开发报批美国FDA的仿制药与相关问题

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,开发报批美国,FDA,的仿制,(fngzh),药与相关问题探讨,上海复星普适医药,(yyo),科技有限公司,何平,第一页，共四十一页。,内容提要,(ni rn t yo),开发仿制药的重要性和机遇,开发仿制药的挑战,申报仿制药的分类,仿制药研发团队,仿制药的研发过程,QbD,在制剂开发中怎么体现,研发,(,高难,),仿制药的一些体会,：,案例,(n l),研究,第二页，共四十一页。,开发,(kif),仿制药的重要性,新药与仿制药,-NDA,and,ANDA,开发仿制药与我国药物研发的海外,(hiwi),战略,药物制剂,目标,(mbio),主流市场,第三页，共四十一页。,开发,(kif),仿制药的挑战性,开发,(kif),仿制药更具挑战性,药物制剂,专利,仿制药的竞争,仿制药厂之间的竞争,由品牌药转成仿制药,第四页，共四十一页。,仿制药竞争,(jngzhng),的方式,HOW TO COMPETE,Cost,-IR Product,Raw Materials,Process,Finished Product,Technology,-Modified Release Products,第五页，共四十一页。,申报,(,仿制,(fngzh),),新药的分类,规范市场,(FDA),1,。,P-I,2,。,P-II,3,。,P-III,4,。,P-IV,(1,st,to file),中国,(zhn u),市场（,sFDA,）,1,类,2,类,3,类,4,类,5,类,6,类,第六页，共四十一页。,仿制,(fngzh),药研发团队,CONCEPT-1 BUILD UP A TEAM,INFORMATION,FORMULATION,PRODUCT,REGULATORY,ANALYTICAL,BIO-PHARMACEUTICAL,PROJECT,LEGEL,第七页，共四十一页。,DRUG DELIVERY SYSTEMS FOR ORAL SOLID FORMULATIONS-MR,MATRIX SYSTEMS,RESERVIOR SYSTEMS,OSMOTICAL PUMP SYSTEMS,COMBO-SYSTEMS,缓控释给药的技术平台,(pngti),和给药系统,CONCEPT-2 BUILD UP A SYSTEM,第八页，共四十一页。,Product Development Roadmap,仿制药的,研发,(yn f),过程,第九页，共四十一页。,Quality,Acceptably low risk of failing to achieve the desired clinical,attributes,Pharmaceutical Quality,=f drug substance,excipients,manufacturing.,QbD,Product and process performance characteristics,scientifically designed to meet specific objectives,not merely,empirically derived from performance of test batches,What is QbD,(,Quality by Design),?,QbD,在制剂,(zhj),开发中怎么体现？,第十页，共四十一页。,WhatisQbD?,QbD,在制剂,(zhj,),开发中怎么,体,体现？,PharmaceuticalQuality byDesign(QbD),QbD meansdesigningand developingformulations and manufacturingprocessesto ensurepredefined productquality,Understanding and controllingformulation andmanufacturingprocess variables affecting the qualityof adrugproduct,第十一页，,共,共四十一页,。,。,Essentialelements of QbD,Definitionof the qualitytarget productprofile,Highlevelquality aspects ofthe product:purity,drugrelease(dissolution/disintegration time),pharmacokineticprofile,etc.,Critical quality attributes(CQAs),for drug product,Characteristics ofDP whichhaveimpact ondesired profile,Conscious attemptto study and control,Critical Process Parameters(CPPs),Identification of,material propertiesand process parameters which have,effect onproduct CQAs,Design Space,:Themultidimensional combinationand interactionof,inputvariablesandprocess parameters that have been demonstrated toprovide assurance ofquality,Identificationof acontrol strategy forcriticalprocess parameters,Whatis QbD?,QbD,在制剂开发,中,中怎么,(znme),体现？,第十二页，,共,共四十一页,。,。,Raw Materials,Equipment,Environment,Operators,Variable,Inputs,x,“,Locked”Process,=,Variable Quality,How Did WeWorkin the Past,Whatis QbD?,QbD,在制剂开发,中,中怎么,(znme),体现？,第十三页，,共,共四十一页,。,。,Raw Materials,Equipment,Environment,Operators,UnderstoodVariableInputs,x,UnderstoodandControlledProcess,=,PredefinedQuality,Flexible Process Design Space,How Can WeWorkin the Future,Whatis QbD?,QbD,在制剂开发,(kif,),中怎么体现,？,？,第十四页，,共,共四十一页,。,。,Whatis QbD?,QbD,在制剂,(zhj,),开发中怎么,体,体现？,Raw Materials,Wet Granulation,FluidBedDrying,Blending,Compression,Product,第十五页，,共,共四十一页,。,。,DrugSubstance,Excipients,Source,Assay,Impurities,LOD,PS,Whatis QbD?,QbD,在制剂开发,(kif,),中怎么体现,？,？,Raw Materials,Wet Granulation,Fluid Bed Drying,Blending,Compression,第十六页，,共,共四十一页,。,。,Water,Binder,Temp,SprayRate,Speed,Time,P.S,Whatis QbD?,QbD,在制剂,(zhj,),开发中怎么,体,体现？,Raw Materials,Wet Granulation,Fluid Bed Drying,Blending,Compression,第十七页，,共,共四十一页,。,。,Whatis QbD?,QbD,在制剂,(zhj,),开发中怎么,体,体现？,Raw Materials,Wet Granulation,Fluid Bed Drying,Blending,Compression,Air Flow,Temp,RH,ShockCycle,P.S.,第十八页，,共,共四十一页,。,。,Whatis QbD?,QbD,在制剂开发,(kif,),中怎么体现,？,？,Raw Materials,Wet Granulation,Fluid Bed Drying,Blending,Compression,FillVolume,Rotation Speed,End Point,(Time),BlendUniformity,Densities,Angleof Repose,第十九页，,共,共四十一页,。,。,Whatis QbD?,QbD,在制剂,(zhj,),开发中怎么,体,体现？,Raw Materials,Wet Granulation,Fluid Bed Drying,Blending,Compression,FeedFrame,Tooling,PunchPenetration Depth,Compression,Force,PressSpeed,Feeder Speed,第二十页，,共,共四十一页,。,。,Quality Assessment underQbR,Question-basedReview(QbR)isa generalframeworkfora scienceand risk-basedassessmentof product quality,QbR contains the important scientific and regulatory reviewquestionsto,Comprehensivelyassess critical formulation and manufacturing processvariables,Set regulatoryspecificationsrelevant to quality,Determinethe levelof risk associated with the manufactureand designof the product,第二十一页,，,，共四十一,页,页。,Examples of QbDquestionsunder QbR,Controlof Drug Substance,Whatis the drug substance specification?Does itinclude all the criticaldrugsubstanceattributes that affect the manufacturing andquality of thedrugproduct,?(2pages),Drug Product,Whatattributesshould the drug pr