




已阅读5页,还剩31页未读, 继续免费阅读
版权说明:本文档由用户提供并上传,收益归属内容提供方,若内容存在侵权,请进行举报或认领
文档简介
ManagingPharmaceuticalQuality:RiskorUncertaintyManagement?,AjazS.Hussain,Ph.D.OfficeofPharmaceuticalScienceCDER,FDAPQRIWorkshopFebruary1,2005,WhatisQuality?,Whatispharmaceuticalquality?consistentdeliveryofthelabelperformanceandlackofcontamination.operationalzedviaasetofpre-specifiedqualityattributes(e.g.,specifications,limits)andthroughtheCGMPregulations.FDA,initsqualitydefinition,isstandinginforthecustomeranditisapparentthathealthcarepractitionersandpatientshighlyvalueanadditionaldrugattribute:productavailabilityGoodpharmaceuticalqualityrepresentsanacceptablylowriskoffailingtoachievethedesiredclinicalattributes.,ManagementGoals,ImprovingqualityandensuringavailabilityOptimaluseofourresourcesAsystemsapproachtoCMCreviewandCGMPinvestigationsBasedonknowledgeandprocessunderstandingAchieving“qualitybydesign”Demonstrating“scienceofdesign”Continuouslearningandimprovementthrough“manufacturingscience”,AnApproachforQualityRiskConnection,ConceptofQualitybyDesign(QbD)Productandprocessperformancecharacteristicsarescientificallydesignedtomeetspecificobjectives,notmerelyempiricallyderivedfromperformanceoftestbatchesCharacteristicsimportanttodesiredperformancemustbederivedfromacombinationofpriorknowledgeandexperimentalassessmentduringproductdevelopment.Fromthisknowledgeanddata,amultivariatemodellinkingproductandprocessmeasurementsanddesiredattributesmaybeconstructed.Clinicalstudywouldthenbeviewedasconfirmatoryperformancetestingofthemodel.,Woodcock,2004,ASystemsApproach,CMCReveiw,CGMPInvestigations,ScienceofDesign,ManufacturingScience,DeliverQualitybyDesign,StateofControlithastobebydesign,“MarketStandards”,ScienceofDesign+ManufacturingScience=QualitybyDesign,Risk/BenefitandQuality,ManagingPharmaceuticalQuality,Qualityofanewmolecularentity(apotentialdrug)Intrinsicpharmacologicalvariabilityaddsadditionaluncertainty)Variabilityintheextentandrateofdeliveryof“activemoiety”tothesitesofactionandvariabilityinthepharmacologicalqualitybydesignisthenthepriorknowledgeandwhateverdevelopmentdataisgenerated(heldatsite),Uncertainty,VariabilityandRisk,/cder/gmp/gmp2004/manufSciWP.pdf,Uncertainty?Variability?Risk?,Uncertainty,VariabilityandRisk,Procrusteanstandardshavetoaddress“worstcase”scenariosUncertaintyisnotrisk,currentlywehavenochoicebuttoforcethisequalityUncertaintyisreducedbyimprovingknowledgeWelearnwhattocontrolandthedegreeofcontrolnecessarytominimizeriskForcontinuousqualityimprovementweshouldfocusonimprovinguncertaintymanagementprocess,ExampleofaCMCRegulatoryDecision:AcceptabilityofaPostApprovalManufacturingProcessChange,OriginalNDAorANDA=CMCQualityCapable?,Unstable,CorrectiveActionsEliminate“SpecialCause”,Reduce“CommonCause”Variability,Frequent,MajorOOS,Minor,OccasionalOOS,OntheContinuousImprovementPath,StateofControl,ImprovingUncertaintyManagement,DemandmanagementSpecifiedandprocrusteanstandardsE.g.,90%CI80-125%,in-processblenduniformitytests,.SOPs,.PassivemanagementQualitybyDesign,demonstrated“robustness”Canwebringasystems(CMCreviewandCGMPinvestigation)perspectivetobetterrecognizeacompanysabilitytoachievequalitybydesignandreducetheneedforpriorapprovalsupplements?ActivemanagementContinuouslearningandleveragingknowledgetocreateflexibilityMovetowardsarisk-basedapproachContinuousimprovement(qualityandproductivity),Opportunities,PATGuidancePATprovidesthepharmaceuticalcontextforLean,SixSigma!CPG7132c.08ComparabilityProtocolQualitySystemsApproachtoPharmaceuticalCGMPsICHQ8,(9?),(10?),PATGuidance,OpensthedoortorealizethebenefitsofconnectingFisherto-Shewartto-DemingFocusonprocessunderstandingleadingtocontrolofprocessend-point!Researchdata,CTD-P2Sec.QbD,“DesignSpace”=f(IntendedUse*Design*Control),JohnCBerridge,Q8Rapporteur(EFPIA).FDAManufacturingSubcommittee,July2004,KnowledgeBasedDecisions:RequireScientificGeneralizeableKnowledgethe“SUPACGAP”,SUPACChangeLevelsbasedonpriorknowledgefromthepharmaceuticalcommunity(AAPSSUPACWorkshops)+Research;Yetdifficulttogeneralizebecauseofmultifactorialaspects+lotofsubjectivity,LimitedinformationinNDA/ANDA,PriorknowledgewithinacompanyandamovetowardsmechanisticUnderstanding(ICHQ8isintendedtofillthisgap),Gap=Uncertainty,UncertaintyManagement:QbDuseofadvancedtechnologies,andtheroleofconformancebatchesintheproductlife-cycle.Afocusonthreefull-scaleproductionbatcheswouldfailtorecognizethecompletestoryonvalidation.,/cder/gmp/gmp2004/GMP_finalreport2004.htm#_Toc84065761,DraftGuidanceforIndustryQualitySystemsApproachtoPharmaceuticalCurrentGoodManufacturingPracticeRegulations,/cder/guidance/6452dft.doc,TraditionalgoalsNon-traditionalgoals(riskbased,flexibility,robustness,scalability,continuousimprovement,innovation,efficiency,.)CharacteristicsComplexity,uncertaintyRelationships(betweengoalsSubjecttoCGMPInspections(no-changeorvariation),Maintain“StateofControl”,“Fisher”-“Shewart”-“Deming”TheoryofexperimentaldesignStatisticalProcessControlTheoryofVariation,ByImprovingUncertaintyManagementwehavebeganaprocessofengineeringaproactivedecisionssystemforpharmaceuticalquality,Reactive(examples)TestingtodocumentqualityRepeatingdeviationandoutofspecificationinvestigationsWaitingforFDAguidancetosubmitANDAdemonstratingtherapeuticequivalenceofgenericproductsPotentialformultipleNDACMCreviewcyclesWaitingforFDAtoapproveapriorapprovalsupplementforprocessoptimizationandcontinuousimprovementeffortsFear,apprehension,Proactive(examples)Qualitybydesignandrealt
温馨提示
- 1. 本站所有资源如无特殊说明,都需要本地电脑安装OFFICE2007和PDF阅读器。图纸软件为CAD,CAXA,PROE,UG,SolidWorks等.压缩文件请下载最新的WinRAR软件解压。
- 2. 本站的文档不包含任何第三方提供的附件图纸等,如果需要附件,请联系上传者。文件的所有权益归上传用户所有。
- 3. 本站RAR压缩包中若带图纸,网页内容里面会有图纸预览,若没有图纸预览就没有图纸。
- 4. 未经权益所有人同意不得将文件中的内容挪作商业或盈利用途。
- 5. 人人文库网仅提供信息存储空间,仅对用户上传内容的表现方式做保护处理,对用户上传分享的文档内容本身不做任何修改或编辑,并不能对任何下载内容负责。
- 6. 下载文件中如有侵权或不适当内容,请与我们联系,我们立即纠正。
- 7. 本站不保证下载资源的准确性、安全性和完整性, 同时也不承担用户因使用这些下载资源对自己和他人造成任何形式的伤害或损失。
最新文档
- 建筑花纹拍摄方案设计说明
- 活动策划方案甘特图
- 食品云集营销方案
- 食杂店活动方案策划
- 直爬梯防护门施工方案
- 鼓楼区店面装修施工方案
- 考点攻克人教版八年级上册物理声现象《声音的特性》重点解析试卷(含答案解析)
- 考点攻克人教版九年级《电与磁》综合测评试题(含答案及解析)
- 2025-2030可穿戴设备持续身份认证技术市场教育成本分析
- 2024-2025学年广东省河源市紫金县七年级下学期期中语文试题
- 资产招商运营管理办法
- 2025年许昌禹州市特招医学院校毕业生招聘86名备考练习试题及答案解析
- 邮政管理毕业论文
- 2025年6月浙江省高考物理试卷真题(含答案解析)
- 血透室医院感染课件
- T-CNCIA 01039-2025 丙烯酸酯副产甲基磺酸钠
- (2025年标准)ktv保安合同协议书
- 英国乡土民居建筑解析
- 2025年秋沪科版八年级数学上册 第12章 函数与一次函数 综合测试卷(含答案)
- 2025年中小学生安全知识知识竞赛试题库及答案
- 2025年执业药师《中药学综合知识与技能》考试真题及答案解析
评论
0/150
提交评论