rèn)為對(duì)藥品安全性及質(zhì)量無危害性時(shí)為止。

教育所有人員，報(bào)告監(jiān)督人員對(duì)藥品有不利影響的健康情況13Sec.211.34Consultants

Consultantsadvisingonthemanufacture,processing,packing,orholdingofdrugproductsshallhavesufficienteducation,training,andexperience,oranycombinationthereof,toadviseonthesubjectforwhichtheyareretained.Recordsshallbemaintainedstatingthename,address,andqualificationsofanyconsultantsandthetypeofservicetheyprovide.14211·34顧問受過足夠的教育，培訓(xùn)，且有豐富的實(shí)踐經(jīng)驗(yàn)。保留他們的姓名、地址、任何的顧問資格及服務(wù)形式等履歷資料顧問應(yīng)對(duì)藥品生產(chǎn)、加工、包裝或倉(cāng)貯提出建議，并保存記錄.15廠房與設(shè)施211.42設(shè)計(jì)與建造211.44照明211.46通風(fēng)、空氣過濾、加熱與冷卻211.48排水211.50污水和廢料211.52洗滌和盥洗設(shè)備211.56衛(wèi)生211.58維護(hù)Sec.211.42Designandconstructionfeatures.Anybuildingorbuildingsusedinthemanufacture,processing,packing,orholdingofadrugproductshallbeofsuitablesize,constructionandlocationtofacilitatecleaning,maintenance,andproperoperations.Anysuchbuildingshallhaveadequatespacefortheorderlyplacementofequipmentandmaterialstopreventmixupsbetweendifferentcomponents,drugproductcontainers,closures,labeling,in-processmaterials,ordrugproducts,andtopreventcontamination.Theflowofcomponents,drugproductcontainers,closures,labeling,in-processmaterials,anddrugproductsthroughthebuildingorbuildingsshallbedesignedtopreventcontamination.16Sec.211.42Designandconstructionfeatures.Operationsshallbeperformedwithinspecificallydefinedareasofadequatesize.Thereshallbeseparateordefinedareasorsuchothercontrolsystemsforthefirm'soperationsasarenecessarytopreventcontaminationormixupsduringthecourseofthefollowingprocedures:(1)Receipt,identification,storage,andwithholdingfromuseofcomponents,drugproductcontainers,closures,andlabeling,pendingtheappropriatesampling,testing,orexaminationbythequalitycontrolunitbeforereleaseformanufacturingorpackaging;(2)Holdingrejectedcomponents,drugproductcontainers,closures,andlabelingbeforedisposition;(3)Storageofreleasedcomponents,drugproductcontainers,closures,andlabeling;(4)Storageofin-processmaterials;(5)Manufacturingandprocessingoperations;(6)Packagingandlabelingoperations;(7)Quarantinestoragebeforereleaseofdrugproducts;(8)Storageofdrugproductsafterrelease;(9)Controlandlaboratoryoperations;17Sec.211.42Designandconstructionfeatures.(10)Asepticprocessing,whichincludesasappropriate:(i)Floors,walls,andceilingsofsmooth,hardsurfacesthatareeasilycleanable;(ii)Temperatureandhumiditycontrols;(iii)Anairsupplyfilteredthroughhigh-efficiencyparticulateairfiltersunderpositivepressure,regardlessofwhetherflowislaminarornonlaminar;(iv)Asystemformonitoringenvironmentalconditions;(v)Asystemforcleaninganddisinfectingtheroomandequipmenttoproduceasepticconditions;(vi)Asystemformaintaininganyequipmentusedtocontroltheasepticconditions.(d)Operationsrelatingtothemanufacture,processing,andpackingofpenicillinshallbeperformedinfacilitiesseparatefromthoseusedforotherdrugproductsforhumanuse.1819211.42設(shè)計(jì)與建造用于藥品生產(chǎn)、加工、包裝或貯存的廠房或建筑群,大小適宜,易于清潔、保養(yǎng)、適合操作。建筑物有足夠空間安裝設(shè)備和放置材料，避免相互混放，防止污染。物料流向在設(shè)計(jì)時(shí)要防止污染。20211.42設(shè)計(jì)與建造操作應(yīng)在明確規(guī)定的、大小適宜的區(qū)域內(nèi)進(jìn)行。分隔區(qū)域，以防污染。下列操作須在單獨(dú)的地區(qū)內(nèi)進(jìn)行：發(fā)放給生產(chǎn)或包裝前，質(zhì)量控制部門取樣期間，成份、藥品容器、密封件及標(biāo)簽的簽收、鑒別、貯存及拒收。在處理前，拒收的成份、藥品容器、密封件及標(biāo)簽的貯存。已發(fā)放的成份、藥品容器、密封件及標(biāo)簽的貯存。中間體的貯存。21211.42設(shè)計(jì)與建造下列操作須在單獨(dú)的地區(qū)內(nèi)進(jìn)行（續(xù)）：生產(chǎn)與加工操作。包裝和貼標(biāo)簽操作。藥品發(fā)放前的隔離貯存。發(fā)放后藥品的貯存?？刂婆c實(shí)驗(yàn)室操作。Sec.211.44Lighting.Adequatelightingshallbeprovidedinallareas.2223211·44照明所有地區(qū)均須充足的照明Sec.211.46

Adequateventilationshallbeprovided.Equipmentforadequatecontroloverairpressure,micro-organisms,dust,humidity,andtemperatureshallbeprovidedwhenappropriateforthemanufacture,processing,packing,orholdingofadrugproduct.Airfiltrationsystems,includingprefiltersandparticulatematterairfilters,shallbeusedwhenappropriateonairsuppliestoproductionareas.Ifairisrecirculatedtoproductionareas,measuresshallbetakentocontrolrecirculationofdustfromproduction.Inareaswhereaircontaminationoccursduringproduction,thereshallbeadequateexhaustsystemsorothersystemsadequatetocontrolcontaminants.Air-handlingsystemsforthemanufacture,processing,andpackingofpenicillinshallbecompletelyseparatefromthoseforotherdrugproductsforhumanuse.24Ventilation,airfiltration,airheatingandcooling.25211·46通風(fēng)、空氣過濾、空氣加熱與冷卻提供足夠的通風(fēng)。設(shè)備足夠控制空氣正壓、微生物、塵土、濕度和溫度，適應(yīng)藥品生產(chǎn)、加工和貯存的需要?？諝膺^濾系統(tǒng)，包括預(yù)過濾器和微粒物質(zhì)空氣過濾器?？諝饨?jīng)過濾才送至生產(chǎn)區(qū)，如果空氣是再循環(huán)到生產(chǎn)區(qū)，應(yīng)測(cè)量塵埃含量。*在生產(chǎn)區(qū)，生產(chǎn)中發(fā)生空氣污染，應(yīng)以排氣系統(tǒng)或其他系統(tǒng)充分抽出空氣，控制污染。Sec.211.48Plumbing.Potablewatershallbesuppliedundercontinuouspositivepressureinaplumbingsystemfreeofdefectsthatcouldcontributecontaminationtoanydrugproduct.PotablewatershallmeetthestandardsprescribedintheEnvironmentalProtectionAgency'sPrimaryDrinkingWaterRegulationssetforthin40CFRpart141.Waternotmeetingsuchstandardsshallnotbepermittedinthepotablewatersystem.Drainsshallbeofadequatesizeand,whereconnecteddirectlytoasewer,shallbeprovidedwithanairbreakorothermechanicaldevicetopreventback-siphonage.2627211·48排水在持續(xù)正壓下，應(yīng)對(duì)藥品無污染的管道系統(tǒng)內(nèi)供應(yīng)飲用水。排水設(shè)備應(yīng)有足夠的大小，可直接連接排水管及安裝防止虹吸倒流的空氣破壞設(shè)備或其他機(jī)械設(shè)備。Sec.211.50Sewageandrefuse./

Sec.211.52Washingandtoiletfacilities.Sewage,trash,andotherrefuseinandfromthebuildingandimmediatepremisesshallbedisposedofinasafeandsanitarymanner.Adequatewashingfacilitiesshallbeprovided,includinghotandcoldwater,soapordetergent,airdriersorsingle-servicetowels,andcleantoiletfacilitieseasilyaccesibletoworkingareas.2829211·50/211·52污水和廢料：來自廠房和附近建筑物的污水、垃圾及其他廢料，用安全、衛(wèi)生的方法處理。洗滌和盥洗設(shè)備：提供適當(dāng)?shù)南礈煸O(shè)備，包括熱、冷水、肥皂、清潔劑、空氣干燥器或?qū)Ｓ妹砑耙走M(jìn)入廁所的清潔設(shè)備。Sec.211.56Sanitation.Anybuildingusedinthemanufacture,processing,packing,orholdingofadrugproductshallbemaintainedinacleanandsanitarycondition,Anysuchbuildingshallbefreeofinfestationbyrodents,birds,insects,andothervermin(otherthanlaboratoryanimals).Trashandorganicwastemattershallbeheldanddisposedofinatimelyandsanitarymanner.Thereshallbewrittenproceduresassigningresponsibilityforsanitationanddescribinginsufficientdetailthecleaningschedules,methods,equipment,andmaterialstobeusedincleaningthebuildingsandfacilities;suchwrittenproceduresshallbefollowed.Thereshallbewrittenproceduresforuseofsuitablerodenticides,insecticides,fungicides,fumigatingagents,andcleaningandsanitizingagents.Suchwrittenproceduresshallbedesignedtopreventthecontaminationofequipment,components,drugproductcontainers,closures,packaging,labelingmaterials,ordrugproductsandshallbefollowed.Rodenticides,insecticides,andfungicidesshallnotbeusedunlessregisteredandusedinaccordancewiththeFederalInsecticide,Fungicide,andRodenticideAct(7U.S.C.135).Sanitationproceduresshallapplytoworkperformedbycontractorsortemporaryemployeesaswellasworkperformedbyfull-timeemployeesduringtheordinarycourseofoperations.3031211·56衛(wèi)生廠房應(yīng)保持清潔、衛(wèi)生的環(huán)境，且不受嚙齒動(dòng)物、鳥類、昆蟲及其他害蟲侵?jǐn)_(實(shí)驗(yàn)動(dòng)物除外)。填寫分配衛(wèi)生清潔任務(wù)和詳細(xì)的清潔項(xiàng)目、方法、設(shè)備、用于清潔廠房和設(shè)施的材料的—覽表。填寫適用的殺鼠劑、殺昆蟲劑、殺真菌劑、熏蒸劑、去垢劑和消毒劑一覽表。防止它們對(duì)設(shè)備、成份、藥品容器、密封件、包裝材料、標(biāo)簽或藥品污染。在平常的操作過程中，環(huán)境衛(wèi)生工作應(yīng)適于合同工或臨時(shí)工及專職人員去完成。Sec.211.58Maintenance.Anybuildingusedinthemanufacture,processing,packing,orholdingofadrugproductshallbemaintainedinagoodstateofrepair.323321l·58維護(hù)任何用于藥品生產(chǎn)、加工、包裝或貯存的廠房應(yīng)保持保養(yǎng)良好狀態(tài)。34D.設(shè)備211.63設(shè)備的設(shè)計(jì)、尺寸及位置211.65設(shè)備構(gòu)造211.67設(shè)備清潔與維護(hù)211.68自動(dòng)化、機(jī)械化和電子化設(shè)備211.72過濾器Sec.211.63/Sec.211.65211.63Equipmentusedinthemanufacture,processing,packing,orholdingofadrugproductshallbeofappropriatedesign,adequatesize,andsuitablylocatedtofacilitateoperationsforitsintendeduseandforitscleaningandmaintenance.211.65(a)Equipmentshallbeconstructedsothatsurfacesthatcontactcomponents,in-processmaterials,ordrugproductsshallnotbereactive,additive,orabsorptivesoastoalterthesafety,identity,strength,quality,orpurityofthedrugproductbeyondtheofficialorotherestablishedrequirements.(b)Anysubstancesrequiredforoperation,suchaslubricantsorcoolants,shallnotcomeintocontactwithcomponents,drugproductcontainers,closures,in-processmaterials,ordrugproductssoastoalterthesafety,identity,strength,quality,orpurityofthedrugproductbeyondtheofficialorotherestablishedrequirements.35Equipmentdesign,size,andlocation./Equipmentconstruction.36211.63/211·65211.63設(shè)備的設(shè)計(jì)、尺寸及位置設(shè)計(jì)合理，大小適當(dāng)，布置合理，便于操作、清潔和保養(yǎng)。211·65設(shè)備制造設(shè)備表面與各種成分、中間體或藥品接觸，不產(chǎn)生化學(xué)反應(yīng)和吸附作用。潤(rùn)滑劑、冷卻劑等不能進(jìn)入設(shè)備里，Sec.211.67Equipmentcleaningandmaintenance.Equipmentandutensilsshallbecleaned,maintained,andsanitizedatappropriateintervalstopreventmalfunctionsorcontaminationthatwouldalterthesafety,identity,strength,quality,orpurityofthedrugproductbeyondtheofficialorotherestablishedrequirements.Writtenproceduresshallbeestablishedandfollowedforcleaningandmaintenanceofequipment,includingutensils,usedinthemanufacture,processing,packing,orholdingofadrugproduct.Theseproceduresshallinclude,butarenotnecessarilylimitedto,thefollowing:(1)Assignmentofresponsibilityforcleaningandmaintainingequipment;(2)Maintenanceandcleaningschedules,including,whereappropriate,sanitizingschedules;(3)Adescriptioninsufficientdetailofthemethods,equipment,andmaterialsusedincleaningandmaintenanceoperations,andthemethodsofdisassemblingandreassemblingequipmentasnecessarytoassurepropercleaningandmaintenance;(4)Removalorobliterationofpreviousbatchidentification;(5)Protectionofcleanequipmentfromcontaminationpriortouse;(6)Inspectionofequipmentforcleanlinessimmediatelybeforeuse.(c)Recordsshallbekeptofmaintenance,cleaning,sanitizing,andinspectionasspecifiedin211.180and211.182.3738211·67設(shè)備清潔與保養(yǎng)相隔一定時(shí)間，對(duì)設(shè)備與工具進(jìn)行清潔、保養(yǎng)和消毒，防止出故障與污染制訂藥品生產(chǎn)、加工、包裝或貯存設(shè)備(包括用具)的清潔和保養(yǎng)文字程序,并執(zhí)行：分配清潔，保養(yǎng)任務(wù)。保養(yǎng)和清潔細(xì)目一覽表，包括消毒一覽表。詳細(xì)說明用于清潔和保養(yǎng)的設(shè)備、物品和方法。拆卸和裝配設(shè)備的方法必須保證適合清潔和保養(yǎng)的要求。除去或擦去前批遺留物的鑒定。已清除了污染的清潔設(shè)備的保護(hù)。使用前檢查清潔的設(shè)備。保留保養(yǎng)、清潔、消毒的記錄。Sec.211.68Automatic,mechanical,orelectronicequipmentorothertypesofequipment,includingcomputers,orrelatedsystemsthatwillperformafunctionsatisfactorily,maybeusedinthemanufacture,processing,packing,andholdingofadrugproduct.Ifsuchequipmentissoused,itshallberoutinelycalibrated,inspected,orcheckedaccordingtoawrittenprogramdesignedtoassureproperperformance.Writtenrecordsofthosecalibrationchecksandinspectionsshallbemaintained.Appropriatecontrolsshallbeexercisedovercomputerorrelatedsystemstoassurethatchangesinmasterproductionandcontrolrecordsorotherrecordsareinstitutedonlybyauthorizedpersonnel.

Inputtoandoutputfromthecomputerorrelatedsystemofformulasorotherrecordsordatashallbecheckedforaccuracy.Thedegreeandfrequencyofinput/outputverificationshallbebasedonthecomplexityandreliabilityofthecomputerorrelatedsystem.Abackupfileofdataenteredintothecomputerorrelatedsystemshallbemaintainedexceptwherecertaindata,suchascalculationsperformedinconnectionwithlaboratoryanalysis,areeliminatedbycomputerizationorotherautomatedprocesses.Insuchinstancesawrittenrecordoftheprogramshallbemaintainedalongwithappropriatevalidationdata.Hardcopyoralternativesystems,suchasduplicates,tapes,ormicrofilm,designedtoassurethatbackupdataareexactandcompleteandthatitissecurefromalteration,inadvertenterasures,orlossshallbemaintained.39Automatic,mechanical,andelectronicequipment.40211·68自動(dòng)化設(shè)備、機(jī)械化設(shè)備和電子設(shè)備自動(dòng)化、機(jī)械化或電子設(shè)備，包括計(jì)算機(jī)或其他類型的設(shè)備。應(yīng)對(duì)其設(shè)計(jì)之成文條款作標(biāo)定、檢查或核對(duì)，保證其工作性能良好。保留檢查、標(biāo)定、核對(duì)等文字記錄。對(duì)保障重要生產(chǎn)變化的計(jì)算機(jī)或有關(guān)系統(tǒng)進(jìn)行操作培訓(xùn)。操作記錄或其他記錄只能由被認(rèn)可的人員制訂。應(yīng)核查輸入或輸出的各種方案、記錄或資料準(zhǔn)確性輸入計(jì)算機(jī)或有關(guān)系統(tǒng)內(nèi)的檔案資料應(yīng)保留，文字記錄與相應(yīng)的證明資料一起保存。復(fù)制品或多種選擇系統(tǒng)應(yīng)保證其支持資料正確、可靠及完整41E．成份、藥品容器和密封件的控制211.80一般規(guī)定211.82未檢驗(yàn)的成份、藥品容器和密封件的接收與貯存211.84成分、藥品容器和封口物品的檢驗(yàn)、批準(zhǔn)或拒收211.86獲準(zhǔn)成分、藥品容器和密封件的使用211.87獲準(zhǔn)成分、藥品容器和密封件的復(fù)檢211.89拒收的成分、藥品容器和密封件211.94藥品密封容器和密封件Sec.211.80Generalrequirements.Thereshallbewrittenproceduresdescribinginsufficientdetailthereceipt,identification,storage,handling,sampling,testing,andapprovalorrejectionofcomponentsanddrugproductcontainersandclosures;suchwrittenproceduresshallbefollowed.Componentsanddrugproductcontainersandclosuresshallatalltimesbehandledandstoredinamannertopreventcontamination.Baggedorboxedcomponentsofdrugproductcontainers,orclosuresshallbestoredoffthefloorandsuitablyspacedtopermitcleaningandinspection.Eachcontainerorgroupingofcontainersforcomponentsordrugproductcontainers,orclosuresshallbeidentifiedwithadistinctivecodeforeachlotineachshipmentreceived.

Thiscodeshallbeusedinrecordingthedispositionofeachlot.Eachlotshallbeappropriatelyidentifiedastoitsstatus(i.e.,quarantined,approved,orrejected).4243211.80一般規(guī)定有文字詳細(xì)說明成份、藥品容器、密封件的簽收、鑒定、貯存、裝運(yùn)、取樣、檢驗(yàn)和批準(zhǔn)或拒收等程序，并遵循。成份、藥品容器和密封件應(yīng)專人管理，并在防止污染的環(huán)境下貯存。藥品容器的包裝袋或包裝箱或密封件應(yīng)離地面放置，保持適當(dāng)間隔，便于清潔和檢查。用明顯的已接收的每裝貨量中的批號(hào)代碼對(duì)成份、藥品容器或密封件加以鑒別。

此代碼用來記錄每批貨的放置地方。對(duì)每批貨的情況，如隔離、批準(zhǔn)或拒收等作檢查。Sec.211.82Uponreceiptandbeforeacceptance,eachcontainerorgroupingofcontainersofcomponents,drugproductcontainers,andclosuresshallbeexaminedvisuallyforappropriatelabelingastocontents,containerdamageorbrokenseals,andcontamination.Components,drugproductcontainers,andclosuresshallbestoredunderquarantineuntiltheyhavebeentestedorexamined,asappropriate,andreleased.Storagewithintheareashallconformtotherequirementsof211.80.44Receiptandstorageofuntestedcomponents,drugproductcontainers,andclosures.45211·82未檢驗(yàn)的成份、藥品容器和密封件的接收與貯存接收時(shí)和驗(yàn)收前，對(duì)每個(gè)或編組的成份容器、藥品容器和密封件進(jìn)行目檢。給內(nèi)容物、容器損壞或拆封和污染等情況作適當(dāng)?shù)臉?biāo)志。成份、藥品容器和密封件應(yīng)隔離貯存，直至經(jīng)檢驗(yàn)為止。合格，可發(fā)放。在符合21l·80要求的地區(qū)中貯存。Sec.211.84Testingandapprovalorrejectionofcomponents,drugproductcontainers,andclosures.Eachlotofcomponents,drugproductcontainers,andclosuresshallbewithheldfromuseuntilthelothasbeensampled,tested,orexamined,asappropriate,andreleasedforusebythequalitycontrolunit.Representativesamplesofeachshipmentofeachlotshallbecollectedfortestingorexamination.Thenumberofcontainerstobesampled,andtheamountofmaterialtobetakenfromeachcontainer,shallbebaseduponappropriatecriteriasuchasstatisticalcriteriaforcomponentvariability,confidencelevels,anddegreeofprecisiondesired,thepastqualityhistoryofthesupplier,andthequantityneededforanalysisandreservewhererequiredby211.170.46Sec.211.84Testingandapprovalorrejectionofcomponents,drugproductcontainers,andclosures.Samplesshallbecollectedinaccordancewiththefollowingprocedures:(1)Thecontainersofcomponentsselectedshallbecleanedwherenecessary,byappropriatemeans.(2)Thecontainersshallbeopened,sampled,andresealedinamannerdesignedtopreventcontaminationoftheircontentsandcontaminationofothercomponents,drugproductcontainers,orclosures.(3)Sterileequipmentandasepticsamplingtechniquesshallbeusedwhennecessary.(4)Ifitisnecessarytosampleacomponentfromthetop,middle,andbottomofitscontainer,suchsamplesubdivisionsshallnotbecompositedfortesting.(5)Samplecontainersshallbeidentifiedsothatthefollowinginformationcanbedetermined:nameofthematerialsampled,thelotnumber,thecontainerfromwhichthesamplewastaken,thedateonwhichthesamplewastaken,andthenameofthepersonwhocollectedthesample.(6)Containersfromwhichsampleshavebeentakenshallbemarkedtoshowthatsampleshavebeenremovedfromthem.47Sec.211.84Testingandapprovalorrejectionofcomponents,drugproductcontainers,andclosures.Samplesshallbeexaminedandtestedasfollows:(1)Atleastonetestshallbeconductedtoverifytheidentityofeachcomponentofadrugproduct.Specificidentitytests,iftheyexist,shallbeused.(2)Eachcomponentshallbetestedforconformitywithallappropriatewrittenspecificationsforpurity,strength,andquality.Inlieuofsuchtestingbythemanufacturer,areportofanalysismaybeacceptedfromthesupplierofacomponent,providedthatatleastonespecificidentitytestisconductedonsuchcomponentbythemanufacturer,andprovidedthatthemanufacturerestablishesthereliabilityofthesupplier'sanalysesthroughappropriatevalidationofthesupplier'stestresultsatappropriateintervals.(3)Containersandclosuresshallbetestedforconformancewithallappropriatewrittenprocedures.Inlieuofsuchtestingbythemanufacturer,acertificateoftestingmaybeacceptedfromthesupplier,providedthatatleastavisualidentificationisconductedonsuchcontainers/closuresbythemanufacturerandprovidedthatthemanufacturerestablishesthereliabilityofthesupplier'stestresultsthroughappropriatevalidationofthesupplier'stestresultsatappropriateintervals.(4)Whenappropriate,componentsshallbemicroscopicallyexamined.48Sec.211.84Testingandapprovalorrejectionofcomponents,drugproductcontainers,andclosures.(5)Eachlotofacomponent,drugproductcontainer,orclosurethatisliabletocontaminationwithfilth,insectinfestation,orotherextraneousadulterantshallbeexaminedagainstestablishedspecificationsforsuchcontamination.(6)Eachlotofacomponent,drugproductcontainer,orclosurethatisliabletomicrobiologicalcontaminationthatisobjectionableinviewofitsintendeduseshallbesubjectedtomicrobiologicaltestsbeforeuse.Anylotofcomponents,drugproductcontainers,orclosuresthatmeetstheappropriatewrittenspecificationsofidentity,strength,quality,andpurityandrelatedtestsunderparagraph(d)ofthissectionmaybeapprovedandreleasedforuse.Anylotofsuchmaterialthatdoesnotmeetsuchspecificationsshallberejected.4950211·84成份、藥品容器和封口物品的試驗(yàn)、批準(zhǔn)或拒收每批成份、藥品容器和封口物品，在未經(jīng)質(zhì)量控制部門取樣、檢查合格前，不準(zhǔn)使用。檢驗(yàn)合格后發(fā)放使用。收集每批的每一裝貨量的代表性樣品，供檢驗(yàn)用。容器的取樣數(shù)目和每—容器里物質(zhì)的取樣量是有適當(dāng)?shù)臉?biāo)準(zhǔn)的，例如,成份的變異性統(tǒng)計(jì)學(xué)標(biāo)準(zhǔn)、可信限、要求的精密度、供應(yīng)商過去的質(zhì)量歷史、211·170要求分析和留樣所需的數(shù)量等。51211·84成份、藥品容器和封口物品的試驗(yàn)、批準(zhǔn)或拒收

收集樣品程序：

(1)用適當(dāng)?shù)姆椒?，清潔選出成份容器。

(2)打開容器，取樣，重新封口，防止其內(nèi)容物受污染和其他成份、藥品容器或密封件的污染。

(3)必要時(shí)，使用滅菌設(shè)備和無菌取樣技術(shù)。

(4)如果需要從容器頂部、中部和底部的成份中取樣，樣品須混合。

(5)鑒定樣品容器，目的是確定如下資料：被取樣的物料名稱、批號(hào)、被取樣的容器、取樣日期及取樣人的名字等。

(6)已取樣的容器，應(yīng)作標(biāo)志，表示樣品已取出。52211·84成份、藥品容器和封口物品的試驗(yàn)、批準(zhǔn)或拒收

樣品檢驗(yàn)程序：一個(gè)藥品的每個(gè)成份，最少做一個(gè)特性試驗(yàn)。如有專—的特性實(shí)驗(yàn)就應(yīng)采用。依照所有成文的規(guī)格標(biāo)準(zhǔn)檢驗(yàn)每個(gè)成份的純度、含量和質(zhì)量。生產(chǎn)廠家替代上述試驗(yàn)，規(guī)定生產(chǎn)廠家最少要做一個(gè)特性鑒別試驗(yàn)，可承認(rèn)這些成份的供應(yīng)者所提供的分析報(bào)告。規(guī)定隔一定時(shí)間，生產(chǎn)廠家定期驗(yàn)證供應(yīng)者的試驗(yàn)結(jié)果，證明供應(yīng)者分析結(jié)果是正確的。依照成文規(guī)程，檢驗(yàn)容器和密封件。生產(chǎn)廠家代替上述試驗(yàn)，規(guī)定生產(chǎn)廠家對(duì)這些容器或封口物品，最少做一次目檢。可承認(rèn)供應(yīng)者的檢驗(yàn)證明書。規(guī)定生產(chǎn)廠家定期驗(yàn)證供應(yīng)者的試驗(yàn)結(jié)果，證明其試驗(yàn)結(jié)果是正確的。53211·84成份、藥品容器和封口物品的試驗(yàn)、批準(zhǔn)或拒收樣品檢驗(yàn)程序（續(xù)）：必要時(shí)，用顯微鏡檢測(cè)成份。每批易受污物、昆蟲或其他外來雜物污染的某—成份、藥品容器或密封件，應(yīng)按照已制訂的規(guī)格標(biāo)準(zhǔn)檢驗(yàn)上述各種污染。每批易受微生物污染的成份、藥品容器或密封件，在使用前，應(yīng)做微生物試驗(yàn)。任何批號(hào)的成份、藥品容器或密封件，若符合已成文的規(guī)格標(biāo)準(zhǔn)和上一點(diǎn)的有關(guān)試驗(yàn)，可批準(zhǔn)使用。任何批號(hào)的上述材料，不符合這些規(guī)格，應(yīng)拒收。Sec.211.86

Components,drugproductcontainers,andclosuresapprovedforuseshallberotatedsothattheoldestapprovedstockisusedfirst.Deviationfromthisrequirementispermittedifsuchdeviationistemporaryandappropriate.54Useofapprovedcomponents,drugproductcontainers,andclosures.55211·86獲準(zhǔn)的成份、藥品容器和密封件的使用

已獲準(zhǔn)使用的成份、藥品容器和密封件，先入庫者先用。若產(chǎn)生的偏差是暫時(shí)的和適當(dāng)?shù)?，這種偏差是容許的。Sec.211.87

Components,drugproductcontainers,andclosuresshallberetestedorreexamined,asappropriate,foridentity,strength,quality,andpurityandapprovedorrejectedbythequalitycontrolunitinaccordancewith211.84asnecessary,e.g.,afterstorageforlongperiodsorafterexposuretoair,heatorotherconditionsthatmightadverselyaffectthecomponent,drugproductcontainer,orclosure.56Retestingofapprovedcomponents,drugproductcontainers,andclosures.57211·87獲準(zhǔn)的成份、藥品容器和密封件的復(fù)檢經(jīng)質(zhì)量控制部門批準(zhǔn)或拒收的成份、藥品容器和密封件，若長(zhǎng)期貯存或曝露在空氣中、熱或其他可能對(duì)其產(chǎn)生不良影響的環(huán)境后，應(yīng)依照211·84，對(duì)均一性、效價(jià)或含量、質(zhì)量、純度等復(fù)檢。Sec.211.89

Rejectedcomponents,drugproductcontainers,andclosuresshallbeidentifiedandcontrolledunderaquarantinesystemdesignedtopreventtheiruseinmanufacturingorprocessingoperationsforwhichtheyareunsuitable.58Rejected

components,drugproductcontainers,andclosures.59211·89拒收的成份、藥品容器和封口物品拒收的成份、藥品容器和封口物品應(yīng)經(jīng)鑒定和在隔離系統(tǒng)下加以控制。防止在生產(chǎn)和加工中使用。

Sec.211.94Drugproductcontainersandclosures.Drugproductcontainersandclosuresshallnotbereactive,additive,orabsorptivesoastoalterthesafety,identity,strength,quality,orpurityofthedrugbeyondtheofficialorestablishedrequirements.Containerclosuresystemsshallprovideadequateprotectionagainstforeseeableexternalfactorsinstorageandusethatcancausedeteriorationorcontaminationofthedrugproduct.Drugproductcontainersandclosuresshallbecleanand,whereindicatedbythenatureofthedrug,sterilizedandprocessedtoremovepyrogenicpropertiestoassurethattheyaresuitablefortheirintendeduse.Standardsorspecifications,methodsoftesting,and,whereindicated,methodsofcleaning,sterilizing,andprocessingtoremovepyrogenicpropertiesshallbewrittenandfollowedfordrugproductcontainersandclosures.6061211.94藥品容器和密封件藥品包裝容器和密封件應(yīng)不起反應(yīng)、不吸著、不吸附、不致改變藥品的安全性、均一性、含量或效價(jià)、質(zhì)量和純度而超出制定的或其它頒布的規(guī)定要求。容器封口系統(tǒng)應(yīng)對(duì)貯藏和使用過程中可預(yù)見的能引起藥品變質(zhì)或污染的外部因素提供足夠的防護(hù)。藥品容器和密封件應(yīng)清潔、滅菌和除熱原，保證其適用于預(yù)期目的。藥品容器和密封件的標(biāo)準(zhǔn)或規(guī)格、檢驗(yàn)方法(指清潔和消毒方法、除熱原過程)應(yīng)成文并遵循。62F．生產(chǎn)和加工控制211.100成文的規(guī)程，偏差211.101成分的投料211.103產(chǎn)量計(jì)算211.105設(shè)備鑒別211.110中間產(chǎn)物和藥品的取樣與檢驗(yàn)211.111生產(chǎn)時(shí)間限制

211.113微生物污染的控制211.115返工Sec.211.100Writtenprocedures;deviations.Thereshallbewrittenproceduresforproductionandprocesscontroldesignedtoassurethatthedrugproductshavetheidentity,strength,quality,andpuritytheypurportorarerepresentedtopossess.Suchproceduresshallincludeallrequireme