API开发生产和法规volume151质量控制和保证中英.docx
Qua1.ityAssuranceandContro1.质量保证和质量控制Michae1.c.VanderzwanPharmaceutica1.Technica1.,RochePhartnaCeUtica1.s,Base1.,Switzer1.andI. IntrodUCtiOn介绍235II. DefiningandAssuringtheQua1.ityoftheActivePharmaceutica1.Ingredient原料药质量的定义和保证240III. TheRegu1.ationsforQua1.ity质量监管245IV. TheQua1.ityContro1.andQua1.ityAssuranceDepartment质员控制和质量保证273AppendixA附录280目录1. INTRODUCnoN介绍4A. TheProduct产品4B. TheProcess工艺5C. TheFaci1.ities设备5D. ThePeop1.e人员6E. TheQua1.ityManagementDCPartInent质量管理部门6F. TheRegu1.atoryAuthorities监管机构7G. TheRegu1.ations法规7I1.DEFININGANDASSURINGTHEQUA1.I11OFTHEACTIVEPHARMACEUTICA1.INGREDIEW原料药质量的定义和质量保证9A. DefiningtheAPIQua1.ity原料药质量的界定9B. TestingtheAPIforItsDefinedAttributes原料药定义的属性测试1()C. DesigningQua1.ityintotheProcess工艺中的质量设计11D. Va1.idationoftheProcess工艺验证12E. Rea1.ity实际13in.theRegi1.ationsforQUA1.1.TY质Ja法规错误!未定义书签。Introduction:TheEmergenceofSpecificRegu1.ationsforAP1.S导言：AP1.具体法规的出现错误!未定义书签.1. ICHQ7SectionI:*'Introduction,第一局部：简介错误!未定义书签.2. ICHQ7ASection2:，'Qua1.ityManagement,第二局部质量管理错误!未定义书筌.3. ICHQ7ASection3:''Personne1.''第：局部人於错误!未定义书签.4. ICHQ7Section4:,4Bui1.dingsandFaci1.ities,第四局部厂房和设施错误!未定义书签.5. ICHQ7ASection5:i'ProcessEquipment,第五局部工艺设备幡误!未定义书签。6. ICHQ7.ASection6:,4DocumentsandRecords'第六局部文件和记录错误!未定义书签.7. ICHQ7Section7:*Materia1.sManagement,'第7局部物料管理298. ICHQ7ASection8:*4ProductionandIn-ProcessContro1.s,第8局部产品和过程控制329. ICHQ7ASection9:''PackagingandIdentification1.abe1.ingofAPIsandInteEediate8''第9局部原料药和中间体的包装和标识标签3410. ICHQ7ASection10:4*StorageandDistribution*'储存和发运11. ICHQ7ASection11:'*1.aboratoryContro1.s*'第11局部实验室拄制3612. ICHQ7ASection12:''Va1.idation''3713. ICHQ7ASection13:，'ChangeContro1.*,第13局部变更控制4114. ICHQ7ASection14:*RjctionandRe-UseofMateria1.s*'第14局部物料的拒收和再用4315. ICHQ7ASection15:''CoP1.aint8andReca1.1.s,第15局部投诉与召回4616. ICHQ7ASection16:'*ContractManufacturers(Inc1.uding1.aboratories)''第16局部协议制造商(包括实验室)47IV.THEQUA1.I11CONTRO1.ANDQUA1.ITYASSURANCEDEPARTW质量控制和质量保证部481. INTRoDUCr1.ON介绍Thequa1.ityofactivepharmaceutica1.ingredients(APIs)isdefinedasmeetingtheappropriatespecificationsfortheAPIandbeingproducedinafaci1.itycomp1.iantwithICHguide1.ines*'Q7A''andFD,scurrentgoodmanufacturingpractices(cGMPs)regu1.ations.Mostcountriesregu1.atethemanufactureofAPIs.Theseregu1.ationsrequireatota1.systemsapproachtoassuringanAPIhastheHppropriate1.eve1.ofqua1.ity.A1.1.ComPOnen1.Sinthissystemmustbeproper1.ydesigned,va1.idated,maintained,andoperatedtoa1.1.owthemanufacturertoassuretheAPIconsistent1.ymeetsqua1.ityrequirements.Tponentsofthesystemaretheprocess,faciIities,andthepeop1.e.Thischapterconcernsthesecomponents,aswe1.1.astheproductqua1.ityitse1.f,theregu1.ations,andthequa1.itymanagement(QM)department.活性药物成分(APIs)的质量应被定义为符合相应的AP1.标准，并且正在建设中的设施应符合ICH指南'Q7A'和I；DA现行的动态药品生产管理标准(CGMP)的规定。大多数国家时原料药的生产制造都有规定。这些法规要求有一个总的系统方法来保证AP【的质量在适当水平。这个系统中的所有组件必须经过正确的设计,验证，维护和操作，以保证制造商的AP1.始终符合侦量要求。该系统中普遍的组件包含工艺过程、设施和人员。本章内容包括这些组件，以及产品质量本身，法规条例和质量管理部(QM)A. TheProduct产品Thequa1.ityofanAPIisdeterminedbytwofactors:itsconformancetopre-estab1.ishedspecificationsandwhetheritisproducedaccordingtoadocumentedva1.idatedprocessinacGMPcop1.ian1.faci1i1.y.TheP1mustpossessappropriatechemica1.andphysica1.attributestoassurethatitde1.iverstheintendedphamacoIogica1.effect.Thechemica1.attributesdescribetheappropriatepurityandimpurity1.imits.Impurityspecificationsareestab1.ishedfromc1.inica1.toxico1.ogica1.studiesandarea1.sobasedonreasonab1.eminimumsexpectedfromregu1.atoryauthoritiesandconsumers.Thephysica1.attributesdescribethenecessarycharacteristicsforre1.iab1.epharmaceutica1.processingintofina1.dosageforms.Theseattributesaredeterminedbyempirica1.evidencefromR)EUIa1.iOntria1.stoproduceuniformandstab1.edosageformsofadequatebioavai1.abi1.ity.AP1.的历量是由两个因素决定：是否与预先建立的标准相一致，是否在符合CGMP耍求的设施内并J1.根据成文的经验证的工艺过程生产出来的。.API必须具有适当的化学和物理属性，以确保它提供预期的药理学作用。化学属性描述了适当的纯度和杂质限度。杂质标准根据临床毒理学研究建立，同时基于从监管部门和消费者那里得到预期的合理最低值。物理属性描述了可躯药物加工成圾终剂型的必要特征。这些屈性由配方试验的经的证据确定，以生产具有足够生物利用度、均匀且稳定的利里。B. TheProcess工艺Thequa1.ityofthePIisdesignedintothemo1.ecu1.ethroughthedeve1.opmentofthefu1.1.manufacturingprocess,fromthe1.aboratorysca1.esyntheticprocessthroughtoendproduct.AP1.的质属通过全面的制造工艺的开展被设计成分子，从实险室规模的合成过程通向最终产品Thesyntheticprocessmustbedesignedtominimizeimpurities,especia1.Iythosethatprovedifficu1.ttoremoveinthe1.aststep.Thus,througheffectiveprocessdeve1.opment,yie1.dsaremaximized,wasteisminimized,andimpuritiesarenotformed,e1.iminated,orcertain1.yminimized.Thespecificcontro1.susedbythedeve1.opmenta1.chemisttoproducethehigh-yie1.d,hih-qua1.ityproductmustbedocumented;thisdocumentationformsthebusisfortheproofofconceptandfortheva1.idationreport.Innear1.ya1.1.countriestoday,regu1.atoryauthoritiesrequiretheAPItobeproducedfromadocumentedprocessthatre1.iab1.ymeetsa1.1.appropriatespecifications.ThiswasstrengthenedbytheissuanceandadoptionoftheInternationa
