顾博士GenericDrug_CMCRequirement_2012Nov1报告.ppt

Quality by Design (QbD)质量源于设计 Definition Systematic approach to development that begins with predefined objectives and emphasizes product and process understanding and process control, based on sound science and quality risk management. 应用合理的科学方法和质量风险管理原则，始于预定产品质量的目标，着重于对产品和工艺的理解以及工艺控制的系统性的研究和开发方法。 Reference: ICH Q8(R)(2) Pharmaceutical Development, 2009 * * Quality by Design质量源于设计 Terminology Quality Target Product Profile 目标产品质量概况 Critical Quality Attributes 关键质量属性 Critical Material Attributes 关键物料属性 Critical Process Parameters 关键工艺参数 Risk Assessment 风险评估 Design Space 设计空间 Control Strategy 控制策略 QbD Approach Process understanding links Critical Material Attributes (CMAs) and Critical Process Parameters (CPPs) to Critical Quality Attributes (CQAs)/specifications and hence to the desired performance of the product 工艺研发应将关健物料参数，关健工艺参数与产品质量标准联系 Implementation of QbD, including establishment of Proven Acceptable Range (PAR), Operational Range (OR), development of design space and control strategy. 应用QbD建立被证明的接受范围，生产控制范围，设计空间，和控制策略等 * * QbD Approach QbD 原则的探讨 Defining Quality Target Product Profile (QTPP) Determine Critical Quality Attributes (CQAs) Link Critical Material Attributes (CMAs) and Critical Process Parameters (CPPs) to CQAs Perform risk assessment Develop a design space (DOE etc.) Design and implement a control strategy Manage product lifecycle, including continual improvement Minimum Elements for Manufacturing Process Development生产工艺研发中的最基本要求 Identifying potential CQAs associated with the product Defining an appropriate manufacturing process CPP, CMA, PAR, OR Defining a control strategy to ensure process performance and drug substance quality * Comparison of Process Development 工艺开发过程的比较 * 1 QbD Concept Approach Traditional Approach QTPP/CQA 2 Process Route Identification Process Route Identification 3 Piloting Scale-up and Process Optimization Piloting Scale-up and Process Optimization 4 Process Characterization CPP, CMA, PAR (OR