00-cMGP中英对照版(21CFR)印刷版-2

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实用21CodeofFederalRegulationsParts210and211Part210-CURRENTGOODMANUFACTURINGPRACTICEINMANUFACTURING,PROCESSING,PACKING,ORHOLDINGOFDRUGS;GENERALPART211 -CURRENTGOODMANUFACTURINGPRACTICEFORFINISHEDPHARMACEUTICALS210部分—人用及兽用药品的生产、加工、包装或贮存的CGMP（概述）211部分—制剂药品的CGMPPart210-CURRENTGOODMANUFACTURINGPRACTICEINMANUFACTURING,PROCESSING,PACKING,ORHOLDINGOFDRUGS;GENERAL210.1Statusofcurrentgoodmanufacturingpracticeregulations.210.2Applicabilityofcurrentgoodmanufacturingpracticeregulations.210.3Definitions.AUTHORITY:Secs.201,501,502,505,506,507,512,701,704oftheFederalFood,Drug,andCosmeticAct(21U.S.C.321,351,352,355,356,357,360b,371,374).SOURCE:43FR45076,Sept.29,1978,unlessotherwisenoted.§210.1Statusofcurrentgood210部分—人用及兽用药品的生产、加工、包装或贮存的CGMP210.1cGMP法规的地位210.2cGMP法规的适用性210.3定义文档 实用manufacturingpracticeregulations.(a)TheregulationssetforthinthispartandinParts211through226ofthischaptercontaintheminimumcurrentgoodmanufacturingpracticeformethodstobeusedin,andthefacilitiesorcontrolstobeusedfor,themanufacture,processing,packing,orholdingofadrugtoassurethatsuchdrugmeetstherequirementsoftheactastosafety,andhastheidentityandstrengthandmeetsthequalityandpuritycharacteristicsthatitpurportsorisrepresentedtopossess.(b)ThefailuretocomplywithanyregulationsetforthinthispartandinParts211through226ofthischapterinthemanufacture,processing,packing,orholdingofadrugshallrendersuchdrugtobeadulteratedundersection501(a)(2)(B)oftheactandsuchdrug,aswellasthepersonwhoisresponsibleforthefailureto210.1cGMP法规的地位(a)在本部分及21CFR211—226部分中陈述的法规是在药品生产、加工、包装或贮存中使用的现行生产质量管理规范及使用的设施或控制的最低标准，以保证该药品符合联邦食品、药品及化妆品法对安全性的要求，具有均一性和效价(或含量)并符合或代表其生产过程的质量及纯度等特征。(b)凡是在药品生产、加工、包装或贮存过程中存在任何不符合本部分及21CFR211—226部分中陈述的法规的药品，依据联邦食品、药品及化妆品法501(a)(2)-(B)，该药应被视为劣药，同时导致该事故发生的负责人应受相应的法规的制裁。文档 实用comply,shallbesubjecttoregulatoryaction.§210.2Applicabilityofcurrentgoodmanufacturingpracticeregulations.(a)TheregulationsinthispartandinParts211through226ofthischapterastheymaypertaintoadrugandinParts600through680ofthischapterastheymaypertaintoabiologicalproductforhumanuse,shallbeconsideredtosupplement,notsupersede,eachother,unlesstheregulationsexplicitlyprovideotherwise.Intheeventthatitisimpossibletocomplywithallapplicableregulationsintheseparts,theregulationsspecificallyapplicabletothedruginquestionshallsupersedethemoregeneral.(b)IfapersonengagesinonlysomeoperationssubjecttotheregulationsinthispartandinParts211through226andParts600through680ofthischapter,and210.2cGMP法规的适用性(a)本部分及21CFR211—226适用于普通药品，21CFR600—680适用于人用生物制品，除非另有明确规定，否则上述两者之间应该是相互补充而不是相互取代。如有上述两部分的法规不适用的药品，则可用特定的具体法规来替代。(b)如果一个人只参与本处法规和211至226和600至680所要求的某些操，且不参与其它时，这个人可以只应用他参与的操作有关的法规。210.3定义(a)在联邦食品、药品及化妆品法201部分中包含的定义和解释、说明适用于21CFR211—226部分中的术语。(b)下面定义的术语适用于本部分及21CFR211—226。文档 实用notinothers,thatpersonneedonlycomplywiththoseregulationsapplicabletotheoperationsinwhichheorsheisengaged.§210.3Definitions.(a)Thedefinitionsandinterpretationscontainedinsection201oftheactshallbeapplicabletosuchtermswhenusedinthispartandinParts211through226ofthischapter.(b)ThefollowingdefinitionsoftermsapplytothispartandtoParts211through226ofthischapter.(1)ActmeanstheFederalFood,Drug,andCosmeticAct,asamended(21U.S.C.301etseq.).(2)Batchmeansaspecificquantityofadrugorothermaterialthatisintendedtohaveuniformcharacterandquality,withinspecifiedlimits,andisproducedaccordingtoasinglemanufacturingorderduringthe(1)法(Act)指联邦食品、药品及化妆品法，修订版(21U.S.C301etseq.)。(2)批(Batch)指在规定限度内，按照某一生产指令在同一生产周期内生产出来的，具有同一性质和质量的一定数量的药品或其它物料。(3)组分(Component)指用于药品生产的所有成份，包括那些未在药品中出现的成份。(4)药品(DrugProduct)指成品制剂(如：片剂、胶囊剂、口服液等)，通常含有一种活性成份并伴有非活性成份(但不是必需的)。本术语也包括不含有活性成份但作为安慰剂使用的成品制剂。(5)纤维(Fiber)指长度大于其宽度的3倍的任何微粒状污染物。(6)无纤维脱落的过滤器(Non-fiber-releasingfilter)指任何经过适当的预处理(如清洗或冲洗)后，不会将纤维脱落到已过滤的组分或药品中的所有过滤器。所有含石棉过滤器均被认为是有纤维脱落的过滤器。文档 实用samecycleofmanufacture.(3)Componentmeansanyingredientintendedforuseinthemanufactureofadrugproduct,includingthosethatmaynotappearinsuchdrugproduct.(4)Drugproductmeansafinisheddosageform,forexample,tablet,capsule,solution,etc.,thatcontainsanactivedrugingredientgenerally,butnotnecessarily,inassociationwithinactiveingredients.Thetermalsoincludesafinisheddosageformthatdoesnotcontainanactiveingredientbutisintendedtobeusedasaplacebo.(5)Fibermeansanyparticulatecontaminantwithalengthatleastthreetimesgreaterthanitswidth.(6)Non-fiber-releasingfiltermeansanyfilter,whichafteranyappropriatepretreatmentsuchaswashingorflushing,willnotreleasefibersintothecomponent(7)活性成份(ActiveIngredient)是指所有用于保证药物活性或其他在疾病的诊断、治愈、缓解、治疗或预防中起直接作用，或影响人或其他动物身体结构或功能的组分。本术语包括那些能承受药品生产中的化学变化和为了保证其指定的活性或作用以一种经调整的形式存在于药品中的组分。(8)非活性成份(Inactiveingredient)指不同于“活性成份”的其他组分。(9)中间产品(In-processmaterial)是指所有经制备、复合、混合或由化学反应得到的用于药品生产或制备的物料。(10)批（lot）指一批或是一批中特定的均一部分，在指定的范围内具有相同的性质和质量；或者若为由连续的生产过程制造出的药品，“批”指在单位时间或单位数量生产出的特定的、均一的部分，并且确保该部分在指定的范围内具有均一性质与质量。(11)批号(Lotnumber,control文档 实用ordrugproductthatisbeingfiltered.Allfilterscomposedofasbestosaredeemedtobefiber-releasingfilters.(7)Activeingredientmeansanycomponentthatisintendedtofurnishpharmacologicalactivityorotherdirecteffectinthediagnosis,cure,mitigation,treatment,orpreventionofdisease,ortoaffectthestructureoranyfunctionofthebodyofmanorotheranimals.Thetermincludesthosecomponentsthatmayundergochemicalchangeinthemanufactureofthedrugproductandbepresentinthedrugproductinamodifiedformintendedtofurnishthespecifiedactivityoreffect.(8)Inactiveingredientmeansanycomponentotherthanan``activeingredient.''(9)In-processmaterialmeansanymaterialnumber，batchnumber)指由字母、数字、符号或他们的组合组成，由此可确定某批药品或物料的生产、加工、包装、贮存或销售的情况。(12)药品的生产、加工、包装或贮存包括药品的包装和标签操作、检验、质量控制。(13)药用物料(medicatedfeed)指在21CFR558.3中定义的B型和C型药用物料。该物料含有联邦食品、药品及化妆品法201(g)部分中定义的一种或一种以上的药物，药用物料的生产应符合21CFR226部分中的要求。(14)药用预混合料(medicatedpremix)指21CFR558.3中定义的A型药用物质。该预混合料含有联邦食品、药品及化妆品法201(g)部分中定义的一种或一种以上的药物。药用预混合料生产应符合21CFR226部分中的要求。(15)质量控制部门(Qualitycontrolunit)指由企业任命负责质量控制相关责任的任何人员或组织机构。(16)含量或效价（Strength）指：(Ⅰ)原料药的浓度(如：以重量/重量、重量/体积、单位剂量/体积为基础)；和/(或)(Ⅱ文档 实用fabricated,compounded,blended,orderivedbychemicalreactionthatisproducedfor,andusedin,thepreparationofthedrugproduct.(10)Lotmeansabatch,oraspecificidentifiedportionofabatch,havinguniformcharacterandqualitywithinspecifiedlimits;or,inthecaseofadrugproductproducedbycontinuousprocess,itisaspecificidentifiedamountproducedinaunitoftimeorquantityinamannerthatassuresitshavinguniformcharacterandqualitywithinspecifiedlimits.(11)Lotnumber,controlnumber,orbatchnumbermeansanydistinctivecombinationofletters,numbers,orsymbols,oranycombinationofthem,fromwhichthecompletehistoryofthemanufacture,processing,packing,holding,anddistributionofabatchorlotofdrugproductorothermaterialcanbe)活性(效价)也即由适当的实验室检测或由足够的临床数据得出的指定的药品治疗活性(如：可表达为对照于某标准的单位的术语)。(17)理论产量(Theoreticalyield)指在生产、加工或包装某种药品的任一适当阶段中，并且基于所使用的组分的数量在实际生产中无任何损失或错误的情况下，应能生产的数量。(18)实际产量(Actualyield)指某种药品在生产、加工、包装的任一适当的阶段实际生产出的数量。(19)比率(Percentageoftheoreticalyield)实际产量(生产、加工或包装某种药品的适当阶段)与理论产量(在相同阶段)的比率，以百分数表示。(20)验收标准(Acceptancecriteria)建立在相应的取样方法基础上的药品的质量检验标准和合格、不合格标准(如合格质量水平和不合格的质量水平)，是决定批准或拒收一批(或其他生产单元的小组)药品的必需因素。(21)代表性样品(Representativesample)文档 实用determined.(12)Manufacture,processing,packing,orholdingofadrugproductincludespackagingandlabelingoperations,testing,andqualitycontrolofdrugproducts.(13)ThetermmedicatedfeedmeansanyTypeBorTypeCmedicatedfeedasdefinedin558.3ofthischapter.Thefeedcontainsoneormoredrugsasdefinedinsection201(g)oftheact.ThemanufactureofmedicatedfeedsissubjecttotherequirementsofPart225ofthischapter.(14)ThetermmedicatedpremixmeansaTypeAmedicatedarticleasdefinedin558.3ofthischapter.Thearticlecontainsoneormoredrugsasdefinedinsection201(g)oftheact.ThemanufactureofmedicatedpremixesissubjecttotherequirementsofPart226ofthischapter.(15)Qualitycontrolunitmeansanyperson指一个样品按合理的标准抽取（如随机取样法），并包含若干单位（元），以能保证样品准确描绘被取样品的物料。（22）联合印刷的贴签（Gang-printedlabeling）指从一张已经印刷了至少一个项目的材料上得到的贴签。211部分—制剂药品的CGMP文档 实用ororganizationalelementdesignatedbythefirmtoberesponsibleforthedutiesrelatingtoqualitycontrol.(16)Strengthmeans:(I)Theconcentrationofthedrugsubstance(forexample,weight/weight,weight/volume,orunitdose/volumebasis),and/or(ii)Thepotency,thatis,thetherapeuticactivityofthedrugproductasindicatedbyappropriatelaboratorytestsorbyadequatelydevelopedandcontrolledclinicaldata(expressed,forexample,intermsofunitsbyreferencetoastandard).(17)Theoreticalyieldmeansthequantitythatwouldbeproducedatanyappropriatephaseofmanufacture,processing,orpackingofaparticulardrugproduct,baseduponthequantityofcomponentstobeused,intheabsenceofanylossorerrorinA.总则211∙1范围211∙3定义B．组织与人员211∙22质量控制部门的职责211∙25人员资格211∙28人员职责211∙34顾问C．厂房和设施211∙42设计与建造特征211∙44照明211∙46通风、空气过滤、空气加热与冷却211∙48管件211∙50污水和废料文档 实用actualproduction(18)Actualyieldmeansthequantitythatisactuallyproducedatanyappropriatephaseofmanufacture,processing,orpackingofaparticulardrugproduct.(19)Percentageoftheoreticalyieldmeanstheratiooftheactualyield(atanyappropriatephaseofmanufacture,processing,orpackingofaparticulardrugproduct)tothetheoreticalyield(atthesamephase),statedasapercentage.(20)Acceptancecriteriameanstheproductspecificationsandacceptance/rejectioncriteria,suchasacceptablequalitylevelandunacceptablequalitylevel,withanassociatedsamplingplan,thatarenecessaryformakingadecisiontoacceptorrejectalotorbatch(oranyotherconvenientsubgroupsofmanufacturedunits).211∙52洗涤和盥洗设备211∙56卫生211∙58保养D．设备211∙63设备的设计、尺寸及位置211∙65设备构造211∙67设备清洁与保养211∙68自动化设备、机械化设备和电子设备211∙72过滤器E．成分、药品容器和密封件控制211∙80总要求211∙82未检验的成份、药品容器和密封件的接收与贮存211∙文档 实用(21)Representativesamplemeansasamplethatconsistsofanumberofunitsthataredrawnbasedonrationalcriteriasuchasrandomsamplingandintendedtoassurethatthesampleaccuratelyportraysthematerialbeingsampled.(22)Gang-printedlabelingmeanslabelingderivedfromasheetofmaterialonwhichmorethanoneitemoflabelingisprinted.[43FR45076,Sept.29,1978,asamendedat51FR7389,Mar.3,1986;58FR41353,Aug.3,1993]EFFECTIVEDATENOTE:At58FR41353,Aug.8,1993,210.3wasamendedbyaddingparagraph(b)(22)effectiveAug.3,1994.Part211-CURRENTGOODMANUFACTURINGPRACTICEFORFINISHEDPHARMACEUTICALS(21CFRPart211AsofApril,1996)Authority:Secs.201,501,502,505,506,507,512,701,704oftheFederalFood,Drug,andCosmeticAct(21U.S.C.321,351,352,355,356,357,360b,371,374).Source:43FR45077,Sept.29,1978,unlessotherwisenoted.SubpartA--GeneralProvisions84成份、药品容器和密封件的试验、批准或拒收211∙86获准的成份、药品容器和密封件的使用211∙87获准的成份、药品容器和密封件的复检211∙89拒收的成份、药品容器和密封件211∙94药品密封容器和密封件F.生产和加工控制211∙100成文的规程、偏差211∙101成分的控制211∙103产量计算211∙105设备鉴别211∙110中间体和药品的取样与检验211∙111生产时间限制211∙113微生物污染的控制211∙115返工文档 实用§211.1-Scope.§211.3-Definitions.SubpartB--OrganizationandPersonnel§211.22-Responsibilitiesofqualitycontrolunit.§211.25-Personnelqualifications.§211.28-Personnelresponsibilities.§211.34-Consultants.SubpartC--BuildingsandFacilities§211.42-Designandconstructionfeatures.§211.44-Lighting.§211.46-Ventilation,airfiltration,airheatingandcooling.§211.48-Plumbing.§211.50-Sewageandrefuse.§211.52-Washingandtoiletfacilities.§211.56-Sanitation.§211.58-Maintenance.SubpartD--Equipment§211.63-Equipmentdesign,size,andlocation.G.包装和标签控制211∙122材料的检查和使用标准211∙125标签的发放211∙130包装和贴签操作211∙132人用非处方药（OTC）保险包装的要求211∙134药品检查211∙137有效期H．贮存和销售211∙142入库程序211∙150销售程序I∙实验室控制211∙160总要求文档 实用§211.65-Equipmentconstruction.§211.67-Equipmentcleaningandmaintenance.§211.68-Automatic,mechanical,andelectronicequipment.   §211.72-Filters.SubpartE--ControlofComponentsandDrugProductContainersandClosures§211.80-Generalrequirements.§211.82-Receiptandstorageofuntestedcomponents,drugproductcontainers,andclosures.§211.84-Testingandapprovalorrejectionofcomponents,drugproductcontainers,andclosures.§211.86-Useofapprovedcomponents,drugproductcontainers,andclosures.§211.87-Retestingofapprovedcomponents,drugproductcontainers,andclosures.§211.89-Rejectedcomponents,drugproductcontainers,andclosures.§211.94-Drugproductcontainersandclosures.SubpartF--ProductionandProcess211∙165销售前的检验与发放211∙166稳定性试验211∙167特别检验要求211∙170留样211∙173实验动物211∙176青霉素污染J．记录和报告211∙180总要求211∙182设备清洁和使用记录211∙184成份、药品容器、密封件及标签记录211∙186主要生产和控制的记录211∙188批生产和控制记录211∙192产品记录复查211∙194实验室记录211∙196销售记录211∙198客户投诉档案文档 实用Controls§211.100-Writtenprocedures;deviations.§211.101-Charge-inofcomponents.§211.103-Calculationofyield.§211.105-Equipmentidentification.§211.110-Samplingandtestingofin-processmaterialsanddrugproducts.§211.111-Timelimitationsonproduction.§211.113-Controlofmicrobiologicalcontamination.§211.115-Reprocessing.SubpartG--PackagingandLabelingControl§211.122-Materialsexaminationandusagecriteria.§211.125-Labelingissuance.§211.130-Packagingandlabelingoperations.§211.132-Tamper-evidentpackagingrequirementsforover-the-counter(OTC)humandrugproducts.§211.134-Drugproductinspection.§211.137-Expirationdating.SubpartH--HoldingandDistribution§211.142-Warehousingprocedures. §211.150-Distributionprocedures.K．退货的药品和回收处理211∙204退货的药品211∙208药品的回收利用A.总则211∙1范围（a）本部分的条例包含人用或兽用药品制备的现行最低限度的药品生产质量管理规范（GMP）（b）在本章里的这些针对药品的现行GMP条例和本章600至800的所有部分针对人用生物制品的现行GMP条例，除非明确另有说明者外，应认为是对本部分条例的补充，而是不代替。本章其他部分或本章600至680各部分和本部分均可适用的条例，前部分的条例可代替本部分条例。文档 实用SubpartI--LaboratoryControls§211.160-Generalrequirements.§211.165-Testingandreleasefordistribution.§211.166-Stabilitytesting.§211.167-Specialtestingrequirements.§211.170-Reservesamples.§211.173-Laboratoryanimals.§211.176-Penicillincontamination.SubpartJ--RecordsandReports§211.180-Generalrequirements.§211.182-Equipmentcleaninganduselog.§211.184-Component,drugproductcontainer,closure,andlabelingrecords.§211.186-Masterproductionandcontrolrecords.§211.188-Batchproductionandcontrolrecords.§211.192-Productionrecordreview.§211.194-Laboratoryrecords.§211.196-Distributionrecords.§211.198-Complaintfiles.SubpartK--ReturnedandSalvagedDrugProducts§211.204-Returneddrugproducts.§211.208-Drugproductsalvaging.SubpartA-GeneralProvisions（c）在考虑经提议的，发表在1978年9月29日联邦注册表（FR）上一项免除时，若产品及其所有成份是以人用物品形式作一般销售和消费且这些产品根据其预期用途，亦可列入药品的范围内，则不应对这些非处方药（OTC）实施本部分条例，直至进一步的通知为止。本章110部分和113至119部分的条例用于鉴别这些变是食品的OTC药品是否按照GMP的要求生产、加工、包装和贮存。211∙3定义本章210∙3中的定义适用于本部分。B．组织与人员211∙22质量控制部门的职责（a）本部门有批准和拒收所有成份、药品包装容器、密封件、中间体、包装材料、标签及药品的职责与权力。复查生产记录和权力，保证不产生差错，或若发生差错，保证他们充分调查这差错。本部门负责根据合同，批准或拒收由其它公司生产、加工、包装或贮存的药品。（b）适当的实验室检验设备、批准（或拒收）各种成份、药品容器、密封件、包装材料及药品，质量控制部门是可以获得的。(c)本部门有批准或驳回影响药品的均一性、效价或含量、质量及纯度的所有程序或规格标准的职责。文档 实用§211.1Scope(a)Theregulationsinthispartcontaintheminimumcurrentgoodmanufacturingpracticeforpreparationofdrugproductsforadministrationtohumansoranimals.(b)Thecurrentgoodmanufacturingpracticeregulationsinthischapter,astheypertaintodrugproducts,andinparts600through680ofthischapter,astheypertaintobiologicalproductsforhumanuse,shallbeconsideredtosupplement,notsupersede,theregulationsinthispartunlesstheregulationsexplicitlyprovideotherwise.Intheeventitisimpossibletocomplywithapplicableregulationsbothinthispartandinotherpartsofthischapterorinparts600through680ofthischapter,theregulationspecificallyapplicabletothedrugproductinquestionshallsupersedetheregulationinthispart.(d)适用于本部门的职责与程序，应成文字材料，并应遵循。211∙25人员资格(a)每位从事药品生产、加工、包装或仓贮工作人员，应接受培训、教育及有实践经验，完成委派的各项职务。培训是按照现行GMP（包括本章中的现行GMP条例和这些条例要求的成文程序）中涉及雇员的内容。邀请合格人员指导，并连续多次培训，保证雇员熟悉现行GMP对他们的要求。(b)负责监督药品的生产、加工、包装或仓贮工作的每一个工作人员，应受教育、培训及有经验，完成委派的各项职务。以此作为提供药品具有安全性、均一性、效价或含量、质量及纯度的保证。文档 实用(c)Pendingconsiderationofaproposedexemption,publishedintheFederalRegisterofSeptember29,1978,therequirementsinthispartshallnotbeenforcedforOTCdrugproductsiftheproductsandalltheiringredientsareordinarilymarketedandconsumedashumanfoods,andwhichproductsmayalsofallwithinthelegaldefinitionofdrugsbyvirtueoftheirintendeduse.Therefore,untilfurthernotice,regulationsunderpart110ofthischapter,andwhereapplicable,parts113to129ofthischapter,shallbeappliedindeterminingwhethertheseOTCdrugproductsthatarealsofoodsaremanufactured,processed,packed,orheldundercurrentgoodmanufacturingpractice.§211.3Definitions.Thedefinitionssetforthin§210.3ofthis(c)有足够数量执行和监督每种药品的生产、加工、包装或仓贮的合格人员。211∙28人员职责(a)从事药品生产、加工、包装或仓贮的人员，应穿着适合于其履行职责的清洁衣服。按需要，头部、脸部、手部、臂部应外罩，防止药物受污染(b)人员保持良好的个人卫生和健康。(c)未经监督人员允许，其他人员不能进入限制进入的建筑物和设施。(d)任何人，在任何时间，明显地表现出现有影响药品安全性和质量的疾病或开放性`损伤，应避免接触各种成份、药品容器、包装设备、密封件、中间体，直至恢复或由资质的医务人员确认不会危害到药品的安生和质量。所有人员应受教育知道，应向负责人报告对药品有不利影响的健康情况。211∙34顾问文档 实用chapterapplyinthispart.SubpartB-OrganizationandPersonnel§211.22Responsibilitiesofqualitycontrolunit.(a)Thereshallbeaqualitycontrolunitthatshallhavetheresponsibilityandauthoritytoapproveorrejectallcomponents,drugproductcontainers,closures,in-processmaterials,packagingmaterial,labeling,anddrugproducts,andtheauthoritytoreviewproductionrecordstoassurethatnoerrorshaveoccurredor,iferrorshaveoccurred,thattheyhavebeenfullyinvestigated.Thequalitycontrolunitshallberesponsibleforapprovingorrejectingdrugproductsmanufactured,processed,packed,orheldundercontractbyanothercompany.(b)Adequatelaboratoryfacilitiesforthetestingandapproval(orrejection)ofcomponents,drugproductcontainers,为了对问题提出意见，聘请顾问。顾问应对药品生产、加工、包装或仓贮提出建议，他们受过足够的教育、培训，且有丰富的实践经验。保留他们的姓名、地址、任何的顾问资格证书及服务形式等履历资料。C．厂房和设施211∙42设计与建造特征(a)任何用于某类药品生产、加工、包装或贮存的厂房或建筑群，大小适宜，结构与位置使其易于清洁、保养、适合操作。(b)建筑物有足够空间来有条理地安装设备和放置材料，避免不同类的成份、药品容器、密封件、标签、中间体或药品等相互混放，防止污染。通过厂房的上述物料其流向在设计时要防止污染。(c)操作应在明确规定的、大小适中的地区内进行。这些地区按规定各自分隔开，以防止污染。下列操作须在单独的地区内进行：文档 实用closures,packagingmaterials,in-processmaterials,anddrugproductsshallbeavailabletothequalitycontrolunit.(c)Thequalitycontrolunitshallhavetheresponsibilityforapprovingorrejectingallproceduresorspecificationsimpactingontheidentity,strength,quality,andpurityofthedrugproduct.(d)Theresponsibilitiesandproceduresapplicabletothequalitycontrolunitshallbeinwriting;suchwrittenproceduresshallbefollowed.§211.25Personnelqualifications.(a)Eachpersonengagedinthemanufacture,processing,packing,orholdingofadrugproductshallhaveeducation,training,andexperience,oranycombinationthereof,toenablethatpersontoperformtheassignedfunctions.Trainingshallbeintheparticularoperationsthat(1)发放给生产或包装前，质量控制部门取样期间，成份、药品容器、密封件及标签的签收、鉴别、贮存及拒收区域。(2)在处理前，拒收的成份、药品容器、密封件及标签的贮存。(3)已放行的成份、药品容器、密封件及标签的贮存。(4)中间体的贮存。(5)生产与加工操作。(6)包装和贴标签操作。(7)药品放行前的待验隔离贮存。(8)放行后药品的贮存。(9)控制室与实验室操作。(10)无菌操作，包括如下适当的（Ⅰ）地板、墙壁和天花板平滑、坚硬、表面易清洁；（Ⅱ）温度与湿度控制（Ⅲ）空气经高效过滤器、在正压下过滤、层流或非层流均可；（Ⅳ）环境监测系统；（Ⅴ）创造无菌环境的房间和设备清洁、消毒系统；文档 实用theemployeeperformsandincurrentgoodmanufacturingpractice(includingthecurrentgoodmanufacturingpracticeregulationsinthischapterandwrittenproceduresrequiredbytheseregulations)astheyrelatetotheemployee'sfunctions.TrainingincurrentgoodmanufacturingpracticeshallbeconductedbyqualifiedindividualsonacontinuingbasisandwithsufficientfrequencytoassurethatemployeesremainfamiliarwithCGMPrequirementsapplicabletothem.(b)Eachpersonresponsibleforsupervisingthemanufacture,processing,packing,orholdingofadrugproductshallhavetheeducation,training,andexperience,oranycombinationthereof,toperformassignedfunctionsinsuchamannerastoprovideassurancethatthedrugproducthasthesafety,identity,strength,quality,andpuritythatitpurportsorisrepresentedto（Ⅵ）控制无菌环境的设备维修系统。（d）青霉素生产、加工及包装设备与生产其他人用药品的设备分开211∙44照明所有地区均须提供充足的照明。211∙46通风、空气过滤、空气加热与冷却(a)提供足够的通风。(b)提供足够能控制空气正压、微生物、尘粒、温度和湿度的设备，适应药品生产、加工和贮存需要。(c)空气过滤系统，包括预过滤器和微粒物质空气过滤器。空气经过滤才送至生产区，如果空气是再循环到生产区，应控制从生产区带来的尘埃。生产中发生空气污染生产区，应以排气系统或其他系统充分抽出空气，控制污染。(d)青霉素生产、加工和包装的空气输送系统应与其他人用药品的空气输送系统完全分开。文档 实用possess.(c)Thereshallbeanadequatenumberofqualifiedpersonneltoperformandsupervisethemanufacture,processing,packing,orholdingofeachdrugproduct.§211.28Personnelresponsibilities.(a)Personnelengagedinthemanufacture,processing,packing,orholdingofadrugproductshallwearcleanclothingappropriateforthedutiestheyperform.Protectiveapparel,suchashead,face,hand,andarmcoverings,shallbewornasnecessarytoprotectdrugproductsfromcontamination.(b)Personnelshallpracticegoodsanitationandhealthhabits.(c)Onlypersonnelauthorizedbysupervisorypersonnelshallenterthoseareasofthebuildingsandfacilities211∙48管件(a)饮用水应在持续正压下、对药品无污染的管道系统内供。饮用水应符合环境保护机构制订的“基本饮用水条例”标准（40CFR141部分）。不符合该标准的水，不许进入水系统。(b)排水设备应有足够的大小，可直接连接排水管及安装防止虹吸倒流的空气破坏设备或其他机械设备。（43FR45077，1978年9月29日，修正于48FR11426，1983年3月18日）。211∙50污水和废料来自附近建筑物的污水、垃圾及其他废料，用安全、卫生的方法处理。211∙52洗涤和盥洗设备提供洗涤和盥洗设备，包括热、冷水，肥皂或清洁剂，空气干燥器或专用毛巾，及干净的盥洗设备，以便于进入进行工作区。211∙56卫生(a)所有用作药品生产、加工、包装及贮存的厂房应保持清洁、卫生的环境，且不受啮齿动物、鸟类及其他害虫侵害扰（实验动物除外）。垃圾和有机废料，定时以卫生的方法控制处理。文档 实用designatedaslimited-accessareas.(d)Anypersonshownatanytime(eitherbymedicalexaminationorsupervisoryobservation)tohaveanapparentillnessoropenlesionsthatmayadverselyaffectthesafetyorqualityofdrugproductsshallbeexcludedfromdirectcontactwithcomponents,drugproductcontainers,closures,in-processmaterials,anddrugproductsuntiltheconditioniscorrectedordeterminedbycompetentmedicalpersonnelnottojeopardizethesafetyorqualityofdrugproducts.Allpersonnelshallbeinstructedtoreporttosupervisorypersonnelanyhealthconditionsthatmayhaveanadverseeffectondrugproducts.§211.34Consultants.Consultantsadvisingonthemanufacture,processing,packing,orholdingofdrugproductsshallhavesufficienteducation,(b)分配卫生清洁任务的详细的清洁项目、方法、设备、用于清洁厂房和设施的材料的一览表,应有成文规定。(c)适用的杀鼠剂、杀昆虫剂、杀真菌剂、熏蒸剂、去垢剂和消毒剂一览表，应有成文规定。防止这些操作对设备、成份、药品容器密封件、包装材料、标签或药品产生污染。除依据联邦杀虫剂、杀真菌剂及杀鼠剂法规（7U.S.C135）已登记和使用的品种外，其他的不能使用。(d)消毒程序应适用于合同雇用或临时雇员，如同全职雇员一样在普通例行的操作时执行。211∙58保养文档 实用training,andexperience,oranycombinationthereof,toadviseonthesubjectforwhichtheyareretained.Recordsshallbemaintainedstatingthename,address,andqualificationsofanyconsultantsandthetypeofservicetheyprovide.SubpartC-BuildingsandFacilities§211.42Designandconstructionfeatures.(a)Anybuildingorbuildingsusedinthemanufacture,processing,packing,orholdingofadrugproductshallbeofsuitablesize,constructionandlocationtofacilitatecleaning,maintenance,andproperoperations.(b)Anysuchbuildingshallhaveadequatespacefortheorderlyplacementofequipmentandmaterialstopreventmixupsbetweendifferentcomponents,任何用于药品生产、加工、包装或贮存的厂房保持良好状态。D．设备211∙63设备的设计、尺寸及位置药品生产、加工、包装或贮存设备，设计合理，大小适当，布置合理，便于操作、清洁和保养。211∙65设备构造(a)设备表面与各种成份、中间体或药品接触，不会发生改变药品的安全性、均一性、效价或含量、质量或纯度的化学反应或吸收作用。(b)操作所需的物质，如润滑剂、冷却剂等不能进入设备里，与成份、药品容器、密封件、中间体或药品接触，保证药品的安全性、均一性、效价或含量、质量或纯度不变。211∙67设备清洁与保养(a)相隔一定时间，对设备与工具进行清洁、保养和消毒，防止出故障与污染，影响药品的安全性、均一性、效价或含量、质量或纯度。文档 实用drugproductcontainers,closures,labeling,in-processmaterials,ordrugproducts,andtopreventcontamination.Theflowofcomponents,drugproductcontainers,closures,labeling,in-processmaterials,anddrugproductsthroughthebuildingorbuildingsshallbedesignedtopreventcontamination.(c)Operationsshallbeperformedwithinspecificallydefinedareasofadequatesize.Thereshallbeseparateordefinedareasforthefirm'soperationstopreventcontaminationormixupsasfollows:(1)Receipt,identification,storage,andwithholdingfromuseofcomponents,drugproductcontainers,closures,andlabeling,pendingtheappropriatesampling,testing,orexaminationbythequalitycontrolunitbeforereleaseformanufacturingorpackaging;(b)制订药品生产、加工包装或贮存设备（包括用具）的清洁和保养文字程序，并执行。这些程序包括，但不一定限于以下内容；(1)分配清洁、保养任务。(2)保养和清洁细目一览表。(3)详细说明用于清洁和保养时使用的方法、设备、物质。拆卸和装配设备的方法必须保证适合清洁和保养的要求。(4)除去或擦去前批遗留物的鉴定。(5)已清除了污染的清洁设备的保护。(6)使用前清洁设备的检查。(7)保留保养、清洁、消毒的记录。按211∙180及211∙182的说明检查。211∙68自动化设备、机械化设备和电子设备文档 实用(2)Holdingrejectedcomponents,drugproductcontainers,closures,andlabelingbeforedisposition;(3)Storageofreleasedcomponents,drugproductcontainers,closures,andlabeling;(4)Storageofin-processmaterials;(5)Manufacturingandprocessingoperations;(6)Packagingandlabelingoperations;(7)Quarantinestoragebeforereleaseofdrugproducts;(8)Storageofdrugproductsafterrelease;(9)Controlandlaboratoryoperations;(10)Asepticprocessing,whichincludesasappropriate:(I)Floors,walls,andceilingsofsmooth,hardsurfacesthatareeasilycleanable;(a)用于药品生产、加工、包装和贮存的自动化、机械化或电子包括计算机或其它类型的设备。按惯例，对其设计之成文条款作标定、检查或核对，保证其工作性能良好。保留检查、标定、核对等文字记录。(b)对保障重要生产变化的计算机或有关系统进行操作培训。操作记录或其他记录只能由被认可的人员制订。向计算机或有关系统输入或从中输出的各种方案、其他记录或资料，应核查其准确性。输入计算机或关系统内的档案资料，除与实验室共同分析计算的结果可消除外，其他的应保留。文字记录与相应的证明资料一起保存。事先设计好的硬件复制品或多台选择系统，如复印件、磁带或微型胶卷等，保证其副本资料正确、可靠及完整。出现资料改动、非人为消除或遗失时，应维修。文档 实用(ii)Temperatureandhumiditycontrols;(iii)Anairsupplyfilteredthroughhigh-efficiencyparticulateairfiltersunderpositivepressure,regardlessofwhetherflowislaminarornonlaminar;(iv)Asystemformonitoringenvironmentalconditions;(v)Asystemforcleaninganddisinfectingtheroomandequipmenttoproduceasepticconditions;(vi)Asystemformaintaininganyequipmentusedtocontroltheasepticconditions.(d)Operationsrelatingtothemanufacture,processing,andpackingofpenicillinshallbeperformedinfacilitiesseparatefromthoseusedforotherdrugproductsforhumanuse.[43FR45077,Sept.29,1978,asamendedat60FR4091,Jan.20,1995]211∙72过滤器用于生产、加工的液体过滤器或人用注射药品的包装材料不许释放出的纤维进入产品。除非不得已，不应在生产、加工中使用释放纤维的过滤器或注射药品的包装材料。若必须使用一种能释放纤维素的过滤器，最后应使用一非释放纷纷物、平均最大孔径为0.22μm(如实际生产条件限制，可用0.45μm)的附加过滤器过滤，降低注射剂内微粒量。使用含石棉的过滤器最后用或不用特殊非释放纤维过滤器均可以，但要根据FDA有关部门提供的该非释放纤维过滤器会或可能损害注射剂的安全性和有效性的证据而定。E．成份、药品容器和密封件控制211∙80总要求(a)有文字详细说明成份、药品容器、密封件的签收、鉴定、贮存、装运取样、检验和批准或拒收程序，并遵循。文档 实用§211.44Lighting.Adequatelightingshallbeprovidedinallareas.§211.46Ventilation,airfiltration,airheatingandcooling.(a)Adequateventilationshallbeprovided.(b)Equipmentforadequatecontroloverairpressure,micro-organisms,dust,humidity,andtemperatureshallbeprovidedwhenappropriateforthemanufacture,processing,packing,orholdingofadrugproduct.(c)Airfiltrationsystems,includingprefiltersandparticulatematterairfilters,shallbeusedwhenappropriateonairsuppliestoproductionareas.Ifairisrecirculatedtoproductionareas,measuresshallbetakentocontrolrecirculationofdustfromproduction.Inareaswhereaircontaminationoccursduringproduction,(b)成份、药品容器和密封件应专人管理和在防止污染的环境下贮存。(c)药品容器的包装袋或包装箱或密封件应离地面放置保持适当间隔，以便清洁和检查。(d)用明显批号代码对已接收的每次到货的成份、药品容器或密封件加以区别。此批号代码用于记录每批货的处理。每批货按其状态应有适当标识，如待验、批准或拒收。211∙82未检验的成份、药品容器和密封件的接收与贮存(a)接收时和验收前，对每个或编组的成份容器、药品容器和密封件进行目检，检查标签与内容物是否一致、容器损坏或拆封和污染等情况(b)成份、药品容器各密封件应隔离贮存，直至经检验为止。合格后，方可发放。在符合211∙80要求的地方中贮存。211∙84成份、药品容器和密封件的试验、批准或拒收(a)每批成份、药品容器和密封件，在未经质量部门取样、检查合格前，不准使用。检验合格后发放使用。文档 实用thereshallbeadequateexhaustsystemsorothersystemsadequatetocontrolcontaminants.(d)Air-handlingsystemsforthemanufacture,processing,andpackingofpenicillinshallbecompletelyseparatefromthoseforotherdrugproductsforhumanuse.§211.48Plumbing.(a)Potablewatershallbesuppliedundercontinuouspositivepressureinaplumbingsystemfreeofdefectsthatcouldcontributecontaminationtoanydrugproduct.PotablewatershallmeetthestandardsprescribedintheEnvironmentalProtectionAgency'sPrimaryDrinkingWaterRegulationssetforthin40CFRpart141.Waternotmeetingsuchstandardsshallnotbepermittedinthepotablewatersystem.(b)每次到货的每个批号应收集代表性样品用于检测或检查。要取样的包装个数以及每个包装应取的样品量应根据适当标准来定，比如成份分可变程度的统计标准、供应商的信用级别、期望的精密度、供应商以往质量历史、以及按照法规§211.170规定的分析和保留的样品及其质量。(c)收集样品程序：(1)必要时，用适当的方法，清洁选出成份容器；(2)打开容器，取样，重新封口，防止其内容物受污染和其他成分、药品容器或密封件的污染。(3)必要时，使用灭菌设备和无菌取样技术。(4)如果需要从容器顶部、中部和底部的成分中取样，这些样品不得混合。(5)标识样品容器，目的是确定如下资料：被取样的材料名称、批号、被取样的容器，取样日期及样品收集人的名字等。(6)已取样的容器，应作标志，表示样品已取出。文档 实用(b)Drainsshallbeofadequatesizeand,whereconnecteddirectlytoasewer,shallbeprovidedwithanairbreakorothermechanicaldevicetopreventback-siphonage.[43FR45077,Sept.29,1978,asamendedat48FR11426,Mar.18,1983]§211.50Sewageandrefuse.Sewage,trash,andotherrefuseinandfromthebuildingandimmediatepremisesshallbedisposedofinasafeandsanitarymanner.§211.52Washingandtoiletfacilities.Adequatewashingfacilitiesshallbeprovided,includinghotandcoldwater,soapordetergent,airdriersorsingle-servicetowels,andcleantoiletfacilitieseasilyaccessibletoworkingareas.§211.56Sanitation.(a)Anybuildingusedinthemanufacture,(d)样品检验程序：(1)一个药品的每个成分，最少做一个特性试验。如有专一特性实验就应采用。(2)依照所有成文的规格标准检验每个成份的纯度、含量和质量。假如通过定期验证供应者的试验结果，证明供应商的分析结果正确可靠的基础上，可以接受以供应商提供的分析报告来代替上述试验，但最少要做个成份特性试验。(3)依照成文规程，检验容器和密封件。假如通过定期验证供应者的试验结果，证明供应商的分析结果正确可靠的基础上，可以接受以供应商提供的分析报告来代替上述试验，但最少做一次目检。(4)必要时，用显微镜检测成分。(5)对于易受污物、昆虫或其他外来杂物污染的某一成份、药品容器或密封件，每批应按制订的标准检查，避免污染。文档 实用processing,packing,orholdingofadrugproductshallbemaintainedinacleanandsanitarycondition,Anysuchbuildingshallbefreeofinfestationbyrodents,birds,insects,andothervermin(otherthanlaboratoryanimals).Trashandorganicwastemattershallbeheldanddisposedofinatimelyandsanitarymanner.(b)Thereshallbewrittenproceduresassigningresponsibilityforsanitationanddescribinginsufficientdetailthecleaningschedules,methods,equipment,andmaterialstobeusedincleaningthebuildingsandfacilities;suchwrittenproceduresshallbefollowed.(c)Thereshallbewrittenproceduresforuseofsuitablerodenticides,insecticides,fungicides,fumigatingagents,andcleaningandsanitizingagents.Suchwrittenproceduresshallbedesignedtopreventthecontaminationofequipment,(6)对于易被微生物污染的某一成份、药品容器或密封件，而且对其预计的用途会产生不良影响，则每批在使用前应当做微生物试验。（e）任何批号的成份、药品容器或密封件，若符合已成文的均一性、效价或含量、质量、纯度等的规格标准和本部分（d）的有关试验，可批准使用。任何批号的上述物料，不符合这些规格，应拒收。211∙86获准的成份、药品容器和密封件的使用获准使用的成份、药品容器和密封件，先入库者先用。若产生的偏差是暂时的和适当，这种偏差是容许的。211∙87获准的成份、药品容器和密封件的复检经质量控制部门批准或拒收的成份、药品容器、密封件，若长期贮存或曝露在空气、热或其他可能对其产生不良影响的环境后，应依照211∙84，对均一性、效价或含量、质量、纯度等复检。211∙89拒收的成份、药品容器和密封件文档 实用components,drugproductcontainers,closures,packaging,labelingmaterials,ordrugproductsandshallbefollowed.Rodenticides,insecticides,andfungicidesshallnotbeusedunlessregisteredandusedinaccordancewiththeFederalInsecticide,Fungicide,andRodenticideAct(7U.S.C.135).(d)Sanitationproceduresshallapplytoworkperformedbycontractorsortemporaryemployeesaswellasworkperformedbyfull-timeemployeesduringtheordinarycourseofoperations.§211.58Maintenance.Anybuildingusedinthemanufacture,processing,packing,orholdingofadrugproductshallbemaintainedinagoodstateofrepair.SubpartD-Equipment§211.63Equipmentdesign,size,and拒收的成份、药品容器和密封件应经鉴定和在隔离系统下加以控制，防止在生产和加工使用。211∙94药品密封容器和密封件(a)药品包装容器和密封件应不起反应、不吸着、不吸附、不致改变药品的安全性、均一性、含量或效价、质量和纯度而超出制定的或其它颁布的规定要求。(b)容器封口系统应对贮藏和使用过程中可预见的能引起药品变质或污染的外部因素提供足够的防护。(c)药品容器和密封件应清洁、灭菌和除热原，保证其适用于预期目的。(d)药品容器和密封件的标准或规格、检验方法（指清洁和消毒方法、除热原过程）应成文并遵循。F.生产和加工控制211∙100成文的规程、偏差(a)编写为保证药品的均一性、含量或效价、质量及纯度而设计的生产和加工控制程序，这些程序包括本部内全部要求。这些成文程序（包括变化）须经有关部门起草、审核和批准，然后再经质量控制部门审核与批准。文档 实用location.Equipmentusedinthemanufacture,processing,packing,orholdingofadrugproductshallbeofappropriatedesign,adequatesize,andsuitablylocatedtofacilitateoperationsforitsintendeduseandforitscleaningandmaintenance.§211.65Equipmentconstruction.(a)Equipmentshallbeconstructedsothatsurfacesthatcontactcomponents,in-processmaterials,ordrugproductsshallnotbereactive,additive,orabsorptivesoastoalterthesafety,identity,strength,quality,orpurityofthedrugproductbeyondtheofficialorotherestablishedrequirements.(b)Anysubstancesrequiredforoperation,suchaslubricantsorcoolants,shallnotcomeintocontactwithcomponents,drugproductcontainers,closures,in-process(b)在实施各种生产和加工控制功能中，遵循已制定的生产和加工控制程序，并在实施时以文件记录加以证明。程序中出现的任何偏差，应作记录，并提出证据。211∙101成分的控制成文的生产和控制程序包括下面的内容，其设计应保证所生产的药品具有的均一性、含量和效价、质量和纯度。(a)按处方配制的药品，保证其活性成份含量不低于100%标示量或规定量。(b)生产药品用的成份应称量、测量或适当粉碎。若一种成份从原来容器转移到另一容器内，新容器上应有下列标识内容：(1)成份名称或项目代码。(2)接收或控制号。(3)在新容器中的重量或份量。(4)使用此成份配制的一批药品，包含其产品名称、规格和批号。(c)文档 实用materials,ordrugproductssoastoalterthesafety,identity,strength,quality,orpurityofthedrugproductbeyondtheofficialorotherestablishedrequirements.§211.67Equipmentcleaningandmaintenance.(a)Equipmentandutensilsshallbecleaned,maintained,andsanitizedatappropriateintervalstopreventmalfunctionsorcontaminationthatwouldalterthesafety,identity,strength,quality,orpurityofthedrugproductbeyondtheofficialorotherestablishedrequirements.(b)Writtenproceduresshallbeestablishedandfollowedforcleaningandmaintenanceofequipment,includingutensils,usedinthemanufacture,processing,packing,orholdingofadrugproduct.Theseproceduresshallinclude,butarenotnecessarilylimitedto,thefollowing:成份的称重、测量或粉碎操作，应受到严密的监督。盛放用于生产成份的每一容器，须经第二人检查，保证：(1)此成份是由质量控制人员放行的。(2)重量或份量正确，与批生产记录一致。(3)容器经严格区别。（d）每一成份投料时，一人操作，另一人核对。211∙103产量计算在药品生产、加工或贮存的每一适当阶段结束时，测算实际产量与理论产量的百分比。这个计算应由一人执行后，由另外一人独立进行核实。211∙105设备鉴别(a)在整个生产周期内，同批药品生产使用的全部混合和贮存容器、生产线和主要设备应严格识别，标示出药品的成份，必要时，还应标出所处的加工阶段。(b)一种药品每批生产使用的主要设备，以一鉴别性识别号或代号加以识别。此鉴别号或代号记录在该批号产品的记录本。若生产中只使用一种特殊型号的设备，可用该设备名字代替鉴别性识别或代号。文档 实用(1)Assignmentofresponsibilityforcleaningandmaintainingequipment;(2)Maintenanceandcleaningschedules,including,whereappropriate,sanitizingschedules;(3)Adescriptioninsufficientdetailofthemethods,equipment,andmaterialsusedincleaningandmaintenanceoperations,andthemethodsofdisassemblingandreassemblingequipmentasnecessarytoassurepropercleaningandmaintenance;(4)Removalorobliterationofpreviousbatchidentification;(5)Protectionofcleanequipmentfromcontaminationpriortouse;(6)Inspectionofequipmentforcleanlinessimmediatelybeforeuse.(7)Recordsshallbekeptofmaintenance,cleaning,sanitizing,andinspectionas211∙110中间体和药品的取样与检验(a)制订和遵循说明每批的加工过程控制及对加工过程中材料的适当样品实行检验或检查的成文程序，保证药品的一致性和完整性。这些控制程序应当建立并用于监控产出和验证生产工艺的性能，考虑可能的引起产品和过程物料的性质变化的原因。上述控制程序包括，但不限于如下内容：(1)片剂或胶囊的重量差异。(2)崩解时间。(3)充分混和，保证均匀。(4)溶解时间和速率。(5)溶液的澄明度、溶解完全性及PH值。(b)考虑上述特性而制定的有效中间加工规格与药品最终规格一致。此中间加工规格应在以前可靠的加工方法稳定性评估和经应用统计学程序断定认为合适的基础上制定的。样品测试，保证药品和中间体符合规格标准。(c)过程物料应当根据适合程度检测鉴别、剂量、质量和纯度，并由质量部门在生产过程中，比如开始或完成重要步骤时或在长期储存以后，确定批准或拒绝使用。文档 实用specifiedin§§211.180and211.182.§211.68Automatic,mechanical,andelectronicequipment.(a)Automatic,mechanical,orelectronicequipmentorothertypesofequipment,includingcomputers,orrelatedsystemsthatwillperformafunctionsatisfactorily,maybeusedinthemanufacture,processing,packing,andholdingofadrugproduct.Ifsuchequipmentissoused,itshallberoutinelycalibrated,inspected,orcheckedaccordingtoawrittenprogramdesignedtoassureproperperformance.Writtenrecordsofthosecalibrationchecksandinspectionsshallbemaintained.(b)Appropriatecontrolsshallbeexercisedovercomputerorrelatedsystemstoassurethatchangesinmasterproductionandcontrolrecordsorotherrecordsareinstitutedonlybyauthorizedpersonnel.(d)不合格的中间体，在隔离系统下标识及控制，防止其在生产或加工操作中使用。211∙111生产时间限制在适当时候，制定完成每一生产阶段的时间限制，保证药品质量。制定的时间限制产生偏差时，如这些偏差不损害药品质量，是可以接受的。这些偏差应有文字文件证明是正当的。211∙113微生物污染的控制(a)制订和遵循预防非无菌药品有害微生物的适当程序。(b)制订和遵循预防无菌药品微生物污染的适当程序。这些程序应包括所有灭菌过程的验证。211∙115返工(a)应建立并执行书面程序，有关不符合标准或质量标准的批的返工处理的系统，所采取的步骤以确保返工的批次符合所有已经建立的标准、质量标准和性质。文档 实用Inputtoandoutputfromthecomputerorrelatedsystemofformulasorotherrecordsordatashallbecheckedforaccuracy.Thedegreeandfrequencyofinput/outputverificationshallbebasedonthecomplexityandreliabilityofthecomputerorrelatedsystem.Abackupfileofdataenteredintothecomputerorrelatedsystemshallbemaintainedexceptwherecertaindata,suchascalculationsperformedinconnectionwithlaboratoryanalysis,areeliminatedbycomputerizationorotherautomatedprocesses.Insuchinstancesawrittenrecordoftheprogramshallbemaintainedalongwithappropriatevalidationdata.Hardcopyoralternativesystems,suchasduplicates,tapes,ormicrofilm,designedtoassurethatbackupdataareexactandcompleteandthatitissecurefromalteration,inadvertenterasures,orlossshallbemaintained.[43FR45077,Sept.29,1978,asamendedat60FR(b)没有质量控制部门审核与批准，不许进行返工。G.包装和标签控制211∙122材料的检查和使用标准(a)制订详细标签和包装材料的接收、鉴别、贮存、搬运、取样、检验的程序，并遵循这些成文程序。在接收、用于药品包装和贴标签前，有代表性地对其取样与检查。(b)只有符合成文规格标准的标签和包装材料，方可批准发放使用。不符合规格者，不得用于生产。(c)收到每次发货的每个不同的标签和包装材料应保留记录，记录应表明接收、检查或检测，以及是否接收或拒收。(d)用于不同药品、规格、剂型及成份数量的标签和包装材料应分别贮存，并挂上适当标识，只限经核准人员接近贮存地区。(e)作废和过时的标签、标示材料及其他包装材料应销毁。文档 实用4091,Jan.20,1995]§211.72Filters.Filtersforliquidfiltrationusedinthemanufacture,processing,orpackingofinjectabledrugproductsintendedforhumanuseshallnotreleasefibersintosuchproducts.Fiber-releasingfiltersmaynotbeusedinthemanufacture,processing,orpackingoftheseinjectabledrugproductsunlessitisnotpossibletomanufacturesuchdrugproductswithouttheuseofsuchfilters.Ifuseofafiber-releasingfilterisnecessary,anadditionalnon-fiber-releasingfilterof0.22micronmaximummeanporosity(0.45micronifthemanufacturingconditionssodictate)shallsubsequentlybeusedtoreducethecontentofparticlesintheinjectabledrugproduct.Useofanasbestos-containingfilter,withorwithoutsubsequentuseofaspecific(f)不同产品或规格或净含量时使用联合印刷是禁止的，除非联合印刷页上的贴签得到足够的区别，比如大小、形状或颜色。(g)如果使用切割标签，在包装和标签时，至少有一项如下的专门的控制过程：(1)不同产品各个剂量应有专用贴签和包装线。(2)使用适当的电子的或电子机械的设备来100%的检查贴签过程或完成操作后的标签正确性。或(3)使用目检来100%检查手工包装的贴签过程或完成操作后的标签正确性。这个检查应由一人执行，并有另外一人独立核实。(h)打印设备，或标签批号打印与产品生产线在一起或有联系时，应监控以确保所有的批号打印与产品批记录一致。文档 实用non-fiber-releasingfilter,ispermissibleonlyuponsubmissionofprooftotheappropriatebureauoftheFoodandDrugAdministrationthatuseofanon-fiber-releasingfilterwill,orislikelyto,compromisethesafetyoreffectivenessoftheinjectabledrugproduct.SubpartE-ControlofComponentsandDrugProductContainersandClosures§211.80Generalrequirements.(a)Thereshallbewrittenproceduresdescribinginsufficientdetailthereceipt,identification,storage,handling,sampling,testing,andapprovalorrejectionofcomponentsanddrugproductcontainersandclosures;suchwrittenproceduresshallbefollowed.(b)Componentsanddrugproductcontainersandclosuresshallatalltimesbehandledandstoredinamannertoprevent211∙125标签的发放(a)严格控制用于药品的标签。(b)已发放的一批标签材料，须认真检查其同一性，应与一批或单批生产记录中说明的标签一致。(c)核对发放的，已使用的及退回的标签，若发现成品数量与发出的标签数量不符，差额超出根据先前历史水平定下的数量范围，则需对这些偏差作出评估，按照211∙192要求调查原因。如果按照211.122(G)(2)执行的100%的贴签正确性检查，则切割或滚动贴签的平衡可以不做。(d)印有批号或控制号的剩余标签，应全部销毁。(e)退回的标签，如保留应加上证明标志贮存，防止混淆。(f)文档 实用contamination.(c)Baggedorboxedcomponentsofdrugproductcontainers,orclosuresshallbestoredoffthefloorandsuitablyspacedtopermitcleaningandinspection.(d)Eachcontainerorgroupingofcontainersforcomponentsordrugproductcontainers,orclosuresshallbeidentifiedwithadistinctivecodeforeachlotineachshipmentreceived.Thiscodeshallbeusedinrecordingthedispositionofeachlot.Eachlotshallbeappropriatelyidentifiedastoitsstatus(i.e.,quarantined,approved,orrejected).§211.82Receiptandstorageofuntestedcomponents,drugproductcontainers,andclosures.(a)Uponreceiptandbeforeacceptance,eachcontainerorgroupingofcontainersofcomponents,drugproductcontainers,and制订发放标签的详细控制程序，并遵循执行。211∙130包装和贴签操作设计保证标签、标示及包装材料正确用于药品的程序，并遵循。这些程序结合下列特征：(a)预防由物理的或其他操作空间物质引起的混淆和交叉污染(b)识别并处理已经装了药品的容器，放在一边，并且控制在未贴签的状态以便以后进行贴签操作，防止单个容器、批或部分批被误贴签。没有必要识别每个容器，但是要足够明确每个容器的名称、剂量、内容物的质量和批号或控制号。(c)用批号或控制号来识别，能确定批生产和控制历史文档 实用closuresshallbeexaminedvisuallyforappropriatelabelingastocontents,containerdamageorbrokenseals,andcontamination.(b)Components,drugproductcontainers,andclosuresshallbestoredunderquarantineuntiltheyhavebeentestedorexamined,asappropriate,andreleased.Storagewithintheareashallconformtotherequirementsof§211.80.§211.84Testingandapprovalorrejectionofcomponents,drugproductcontainers,andclosures.(a)Eachlotofcomponents,drugproductcontainers,andclosuresshallbewithheldfromuseuntilthelothasbeensampled,tested,orexamined,asappropriate,andreleasedforusebythequalitycontrolunit.(b)Representativesamplesofeachshipmentofeachlotshallbecollectedfor(d)包装工作开展前，检查包装和标签材料的适用性和正确性，且这些检验所提供的证明文件应符合批生产记录。(e)使用前立即检查包装和贴签设施，确保前次操作的药品已经被除去。也应检查并确保不能用来包装和贴签的物料已经被除去。检查结果应记录在产品批记录里面。211∙132人用非处方药（OTC）保险包装的要求(a)文档 实用testingorexamination.Thenumberofcontainerstobesampled,andtheamountofmaterialtobetakenfromeachcontainer,shallbebaseduponappropriatecriteriasuchasstatisticalcriteriaforcomponentvariability,confidencelevels,anddegreeofprecisiondesired,thepastqualityhistoryofthesupplier,andthequantityneededforanalysisandreservewhererequiredby§211.170.(c)Samplesshallbecollectedinaccordancewiththefollowingprocedures:(1)Thecontainersofcomponentsselectedshallbecleanedwherenecessary,byappropriatemeans.(2)Thecontainersshallbeopened,sampled,andresealedinamannerdesignedtopreventcontaminationoftheircontentsandcontaminationofothercomponents,drugproductcontainers,or一般来说，在联邦食品、药物和化妆品法规下，FDA有权制定非处方药保险包装的统一国家要求。提高非处方药包装的可靠性和有助保证非自主药的安全与效果。一种零售OTC药品（除皮肤科药、洁牙剂、胰岛素、喉片除外）没有包装在保险包装内或没有适当的标签，根据联邦法规501部分，属掺假药；根据502部分或两者，此类属错贴标签。(b)每个OTC药品（皮肤科药、洁牙剂、胰岛素、喉片除外）生产者和包装者，应将零售OTC药品装入保险包装内，若此药易受公众影响，该药应在内保持至售出。保险包装是内有一个或多个指示物或障碍物的药品包装。若缺损或失落，能适当地给顾客提供已发生破损的明显证据。如果因缺损而使产品受损，则要求此包装在设计上应有特色（例如喷雾产品容器）或使用一个或多个有鉴别性指示物或障碍物加进包装内（例如图案、名称、注册商标、标识或图画等）。上述“在设计上有特色”之意，即此包装不能用一般的通用材料和加工工艺来复制。术语“喷雾产品”即用液化气体或压缩气体将成份从容器中喷出。保险包装可以是能提供目视其中包装完整性的密闭容器、第二容器、封闭系统或任何联合系统。这些保险装置被设计成在生产、分装和销售陈列期间，以适当方法搬运，保持不致受损坏。文档 实用closures.(3)Sterileequipmentandasepticsamplingtechniquesshallbeusedwhennecessary.(4)Ifitisnecessarytosampleacomponentfromthetop,middle,andbottomofitscontainer,suchsamplesubdivisionsshallnotbecompositedfortesting.(5)Samplecontainersshallbeidentifiedsothatthefollowinginformationcanbedetermined:nameofthematerialsampled,thelotnumber,thecontainerfromwhichthesamplewastaken,thedateonwhichthesamplewastaken,andthenameofthepersonwhocollectedthesample.(6)Containersfromwhichsampleshavebeentakenshallbemarkedtoshowthatsampleshavebeenremovedfromthem.(d)Samplesshallbeexaminedandtestedasfollows:(1)两段式明胶硬胶囊产品，除非包装工艺密封的外，最少需二个保险装置。(2)所有其他产品，包括经保险工艺密封的二段式明胶硬胶囊，最少需要一个保险装置。(c)标签。除在易拆安瓿中氨吸入物、本部分的（b）节规定的喷雾产品或压缩医用氧容器外，本部分涉及的非处方药的每个零售包装，要求带有一“声明”放置在一明显的地方，使顾客对包装的特殊保险装置有所警觉。此标签“声明”不要求放置于适当的地方，当包装的保险装置破损或失落时，不受影响。如果选择符合本部分（b）节要求的保险装置是使用识别性质的话，那要参考标签“声明”。例如，在带有一收缩套的瓶上的标签“声明”应写“为了此瓶周围印有标志”。文档 实用(1)Atleastonetestshallbeconductedtoverifytheidentityofeachcomponentofadrugproduct.Specificidentitytests,iftheyexist,shallbeused.(2)Eachcomponentshallbetestedforconformitywithallappropriatewrittenspecificationsforpurity,strength,andquality.Inlieuofsuchtestingbythemanufacturer,areportofanalysismaybeacceptedfromthesupplierofacomponent,providedthatatleastonespecificidentitytestisconductedonsuchcomponentbythemanufacturer,andprovidedthatthemanufacturerestablishesthereliabilityofthesupplier'sanalysesthroughappropriatevalidationofthesupplier'stestresultsatappropriateintervals.(3)Containersandclosuresshallbetestedforconformancewithallappropriatewrittenprocedures.Inlieuofsuchtesting(d)申请免除对包装和标签的要求。生产者和馐者可申请免除本部分对包装和标签的要求。一个免除申请，要求按本章10∙30，以公民申请形式提交，且根据“免除保险包装申请条例”加以鉴别。申请所需之内容如下：(1)药品名称。若申请的是某一类药，需列出类别名称，并列出该类药中的产品表。(2)药品没必要实施或不能达到本部分的保险包装或标签的要求的理由。(3)其他措施有描述，或当早已采取的措施有描述，以减少恶意掺假的可能性。(4)证明免除是合理的其他资料。(e)非处方药受已被批准的新药申请管辖。要求非处方药原被批准的新药申请持有人，根据本章314∙70（c）提供的要求，可在FDA批准前实施。根据本章314∙70（b），胶囊密封的生产改进需FDA先批准。文档 实用bythemanufacturer,acertificateoftestingmaybeacceptedfromthesupplier,providedthatatleastavisualidentificationisconductedonsuchcontainers/closuresbythemanufacturerandprovidedthatthemanufacturerestablishesthereliabilityofthesupplier'stestresultsthroughappropriatevalidationofthesupplier'stestresultsatappropriateintervals.(4)Whenappropriate,componentsshallbemicroscopicallyexamined.(5)Eachlotofacomponent,drugproductcontainer,orclosurethatisliabletocontaminationwithfilth,insectinfestation,orotherextraneousadulterantshallbeexaminedagainstestablishedspecificationsforsuchcontamination.(6)Eachlotofacomponent,drugproductcontainer,orclosurethatisliabletomicrobiologicalcontaminationthatis(f)1970年毒药预防包装条例。本部分不影响本章310∙3（L）规定的特殊包装的任何要求和1970年毒药保护包装条例的要求（经管理和预算处批准，控制号0910149）[54联邦注册5228，1989年2月2日]。211∙134药品检查(a)在结束工作时，应检查已包装和贴标签的产品，保证本批容器和包装的标签正确无误。(b)操作结束时，每组收集一个代表性样品，同时检查标签。(c)检查结果记录在该批的生产或控制记录中。211∙137有效期(a)保证一个产品在使用时符合均一性、效价或含量、质量和纯度等标准，应提供一个有效期。有效期按211∙166所述的稳定性试验测定。(b)有效期是在符合标签上规定的贮存条件下，按211∙166所述的稳定性试验测定。文档 实用objectionableinviewofitsintendeduseshallbesubjectedtomicrobiologicaltestsbeforeuse.(e)Anylotofcomponents,drugproductcontainers,orclosuresthatmeetstheappropriatewrittenspecificationsofidentity,strength,quality,andpurityandrelatedtestsunderparagraph(d)ofthissectionmaybeapprovedandreleasedforuse.Anylotofsuchmaterialthatdoesnotmeetsuchspecificationsshallberejected.§211.86Useofapprovedcomponents,drugproductcontainers,andclosures.Components,drugproductcontainers,andclosuresapprovedforuseshallberotatedsothattheoldestapprovedstockisusedfirst.Deviationfromthisrequirementispermittedifsuchdeviationistemporaryandappropriate.§211.87Retestingofapprovedcomponents,drugproductcontainers,andclosures.(c)如药品在配制时要重新配伍，那重新配伍好的和未重新配伍的两种药品标签上均须提供有效日期。(d)根据本章201∙17的要求，有效日期应标在标签上。(e)顺势治疗（homeopathic）药品免除本部分的要求。(f)标“没有美国效价标准”的变应原提取物免除本部分要求。(g)对于调查研究用新药，如果它们符合合适的标准或规格，并在临床研究使用能证明其稳定性，可以免除本部分要求。如研究用新药在配制时要重新配伍，那重新配伍好的药品标签上须标明有效日期。(h)1978年9月29日联邦注册发表了一个未决的免除提议，本章的要求可以对人用OTC药品不执行，只要它们的标签不包括剂量限制而且在3年内稳定并有适当的稳定性数据来支持。文档 实用Components,drugproductcontainers,andclosuresshallberetestedorreexamined,asappropriate,foridentity,strength,quality,andpurityandapprovedorrejectedbythequalitycontrolunitinaccordancewith§211.84asnecessary,e.g.,afterstorageforlongperiodsorafterexposuretoair,heatorotherconditionsthatmightadverselyaffectthecomponent,drugproductcontainer,orclosure.§211.89Rejectedcomponents,drugproductcontainers,andclosures.Rejectedcomponents,drugproductcontainers,andclosuresshallbeidentifiedandcontrolledunderaquarantinesystemdesignedtopreventtheiruseinmanufacturingorprocessingoperationsforwhichtheyareunsuitable.§211.94Drugproductcontainersandclosures.[43联邦注册45077，1978年9月29日，修正，在46联邦56412，1981年11月17日，在60联邦4091，1995年1月20]。H．贮存和销售211∙142入库程序制订和遵循药品入库程序，包括：(a)在质量控制部门放行前，药品待验。(b)药品在适当的温度、湿度和照明下贮存，不影响药品的均一性、效价或含量、质量及纯度。211∙150销售程序制订和遵循药品销售程序，包括：(a)最早批准入库的药品，应先销售。若违背本要求的地方是暂时和适可的，这是允许的。(b)通过每批药品的销售系统，能迅速追查药品，便于有必要召回。I∙实验室控制211∙160总要求(a)文档 实用(a)Drugproductcontainersandclosuresshallnotbereactive,additive,orabsorptivesoastoalterthesafety,identity,strength,quality,orpurityofthedrugbeyondtheofficialorestablishedrequirements.(b)Containerclosuresystemsshallprovideadequateprotectionagainstforeseeableexternalfactorsinstorageandusethatcancausedeteriorationorcontaminationofthedrugproduct.(c)Drugproductcontainersandclosuresshallbecleanand,whereindicatedbythenatureofthedrug,sterilizedandprocessedtoremovepyrogenicpropertiestoassurethattheyaresuitablefortheirintendeduse.(d)Standardsorspecifications,methodsoftesting,and,whereindicated,methodsofcleaning,sterilizing,andprocessingtoremovepyrogenicpropertiesshallbe按本部分的要求，制订规格、标准、取样方法、试验程序或其他实验室控制机制，包括上述内容的修改，由有关部门起草，并经质量控制部门审核、批准。遵守本部分中各要求，在实施时，提供证明文件。任何超出成文的规格、标准、取样方法、试验程序或其他实验室控制机制的偏差，应作记录，并提供证明。(b)实验室控制内容，包括科学地制订完善、合理的规格、标准、取样方法及为保证各种成份、药品容器、密封件、中间体、标签和药品符合均一性、效价和含量、质量与纯度标准而设计的检验程序。实验室控制包括：(1)根据接收的规格，测定用于药品生产、加工包装及贮存的每装货量中的每批的成份、药品容器、密封件和标签。保证它们符合制定的规格标准。此规格包括使用的取样和检验程序说明。样品有代表性及经适当鉴别。这些程序亦要求对任何变质的成份、药品容器或密封件作重复检验。(2)根据中间体的成文规格和取样及检验程序，测定中间体。样品应有代表性和经适当鉴定。(3)根据产品的成文规格和取样及检验程序，测定产品。样品应有代表性和经适当鉴定。文档 实用writtenandfollowedfordrugproductcontainersandclosures.SubpartF-ProductionandProcessControls§211.100Writtenprocedures;deviations.(a)Thereshallbewrittenproceduresforproductionandprocesscontroldesignedtoassurethatthedrugproductshavetheidentity,strength,quality,andpuritytheypurportorarerepresentedtopossess.Suchproceduresshallincludeallrequirementsinthissubpart.Thesewrittenprocedures,includinganychanges,shallbedrafted,reviewed,andapprovedbytheappropriateorganizationalunitsandreviewedandapprovedbythequalitycontrolunit.(b)Writtenproductionandprocesscontrolproceduresshallbefollowedintheexecutionofthevariousproductionand(4)设备、仪器、量具和记录设备的校验有适当的间隔，符合已经建立的书面程序，该程序包括详细的指导、时间表、准确度和精密度的限度、当准确度/精密度不符合限度时的校正措施。设备、仪器、量具和记录设备不符合已经建立的质量标准时不得使用。211∙165销售前的检验与放行(a)每批药品发放前须经实验室检测，保证其符合药品的最终规格标准，包括均一性和活性成份的含量。对有效期短的，需无菌和/或热原试验的放射药物特殊批号，可在无菌和/或热原试验完成前放行，但应规定尽快完成试验。(b)根据需要，每批药品应进行适当的实验室有害微生物检验。(c)任何取样和检验方法，应在成文程序中说明。此程序包括取样方法和每批检验的取样数量，并遵循。文档 实用processcontrolfunctionsandshallbedocumentedatthetimeofperformance.Anydeviationfromthewrittenproceduresshallberecordedandjustified.§211.101Charge-inofcomponents.Writtenproductionandcontrolproceduresshallincludethefollowing,whicharedesignedtoassurethatthedrugproductsproducedhavetheidentity,strength,quality,andpuritytheypurportorarerepresentedtopossess:(a)Thebatchshallbeformulatedwiththeintenttoprovidenotlessthan100percentofthelabeledorestablishedamountofactiveingredient.(b)Componentsfordrugproductmanufacturingshallbeweighed,measured,orsubdividedasappropriate.Ifacomponentisremovedfromtheoriginalcontainertoanother,thenewcontainer(d)对质量控制部门的取样和检验的接收标准是满足保证那些药品符合各自的规格标准和统计学的质量控制标准。这些标准是批准和发放药品的条件。此统计学质量控制标准包括适当的接收水平和/或适当的拒收水平。(e)证实和提供文件证明经严格使用的检验方法的准确性、灵敏性、专属性和重现性。此验证和文件，可按照211∙194（a）(2)项完成。(f)不符合制订的标准、规格和其他有关质量控制标准的药品，应拒收，但可返工。被返工的药品，在接收和应用前，须符合标准、规格和其他有关标准211∙166稳定性试验(a)有一个设计确定药品稳定性的成文试验方案。此试验用于测定合适的贮存条件和有效期。该方案应包括：(1)样品量和检测周期。是基于各自的检查特征的统计学标准而定，保障稳定性评价的正确性。(2)保留样品的贮存条件。(3)可靠的、有意义和有效的试验方法。文档 实用shallbeidentifiedwiththefollowinginformation:(1)Componentnameoritemcode;(2)Receivingorcontrolnumber;(3)Weightormeasureinnewcontainer;(4)Batchforwhichcomponentwasdispensed,includingitsproductname,strength,andlotnumber.(c)Weighing,measuring,orsubdividingoperationsforcomponentsshallbeadequatelysupervised.Eachcontainerofcomponentdispensedtomanufacturingshallbeexaminedbyasecondpersontoassurethat:(1)Thecomponentwasreleasedbythequalitycontrolunit;(2)Theweightormeasureiscorrectasstatedinthebatchproductionrecords;(4)使用与上市销售药品相同的容器密闭系统。(5)配制时，配伍的药品（按标签指出的）和配制后的药品的检验。(b)每个药品有足够批号受检，测定一个适当的有效期，并保留这些资料。结合成份、药品及容器-封闭系统的基本稳定性资料的“加速实验”，用于支持提供足够的货架寿命的实验性有效期是不合适的，而且，这种研究正在实行。使用“加速实验”提供的资料，设计实验性有效期，此有效期是后于由实际货架研究支持的日期。必须实施产品稳定性试验，包括适当检验周期，直至此实验性有效期被证实或被确定为止。(c)本部分对顺势治疗药品的要求如下：(1)对各成份间的可配伍性，有一个基于药品的检验或测定的稳定性文字评价。同时，根据药品销售经验，证明正常的或预期的使用期内，药品没有降解变质。(2)稳定性评价应建立在与上市销售相同的容器封闭系统基础上。文档 实用(3)Thecontainersareproperlyidentified.(d)Eachcomponentshallbeaddedtothebatchbyonepersonandverifiedbyasecondperson.§211.103Calculationofyield.Actualyieldsandpercentagesoftheoreticalyieldshallbedeterminedattheconclusionofeachappropriatephaseofmanufacturing,processing,packaging,orholdingofthedrugproduct.Suchcalculationsshallbeperformedbyonepersonandindependentlyverifiedbyasecondperson.§211.105Equipmentidentification(a)Allcompoundingandstoragecontainers,processinglines,andmajorequipmentusedduringtheproductionofabatchofadrugproductshallbeproperlyidentifiedatalltimestoindicatetheircontentsand,whennecessary,thephaseof(d)标有“没有美国效价标准”变应原提取物，免除本部分要求[43联邦注册4507，1978年9月29日，修正，在46联邦56412，1981年11月17日]211∙167特殊检验要求(a)对于标明无菌和/或无热原的每批药品，应有检查符合此要求的实验室检验。检验程序应成文并遵循。(b)对于每批眼膏，应有测定符合有关外部微粒，粗糙或磨蚀物质存在的检验。检验程序应成文并遵循。(c)每批控释制剂都有一实验室检验，测定每一活性成份释放比率。该检验程序应成文并遵循。211∙170留样(a)每次到货的每批活性成份经鉴别后，留样。留样最少二倍于满足全部测定所需样品数量，无菌和热原检验所需量除外。保留时间要求如下：(1)药品中的活性成份，除按符合本段（a）（2）和（3）要求外，留样至含该批活性成份的最后一批产品的有效期后一年。文档 实用processingofthebatch.(b)Majorequipmentshallbeidentifiedbyadistinctiveidentificationnumberorcodethatshallberecordedinthebatchproductionrecordtoshowthespecificequipmentusedinthemanufactureofeachbatchofadrugproduct.Incaseswhereonlyoneofaparticulartypeofequipmentexistsinamanufacturingfacility,thenameoftheequipmentmaybeusedinlieuofadistinctiveidentificationnumberorcode.§211.110Samplingandtestingofin-processmaterialsanddrugproducts.(a)Toassurebatchuniformityandintegrityofdrugproducts,writtenproceduresshallbeestablishedandfollowedthatdescribethein-processcontrols,andtests,orexaminationstobeconductedonappropriatesamplesofin-process(2)放射性药品中的活性成份（非放射活性试剂盒除外）的留样保留：(I)如果药品有效期是三十天或以内，留样保留期是含此活性成份的最后一批药品的有效期满后三个月。(ii)如果药品有效期是三十天以上，留样保留期是含此活性成份的最后一批药品的有效期满后六个月。(3)根据211∙137免除有效期的非处方药，其活性成分留样，是含此活性成份药品的最后一批药品销售后三年。(b)经鉴别，代表每批药品的留样，在药品标签指定的条件贮存。留样贮存在与上市销售药品的同样容器封闭系统内或基本上相同的容器系统内。留样应最少二倍于满足全检需要量，无菌和热原检验的留样除外。每年至少目检留样（除（b）（2）中述及的药品外）一次，检查其变质迹象，除非目检会影响留样的完整性。对留样变质迹象，根据211∙192加以研究。留样观察结果的记录应和该药品的稳定性资料一起保留。医用压缩气体不需留样。药品留样保留时间如下：文档 实用materialsofeachbatch.Suchcontrolproceduresshallbeestablishedtomonitortheoutputandtovalidatetheperformanceofthosemanufacturingprocessesthatmayberesponsibleforcausingvariabilityinthecharacteristicsofin-processmaterialandthedrugproduct.Suchcontrolproceduresshallinclude,butarenotlimitedto,thefollowing,whereappropriate:(1)Tabletorcapsuleweightvariation;(2)Disintegrationtime;(3)Adequacyofmixingtoassureuniformityandhomogeneity;(4)Dissolutiontimeandrate;(5)Clarity,completeness,orpHofsolutions.(b)Validin-processspecificationsforsuchcharacteristicsshallbeconsistentwithdrugproductfinalspecificationsandshallbe(1)除本部分（b）（2）和（3）中述及的药品外的药品，留样保留时间是该药有效期满后一年。（2）非放射性试剂盒除外，放射活性药品的留样保留：(I)如药品有效期为三十天或以内，则留样至该药品有效期满后保留三个月；(ii)如有效期超过三十天，则留样至药品有效期满后保留六个月。（3）根据211∙137，免除有效期的非处方药品，留样至药品销售后保留三年。[48联邦注册13025，1983年3月29日；修正60联邦注册4091，1995年1月20日]。文档 实用derivedfrompreviousacceptableprocessaverageandprocessvariabilityestimateswherepossibleanddeterminedbytheapplicationofsuitablestatisticalprocedureswhereappropriate.Examinationandtestingofsamplesshallassurethatthedrugproductandin-processmaterialconformtospecifications.(c)In-processmaterialsshallbetestedforidentity,strength,quality,andpurityasappropriate,andapprovedorrejectedbythequalitycontrolunit,duringtheproductionprocess,e.g.,atcommencementorcompletionofsignificantphasesorafterstorageforlongperiods.(d)Rejectedin-processmaterialsshallbeidentifiedandcontrolledunderaquarantinesystemdesignedtopreventtheiruseinmanufacturingorprocessing211∙173实验动物用于检测成份、加工过程中材料或药品规格的动物，应被适当地饲养和控制，保证其适合预期的用途。动物应能区别，并保留其使用情况的历史记录。211∙176青霉素污染若一种非青霉素药品有可能被青霉素交叉感染，此非青霉素药品应检测青霉素的存在。按药品中青霉素污染和测量程序（通过相关参考文献）中规定的方法检验，如青霉素达到可检出水平，该药品不许销售。该文件可从FDA药品评价和研究中心研究和检测部门（HFD470）（200CSt.Sw.WashingtonDC2024）,或从联邦注册处（1100LSt.Nw.,Washington,DC2048）得到。[43联邦注册45077，1978年9月29日，修正47联邦注册9396，1982年3月5日；50联邦注册8996，1985年3月6日；55联邦注册11577，1990年3月29日]。J．记录和报告211∙180总要求(a)任何生产、控制或销售记录，须依照本部分要求保留，特别是与一批药品有关的上述记录，该批药品有效期满后保留一年以上。对于一些符合211∙文档 实用operationsforwhichtheyareunsuitable.§211.111Timelimitationsonproduction.Whenappropriate,timelimitsforthecompletionofeachphaseofproductionshallbeestablishedtoassurethequalityofthedrugproduct.Deviationfromestablishedtimelimitsmaybeacceptableifsuchdeviationdoesnotcompromisethequalityofthedrugproduct.Suchdeviationshallbejustifiedanddocumented.§211.113Controlofmicrobiologicalcontamination.(a)Appropriatewrittenprocedures,designedtopreventobjectionablemicroorganismsindrugproductsnotrequiredtobesterile,shallbeestablishedandfollowed.(b)Appropriatewrittenprocedures,designedtopreventmicrobiologicalcontaminationofdrugproductspurporting137免除标准的无有效期的非处方药品，记录保存至在该批药品销售后，保留三年。(b)全部成份，药品容器、密封件及标签的相关记录，在有效期满后，保留一年以上。对于一些符合211∙137免除标准的无有效期的非处方药品，从销售最后一批药品计，上述记录保留三年。(c)本部分要求的全部记录或它们的复印件，应便于查找，能在保存期内对所有生产活动进行复核检查。因此，在检查中，这些记录可以复印或其他方法复制。直接从电子计算机或其它设备中提出的记录，符合本段的要求。(d)本部分要求的记录，可用原始记录或使用原始记录的复印件，如影印、缩微胶卷或其它复制方式。所使用的复印技术，应适合阅读，且复印设备易得。(e)保留本部分所要求的文字记录，其中的资料可用作每年度每个药品的质量评估，决定药品的标准、生产或控制程序中是否需要变更。该评估应制订成文并遵循，应包括下列条款：文档 实用tobesterile,shallbeestablishedandfollowed.Suchproceduresshallincludevalidationofanysterilizationprocess.§211.115Reprocessing.(a)Writtenproceduresshallbeestablishedandfollowedprescribingasystemforreprocessingbatchesthatdonotconformtostandardsorspecificationsandthestepstobetakentoinsurethatthereprocessedbatcheswillconformwithallestablishedstandards,specifications,andcharacteristics.(b)Reprocessingshallnotbeperformedwithoutthereviewandapprovalofthequalitycontrolunit.SubpartG-PackagingandLabelingControl§211.122Materialsexaminationandusagecriteria.(1)回顾一定数量有代表性的批次，不论是批准或拒收，所有与此有关的记录。(2)回顾投诉、召回、退货或回收处理药品，按211∙192对每个药品进行调查。(f)应建立程序以保证企业负责人责任。如果他们不亲自参与或不能立即知道上述的行为，应以书面形式他们，按211∙198、211∙204或211∙208等条款实施的任何调查结果、任何召回、FDA发出的检测报告或与FDA通过的GMP有关的受规章限制的任何活动。[43联邦注册45077，1978年9月29日，修正60联邦注册4901，1995年1月20日]。211∙182设备清洁和使用记录文档 实用(a)Thereshallbewrittenproceduresdescribinginsufficientdetailthereceipt,identification,storage,handling,sampling,examination,and/ortestingoflabelingandpackagingmaterials;suchwrittenproceduresshallbefollowed.Labelingandpackagingmaterialsshallberepresentativelysampled,andexaminedortesteduponreceiptandbeforeuseinpackagingorlabelingofadrugproduct.(b)Anylabelingorpackagingmaterialsmeetingappropriatewrittenspecificationsmaybeapprovedandreleasedforuse.Anylabelingorpackagingmaterialsthatdonotmeetsuchspecificationsshallberejectedtopreventtheiruseinoperationsforwhichtheyareunsuitable.(c)Recordsshallbemaintainedforeachshipmentreceivedofeachdifferentlabelingandpackagingmaterialindicatingreceipt,examinationortesting,and主要设备的清洁、保养（常规保养，如润滑、调整等除外）和使用文字记录，包括在单独的设备记录内，此记录列有日期、时间、产品和加工批号等内容。若设备专用于生产一种药品，药品批号（单批或整批）按号码排列，且按顺序号生产，那么，不要求单独的设备记录。使用专用设备时，其清洁、保养和使用记录是批生产记录的一部分。清洁和保养的操作人员和复核人员，应在记录上填写日期、签名和填写操作记录，证明该项工作已做过。记录应按年月顺序进行。211∙184成份、药品容器、密封件及标签记录这些记录包括如下内容：(a)每次至货的每批成份、药品容器、密封件和标签的鉴别与数量，供应商名称；供应商的批号（如知道）、按21∙80指定的接收代码、接收日期。原始生产商的名称和地址，若与供应商不同，若知道应列出。(b)任何检验结果（包括按211∙82（a）211∙84(d)或211∙122（a）的要求进行的检验结果）和从那里得到的结论。(c)每个成份、药品容器、密封件的单独存货记录和每批使用的成份核对表（对各成份来说）。此存货记录应有使用各成份、药品容器和密封件的各批（整批或小批）药品的详细资料。(d)按211∙122（c）和211∙130（c）制订的规定，检查或复查标签和贴标签所提供的文件。(e)不合格成份、药品容器、密封件和标签的处理。文档 实用whetheracceptedorrejected.(d)Labelsandotherlabelingmaterialsforeachdifferentdrugproduct,strength,dosageform,orquantityofcontentsshallbestoredseparatelywithsuitableidentification.Accesstothestorageareashallbelimitedtoauthorizedpersonnel.(e)Obsoleteandoutdatedlabels,labeling,andotherpackagingmaterialsshallbedestroyed.(f)Useofgangprintingoflabelingfordifferentdrugproductsordifferentstrengthsornetcontentsofthesamedrugproduct,isprohibitedunlessthelabelingfromgang-printedsheetsisadequatelydifferentiatedbysize,shape,orcolor.(g)Ifcutlabelingisused,packagingandlabelingoperationsshallincludeoneofthefollowingspecialcontrolprocedures:(1)Dedicationoflabelingandpackaging211∙186主要生产和控制的记录(a)保障批与批间的一致性，准备各批药品的主要生产和控制记录（包括各批的量），由一人填写日期和签名（手写、签全名）。由另一个单独核实，填写日期和签名。此主要生产和控制记录的准备，应成文字程序加以说明，并遵循。(b)主要生产和控制记录包括：(1)产品名称、规格和剂型的说明。(2)每剂量单位或每重量单位中各活性成份的名称、重量或容量；任何剂量单位的总重量或容量。(3)一份完整的、以名称或代码表示的成份列表，能充分显示特定的质量特性。(4)准确描述各成份的重量或容量，使用相同计量系统（公制、常衡或药衡制）。合理的变更是允许的，如果制备而不可避免地造成该剂型中各份量的改变，并且它们在该主要生产和控制记录中被证明是合理的。(5)有关任何成份超过量的计算说明。(6)在适当加工阶段，理论重量或容量的说明。文档 实用linestoeachdifferentstrengthofeachdifferentdrugproduct.(2)Useofappropriateelectronicorelectromechanicalequipmenttoconducta100-percentexaminationforcorrectlabelingduringoraftercompletionoffinishingoperations;or(3)Useofvisualinspectiontoconducta100-percentexaminationforcorrectlabelingduringoraftercompletionoffinishingoperationsforhand-appliedlabeling.Suchexaminationshallbeperformedbyonepersonandindependentlyverifiedbyasecondperson.(h)Printingdeviceson,orassociatedwith,manufacturinglinesusedtoimprintlabelinguponthedrugproductunitlabelorcaseshallbemonitoredtoassurethatallimprintingconformstotheprintspecifiedinthebatchproductionrecord.[43FR45077,Sept.29,1978,asamendedat58FR(7)理论产量的说明，包括根据211∙192要求，对超过理论产量最大和最小百分率的调查说明。(8)药品容器、密封件和包装材料的说明，包括标签和全部其它标签的样本或复制件的说明。这些样本或复制件经对此负责的人员签名和注明日期。(9)完整的生产和控制指令，取样和检验程序、各种规格标准，各种特殊的注解和各种预防方法均需遵照执行。211∙188批生产和控制记录每批药品应有批生产和控制记录，包括每批有关生产和控制的完整资料。这些记录包括：(a)适当的主生产或控制记录，复查其正确性，签名及注明日期。(b)完成本批的生产、加工、包装、贮存中各项重要措施须提供的资料，包括：(1)日期。(2)使用的重要设备和生产线的识别号。(3)使用的每批成份或中间体的特殊识别号。文档 实用41353,Aug.3,1993]§211.125Labelingissuance.(a)Strictcontrolshallbeexercisedoverlabelingissuedforuseindrugproductlabelingoperations.(b)Labelingmaterialsissuedforabatchshallbecarefullyexaminedforidentityandconformitytothelabelingspecifiedinthemasterorbatchproductionrecords.(c)Proceduresshallbeutilizedtoreconcilethequantitiesoflabelingissued,used,andreturned,andshallrequireevaluationofdiscrepanciesfoundbetweenthequantityofdrugproductfinishedandthequantityoflabelingissuedwhensuchdiscrepanciesareoutsidenarrowpresetlimitsbasedonhistoricaloperatingdata.Suchdiscrepanciesshallbeinvestigatedinaccordancewith§211.192.Labelingreconciliationiswaivedforcutorrolllabelingifa100-percentexaminationfor(4)加工过程中使用的成份的重量和容量。(5)生产过程中控制和实验室控制结果。(6)使用前、后，包装和贴标签区域的检查。(7)在适当加工阶段，实际产量和理论百分收率的说明。(8)完整的标签控制记录，包括所有使用的标签样本或复制件。(9)药品容器和密封件的说明。(10)取样实施。(11)生产中，操作和直接监督或复查各个重要过程的人员身份证明。(12)按211∙192进行的任何调查。(13)按211∙134处理的检查结果。211∙192产品记录审核所有药品生产和控制记录，包括包装和标签记录，应经质量控制部门审核、批准，确认符合要求，并应在产品发放或销售前完成。一些非解释性差异（包括超过在主要生产和控制记录中制订的最大或最小理论收率）或一批或任何一个成份不符合其质量标准中任一项，则应作彻底调查，不管这批药品是否已销售。这种调查应扩展到与此相关的其它批号或其它药品。调查应写成文字记录，包括结论和追踪。文档 实用correctlabelingisperformedinaccordancewith§211.122(g)(2).(d)Allexcesslabelingbearinglotorcontrolnumbersshallbedestroyed.(e)Returnedlabelingshallbemaintainedandstoredinamannertopreventmixupsandprovideproperidentification.(f)Proceduresshallbewrittendescribinginsufficientdetailthecontrolproceduresemployedfortheissuanceoflabeling;suchwrittenproceduresshallbefollowed.[43FR45077,Sept.29,1978,asamendedat58FR41345,Aug.3,1993]§211.130Packagingandlabelingoperations.Thereshallbewrittenproceduresdesignedtoassurethatcorrectlabels,labeling,andpackagingmaterialsareusedfordrugproducts;suchwrittenproceduresshallbefollowed.Theseproceduresshall211∙194实验室记录(a)实验室记录包括保证符合已制订的规格和标准的全部完整的检验（包括检查和分析）资料。包括：(1)与接收的检验样品有关的资料：来源（取样地方）、数量、批号或其他的特性代码，取样日期及样品接收日期。(2)样品检测使用的每个检测方法的说明。此说明应指出制订样品检验方法的资料出处，符合适当的准确度和可靠性标准，如应用于药品的检测。（若使用的方法是在最新修订版美国药典、国家处方集、官方的分析化学协会（ABABC）、分析方法类书籍或在其它公认的标准文献或在已批准的新药申请中详述，文献方法没有修改，则一份声明表明该方法和参考资料就足够了）。在实际使用时，所有分析方法的适应性都要核实。{2}文档 实用incorporatethefollowingfeatures:(a)Preventionofmixupsandcross-contaminationbyphysicalorspatialseparationfromoperationsonotherdrugproducts.(b)Identificationandhandlingoffilleddrugproductcontainersthataresetasideandheldinunlabeledconditionforfuturelabelingoperationstoprecludemislabelingofindividualcontainers,lots,orportionsoflots.Identificationneednotbeappliedtoeachindividualcontainerbutshallbesufficienttodeterminename,strength,quantityofcontents,andlotorcontrolnumberofeachcontainer.(c)Identificationofthedrugproductwithalotorcontrolnumberthatpermitsdeterminationofthehistoryofthemanufactureandcontrolofthebatch.(d)Examinationofpackagingandlabeling可以从这里得到复印件：官方分析化学家协会，2200WilsonBlvd.,Suite400,阿灵顿,VA22201-3301.(3)每项检验用样品的适当重量或容量的说明。(4)各检验过程中获得的全部资料的完整记录，包括：实验仪器测定成份、药品容器、密封件、中间体或药品的全部图表、曲线和光谱及检验的批量。(5)与检验有关的全部计算记录，包括测量单位、换算系数和当量系数。(6)说明检验结果及结果与被检的成份、药品容器、密封件、中间体或药品的已制订的特性、含量或效价、质量和纯度标准作比较的过程。(7)每个检验人员签名及完成日期。(8)依照制订的标准，由另一人员复查原始记录的准确性和完整性。复核人签名。(b)保留检验过程中任何修改已制订、应用的检验方法的完整记录。此记录包括修改的原因和证明检验结果同修改前方法的结果同样准确的可靠资料。文档 实用materialsforsuitabilityandcorrectnessbeforepackagingoperations,anddocumentationofsuchexaminationinthebatchproductionrecord.(e)Inspectionofthepackagingandlabelingfacilitiesimmediatelybeforeusetoassurethatalldrugproductshavebeenremovedfrompreviousoperations.Inspectionshallalsobemadetoassurethatpackagingandlabelingmaterialsnotsuitableforsubsequentoperationshavebeenremoved.Resultsofinspectionshallbedocumentedinthebatchproductionrecords.[43FR45077,Sept.29,1978,asamendedat58FR41354,Aug.3,1993]§211.132Tamper-resistantpackagingrequirementsforover-the-counter(OTC)humandrugproducts.(a)General.TheFoodandDrugAdministrationhastheauthorityunderthe(c)保留任何检验和实验室参考标准、试剂和标准溶液的完整记录。(d)保留按211∙160（b）(4)的要求，实验室仪器器具和量具、记录装置的定期校正的完整记录。(e)保留按21∙166要求实施的全部稳定性试验的完整记录。[43FR45077，1978年9月29日，修正，55FR11577，1990年3月29日]211∙196销售记录销售记录包括产品名称、规格、剂型的说明，收货人的姓名和地址、装运日期和数量、药品批号或控制号。对压缩医用气体产品，销售记录不要求包括批号或控制号。（经管理和预算处根据控制号09100139批准）[49FR45077，1978年9月29日]211∙198客户投诉档案(a)制订和遵循说明处理与药品有关的全部文字和口头投诉的成文程序。此程序包括经质量控制部门复查这一条款。任一投诉中，药品有任一项不符合其规格的可能性，则根据211∙192，对该药品进行测定，做调查。这些程序应包括复查条款，检查此投诉是否属严重的和意外的不良反应，根据本章310∙305，该不良反应须向FDA报告。文档 实用FederalFood,Drug,andCosmeticAct(theact)toestablishauniformnationalrequirementfortamper-resistantpackagingofOTCdrugproductsthatwillimprovethesecurityofOTCdrugpackagingandhelpassurethesafetyandeffectivenessofOTCdrugproducts.AnOTCdrugproduct(exceptadermatological,dentifrice,insulin,orthroatlozengeproduct)forretailsalethatisnotpackagedinatamper-resistantpackageorthatisnotproperlylabeledunderthissectionisadulteratedundersection501oftheactormisbrandedundersection502oftheact,orboth.(b)Requirementfortamper-resistantpackage.EachmanufacturerandpackerwhopackagesanOTCdrugproduct(exceptadermatological,dentifrice,insulin,orthroatlozengeproduct)forretailsaleshallpackagetheproductina(b)每个投诉的文字记录保存在药品专用档案内。与该药品投诉有关的档案，保存在企业生产、加工或包装该药品的资料中，若存放于别的地方会更有利于检查，可在那里保存。涉及药品的文字记录，从该品的有效期满计，保存一年以上或从收到投诉日期计，保存一年，按其中时间较长者决定。在某些符合211∙137中免除条例的无有效期的非处方药品，这些文字记录的保存时间应是从该药品销售后三年。(1)投诉文字记录包括如下信息：药品名称、规格、批号，投诉者姓名、投诉性质及投诉答复等。(2)根据211∙192指导的执行调查，记录包括此调查和跟踪中的发现。调查报告记录或其复印件，根据211∙180（c），保存在作该调查的企业中。(3)若没有按211∙192要求执行调查，此文字报告应包括没必要调查的原因和负责作此决定的负责人姓名。文档 实用tamper-resistantpackage,ifthisproductisaccessibletothepublicwhileheldforsale.Atamper-resistantpackageisonehavingoneormoreindicatorsorbarrierstoentrywhich,ifbreachedormissing,canreasonablybeexpectedtoprovidevisibleevidencetoconsumersthattamperinghasoccurred.Toreducethelikelihoodofsuccessfultamperingandtoincreasethelikelihoodthatconsumerswilldiscoverifaproducthasbeentamperedwith,thepackageisrequiredtobedistinctivebydesign(e.g.,anaerosolproductcontainer)orbytheuseofoneormoreindicatorsorbarrierstoentrythatemployanidentifyingcharacteristic(e.g.,apattern,name,registeredtrademark,logo,orpicture).Forpurposesofthissection,theterm"distinctivebydesign''meansthepackagingcannotbeduplicatedwithcommonlyavailablematerialsorthroughcommonlyavailableprocesses.For[43FR45077，1978年9月29日，修正51FR24479，1986年7月3日]。K．退货的药品和回收处理211∙204退货的药品退货的药品按原样作鉴定和保存。应考虑退回药品在退回前或退回期间的贮存、装运条件或原药品容器、纸板盒或标签是否有问题，由于贮存或装运的原因，令人怀疑药品的安全性、均一性、含量或效价、质量或纯度有问题，除非经检验、检查或调查，证明此药品符合其安全、均一性、含量或效价、质量或纯度标准，否则，应将退回药品销毁。但药品可返工，保证其符合标准、规格和特性。退回药品的记录应保存，记录包括退回药品的名称、制剂的功效、批号（控制号或整批批号）、退货原因、退货数量、处理日期及最终处理日期。若退货原因牵涉到其它批号产品，应依照211∙192的要求进行调查。退货药品的贮存、检验、返工程序应制订成文规定并遵循。211∙208药品的回收利用文档 实用purposesofthissection,theterm"aerosolproduct''meansaproductwhichdependsuponthepowerofaliquifiedorcompressedgastoexpelthecontentsfromthecontainer.Atamper-resistantpackagemayinvolveanimmediate-containerandclosuresystemorsecondary-containerorcartonsystemoranycombinationofsystemsintendedtoprovideavisualindicationofpackageintegrity.Thetamper-resistantfeatureshallbedesignedtoandshallremainintactwhenhandledinareasonablemannerduringmanufacture,distribution,andretaildisplay.(1)Fortwo-piece,hardgelatincapsuleproductssubjecttothisrequirement,aminimumoftwotamper-resistantpackagingfeaturesisrequired,unlessthecapsulesaresealedbyatamper-resistanttechnology(2)Forallotherproductssubjecttothis遭受不良贮存条件（包括极高的温度、湿度、烟薰、压力、贮存期过长、自然灾害造成的辐射、火灾、意外事故或仪器失灵等）影响的药品，不能回收利用和不准重新销售。每当有药品不论是否受上述条件影响的问题存在时，只有当下列情况时才可进行回收药品工作。(a)实验室检验和分析（包括可能的动物饲养研究）证明，完全符合均一性、含量或效价、质量和纯度标准。(b)检查药品及其有关包装，证明其没有遭到天灾或事故等不适当贮存条件的影响。可接受特殊感观的检查，但仅作药品符合均一性、含量或效价、质量和纯度标准的补充证据。按本部分要求，记录包括药品名称、批号、和处理等，且须保存。文档 实用requirement,includingtwo-piece,hardgelatincapsulesthataresealedbyatamper-resistanttechnology,aminimumofonetamper-resistantfeatureisrequired.(c)Labeling.EachretailpackageofanOTCdrugproductcoveredbythissection,exceptammoniainhalantincrushableglassampules,aerosolproductsasdefinedinparagraph(b)ofthissection,orcontainersofcompressedmedicaloxygen,isrequiredtobearastatementthatisprominentlyplacedsothatconsumersarealertedtothespecifictamper-resistantfeatureofthepackage.Thelabelingstatementisalsorequiredtobesoplacedthatitwillbeunaffectedifthetamper-resistantfeatureofthepackageisbreachedormissing.Ifthetamper-resistantfeaturechosentomeettherequirementinparagraph(b)ofthissectionisonethatusesanidentifyingcharacteristic,thatcharacteristicisrequired文档 实用tobereferredtointhelabelingstatement.Forexample,thelabelingstatementonabottlewithashrinkbandcouldsay"Foryourprotection,thisbottlehasanimprintedsealaroundtheneck.''(d)Requestforexemptionsfrompackagingandlabelingrequirements.Amanufacturerorpackermayrequestanexemptionfromthepackagingandlabelingrequirementsofthissection.Arequestforanexemptionisrequiredtobesubmittedintheformofacitizenpetitionunder§10.30ofthischapterandshouldbeclearlyidentifiedontheenvelopeasa"RequestforExemptionfromTamper-ResistantRule.''Thepetitionisrequiredtocontainthefollowing:(1)Thenameofthedrugproductor,ifthepetitionseeksanexemptionforadrugclass,thenameofthedrugclass,andalistofproductswithinthatclass.文档 实用(2)Thereasonsthatthedrugproduct'scompliancewiththetamper-resistantpackagingorlabelingrequirementsofthissectionisunnecessaryorcannotbeachieved.(3)Adescriptionofalternativestepsthatareavailable,orthatthepetitionerhasalreadytaken,toreducethelikelihoodthattheproductordrugclasswillbethesubjectofmaliciousadulteration.(4)Otherinformationjustifyinganexemption.(e)OTCdrugproductssubjecttoapprovednewdrugapplications.HoldersofapprovednewdrugapplicationsforOTCdrugproductsarerequiredunder§314.70ofthischaptertoprovidetheagencywithnotificationofchangesinpackagingandlabelingtocomplywiththerequirementsofthissection.Changesinpackagingand文档 实用labelingrequiredbythisregulationmaybemadebeforeFDAapproval,asprovidedunder§314.70(c)ofthischapter.ManufacturingchangesbywhichcapsulesaretobesealedrequirepriorFDAapprovalunder§314.70(b)ofthischapter.(f)PoisonPreventionPackagingActof1970.Thissectiondoesnotaffectanyrequirementsfor"specialpackaging''asdefinedunder§310.3(l)ofthischapterandrequiredunderthePoisonPreventionPackagingActof1970.(ApprovedbytheOfficeofManagementandBudgetunderOMBcontrolnumber0910-0149)[54FR5228,Feb.2,1989]§211.134Drugproductinspection.(a)Packagedandlabeledproductsshallbeexaminedduringfinishingoperationsto文档 实用provideassurancethatcontainersandpackagesinthelothavethecorrectlabel.(b)Arepresentativesampleofunitsshallbecollectedatthecompletionoffinishingoperationsandshallbevisuallyexaminedforcorrectlabeling.(c)Resultsoftheseexaminationsshallberecordedinthebatchproductionorcontrolrecords.§211.137Expirationdating.(a)Toassurethatadrugproductmeetsapplicablestandardsofidentity,strength,quality,andpurityatthetimeofuse,itshallbearanexpirationdatedeterminedbyappropriatestabilitytestingdescribedin§211.166.(b)Expirationdatesshallberelatedtoanystorageconditionsstatedonthelabeling,文档 实用asdeterminedbystabilitystudiesdescribedin§211.166.(c)Ifthedrugproductistobereconstitutedatthetimeofdispensing,itslabelingshallbearexpirationinformationforboththereconstitutedandunreconstituteddrugproducts.(d)Expirationdatesshallappearonlabelinginaccordancewiththerequirementsof§201.17ofthischapter.(e)Homeopathicdrugproductsshallbeexemptfromtherequirementsofthissection.(f)Allergenicextractsthatarelabeled"NoU.S.StandardofPotency''areexemptfromtherequirementsofthissection.(g)Newdrugproductsforinvestigational文档 实用useareexemptfromtherequirementsofthissection,providedthattheymeetappropriatestandardsorspecificationsasdemonstratedbystabilitystudiesduringtheiruseinclinicalinvestigations.Wherenewdrugproductsforinvestigationalusearetobereconstitutedatthetimeofdispensing,theirlabelingshallbearexpirationinformationforthereconstituteddrugproduct.(h)Pendingconsiderationofaproposedexemption,publishedintheFederalRegisterofSeptember29,1978,therequirementsinthissectionshallnotbeenforcedforhumanOTCdrugproductsiftheirlabelingdoesnotbeardosagelimitationsandtheyarestableforatleast3yearsassupportedbyappropriatestabilitydata.[43FR45077,Sept.29,1978,asamendedat46FR56412,Nov.17,1981;60FR4091,Jan.20,1995]文档 实用SubpartH-HoldingandDistribution§211.142Warehousingprocedures.Writtenproceduresdescribingthewarehousingofdrugproductsshallbeestablishedandfollowed.Theyshallinclude:(a)Quarantineofdrugproductsbeforereleasebythequalitycontrolunit.(b)Storageofdrugproductsunderappropriateconditionsoftemperature,humidity,andlightsothattheidentity,strength,quality,andpurityofthedrugproductsarenotaffected.§211.150Distributionprocedures.Writtenproceduresshallbeestablished,andfollowed,describingthedistributionofdrugproducts.Theyshallinclude:文档 实用(a)Aprocedurewherebytheoldestapprovedstockofadrugproductisdistributedfirst.Deviationfromthisrequirementispermittedifsuchdeviationistemporaryandappropriate.(b)Asystembywhichthedistributionofeachlotofdrugproductcanbereadilydeterminedtofacilitateitsrecallifnecessary.SubpartI-LaboratoryControls§211.160Generalrequirements.(a)Theestablishmentofanyspecifications,standards,samplingplans,testprocedures,orotherlaboratorycontrolmechanismsrequiredbythissubpart,includinganychangeinsuchspecifications,standards,samplingplans,testprocedures,orotherlaboratorycontrolmechanisms,shallbedraftedbytheappropriateorganizationalunitandreviewedandapprovedbythe文档 实用qualitycontrolunit.Therequirementsinthissubpartshallbefollowedandshallbedocumentedatthetimeofperformance.Anydeviationfromthewrittenspecifications,standards,samplingplans,testprocedures,orotherlaboratorycontrolmechanismsshallberecordedandjustified.(b)Laboratorycontrolsshallincludetheestablishmentofscientificallysoundandappropriatespecifications,standards,samplingplans,andtestproceduresdesignedtoassurethatcomponents,drugproductcontainers,closures,in-processmaterials,labeling,anddrugproductsconformtoappropriatestandardsofidentity,strength,quality,andpurity.Laboratorycontrolsshallinclude:(1)Determinationofconformancetoappropriatewrittenspecificationsforthe文档 实用acceptanceofeachlotwithineachshipmentofcomponents,drugproductcontainers,closures,andlabelingusedinthemanufacture,processing,packing,orholdingofdrugproducts.Thespecificationsshallincludeadescriptionofthesamplingandtestingproceduresused.Samplesshallberepresentativeandadequatelyidentified.Suchproceduresshallalsorequireappropriateretestingofanycomponent,drugproductcontainer,orclosurethatissubjecttodeterioration.(2)Determinationofconformancetowrittenspecificationsandadescriptionofsamplingandtestingproceduresforin-processmaterials.Suchsamplesshallberepresentativeandproperlyidentified.(3)Determinationofconformancetowrittendescriptionsofsamplingproceduresandappropriatespecifications文档 实用fordrugproducts.Suchsamplesshallberepresentativeandproperlyidentified.(4)Thecalibrationofinstruments,apparatus,gauges,andrecordingdevicesatsuitableintervalsinaccordancewithanestablishedwrittenprogramcontainingspecificdirections,schedules,limitsforaccuracyandprecision,andprovisionsforremedialactionintheeventaccuracyand/orprecisionlimitsarenotmet.Instruments,apparatus,gauges,andrecordingdevicesnotmeetingestablishedspecificationsshallnotbeused.§211.165Testingandreleasefordistribution.(a)Foreachbatchofdrugproduct,thereshallbeappropriatelaboratorydeterminationofsatisfactoryconformance文档 实用tofinalspecificationsforthedrugproduct,includingtheidentityandstrengthofeachactiveingredient,priortorelease.Wheresterilityand/orpyrogentestingareconductedonspecificbatchesofshortlivedradiopharmaceuticals,suchbatchesmaybereleasedpriortocompletionofsterilityand/orpyrogentesting,providedsuchtestingiscompletedassoonaspossible.(b)Thereshallbeappropriatelaboratorytesting,asnecessary,ofeachbatchofdrugproductrequiredtobefreeofobjectionablemicroorganisms.(c)Anysamplingandtestingplansshallbedescribedinwrittenproceduresthatshallincludethemethodofsamplingandthenumberofunitsperbatchtobetested;suchwrittenprocedureshallbefollowed.(d)Acceptancecriteriaforthesamplingandtestingconductedbythequality文档 实用controlunitshallbeadequatetoassurethatbatchesofdrugproductsmeeteachappropriatespecificationandappropriatestatisticalqualitycontrolcriteriaasaconditionfortheirapprovalandrelease.Thestatisticalqualitycontrolcriteriashallincludeappropriateacceptancelevelsand/orappropriaterejectionlevels.(e)Theaccuracy,sensitivity,specificity,andreproducibilityoftestmethodsemployedbythefirmshallbeestablishedanddocumented.Suchvalidationanddocumentationmaybeaccomplishedinaccordancewith§211.194(a)(2).(f)Drugproductsfailingtomeetestablishedstandardsorspecificationsandanyotherrelevantqualitycontrolcriteriashallberejected.Reprocessingmaybeperformed.Priortoacceptanceanduse,reprocessedmaterialmustmeetappropriatestandards,specifications,and文档 实用anyotherrelevantcriteria.§211.166Stabilitytesting.(a)Thereshallbeawrittentestingprogramdesignedtoassessthestabilitycharacteristicsofdrugproducts.Theresultsofsuchstabilitytestingshallbeusedindeterminingappropriatestorageconditionsandexpirationdates.Thewrittenprogramshallbefollowedandshallinclude:(1)Samplesizeandtestintervalsbasedonstatisticalcriteriaforeachattributeexaminedtoassurevalidestimatesofstability;(2)Storageconditionsforsamplesretainedfortesting;(3)Reliable,meaningful,andspecifictestmethods;(4)Testingofthedrugproductinthe文档 实用samecontainer-closuresystemasthatinwhichthedrugproductismarketed;(5)Testingofdrugproductsforreconstitutionatthetimeofdispensing(asdirectedinthelabeling)aswellasaftertheyarereconstituted.(b)Anadequatenumberofbatchesofeachdrugproductshallbetestedtodetermineanappropriateexpirationdateandarecordofsuchdatashallbemaintained.Acceleratedstudies,combinedwithbasicstabilityinformationonthecomponents,drugproducts,andcontainer-closuresystem,maybeusedtosupporttentativeexpirationdatesprovidedfullshelflifestudiesarenotavailableandarebeingconducted.Wheredatafromacceleratedstudiesareusedtoprojectatentativeexpirationdatethatisbeyondadatesupportedbyactualshelflifestudies,theremustbestabilitystudiesconducted,文档 实用includingdrugproducttestingatappropriateintervals,untilthetentativeexpirationdateisverifiedortheappropriateexpirationdatedetermined.(c)Forhomeopathicdrugproducts,therequirementsofthissectionareasfollows:(1)Thereshallbeawrittenassessmentofstabilitybasedatleastontestingorexaminationofthedrugproductforcompatibilityoftheingredients,andbasedonmarketingexperiencewiththedrugproducttoindicatethatthereisnodegradationoftheproductforthenormalorexpectedperiodofuse.(2)Evaluationofstabilityshallbebasedonthesamecontainer-closuresysteminwhichthedrugproductisbeingmarketed.(d)Allergenicextractsthatarelabeled"NoU.S.StandardofPotency''areexemptfromtherequirementsofthissection.文档 实用[43FR45077,Sept.29,1978,asamendedat46FR56412,Nov.17,1981]§211.167Specialtestingrequirements.(a)Foreachbatchofdrugproductpurportingtobesterileand/orpyrogen-free,thereshallbeappropriatelaboratorytestingtodetermineconformancetosuchrequirements.Thetestproceduresshallbeinwritingandshallbefollowed.(b)Foreachbatchofophthalmicointment,thereshallbeappropriatetestingtodetermineconformancetospecificationsregardingthepresenceofforeignparticlesandharshorabrasivesubstances.Thetestproceduresshallbeinwritingandshallbefollowed.(c)Foreachbatchofcontrolled-releasedosageform,thereshallbeappropriatelaboratorytestingtodetermineconformancetothespecificationsforthe文档 实用rateofreleaseofeachactiveingredient.Thetestproceduresshallbeinwritingandshallbefollowed.§211.170Reservesamples.(a)Anappropriatelyidentifiedreservesamplethatisrepresentativeofeachlotineachshipmentofeachactiveingredientshallberetained.Thereservesampleconsistsofatleasttwicethequantitynecessaryforalltestsrequiredtodeterminewhethertheactiveingredientmeetsitsestablishedspecifications,exceptforsterilityandpyrogentesting.Theretentiontimeisasfollows:(1)Foranactiveingredientinadrugproductotherthanthosedescribedinparagraphs(a)(2)and(3)ofthissection,thereservesampleshallberetainedfor1yearaftertheexpirationdateofthelastlotofthedrugproductcontainingtheactive文档 实用ingredient.(2)Foranactiveingredientinaradioactivedrugproduct,exceptfornonradioactivereagentkits,thereservesampleshallberetainedfor:(I)Threemonthsaftertheexpirationdateofthelastlotofthedrugproductcontainingtheactiveingredientiftheexpirationdatingperiodofthedrugproductis30daysorless;or(ii)Sixmonthsaftertheexpirationdateofthelastlotofthedrugproductcontainingtheactiveingredientiftheexpirationdatingperiodofthedrugproductismorethan30days.(3)ForanactiveingredientinanOTCdrugproductthatisexemptfrombearinganexpirationdateunder§211.137,thereservesampleshallberetainedfor3yearsafterdistributionofthelastlotofthedrug文档 实用productcontainingtheactiveingredient.(b)Anappropriatelyidentifiedreservesamplethatisrepresentativeofeachlotorbatchofdrugproductshallberetainedandstoredunderconditionsconsistentwithproductlabeling.Thereservesampleshallbestoredinthesameimmediatecontainer-closuresysteminwhichthedrugproductismarketedorinonethathasessentiallythesamecharacteristics.Thereservesampleconsistsofatleasttwicethequantitynecessarytoperformalltherequiredtests,exceptthoseforsterilityandpyrogens.Exceptforthosedrugproductsdescribedinparagraph(b)(2)ofthissection,reservesamplesfromrepresentativesamplelotsorbatchesselectedbyacceptablestatisticalproceduresshallbeexaminedvisuallyatleastonceayearforevidenceofdeteriorationunlessvisualexamination文档 实用wouldaffecttheintegrityofthereservesample.Anyevidenceofreservesampledeteriorationshallbeinvestigatedinaccordancewith§211.192.Theresultsofexaminationshallberecordedandmaintainedwithotherstabilitydataonthedrugproduct.Reservesamplesofcompressedmedicalgasesneednotberetained.Theretentiontimeisasfollows:(1)Foradrugproductotherthanthosedescribedinparagraphs(b)(2)and(3)ofthissection,thereservesampleshallberetainedfor1yearaftertheexpirationdateofthedrugproduct.(2)Foraradioactivedrugproduct,exceptfornonradioactivereagentkits,thereservesampleshallberetainedfor:(I)Threemonthsaftertheexpirationdateofthedrugproductiftheexpirationdatingperiodofthedrugproductis30daysor文档 实用less;or(ii)Sixmonthsaftertheexpirationdateofthedrugproductiftheexpirationdatingperiodofthedrugproductismorethan30days.(3)ForanOTCdrugproductthatisexemptforbearinganexpirationdateunder§211.137,thereservesamplemustberetainedfor3yearsafterthelotorbatchofdrugproductisdistributed.[48FR13025,Mar.29,1983,asamendedat60FR4091,Jan.20,1995]§211.173Laboratoryanimals.Animalsusedintestingcomponents,in-processmaterials,ordrugproductsforcompliancewithestablishedspecificationsshallbemaintainedandcontrolledinamannerthatassurestheirsuitabilityfortheirintendeduse.Theyshallbeidentified,andadequaterecordsshallbemaintained文档 实用showingthehistoryoftheiruse.§211.176Penicillincontamination.Ifareasonablepossibilityexiststhatanon-penicillindrugproducthasbeenexposedtocross-contaminationwithpenicillin,thenon-penicillindrugproductshallbetestedforthepresenceofpenicillin.Suchdrugproductshallnotbemarketedifdetectablelevelsarefoundwhentestedaccordingtoproceduresspecifiedin`ProceduresforDetectingandMeasuringPenicillinContaminationinDrugs,'whichisincorporatedbyreference.CopiesareavailablefromtheDivisionofResearchandTesting(HFD-470),CenterforDrugEvaluationandResearch,FoodandDrugAdministration,200CSt.SW.,Washington,DC20204,oravailableforinspectionattheOfficeoftheFederalRegister,800NorthCapitolStreet,NW.,suite700,Washington,DC20408.文档 实用[43FR45077,Sept.29,1978,asamendedat47FR9396,Mar.5,1982;50FR8996,Mar.6,1985;55FR11577,Mar.29,1990]SubpartJ-RecordsandReports§211.180Generalrequirements.(a)Anyproduction,control,ordistributionrecordthatisrequiredtobemaintainedincompliancewiththispartandisspecificallyassociatedwithabatchofadrugproductshallberetainedforatleast1yearaftertheexpirationdateofthebatchor,inthecaseofcertainOTCdrugproductslackingexpirationdatingbecausetheymeetthecriteriaforexemptionunder§211.137,3yearsafterdistributionofthebatch.(b)Recordsshallbemaintainedforallcomponents,drugproductcontainers,closures,andlabelingforatleast1yearaftertheexpirationdateor,inthecaseofcertainOTCdrugproductslackingexpirationdatingbecausetheymeetthecriteriaforexemptionunder§211.137,3文档 实用yearsafterdistributionofthelastlotofdrugproductincorporatingthecomponentorusingthecontainer,closure,orlabeling.(c)Allrecordsrequiredunderthispart,orcopiesofsuchrecords,shallbereadilyavailableforauthorizedinspectionduringtheretentionperiodattheestablishmentwheretheactivitiesdescribedinsuchrecordsoccurred.Theserecordsorcopiesthereofshallbesubjecttophotocopyingorothermeansofreproductionaspartofsuchinspection.Recordsthatcanbeimmediatelyretrievedfromanotherlocationbycomputerorotherelectronicmeansshallbeconsideredasmeetingtherequirementsofthisparagraph.(d)Recordsrequiredunderthispartmayberetainedeitherasoriginalrecordsorastruecopiessuchasphotocopies,microfilm,microfiche,orotheraccuratereproductionsoftheoriginalrecords.Wherereduction文档 实用techniques,suchasmicrofilming,areused,suitablereaderandphotocopyingequipmentshallbereadilyavailable.(e)Writtenrecordsrequiredbythispartshallbemaintainedsothatdatathereincanbeusedforevaluating,atleastannually,thequalitystandardsofeachdrugproducttodeterminetheneedforchangesindrugproductspecificationsormanufacturingorcontrolprocedures.Writtenproceduresshallbeestablishedandfollowedforsuchevaluationsandshallincludeprovisionsfor:(1)Areviewofarepresentativenumberofbatches,whetherapprovedorrejected,and,whereapplicable,recordsassociatedwiththebatch.(2)Areviewofcomplaints,recalls,returnedorsalvageddrugproducts,andinvestigationsconductedunder§211.192文档 实用foreachdrugproduct.(f)Proceduresshallbeestablishedtoassurethattheresponsibleofficialsofthefirm,iftheyarenotpersonallyinvolvedinorimmediatelyawareofsuchactions,arenotifiedinwritingofanyinvestigationsconductedunder§§211.198,211.204,or211.208oftheseregulations,anyrecalls,reportsofinspectionalobservationsissuedbytheFoodandDrugAdministration,oranyregulatoryactionsrelatingtogoodmanufacturingpracticesbroughtbytheFoodandDrugAdministration.[43FR45077,Sept.29,1978,asamendedat60FR4901,Jan.20,1995]§211.182Equipmentcleaninganduselog.Awrittenrecordofmajorequipmentcleaning,maintenance(exceptroutinemaintenancesuchaslubricationandadjustments),anduseshallbeincludedin文档 实用individualequipmentlogsthatshowthedate,time,product,andlotnumberofeachbatchprocessed.Ifequipmentisdedicatedtomanufactureofoneproduct,thenindividualequipmentlogsarenotrequired,providedthatlotsorbatchesofsuchproductfollowinnumericalorderandaremanufacturedinnumericalsequence.Incaseswherededicatedequipmentisemployed,therecordsofcleaning,maintenance,anduseshallbepartofthebatchrecord.Thepersonsperforminganddouble-checkingthecleaningandmaintenanceshalldateandsignorinitialthelogindicatingthattheworkwasperformed.Entriesinthelogshallbeinchronologicalorder.§211.184Component,drugproductcontainer,closure,andlabelingrecords.Theserecordsshallincludethefollowing:文档 实用(a)Theidentityandquantityofeachshipmentofeachlotofcomponents,drugproductcontainers,closures,andlabeling;thenameofthesupplier;thesupplier'slotnumber(s)ifknown;thereceivingcodeasspecifiedin§211.80;andthedateofreceipt.Thenameandlocationoftheprimemanufacturer,ifdifferentfromthesupplier,shallbelistedifknown.(b)Theresultsofanytestorexaminationperformed(includingthoseperformedasrequiredby§211.82(a),§211.84(d),or§211.122(a))andtheconclusionsderivedtherefrom.(c)Anindividualinventoryrecordofeachcomponent,drugproductcontainer,andclosureand,foreachcomponent,areconciliationoftheuseofeachlotofsuchcomponent.Theinventoryrecordshallcontainsufficientinformationtoallowdeterminationofanybatchorlotofdrug文档 实用productassociatedwiththeuseofeachcomponent,drugproductcontainer,andclosure.(d)Documentationoftheexaminationandreviewoflabelsandlabelingforconformitywithestablishedspecificationsinaccordwith§§211.122(c)and211.130(c).(e)Thedispositionofrejectedcomponents,drugproductcontainers,closure,andlabeling.§211.186Masterproductionandcontrolrecords.(a)Toassureuniformityfrombatchtobatch,masterproductionandcontrolrecordsforeachdrugproduct,includingeachbatchsizethereof,shallbeprepared,dated,andsigned(fullsignature,handwritten)byonepersonandindependentlychecked,dated,andsigned文档 实用byasecondperson.Thepreparationofmasterproductionandcontrolrecordsshallbedescribedinawrittenprocedureandsuchwrittenprocedureshallbefollowed.(b)Masterproductionandcontrolrecordsshallinclude:(1)Thenameandstrengthoftheproductandadescriptionofthedosageform;(2)Thenameandweightormeasureofeachactiveingredientperdosageunitorperunitofweightormeasureofthedrugproduct,andastatementofthetotalweightormeasureofanydosageunit;(3)Acompletelistofcomponentsdesignatedbynamesorcodessufficientlyspecifictoindicateanyspecialqualitycharacteristic;(4)Anaccuratestatementoftheweightormeasureofeachcomponent,usingthe文档 实用sameweightsystem(metric,avoirdupois,orapothecary)foreachcomponent.Reasonablevariationsmaybepermitted,however,intheamountofcomponentsnecessaryforthepreparationinthedosageform,providedtheyarejustifiedinthemasterproductionandcontrolrecords;(5)Astatementconcerninganycalculatedexcessofcomponent;(6)Astatementoftheoreticalweightormeasureatappropriatephasesofprocessing;(7)Astatementoftheoreticalyield,includingthemaximumandminimumpercentagesoftheoreticalyieldbeyondwhichinvestigationaccordingto§211.192isrequired;(8)Adescriptionofthedrugproductcontainers,closures,andpackagingmaterials,includingaspecimenorcopyof文档 实用eachlabelandallotherlabelingsignedanddatedbythepersonorpersonsresponsibleforapprovalofsuchlabeling;(9)Completemanufacturingandcontrolinstructions,samplingandtestingprocedures,specifications,specialnotations,andprecautionstobefollowed.§211.188Batchproductionandcontrolrecords.Batchproductionandcontrolrecordsshallbepreparedforeachbatchofdrugproductproducedandshallincludecompleteinformationrelatingtotheproductionandcontrolofeachbatch.Theserecordsshallinclude:(a)Anaccuratereproductionoftheappropriatemasterproductionorcontrolrecord,checkedforaccuracy,dated,andsigned;(b)Documentationthateachsignificant文档 实用stepinthemanufacture,processing,packing,orholdingofthebatchwasaccomplished,including:(1)Dates;(2)Identityofindividualmajorequipmentandlinesused;(3)Specificidentificationofeachbatchofcomponentorin-processmaterialused;(4)Weightsandmeasuresofcomponentsusedinthecourseofprocessing;(5)In-processandlaboratorycontrolresults;(6)Inspectionofthepackagingandlabelingareabeforeandafteruse;(7)Astatementoftheactualyieldandastatementofthepercentageoftheoreticalyieldatappropriatephasesofprocessing;(8)Completelabelingcontrolrecords,文档 实用includingspecimensorcopiesofalllabelingused;(9)Descriptionofdrugproductcontainersandclosures;(10)Anysamplingperformed;(11)Identificationofthepersonsperforminganddirectlysupervisingorcheckingeachsignificantstepintheoperation;(12)Anyinvestigationmadeaccordingto§211.192.(13)Resultsofexaminationsmadeinaccordancewith§211.134.§211.192Productionrecordreview.Alldrugproductproductionandcontrolrecords,includingthoseforpackagingandlabeling,shallbereviewedandapprovedbythequalitycontrolunittodeterminecompliancewithallestablished,approved文档 实用writtenproceduresbeforeabatchisreleasedordistributed.Anyunexplaineddiscrepancy(includingapercentageoftheoreticalyieldexceedingthemaximumorminimumpercentagesestablishedinmasterproductionandcontrolrecords)orthefailureofabatchoranyofitscomponentstomeetanyofitsspecificationsshallbethoroughlyinvestigated,whetherornotthebatchhasalreadybeendistributed.Theinvestigationshallextendtootherbatchesofthesamedrugproductandotherdrugproductsthatmayhavebeenassociatedwiththespecificfailureordiscrepancy.Awrittenrecordoftheinvestigationshallbemadeandshallincludetheconclusionsandfollowup.§211.194Laboratoryrecords.(a)Laboratoryrecordsshallincludecompletedataderivedfromalltestsnecessarytoassurecompliancewith文档 实用establishedspecificationsandstandards,includingexaminationsandassays,asfollows:(1)Adescriptionofthesamplereceivedfortestingwithidentificationofsource(thatis,locationfromwheresamplewasobtained),quantity,lotnumberorotherdistinctivecode,datesamplewastaken,anddatesamplewasreceivedfortesting.(2)Astatementofeachmethodusedinthetestingofthesample.Thestatementshallindicatethelocationofdatathatestablishthatthemethodsusedinthetestingofthesamplemeetproperstandardsofaccuracyandreliabilityasappliedtotheproducttested.(IfthemethodemployedisinthecurrentrevisionoftheUnitedStatesPharmacopeia,NationalFormulary,AssociationofOfficialAnalyticalChemists,BookofMethods,{2}orinotherrecognizedstandardreferences,or文档 实用isdetailedinanapprovednewdrugapplicationandthereferencedmethodisnotmodified,astatementindicatingthemethodandreferencewillsuffice).Thesuitabilityofalltestingmethodsusedshallbeverifiedunderactualconditionsofuse.{2}Copiesmaybeobtainedfrom:AssociationofOfficialAnalyticalChemists,2200WilsonBlvd.,Suite400,Arlington,VA22201-3301.(3)Astatementoftheweightormeasureofsampleusedforeachtest,whereappropriate.(4)Acompleterecordofalldatasecuredinthecourseofeachtest,includingallgraphs,charts,andspectrafromlaboratoryinstrumentation,properlyidentifiedtoshowthespecificcomponent,drugproductcontainer,closure,in-processmaterial,ordrugproduct,andlottested.文档 实用(5)Arecordofallcalculationsperformedinconnectionwiththetest,includingunitsofmeasure,conversionfactors,andequivalencyfactors.(6)Astatementoftheresultsoftestsandhowtheresultscomparewithestablishedstandardsofidentity,strength,quality,andpurityforthecomponent,drugproductcontainer,closure,in-processmaterial,ordrugproducttested.(7)Theinitialsorsignatureofthepersonwhoperformseachtestandthedate(s)thetestswereperformed.(8)Theinitialsorsignatureofasecondpersonshowingthattheoriginalrecordshavebeenreviewedforaccuracy,completeness,andcompliancewithestablishedstandards.(b)Completerecordsshallbemaintainedofanymodificationofanestablished文档 实用methodemployedintesting.Suchrecordsshallincludethereasonforthemodificationanddatatoverifythatthemodificationproducedresultsthatareatleastasaccurateandreliableforthematerialbeingtestedastheestablishedmethod.(c)Completerecordsshallbemaintainedofanytestingandstandardizationoflaboratoryreferencestandards,reagents,andstandardsolutions.(d)Completerecordsshallbemaintainedoftheperiodiccalibrationoflaboratoryinstruments,apparatus,gauges,andrecordingdevicesrequiredby§211.160(b)(4).(e)Completerecordsshallbemaintainedofallstabilitytestingperformedinaccordancewith§211.166.[43FR45077,Sept.29,1978,asamendedat55FR11577,Mar.29,1990]文档 实用§211.196Distributionrecords.Distributionrecordsshallcontainthenameandstrengthoftheproductanddescriptionofthedosageform,nameandaddressoftheconsignee,dateandquantityshipped,andlotorcontrolnumberofthedrugproduct.Forcompressedmedicalgasproducts,distributionrecordsarenotrequiredtocontainlotorcontrolnumbers.(ApprovedbytheOfficeofManagementandBudgetundercontrolnumber0910-0139)[49FR9865,Mar.16,1984]§211.198Complaintfiles.(a)Writtenproceduresdescribingthehandlingofallwrittenandoralcomplaintsregardingadrugproductshallbeestablishedandfollowed.Suchproceduresshallincludeprovisionsforreviewbythe文档 实用qualitycontrolunit,ofanycomplaintinvolvingthepossiblefailureofadrugproducttomeetanyofitsspecificationsand,forsuchdrugproducts,adeterminationastotheneedforaninvestigationinaccordancewith§211.192.SuchproceduresshallincludeprovisionsforreviewtodeterminewhetherthecomplaintrepresentsaseriousandunexpectedadversedrugexperiencewhichisrequiredtobereportedtotheFoodandDrugAdministrationinaccordancewith§310.305ofthischapter.(b)Awrittenrecordofeachcomplaintshallbemaintainedinafiledesignatedfordrugproductcomplaints.Thefileregardingsuchdrugproductcomplaintsshallbemaintainedattheestablishmentwherethedrugproductinvolvedwasmanufactured,processed,orpacked,orsuchfilemaybemaintainedatanother文档 实用facilityifthewrittenrecordsinsuchfilesarereadilyavailableforinspectionatthatotherfacility.Writtenrecordsinvolvingadrugproductshallbemaintaineduntilatleast1yearaftertheexpirationdateofthedrugproduct,or1yearafterthedatethatthecomplaintwasreceived,whicheverislonger.InthecaseofcertainOTCdrugproductslackingexpirationdatingbecausetheymeetthecriteriaforexemptionunder§211.137,suchwrittenrecordsshallbemaintainedfor3yearsafterdistributionofthedrugproduct.(1)Thewrittenrecordshallincludethefollowinginformation,whereknown:thenameandstrengthofthedrugproduct,lotnumber,nameofcomplainant,natureofcomplaint,andreplytocomplainant.(2)Whereaninvestigationunder§211.192isconducted,thewrittenrecordshallincludethefindingsoftheinvestigation文档 实用andfollowup.Therecordorcopyoftherecordoftheinvestigationshallbemaintainedattheestablishmentwheretheinvestigationoccurredinaccordancewith§211.180(c).(3)Whereaninvestigationunder§211.192isnotconducted,thewrittenrecordshallincludethereasonthataninvestigationwasfoundnottobenecessaryandthenameoftheresponsiblepersonmakingsuchadetermination.[43FR45077,Sept.29,1978,asamendedat51FR24479,July3,1986]SubpartK-ReturnedandSalvagedDrugProducts§211.204Returneddrugproducts.Returneddrugproductsshallbeidentifiedassuchandheld.Iftheconditionsunderwhichreturneddrugproductshavebeenheld,stored,orshippedbeforeorduringtheirreturn,oriftheconditionofthedrug文档 实用product,itscontainer,carton,orlabeling,asaresultofstorageorshipping,castsdoubtonthesafety,identity,strength,qualityorpurityofthedrugproduct,thereturneddrugproductshallbedestroyedunlessexamination,testing,orotherinvestigationsprovethedrugproductmeetsappropriatestandardsofsafety,identity,strength,quality,orpurity.Adrugproductmaybereprocessedprovidedthesubsequentdrugproductmeetsappropriatestandards,specifications,andcharacteristics.Recordsofreturneddrugproductsshallbemaintainedandshallincludethenameandlabelpotencyofthedrugproductdosageform,lotnumber(orcontrolnumberorbatchnumber),reasonforthereturn,quantityreturned,dateofdisposition,andultimatedispositionofthereturneddrugproduct.Ifthereasonforadrugproductbeingreturnedimplicatesassociatedbatches,anappropriate文档 实用investigationshallbeconductedinaccordancewiththerequirementsof§211.192.Proceduresfortheholding,testing,andreprocessingofreturneddrugproductsshallbeinwritingandshallbefollowed.§211.208Drugproductsalvaging.Drugproductsthathavebeensubjectedtoimproperstorageconditionsincludingextremesintemperature,humidity,smoke,fumes,pressure,age,orradiationduetonaturaldisasters,fires,accidents,orequipmentfailuresshallnotbesalvagedandreturnedtothemarketplace.Wheneverthereisaquestionwhetherdrugproductshavebeensubjectedtosuchconditions,salvagingoperationsmaybeconductedonlyifthereis(a)evidencefromlaboratorytestsandassays(includinganimalfeedingstudies文档 实用whereapplicable)thatthedrugproductsmeetallapplicablestandardsofidentity,strength,quality,andpurityand(b)evidencefrominspectionofthepremisesthatthedrugproductsandtheirassociatedpackagingwerenotsubjectedtoimproperstorageconditionsasaresultofthedisasteroraccident.Organolepticexaminationsshallbeacceptableonlyassupplementalevidencethatthedrugproductsmeetappropriatestandardsofidentity,strength,quality,andpurity.Recordsincludingname,lotnumber,anddispositionshallbemaintainedfordrugproductssubjecttothissection.文档