美国FDA原料药生产质量管理规范中英文样本

DIRECTIONOFGMP(GOODMANUFACTURINGPRACTICE)OFRAWMATERIALSBYFDA美国FDA原料药生产质量管理规范（

中英文）

TableofContents

目录1.INTRODUCTION

简介1.1Objective

目1.2RegulatoryApplicability法规合用性1.3Scope

范畴

2.QUALITYMANAGEMENT

.质量管理2.1Principles

总则2.2ResponsibilitiesoftheQualityUnit(s)

质量部门责任2.3ResponsibilityforProductionActivities

生产作业职责2.4InternalAudits(SelfInspection)

内部审计（自检）2.5ProductQualityReview

产品质量审核

3.PERSONNEL

人员3.1PersonnelQualifications

人员资质3.2PersonnelHygiene

人员卫生3.3Consultants

顾问

4.BUILDINGSANDFACILITIES

建筑和设施4.1DesignandConstruction

设计和构造4.2Utilities

公用设施4.3Water

水4.4Containment

限制4.5Lighting

照明4.6SewageandRefuse

排污和垃圾4.7SanitationandMaintenance

卫生和保养

5.PROCESSEQUIPMENT

工艺设备5.1DesignandConstruction

设计和构造5.2EquipmentMaintenanceandCleaning

设备保养和清洁5.3Calibration.校验5.4ComputerizedSystems

计算机控制系统

6.DOCUMENTATIONANDRECORDS文献和记录6.1DocumentationSystemandSpecifications

文献系统和质量原则6.2EquipmentcleaningandUseRecord

设备清洁和使用记录6.3RecordsofRawMaterials，Intermediates，APILabelingandPackagingMaterials

原料、中间体、原料药标签和包装材料记录6.4MasterProductionInstructions(MasterProductionandControlRecords)

生产工艺规程（主生产和控制记录）6.5BatchProductionRecords(BatchProductionandControlRecords)

批生产记录（批生产和控制记录）6.6LaboratoryControlRecords

实验室控制记录6.7BatchProductionRecordReview

批生产记录审核

7.MATERIALSMANAGEMENT

物料管理7.1GeneralControls

控制通则7.2ReceiptandQuarantine

接受和待验7.3SamplingandTestingofIncomingProductionMaterials进厂物料取样与测试7.4Storage

储存7.5Re-evaluation

复验

8.PRODUCTIONANDIN-PROCESSCONTROLS

生产和过程控制8.1ProductionOperations

生产操作8.2TimeLimits

时限8.3In-processSamplingandControls

工序取样和控制8.4BlendingBatchesofIntermediatesorAPIs

中间体或原料药混批8.5ContaminationControl

污染控制

9.PACKAGINGANDIDENTIFICATIONLABELINGOFAPIsANDINTERMEDIATES

原料药和中间体包装和贴签9.1General

总则9.2PackagingMaterials包装材料9.3LabelIssuanceandControl

标签发放与控制9.4PackagingandLabelingOperations包装和贴签操作

10.STORAGEANDDISTRIBUTION.储存和分发10.1WarehousingProcedures入库程序10.2DistributionProcedures分发程序

11.LABORATORYCONTROLS

实验室控制11.1GeneralControls

控制通则11.2TestingofIntermediatesandAPIs中间体和原料药测试11.3ValidationofAnalyticalProcedures

分析办法验证11.4CertificatesofAnalysis分析报告单11.5StabilityMonitoringofAPIs原料药稳定性监测11.6ExpiryandRetestDating

有效期和复验期11.7Reserve/RetentionSamples

留样

12.VALIDATION

.验证12.1ValidationPolicy

验证方针12.2ValidationDocumentation

验证文献12.3Qualification

确认12.4ApproachestoProcessValidation

工艺验证办法12.5ProcessValidationProgram

工艺验证程序12.6PeriodicReviewofValidatedSystems

验证系统定期审核12.7CleaningValidation

清洗验证12.8ValidationofAnalyticalMethods分析办法验证

13.CHANGECONTROL

变更控制

14.REJECTIONANDRE-USEOFMATERIALS.拒收和物料再运用14.1Rejection拒收14.2Reprocessing

返工14.3Reworking

重新加工14.4RecoveryofMaterialsandSolvents

物料与溶剂回收14.5Returns

退货

15.COMPLAINTSANDRECALLS

投诉与召回

16.CONTRACTMANUFACTURERS(INCLUDINGLABORATORIES)合同生产商（涉及实验室）

17.AGENTS，BROKERS，TRADERS，DISTRIBUTORS，REPACKERS，ANDRELABELLERS

代理商、经纪人、贸易商、经销商、重新包装者和重新贴签者17.1Applicability

合用性17.2TraceabilityofDistributedAPIsandIntermediates已分发原料药和中间体可追溯性17.3QualityManagement

质量管理17.4Repackaging，Relabeling，andHoldingofAPIsandIntermediates原料药和中间体重新包装、重新贴签和待检17.5Stability

稳定性17.6TransferofInformation信息传达17.7HandlingofComplaintsandRecalls

投诉和召回解决17.8HandlingofReturns

退货解决

18.SpecificGuidanceforAPIsManufacturedbyCellCulture/Fermentation

用细胞繁殖/发酵生产原料药特殊指南18.1General

总则18.2CellBankMaintenanceandRecordKeeping

细胞库维护和记录保存18.3CellCulture/Fermentation

细胞繁殖/发酵18.4Harvesting，IsolationandPurification

收取、分离和精制18.5ViralRemoval/Inactivationsteps

病毒去除/灭活环节

19.APIsforUseinClinicalTrials用于临床研究原料药19.1General

总则19.2Quality

质量19.3EquipmentandFacilities设备和设施19.4ControlofRawMaterials原料控制19.5Production

生产19.6Validation

验证19.7Changes

变更19.8LaboratoryControls

实验室控制19.9Documentation

文献20.Glossary

术语

1.INTRODUCTION

1.简介1.1Objective

1.1目Thisdocumentisintendedtoprovideguidanceregardinggoodmanufacturingpractice(GMP)forthemanufacturingofactivepharmaceuticalingredients(APIs)underanappropriatesystemformanagingquality.ItisalsointendedtohelpensurethatAPIsmeetthequalityandpuritycharacteristicsthattheypurport，orarerepresented，topossess.

本文献旨在为在适当质量管理体系下制造活性药用成分（如下称原料药）提供关于优良药物生产管理规范（GMP）提供指南。它也着眼于协助保证原料药符合其旨在达到或表白拥有质量与纯度规定。

Inthisguidance，thetermmanufacturingisdefinedtoincludealloperationsofreceiptofmaterials，production，packaging，repackaging，labeling，relabeling，qualitycontrol，release，storageanddistributionofAPIsandtherelatedcontrols.Inthisguidance，thetermshouldidentifiesrecommendationsthat，whenfollowed，willensurecompliancewithCGMPs.Analternativeapproachmaybeusedifsuchapproachsatisfiestherequirementsoftheapplicablestatues.Forthepurposesofthisguidance，thetermscurrentgoodmanufacturingpracticesandgoodmanufacturingpracticesareequivalent.本指南中所指“制造”涉及物料接受、生产、包装、重新包装、贴签、重新贴签、质量控制、放行、原料药储存和分发及其有关控制所有操作。本指南中，“应当”一词表达但愿采用建议，除非证明其不合用或者可用一种已证明有同等或更高质量保证水平供选物来代替。本指南中“现行优良生产管理规范（cGMP）”和“优良生产管理规范（GMP）”是等同。

Theguidanceasawholedoesnotcoversafetyaspectsforthepersonnelengagedinmanufacturing，noraspectsrelatedtoprotectingtheenvironment.Thesecontrolsareinherentresponsibilitiesofthemanufacturerandaregovernedbynationallaws.

本指南在总体上未涉及生产人员安全问题，亦不涉及环保方面内容。这方面管理是生产者固有责任，也是国家法律规定。

Thisguidanceisnotintendedtodefineregistrationand/orfilingrequirementsormodifypharmacopoeialrequirements.Thisguidancedoesnotaffecttheabilityoftheresponsibleregulatoryagencytoestablishspecificregistration/filingrequirementsregardingAPIswithinthecontextofmarketing/manufacturingauthorizationsordrugapplications.Allcommitmentsinregistration/filingdocumentsshouldbemet.

本指南未规定注册/归档规定、或修改药典规定。本指南不影响负责药政审理部门在原料药上市/制造授权或药物申请方面建立特定注册/归档规定能力。注册/归档所有承诺必要做到。

1.2RegulatoryApplicability

1.2法规合用性Withintheworldcommunity，materialsmayvaryastotheirlegalclassificationasanAPI.WhenamaterialisclassifiedasanAPIintheregionorcountryinwhichitismanufacturedorusedinadrugproduct，itshouldbemanufacturedaccordingtothisguidance.

在世界范畴内对原料药法定定义是各不相似。当某种物料在其制造或用于药物地区或国家被称为原料药，就应当按照本指南进行生产。

1.3Scope

1.3范畴ThisguidanceappliestothemanufactureofAPIsforuseinhumandrug(medicinal)products.ItappliestothemanufactureofsterileAPIsonlyuptothepointimmediatelypriortotheAPIsbeingrenderedsterile.ThesterilizationandasepticprocessingofsterileAPIsarenotcoveredbythisguidance，butshouldbeperformedinaccordancewithGMPguidancesfordrug(medicinal)productsasdefinedbylocalauthorities.

本文献合用于人用药物（医疗用品）所含原料药生产。它合用于无菌原料药在灭菌前环节。本指南不涉及无菌原料药消毒和灭菌工艺，但是，应当符合地方当局所规定药物（医疗用品）生产GMP指南。

ThisguidancecoversAPIsthataremanufacturedbychemicalsynthesis，extraction，cellculture/fermentation，recoveryfromnaturalsources，oranycombinationoftheseprocesses.SpecificguidanceforAPIsmanufacturedbycellculture/fermentationisdescribedinSection18.本文献合用于通过化学合成、提取、细胞培养/发酵，通过从自然资源回收，或通过这些工艺结合而得到原料药。通过细胞培养/发酵生产原料药特殊指南则在第18章阐述。

Thisguidanceexcludesallvaccines，wholecells，wholebloodandplasma，bloodandplasmaderivatives(plasmafractionation)，andgenetherapyAPIs.However，itdoesincludeAPIsthatareproducedusingbloodorplasmaasrawmaterials.Notethatcellsubstrates(mammalian，plant，insectormicrobialcells，tissueoranimalsourcesincludingtransgenicanimals)andearlyprocessstepsmaybesubjecttoGMPbutarenotcoveredbythisguidance.Inaddition，theguidancedoesnotapplytomedicalgases，bulk-packageddrug(medicinal)products(e.g.，tabletsorcapsulesinbulkcontainers)，orradiopharmaceuticals.

本指南不涉及所有疫苗、完整细胞、全血和血浆、全血和血浆衍生物（血浆成分）和基因治疗原料药。但是却涉及以血或血浆为原材料生产原料药。值得注意是细胞培养基（哺乳动物、植物、昆虫或微生物细胞、组织或动物源涉及转基因动物）和前期生产也许应遵循GMP规范，但不涉及在本指南之内。此外，本指南不合用于医用气体、散装制剂药（例如，散装片剂和胶囊）和放射性药物生产。

Section19containsguidancethatonlyappliestothemanufactureofAPIsusedintheproductionofdrug(medicinal)productsspecificallyforclinicaltrials(investigationalmedicinalproducts).第19章指南只合用于用在药物（医疗用品）生产中原料药制造，特别是临床实验用药（研究用医疗产品）原料药制造。

AnAPIstartingmaterialisarawmaterial，anintermediate，oranAPIthatisusedintheproductionofanAPIandthatisincorporatedasasignificantstructuralfragmentintothestructureoftheAPI.AnAPIstartingmaterialcanbeanarticleofcommerce，amaterialpurchasedfromoneormoresuppliersundercontractorcommercialagreement，orproducedin-house.APIstartingmaterialsnormallyhavedefinedchemicalpropertiesandstructure.

“原料药起始物料”是指一种原料、中间体或原料药，用来生产一种原料药，或者以重要构造单元形式被结合进原料药构造中。原料药起始物料也许是在市场上有售、可以通过合同或商业合同从一种或各种供应商处购得，或由生产厂家自制。原料药起始物料普通来说有特定化学特性和构造。

ThecompanyshoulddesignateanddocumenttherationaleforthepointatwhichproductionoftheAPIbegins.Forsyntheticprocesses，thisisknownasthepointatwhichAPIstartingmaterialsareenteredintotheprocess.Forotherprocesses(e.g.，fermentation，extraction，purification)，thisrationaleshouldbeestablishedonacase-by-casebasis.Table1givesguidanceonthepointatwhichtheAPIstartingmaterialisnormallyintroducedintotheprocess.生产厂商要指定并用书面文献阐明原料药生产从何处开始理论根据。对于合成工艺而言，就是“原料药起始物料”进入工艺那一点。对其她工艺（如：发酵，提取，纯化等）也许需要详细问题详细对待。表1给出了原料药起始物料从哪一点引入工艺过程指引原则。

Fromthispointon，appropriateGMPasdefinedinthisguidanceshouldbeappliedtotheseintermediateand/orAPImanufacturingsteps.ThiswouldincludethevalidationofcriticalprocessstepsdeterminedtoimpactthequalityoftheAPI.However，itshouldbenotedthatthefactthatacompanychoosestovalidateaprocessstepdoesnotnecessarilydefinethatstepsascritical.

从这步开始，本指南中关于GMP规范应当应用在这些中间体和/或原料药制造中。这涉及对原料药质量有影响核心工艺环节验证。但是，值得注意是厂商选取某一环节进行验证，并不一定将该环节定为核心环节。

TheguidanceinthisdocumentwouldnormallybeappliedtothestepsshowningrayinTable1.However，allstepsshownmaynotbecompleted.ThestringencyofGMPinAPImanufacturingshouldincreaseastheprocessproceedsfromearlyAPIstepstofinalsteps，purification，andpackaging.PhysicalprocessingofAPIs，suchasgranulation，coatingorphysicalmanipulationofparticlesize(e.g.，milling，micronizing)shouldbeconductedaccordingtothisguidance.

本文献指南普通合用于表1中灰色环节。但在表中体现所有环节并不是将应用GMP管理所有环节所有体现出来了。原料药生产中GMP规定应当随着工艺进行，从原料药前几步到最后几步，精制和包装，越来越严格。原料药物理加工，如制粒、包衣或颗粒度物理解决（例如制粉、微粉化）应当按本指南原则进行。

ThisGMPguidancedoesnotapplytostepspriortotheintroductionofthedefinedAPIstartingmaterial.本GMP指南不合用于引入定义了“原料药起始物料”此前环节。

2.QUALITYMANAGEMENT

2．质量管理2.1Principles

2.1总则2.10Qualityshouldbetheresponsibilitiesofallpersonsinvolvedinmanufacturing.

参加原料药生产每一种人都应当对质量负责。

2.11Eachmanufacturershouldestablish，document，andimplementaneffectivesystemformanagingqualitythatinvolvestheactiveparticipationofmanagementandappropriatemanufacturingpersonnel.

每一种生产商都应当建立并执行一套有管理人员和关于员工积极参加有效质量管理体系，并使其文献化。

2.12Thesystemformanagingqualityshouldencompasstheorganizationalstructure，procedures，processandresources，aswellasactivitiestoensureconfidencethattheAPIwillmeetitsintendedspecificationsforqualityandpurity.Allquality-relatedactivitiesshouldbedefinedanddocumented.

质量管理体系应当涉及组织机构、规程、工艺和资源，以及保证原料药会符合其预期质量与纯度规定所必须活动。所有涉及质量管理活动都应当明确规定，并使其文献化。

2.13Thereshouldbeaqualityunit(s)thatisindependentofproductionandthatfulfillsbothqualityassurance(QA)andqualitycontrol(QC)responsibilities.ThequalityunitcanbeintheformofseparateQAandQCunitsorasingleindividualorgroup，dependinguponthesizeandstructureoftheorganization.

2.13应当设立一种独立于生产部门质量部门，同步履行质量保证(QA)和质量控制(QC)职责。依照组织机构大小，可以是分开QA和QC部门，或者只是一种人或小组。

2.14ThepersonsauthorizedtoreleaseintermediatesandAPIsshouldbespecified.

2.14应当指定授权发放中间体和原料药人员。

2.15Allquality-relatedactivitiesshouldberecordedatthetimetheyareperformed.

2.15所有关于质量活动应当在其执行时就记录。

2.16Anydeviationfromestablishedproceduresshouldbedocumentedandexplained.Criticaldeviationsshouldbeinvestigated，andtheinvestigationanditsconclusionsshouldbedocumented.2.16任何偏离既定规程状况都应当有文字记录并加以解释。对于核心性偏差应当进行调查，并记录调查通过及其成果。

2.17Nomaterialsshouldbereleasedorusedbeforethesatisfactorycompletionofevaluationbythequalityunit(s)unlessthereareappropriatesystemsinplacetoallowforsuchuse(e.g.，releaseunderquarantineasdescribedinSection10ortheuseofrawmaterialsorintermediatespendingcompletionofevaluation).

2.17在质量部门对物料完毕满意评价之前，任何物料都不应当发放或使用，除非有适当系统容许此类使用（如10.20条款所述待检状况下使用，或是原料或中间体在等待评价结束时使用）。

2.18Proceduresshouldexistfornotifyingresponsiblemanagementinatimelymannerofregulatoryinspections，seriousGMPdeficiencies，productdefectsandrelatedactions(e.g.，quality-relatedcomplaints，recalls，andregulatoryactions).2.18应当有规程能保证公司责任管理部门能及时得到关于药政检查、严重GMP缺陷、产品缺陷及其有关活动（如质量投诉，召回，药政活动等）告知。

2.2ResponsibilitiesoftheQualityUnit(s)

2.2质量部门责任2.20Thequalityunit(s)shouldbeinvolvedinallquality-relatedmatters.

2.20质量部门应当参加所有与质量关于事物。

2.21Thequalityunit(s)shouldreviewandapproveallappropriatequality-relateddocuments.2.21所有与质量关于文献应当由质量部门审核批准。

2.22Themainresponsibilitiesoftheindependentqualityunit(s)shouldnotbedelegated.Theseresponsibilitiesshouldbedescribedinwritingandshouldinclude，butnotnecessarilybelimitedto:1.

ReleasingorrejectingallAPIs.Releasingorrejectingintermediatesforuseoutsidethecontrolofthemanufacturingcompany2.

Establishingasystemtoreleaseorrejectrawmaterials，intermediates，packaging，andlabelingmaterials3.

ReviewingcompletedbatchproductionandlaboratorycontrolrecordsofcriticalprocessstepsbeforereleaseoftheAPIfordistribution4.

Makingsurethatcriticaldeviationsareinvestigatedandresolved5.

Approvingallspecificationsandmasterproductioninstructions6.

ApprovingallproceduresaffectingthequalityofintermediatesorAPIs7.

Makingsurethatinternalaudits(self-inspections)areperformed8.

ApprovingintermediateandAPIcontractmanufacturers9.

ApprovingchangesthatpotentiallyaffectintermediateorAPIquality10.

Reviewingandapprovingvalidationprotocolsandreports11.

Makingsurethatquality-relatedcomplaintsareinvestigatedandresolved12.

Makingsurethateffectivesystemsareusedformaintainingandcalibratingcriticalequipment13.

Makingsurethatmaterialsareappropriatelytestedandtheresultsarereported14.

MakingsurethatthereisstabilitydatatosupportretestorexpirydatesandstorageconditionsonAPIsand/orintermediates，whereappropriate15.

Performingproductqualityreviews(asdefinedinSection2.5)

2.22独立质量部门重要职责不应当委派给她人。这些责任应当以文字形式加以阐明，并且应当涉及，但不限于：1.

所有原料药放行与否。用于生产商控制范畴以外中间体放行与否；2.

建立一种放行与拒收原材料、中间体、包装材料和标签系统；3.

在供销售原料药放行前，审核已完毕核心环节批生产记录和实验室检查记录；4.

保证已对重大偏差进行了调查并已解决；5.

批准所有规格原则和主生产指令；6.

批准所有也许影响原料药和中间体质量规程；7.

保证进行内部审计（自检）；8.

批准中间体或原料药委托生产商；9.

批准也许影响到中间体或原料药质量变更；10.

审核并批准验证方案和报告；11.

保证调查并解决质量问题投诉；12.

保证用有效体系来维护和校验核心设备；13.

保证物料都通过了恰当检查并报告成果；14.

保证有稳定性数据支持中间体或原料药复验期或有效期和储存条件；15.

开展产品质量审核（详见2.5节）。

2.3ResponsibilityforProductionActivities

2.3生产作业职责Theresponsibilityforproductionactivitiesshouldbedescribedinwritingandshouldinclude，butnotnecessarilybelimitedto:1.

Preparing，reviewing，approving，anddistributingtheinstructionsfortheproductionofintermediatesorAPIsaccordingtowrittenprocedures2.

ProducingAPIsand，whenappropriate，intermediatesaccordingtopre-approvedinstructions3.

Reviewingallproductionbatchrecordsandensuringthatthesearecompletedandsigned4.

Makingsurethatallproductiondeviationsarereportedandevaluatedandthatcriticaldeviationsareinvestigatedandtheconclusionsarerecorded5.

Makingsurethatproductionfacilitiesarecleanand，whenappropriate，disinfected6.

Makingsurethatthenecessarycalibrationsareperformedandrecordskept7.

Makingsurethatthepremisesandequipmentaremaintainedandrecordskept8.

Makingsurethatvalidationprotocolsandreportsarereviewedandapproved9.

Evaluatingproposedchangesinproduct，processorequipment10.

Makingsurethatnewand，whenappropriate，modifiedfacilitiesandequipmentarequalified

生产作业职责应当以文字形式加以阐明，并应当涉及，但不限于如下内容：1.

按书面程序起草、审核、批准和分发中间体或原料药生产指令；2.

按照已批准指令生产原料药或者中间体；3.

审核所有批生产记录保证其完整并有签名；4.

保证所有生产偏差都已报告、评价，对核心偏差已做了调查，并记录结论；5.

保证生产设施清洁，必要时要消毒；6.

保证进行必要校验，并有记录；7.

保证对厂房和设备进行保养，并有记录；8.

保证验证方案和报告审核与批准；9.

对产品、工艺或设备拟作变更进行评估；10.

保证新或已改进生产设施和设备通过了确认。

2.4InternalAudits(SelfInspection)

2.4内部审计（自检）2.40ToverifycompliancewiththeprinciplesofGMPforAPIs，regularinternalauditsshouldbeperformedinaccordancewithanapprovedschedule.2.40为的确符合原料药GMP原则，应当按照批准筹划进行定期内部审计。

2.41Auditfindingsandcorrectiveactionsshouldbedocumentedandbroughttotheattentionofresponsiblemanagementofthefirm.Agreedcorrectiveactionsshouldbecompletedinatimelyandeffectivemanner.

2.41审计成果及整治办法应当形成文献，并引起公司责任管理人员注重。获准整治办法应当及时、有效地完毕。

2.5ProductQualityReview

2.5产品质量审核2.50Regularquality-reviewsofAPIsshouldbeconductedwiththeobjectiveofverifyingtheconsistencyoftheprocess.Suchreviewsshouldnormallybeconductedanddocumentedannuallyandshouldincludeatleast:

Areviewofcriticalin-processcontrolandcriticalAPItestresults

Areviewofallbatchesthatfailedtomeetestablishedspecification(s)

Areviewofallcriticaldeviationsornonconformancesandrelatedinvestigations

Areviewofanychangescarriedouttotheprocessesoranalyticalmethods

Areviewofresultsofthestabilitymonitoringprogram

Areviewofallquality-relatedreturns，complaintsandrecalls

Areviewofadequacyofcorrectiveactions

2.50原料药定期质量审核应当以证明工艺一致性为目来进行。此种审核普通应当每年进行一次，并记录，内容至少应当涉及：

核心工艺控制以及原料药核心测试成果审核；

所有不符合既定质量原则产品批号审核；

所有核心偏差或违规行为及关于调查审核；

任何工艺或分析办法变动审核；

稳定性监测审核；

所有与质量关于退货、投诉和召回审核；

整治办法恰当性审核。

2.51Theresultsofthisreviewshouldbeevaluatedandanassessmentmadeofwhethercorrectiveactionoranyrevalidationshouldbeundertaken.Reasonsforsuchcorrectiveactionshouldbedocumented.Agreedcorrectiveactionsshouldbecompletedinatimelyandeffectivemanner.

应当对质量审核成果进行评估，并做出与否需要整治或做任何再验证评价。此类整治办法理由应当文献化。获准整治办法应当及时、有效地完毕。

3.PERSONNEL

3.人员3.1PersonnelQualifications

3.1员工资质3.10Thereshouldbeanadequatenumberofpersonnelqualifiedbyappropriateeducation，training，and/orexperiencetoperformandsupervisethemanufactureofintermediatesandAPIs.

3.10应当有足够数量员工具备从事和监管原料药和中间体生产教诲、培训和/或经历等资格。

3.11TheresponsibilitiesofallpersonnelengagedinthemanufactureofintermediatesandAPIsshouldbespecifiedinwriting.

3.11参加原料药和中间体生产所有人员职责应当书面规定。

3.12Trainingshouldberegularlyconductedbyqualifiedindividualsandshouldcover，ataminimum，theparticularoperationsthattheemployeeperformsandGMPasitrelatestotheemployee’sfunctions.Recordsoftrainingshouldbemaintained.Trainingshouldbeperiodicallyassessed.

3.12应当由有资格人员定期进行培训，内容至少应当涉及员工所从事特定操作和与其职能关于GMP。培训记录应当保存，并应当定期对培训进行评估。

3.2PersonnelHygiene

3.2员工卫生3.20Personnelshouldpracticegoodsanitationandhealthhabits.

3.20员工应当养成良好卫生和健康习惯。

3.21Personnelshouldwearcleanclothingsuitableforthemanufacturingactivitywithwhichtheyareinvolvedandthisclothingshouldbechanged，whenappropriate.Additionalprotectiveapparel，suchashead，face，hand，andarmcoverings，shouldbeworn，whennecessary，toprotectintermediatesandAPIsfromcontamination.

3.21员工应当穿着适合其所从事生产操作干净服装，必要时应当更换。其他保护性用品如头、脸、手和臂等遮护用品必要时也应当佩带，以免原料药和中间体受到污染。

3.22PersonnelshouldavoiddirectcontactwithintermediatesandAPIs.

3.22员工应当避免与中间体或原料药直接接触。

3.23Smoking，eating，drinking，chewingandthestorageoffoodshouldberestrictedtocertaindesignatedareasseparatefromthemanufacturingareas.

3.23吸烟、吃、喝、咀嚼及存储食品仅限于与生产区隔开指定区域。

3.24PersonnelsufferingfromaninfectiousdiseaseorhavingopenlesionsontheexposedsurfaceofthebodyshouldnotengageinactivitiesthatcouldresultincompromisingthequalityofAPIs.Anypersonshownatanytime(eitherbymedicalexaminationorsupervisoryobservation)tohaveanapparentillnessoropenlesionsshouldbeexcludedfromactivitieswheretheconditioncouldadverselyaffectthequalityoftheAPIsuntiltheconditioniscorrectedorqualifiedmedicalpersonneldeterminethattheperson’sinclusionwouldnotjeopardizethesafetyorqualityoftheAPIs.3.24患传染性疾病或身体表面有开放性创伤员工不应当从事危及原料药质量生产活动。在任何时候（经医学检查或监控检查）任何患有危及到原料药质量疾病或创伤人员都不应当参加作业，直到健康状况已恢复，或者有资格医学人员确认该员工不会危及到原料药安全性和质量。

3.3Consultants

3.3顾问3.30ConsultantsadvisingonthemanufactureandcontrolofintermediatesorAPIsshouldhavesufficienteducation，training，andexperience，oranycombinationthereof，toadviseonthesubjectforwhichtheyareretained.

3.30中间体或原料药生产和控制顾问应当有足够学历，受训和经验，能胜任所承担工作。

3.31Recordsshouldbemaintainedstatingthename，address，qualifications，andtypeofserviceprovidedbytheseconsultants.3.31顾问姓名、地址、资格和提供服务类型都应当有文字记录。

4.BUILDINGSANDFACILITIES

4.建筑和设施4.1DesignandConstruction

4.1设计和构造4.10BuildingsandfacilitiesusedinthemanufactureofintermediatesandAPIsshouldbelocated，designed，andconstructedtofacilitatecleaning，maintenance，andoperationsasappropriatetothetypeandstageofmanufacture.Facilitiesshouldalsobedesignedtominimizepotentialcontamination.WheremicrobiologicalspecificationshavebeenestablishedfortheintermediateorAPI，facilitiesshouldalsobedesignedtolimitexposuretoobjectionablemicrobiologicalcontaminants，asappropriate.

4.10用于中间体和原料药生产厂房和设施选址、设计和建造应当便于清洁，维护和适应一定类型和阶段生产操作。设施设计应尽量减少潜在污染。如果中间体或原料药生产有微生物限度规定，那么设施设计应相应限制有害微生物污染。

4.11Buildingsandfacilitiesshouldhaveadequatespacefortheorderlyplacementofequipmentandmaterialstopreventmix-upsandcontamination.

4.11厂房和设施应有足够空间，以便有秩序地放置设备和物料，防止混淆和污染。

4.12Wheretheequipmentitself(e.g.，closedorcontainedsystem)providesadequateprotectionofthematerial，suchequipmentcanbelocatedoutdoors.

4.12自身能对物料提供足够保护设备（如关闭或封闭系统），可以在户外放置。

4.13Theflowofmaterialsandpersonnelthroughthebuildingorfacilitiesshouldbedesignedtopreventmix-upsandcontamination.

4.13通过厂房和设施物流和人流设计应当能防止混杂和污染。

4.14Thereshouldbedefinedareasorothercontrolsystemsforthefollowingactivities:

如下活动应当有指定区域或其他控制系统：

4.15Adequateandcleanwashingandtoiletfacilitiesshouldbeprovidedforpersonnel.Thesefacilitiesshouldbeequippedwithhotandcoldwater，asappropriate，soapordetergent，airdryers，orsingleservicetowels.Thewashingandtoiletfacilitiesshouldbeseparatefrom，buteasilyaccessibleto，manufacturingareas.Adequatefacilitiesforshoweringand/orchangingclothesshouldbeprovided，whenappropriate.

4.15应当为员工提供足够和清洁盥洗设施。这些盥洗设施应当装有冷热水（视状况而定）、肥皂或洗涤剂，干手机和一次性毛巾。盥洗室应当与生产区隔离，但要便于达到。应当依照状况提供足够淋浴和/或更衣设施。

4.16Laboratoryareas/operationsshouldnormallybeseparatedfromproductionareas.Somelaboratoryareas，inparticularthoseusedforin-processcontrols，canbelocatedinproductionareas，providedtheoperationsoftheproductionprocessdonotadverselyaffecttheaccuracyofthelaboratorymeasurements，andthelaboratoryanditsoperationsdonotadverselyaffecttheproductionprocess，intermediate，orAPI.4.16实验室区域/操作普通应当与生产区隔离。有些实验室区域，特别是用于中间控制，可以位于生产区内，只要生产工艺操作对实验室测量精确性没有负面影响，并且，实验室及其操作对生产过程，或中间体，或原料药也没有负面影响。

4.2Utilities

4.2公用设施4.20Allutilitiesthatcouldaffectproductquality(e.g.，steam，gas，compressedair，heating，ventilation，andairconditioning)shouldbequalifiedandappropriatelymonitoredandactionshouldbetakenwhenlimitsareexceeded.Drawingsfortheseutilitysystemsshouldbeavailable.4.20对产品质量会有影响所有公用设施（如蒸汽，气体，压缩空气和加热，通风及空调）都应当确认合格，并进行恰当监控，在超过限度时应当采用相应办法。应当有这些公用设施系统图。

4.21Adequateventilation，airfiltrationandexhaustsystemsshouldbeprovided，whereappropriate.Thesesystemsshouldbedesignedandconstructedtominimizerisksofcontaminationandcross-contaminationandshouldincludeequipmentforcontrolofairpressure，microorganisms(ifappropriate)，dust，humidity，andtemperature，asappropriatetothestageofmanufacture.ParticularattentionshouldbegivingtoareaswhereAPIsareexposedtotheenvironment.

4.21应当依照状况，提供足够通风、空气过滤和排气系统。这些系统应当依照相应生产阶段，设计和建导致将污染和交叉污染降至最低限度，并涉及控制气压、微生物（如果合用）、灰尘、湿度和温度设备。特别值得注意是原料药暴露区域。

4.22Ifairisrecirculatedtoproductionareas，appropriatemeasuresshouldbetakentocontrolrisksofcontaminationandcross-contamination.4.22如果空气再循环到生产区域，应当采用恰当控制污染和交叉污染风险。

4.23Permanentlyinstalledpipeworkshouldbeappropriatelyidentified.Thiscanbeaccomplishedbyidentifyingindividuallines，documentation，computercontrolsystem，oralternativemeans.PipeworkshouldbelocatedtoavoidrisksofcontaminationoftheintermediateorApI.

4.23永久性安装管道应当有适当标记。这可以通过标记每根管道、提供证明文献、计算机控制系统，或其他代替办法来达到。管道安装处应当防止污染中间体或原料药。

4.24Drainsshouldbeofadequatesizeandshouldbeprovidedwithanairbreakorasuitabledevicetopreventback-siphonage，whenappropriate.

4.24排水沟应当有足够尺寸，并且应当依照状况装有空断器或恰当装置，防止倒虹吸。

4.3Water

4.3水4.30WaterusedinthemanufactureofAPIsshouldbedemonstratedtobesuitableforitsintendeduse.

4.30原料药生产中使用水应当证明适合于其预定用途。

4.31Unlessotherwisejustified，processwatershould，ataminimum，meetWorldHealthOrganization(WHO)guidelinesfordrinking(portable)waterquality.

除非有其他理由，工艺用水最低限度应当符合世界卫生组织（WHO）饮用水质量指南。

4.32Ifdrinking(portable)waterisinsufficienttoensureAPIqualityandtighterchemicaland/ormicrobiologicalwaterqualityspecificationsarecalledfor，appropriatespecificationsforphysical/chemicalattributes，totalmicrobialcounts，objectionableorganisms，and/orendotoxinsshouldbeestablished.

4.32如果饮用水局限性以保证原料质量，并规定更为严格化学和/或微生物水质规格原则，应当指定适当物理/化学特性、微生物总数、控制菌和/或内毒素规格原则。

4.33Wherewaterusedintheprocessistreatedbythemanufacturertoachieveadefinedquality，thetreatmentprocessshouldbevalidatedandmonitoredwithappropriateactionl