报批美国FDA仿制药研发与相关问题探讨-Final.ppt

1、开发报批美国开发报批美国FDA的仿制药的仿制药与相关问题探讨与相关问题探讨上海复星普适医药科技有限公司上海复星普适医药科技有限公司上海复星普适医药科技有限公司上海复星普适医药科技有限公司何平何平何平何平内容提要内容提要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：案例研究开发仿制药的重要性 新药与仿制药新药与仿制药-NDA-NDA andand ANDAANDA开发仿制药与我国药物研发的海外战略开发仿制药与我国药物研发的海外战略药物制剂药物制剂目标主流市场目标主流市场开发仿制药的挑战性 开发仿制药

2、更具挑战性药物制剂药物制剂专利专利 仿制药的竞争仿制药的竞争仿制药厂之间的竞争仿制药厂之间的竞争由品牌药转成仿制药由品牌药转成仿制药仿制药竞争的方式HOW TO COMPETE Cost-IR ProductRaw MaterialsRaw MaterialsProcessProcessFinished ProductFinished ProductTechnology-Modified Release Products申报(仿制)新药的分类规范市场规范市场(FDA)1。P-I2。P-II3。P-III4。P-IV(1(1stst to file)to file)中国市场（中国市场（sFDA）

3、1 1类类类类2 2类类类类3 3类类类类4 4类类类类5 5类类类类6 6类类类类仿制药研发团队CONCEPT-1 BUILD UP A TEAMINFORMATIONFORMULATIONPRODUCTREGULATORYANALYTICALBIO-PHARMACEUTICALPROJECTLEGELDRUG DELIVERY SYSTEMS FOR ORAL SOLID FORMULATIONS-MRMATRIX SYSTEMSMATRIX SYSTEMSRESERVIOR SYSTEMSRESERVIOR SYSTEMSOSMOTICAL PUMP SYSTEMSOSMOTICAL P

4、UMP SYSTEMSCOMBO-SYSTEMSCOMBO-SYSTEMS缓控释给药的技术平台和给药系统CONCEPT-2 BUILD UP A SYSTEMProduct Development Roadmap仿制药的仿制药的研发过程研发过程 Quality Acceptably low risk of failing to achieve the desired clinical attributes Pharmaceutical Quality=f drug substance,excipients,manufacturing.QbD Product and process perfor

5、mance characteristicsscientifically designed to meet specific objectives,not merely empirically derived from performance of test batchesWhat is QbD(Quality by Design)?QbDQbD在制剂开发中怎么体现？在制剂开发中怎么体现？What is QbD?QbDQbD在制剂开发中怎么体现？在制剂开发中怎么体现？Pharmaceutical Quality by Design(QbD)QbD means designing and deve

6、loping QbD means designing and developing formulations and manufacturing processes to formulations and manufacturing processes to ensure predefined product qualityensure predefined product qualityUnderstanding and controlling formulation and Understanding and controlling formulation and manufacturin

7、g process variables affecting the manufacturing process variables affecting the quality of a drug productquality of a drug productEssential elements of QbD Definition of the quality target product profileHigh level quality aspects of the product:purity,drug release(dissolution/disintegration time),p

8、harmacokinetic profile,etc.Critical quality attributes(CQAs)for drug product Characteristics of DP which have impact on desired profile Conscious attempt to study and control Critical Process Parameters(CPPs)Identification of material properties and process parameters which haveeffect on product CQA

9、s Design Space:The multidimensional combination and interaction ofinput variables and process parameters that have been demonstrated to provide assurance of quality Identification of a control strategy for critical process parametersWhat is QbD?QbDQbD在制剂开发中怎么体现？在制剂开发中怎么体现？Raw MaterialsEquipmentEnvir

10、onmentOperatorsVariable Inputs x“Locked”Process=Variable QualityHow Did We Work in the PastWhat is QbD?QbDQbD在制剂开发中怎么体现？在制剂开发中怎么体现？Raw MaterialsEquipmentEnvironmentOperatorsUnderstood Variable InputsxUnderstood and Controlled Process=Predefined QualityFlexible Process Design SpaceHow Can We Work in

11、the FutureWhat is QbD?QbDQbD在制剂开发中怎么体现？在制剂开发中怎么体现？What is QbD?QbDQbD在制剂开发中怎么体现？在制剂开发中怎么体现？Raw MaterialsWet GranulationFluid Bed DryingBlendingCompressionProductDrug SubstanceExcipientsSourceAssayImpurities LODPS What is QbD?QbDQbD在制剂开发中怎么体现？在制剂开发中怎么体现？Raw MaterialsWet GranulationFluid Bed DryingBlen

12、dingCompressionWaterBinderTempSpray RateSpeedTimeP.SWhat is QbD?QbDQbD在制剂开发中怎么体现？在制剂开发中怎么体现？Raw MaterialsWet GranulationFluid Bed DryingBlendingCompressionWhat is QbD?QbDQbD在制剂开发中怎么体现？在制剂开发中怎么体现？Raw MaterialsWet GranulationFluid Bed DryingBlendingCompressionAir FlowTempRHShock CycleP.S.What is QbD?Q

13、bDQbD在制剂开发中怎么体现？在制剂开发中怎么体现？Raw MaterialsWet GranulationFluid Bed DryingBlendingCompressionFill VolumeRotation SpeedEnd Point(Time)Blend UniformityDensitiesAngle of ReposeWhat is QbD?QbDQbD在制剂开发中怎么体现？在制剂开发中怎么体现？Raw MaterialsWet GranulationFluid Bed DryingBlendingCompressionFeed FrameToolingPunch Pene

14、tration DepthCompression ForcePress SpeedFeeder Speed Quality Assessment under QbRQuestion-based Review(QbR)is a general Question-based Review(QbR)is a general framework for a science and risk-based framework for a science and risk-based assessment of product qualityassessment of product qualityQbR

15、contains the important scientific and QbR contains the important scientific and regulatory review questions toregulatory review questions to Comprehensively assess critical formulation and Comprehensively assess critical formulation and manufacturing process variablesmanufacturing process variables

16、Set regulatory specifications relevant to qualitySet regulatory specifications relevant to quality Determine the level of risk associated with the Determine the level of risk associated with the manufacture and design of the productmanufacture and design of the productExamples of QbD questions under QbR Control of Drug Substance What is the drug substance specification?Does it include all the critical drug substance attributes that affect the manufacturing and quality of the drug product?(2 page