GMP对QA的要求（法规综述）

对的要求（法规综述）GMP QA质量保证QA QualityAssurance,

一、中国对的要求GMP QA第二节质量保证第八条质量保证是质量管理体系的一部分企业必须建立质量保证系统，同时建立完整的文件体系，以保证系统有效运行第九条质量保证系统应当确保

（一）药品的设计与研发体现本规范的要求；

（二）生产管理和质量控制活动符合本规范的要求；

（三）管理职责明确；

（四）采购和使用的原辅料和包装材料正确无误；

（五）中间产品得到有效控制；

（六）确认、验证的实施；卜七）严格按照规程进行生产、检查、检验和复核；

（八）每批产品经质量受权人批准后方可放行；

（九）在贮存、发运和随后的各种操作过程中有保证药品质量的适当措施；

（十）按照自检操作规程，定期检查评估质量保证系统的有效性和适用性第十条药品生产质量管理的基本要求

（一）制定生产工艺，系统地回顾并证明其可持续稳定地生产出符合要求的产品；

（二）生产工艺及其重大变更均经过验证；

（三）配备所需的资源，至少包括,具有适当的资质并经培训合格的人员；1,足够的厂房和空间；

2.适用的设备和维修保障；

3.正确的原辅料、包装材料和标签；4,经批准的工艺规程和操作规程；

5.适当的贮运条件6

（四）应当使用准确、易懂的语言制定操作规程；

（五）操作人员经过培训，能够按照操作规程正确操作；

（六）生产全过程应当有记录，偏差均经过调查并记录；

（七）批记录和发运记录应当能够追溯批产品的完整历史，并妥善保存、便于查阅；

（八）降低药品发运过程中的质量风险；

（九）建立药品召回系统，确保能够召回任何一批已发运销售的产品；

（十）调查导致药品投诉和质量缺陷的原因，并采取措施，防止类似质量缺陷再次发生

二、中对质量管理的描述ICH Q7质量管理QUALITY MANAGEMENT原则

2.1Principles

2.10Quality should be the responsibility of all personsinvolved inmanufacturing.质量应该是所有参与生产的人员的职责

2.11Each manufacturershould establish,document,and implementan effectivesystem formanagingquality thatinvolves theactive participationof management and appropriatemanufacturingpersonnel.每个生产企业应该建立、文件化并执行一个有管理层和适当的生产人员参与的有效的管理质量的体系

2.12The system for managingquality shouldencompass theorganisational structure,procedures,processes andresources,as wellas activitiesnecessary to ensure confidence that the API willmeet itsintendedspecifications for quality andpurity.All qualityrelated activitiesshould bedefined anddocumented.管理质量的体系应该包含组织架构、程序、流程和资源，以及确保原料药有信心符合预期的质量和纯度标准的必要的活动所有质量相关的活动都应该规定并使其文件化

2.13There should be aquality unitsthat isindependent ofproduction andthat fulfillsboth qualityassuranceQA and quality controlQC responsibilities.This canbe in the formof separateQA andQCunits ora singleindividual orgroup,depending uponthe sizeand structureof theorgnization.应该有一个独立于生产并且要履行质量保证和质量控制职责的质量单元或质量部门QA QC根据组织的大小和架构，这个质量单元可以由单独的和单元或一个人或团队组成QA QC

2.14The personsauthorised torelease intermediatesand APIsshould bespecified.应当指定被授权放行中间体和原料药的人员

2.15All qualityrelated activitiesshould berecorded atthe timethey are performed.所有质量相关的活动都应该在其执行的时候就记录

2.16Any deviationfrom establishedprocedures shouldbe documented and explained.Criticaldeviations shouldbe investigated,and theinvestigation andits conclusionsshouldbedocumented.任何与已经建立的程序的偏离都应该记录或登记在案并解释

2.17No materialsshouldbereleased orused before the satisfactorycompletion ofevaluation by thequality unitsunless thereare appropriatesystems inplace toallow forsuch usee.g.release underquarantineas describedin Section

10.20or theuse ofraw materialsor intermediatespendingcompletion ofevaluation.在质量单元部门圆满完成评价前物料不应该放行或使用，除非在合适的位置有合适的系统允许这样的使用比如在第章节中描述的待验状态下的放行或等待完成评价时的原料或中间

10.20体的使用

2.18Procedures shouldexist fornotifying responsiblemanagement in a timelymanner ofregulatoryinspections,serious GMPdeficiencies,product defectsand relatedactions e.g.,quality relatedcomplaints,recalls,regulatory actions,etc..应该存在以一种及时的方式通知负责的管理层相关监管检查、严重的缺陷、产品缺陷和相GMP关措施的程序比如质量相关的投诉、召回、监管行动等

2.19Responsibilities of the QualityUnits质量单元的职责

2.20The quality units shouldbe involvedin allquality-related matters.质量单元应该参与所有质量相关的事项质量单

2.21The qualityunits shouldreview andapprove allappropriate quality-related documents.元应该审核和批准所有质量相关的文件

2.22The mainresponsibilities of the independentqualityunitsshould notbe delegated.Theseresponsibilities shouldbe describedin writingand shouldinclude butnot necessarilybe limitedto:独立的质量单元的主要职责不应该被委托（给他人）这些职责应该书面描述并应该包括但不必限于以下内容

1.Releasing orrejecting allAPIs.Releasing orrejecting intermediatesfor useoutside the controlof themanufacturing company;放行或拒收所有原料药放行或拒收在生产企业控制范围之外使用的中间体；

2.Establishing asystem torelease orreject rawmaterials,intermediates,packaging andlabelling materials;建立一个放行或拒收原料、中间体、包材和标签的系统；

3.Reviewing completedbatch productionand laboratorycontrol recordsof criticalprocess stepsbeforerelease of theAPIfor distribution;放行销售的原料药前审核关键工艺步骤的已完成的批生产记录和实验控制记录；

4.Making surethat criticaldeviations are investigated and resolved;确保关键偏差得到调查和解决；

5.Approving allspecifications andmaster productioninstructions;批准所有标准和生产工艺规程；

6.Approving allprocedures impactingthe quality of intermediatesor APIs;批准所有影响中间体或原料药质量的规程；（）

7.Making surethat internalaudits self-inspections areperformed;确保进行内部审计（自检）；

8.Approving intermediateand APIcontract manufacturers;批准中间体和原料药的合同生产商；

9.Approving changesthat potentiallyimpact intermediateor APIquality;批准潜在影响中间体或原料药质量的变更；

10.Reviewing andapproving validationprotocols andreports;审核和批准验证方案和报告；

11.Making surethat qualityrelated complaintsareinvestigated andresolved;确保质量相关的投诉得到调查和解决；

12.Making surethat effectivesystems areused formaintaining andcalibrating criticalequipment;确保有有效的系统用于维护和校验关键设备；

13.Making surethat materialsare appropriatelytested and the resultsare reported;确保物料都得到适宜的检测并报告其结果；

14.Making surethat thereis stabilitydata tosupport retestor expirydates andstorage conditionsonAPIs and/or intermediateswhere appropriate;确保在适当的情况下，有稳定性数据支持中间体或原料药的复验期或有效期和储存条件（）

15.Performing product quality reviewsas definedin Section

2.

5.进行产品质量回顾（在章节中定义）

三、中的描述

2.5WH0GMP医药行业的质量管理Quality managementinthe drug industryInthedrugindustry atlarge,quality managementis usuallydefined asthe aspectof managementfunctionthat determinesand implementsthe qualitypolicy^i.e.the overallintention anddirection ofanorganization regardingquality,as formallyexpressed andauthorized bytop management.Thebasic elementsof quality management are:在大的医药行业中，质量管理常常被定义为管理职能中规定并执行“质量政策”的那方面职能比如组织质量相关的总体意图和方向，由最高管理层正式表达和授权质量管理的基本要素有\——an appropriateinfrastructure orquality system”,encompassing theorganizational structure,procedures,processes andresources;一个适当的基础架构或“质量体系”，包含组织架构、程序、流程和资源；——systematic actionsnecessary toensure adequateconfidencethata productor servicewillsatisfy givenrequirements forquality.The totalityof theseactions istermed quality assurance.确保一个产品或服务有足够信心会满足质量要求的不要的系统化的行动全部这些行动被称之为“质量保证”Within anorganization,quality assuranceserves asa managementtool.In contractualsituations,quality assurancealso servesto generateconfidence inthe supplier.The conceptsof qualityassurance,GMP andquality controlare interrelatedaspects of qualitymanagement.They aredescribed hereinorder toemphasize theirrelationship andtheir fundamentalimportance to the productionandcontrol of pharmaceutical products.在一个组织内，质量保证是一种管理工具在委托情况下，质量保证也用于产生对供应商的信心质量保证、和质量控制的概念是质量管理的相关要素它们在这里描述是为了强调它GMP们的关系和它们对于药品生产和控制的根本的重要性质量保证

1.Quality assurance原贝

1.1Principle.ij“Quality assuranceis awide-ranging conceptcovering allmatters thatindividually orcollectivelyinfluence the qualityofa product.It isthe totalityof thearrangements madewith theobject ofensuringthat pharmaceutical products areof the quality requiredfor their intended use.Qualityassurance thereforeincorporates GMP and otherfactors,including thoseoutsidethescope ofthisguide suchas productdesign anddevelopment.“质量保证”是一个涵盖所有个体或集体影响产品质量的因素很宽泛的概念它是做出的确保药品质量符合其预定用途的目标的所有安排的总和所以质量保证整合了和其他因素，GMP包括那些不在本指南范围比如产品设计和开发内的那些因素

1.2The system of qualityassurance appropriateto themanufacture ofpharmaceutical productsshouldensure that:适用于药品生产的质量保证体系应该确保a pharmaceutical products aredesigned anddeveloped in a waythat takesaccount of therequirements ofGMP andother associatedcodes suchas thoseof goodlaboratory practiceGLP1and goodclinical practiceGCP;药品在一定程度上考虑和其他相关法规比如和的要求进行设计和开发；GMP GLPGCPb productionand controloperations are clearly specifiedinawritten formand GMPrequirementsare adopted;用书面的形式明确规定生产和控制操作并采用要求；GMP cmanagerial responsibilitiesare clearlyspecifiedin jobdescriptions;在岗位描述中明确规定管理职责；d arrangementsare madefor themanufacture,supply anduse of the correctstarting andpackagingmaterials;为正确的起始物料和包装材料的生产、供应和使用做出一些安排；e allnecessary controlson startingmaterials,intermediate products,and bulkproducts andotherin-process controls,calibrations,and validationsare carriedout;实施所有对起始物料、中间产品和最终产品的必要的控制和其他中间过程控制、校验和验证;fthefinished productis correctlyprocessed andchecked,according tothe defined procedures;按照规定的程序正确地加工和检查最终产品；g pharmaceutical products arenot soldor suppliedbeforetheauthorizedpersons seealso sections

9.11and

9.12have certifiedthat eachproduction batchhas beenproducedand controlledin accordancewith the requirements of the marketing authorization andany other在被授权的regulations relevanttotheproduction,control andrelease ofpharmaceutical products;人员确认每批产品已经按照上市许可和其他与药品的生产、控制和放行相关的法规生产和控制前药品不能销售或供应；h satisfactoryarrangements existtoensure,as faras possible,that thepharmaceuticalproducts arestored by the manufacturer,distributed,and subsequentlyhandled sothat qualityis maintainedthroughouttheir shelf-life;存在尽可能确保药品由生产企业储存、销售和后续处理的满意的安排以确保质量在它们整个货架期都得到保持；i thereis aprocedure forself-inspection and/orqualityaudit thatregularly appraisestheeffectiveness andapplicability of the qualityassurance system;有一个定期评价质量保证体系的质量和适用性的自检和/或质量审计程序；j deviations are reported,investigatedandrecorded;偏差被报告、调查和记录；k thereis asystemforapproving changesthat mayhave animpact onproductquality;有批准可能对产品质量有影响的变更；l regularevaluations ofthe qualityofpharmaceuticalproducts shouldbe conductedwith theobjectiveof verifyingthe consistencyoftheprocess andensuring itscontinuous improvement.应该执行对药品质量的定期评价，目标是确认工艺的一致性并确保其持续改进

1.3The manufacturermust assumeresponsibility forthe qualityofthepharmaceuticalproducts toensure thatthey arefit fortheirintended use,comply with therequirementsofthemarketingauthorization anddo notplace patientsat riskdue toinadequate safety,quality orefficacy.Theattainment ofthis qualityobjective istheresponsibilityof seniormanagementandrequires theparticipationand commitmentof staffin manydifferent departmentsand atall levelswithin thecompany,the company/s suppliers,andthedistributors.To achievethequalityobjective reliablytheremust bea comprehensivelydesigned andcorrectly implementedsystemof quality assuranceincorporatingGMPandquality control.It shouldbe fullydocumentedandits effectivenessmonitored.All partsofthequalityassurancesystem shouldbe adequatelystaffed withcompetent personnel,andshould havesuitable andsufficient premises,equipment,and facilities.生产企业必须承担药品质量的职责以确保它们适用于其既定的用途，符合上市许可的要求并且没有因为安全性、质量和功效不足对患者产生风险达到这个质量目标是高层管理者的职责需要公司内不同部门和所有层级的员工、公司的供应商和经销商的参与和承诺为了可靠地达到质量目标必须有一个全面设计和正确实施的质量保证结合和质量控制的体系这个体系应GMP该完全文件化并监控其有效性质量保证体系的所有部分都要配备足够的有资质的人员并且应该合适和足够的厂房、设备和设施

2.Good manufacturingpractices forpharmaceuticalproductsGMP药品的GMP

2.1Good manufacturingpractice isthat partofqualityassurance whichensures thatproducts areconsistentlyproduced andcontrolled tothequalitystandards appropriateto theirintendeduseandas requiredbythemarketingauthorization.GMP areaimed primarilyat diminishingthe risksinherentin anypharmaceuticalproduction.Such risksare essentiallyof twotypes:cross contaminationin particularofunexpected contaminantsand mix-upsconfusion causedby,for example,false labelsbeing puton containers.Under GMP:是质量保证的一部分，确保产品可以被持续地生产和控制以符合适用其预期用途和满足上GMP市许可的质量标准的主要目标是减少药品生产的固有风险这些风险基本有两个类型GMP交叉污染特别是非预期的污染和混乱混淆例如由贴在容器上的错误标签引起的在下GMPa allmanufacturing processesareclearlydefined,systematically reviewedinthe lightof experience,and shownto becapable ofconsistently manufacturingpharmaceuticalproducts ofthe requiredquality thatcomply withtheir specifications;所有生产工艺都要明确规定、根据经验系统审核并证明其能够有能力持续一致地生产要求符合它们标准的质量的药品；b qualificationand validationareperformed;进行确认和验证；c allnecessary resourcesare provided,including:提供所有必须的资源，包括i appropriatelyqualified andtrained personnel;合适的有资质并经过培训的人员；ii adequatepremises andspace;足够的厂房和空间；iii suitableequipment andservices;合适的设备和服务；iv appropriatematerials,containers andlabels;合适的物料、容器和标签；v approvedprocedures and instructions;批准的程序和工艺规程；vi suitablestorage andtransport;合适的储存和运输；vii adequatepersonnel,laboratories andequipment forin-process controls;足够的人员、实验室和设备用于中间过程控制；dinstructionsand proceduresare writtenin clearand unambiguouslanguage,specifically applicabletothe facilitiesprovided;用清晰并没有歧义的语言编写的说明书和程序e operatorsare trainedto carryout procedurescorrectly;培训操作人员正确地执行程序；f recordsare mademanually and/or byrecording instrumentsduring manufactureto showthat allthesteps requiredbythedefinedproceduresand instructionshave infact beentaken andthat thequantityandqualityoftheproduct areas expected;any significantdeviationsarefully recordedandinvestigated;在生产中做记录手工和/或通过记录仪以显示所有由规定的程序和规程要求的所有步骤都已经在事实上被执行，产品的数量和质量跟期望的一样；任何重大偏差都被完整记录并调查；g recordscovering manufactureand distribution,which enablethe completehistoryofabatch tobe traced,are retainedinacomprehensible andaccessible form;以可理解和可以获取的形式保存涵盖生产和销售的可以帮助追踪到一批产品的完整的历史的记录；htheproper storageand distributionoftheproducts minimizesany riskto theirquality;正确地储存和分发产品减少对其质量的风险；i asystem isavailable torecall anybatch ofproduct fromsale orsupply;可用的从销售或供应端召回任意批产品的系统；j complaintsabout marketedproductsareexamined,the causesofqualitydefects investigated,andappropriate measurestaken inrespect ofthe defectiveproductstoprevent recurrence.对已销售产品的投诉进行检查、调查质量缺陷的原因并采取适当措施避免缺陷产品再次出现。