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Q9’s Sample Process 示例流程
Initiate Quality Risk Management Process Risk Assessment Risk Identification 风险鉴定 Risk Analysis 启动质量风险管理
风险评估
风险分析
Risk Management Tools
Increasing Severity of Harm/Consequence 危害/后果严重程度的递增
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History of Pharmaceutical Quality Management
药品质量管理的历史
• Early 1970’s: added quality assurance & GMP 20世纪70年代早期：增加了质量保证和 GMP – Written procedures 书面规程 – Focus on production process 侧重于生产过程 – Defect prevention using process controls 通过过程控制来预防缺陷 • Advantages 优势 – Documented systems 书面记录的系统 – Improved quality 提高了质量
风险质量管理的效果/结 果
事件审核
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Concept: Link Back to Patient Risk 理念： 理念：与患者风险相联系
Opportunities to impact risk using quality risk management
使用质量风险管理影响风险的机会
Design 设计 Process 工艺 Materials 物料 Facilities 厂房 Manufacturing 生产 Distribution 销售 Patient 患者
ICH Q8, Q9, Q10
人用药物注册技术要求国际协调 会议
Brenda Uratani, Ph.D. Assistant Country Director (Drugs) FDA China Office, Beijing
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History of Pharmaceutical Quality Management 药品质量管理的历史
v2
design space v1
设计空间
v3 Design parameters and their intersection in a “design space” concept “设计空间“概念下的设 计参数及其相互作用
What is the chance (probability) of “falling outside” of the design space per unit time?
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QRM and the Design Space 质量风险管理（ 质量风险管理（QRM）和设计空间 ）
Risk analysts estimate probabilities of being outside (or inside!) of design limits, given various scenarios. 在不同情况下，风险分析师评估了在设计范围之外 的（或在之内！）的概率。
• 1960’s and before: Reliant solely on quality control 20世纪60年代以前：仅仅依靠质量控制 – Focused on the Product Specification 专注于产品质量标准 – Defect detection by end product testing 通过最终产品测试来检测缺陷 • Advantage 优势 – Sometimes detects defects 有时能检测出缺陷 • Disadvantage 劣势 – Faults found too late 故障发现为时已晚 – Often fails 经常失败 – High cost 成本高
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Pharmaceutical Quality System 药品质量体系
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ICH Q8, Q9, Q10
A harmonized pharmaceutical quality system applicable across the life cycle of the product emphasizing an integrated approach to quality risk management and science 开发一个和谐完整的制药质量体系，该体系强调风险管理与科学一体 化，并贯穿于整个 药物开发 – Q9, quality risk management 质量风险管理 – Q10, pharmaceutical quality system 药品质量体系
Risk Communication
Risk Evaluation
unacceptable
风 险 交 流
风险评估
不 合 格
Risk Control Risk Reduction
风 险 管 理 工 具
Risk Acceptance
风 险 控 制
风险降低
风险接受
Output / Result of the Quality Risk Management Process Risk Review Review Events
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A New Approach to Regulation 一种新的监管方法
U.S. FDA 21st Century GMP initiatives 美国FDA 21世纪GMP动议 • Process analytical technology (PAT) 过程分析技术 (PAT) Process understanding 过程的理解 – Control in-process rather than end-product testing 对过程 过程进行控制，而非对最终产品进行检测 过程 – Minimize risks of poor quality 质量低劣风险最小化 – Identify the parameters that are critical to product quality 确定对产品质量关键 关键的参数 关键 • Measure these parameters 测量 测量这些参数 • Control these parameters (feed back, feed forward) 控制这些参数（反馈、前馈） 控制
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Flexible Regulatory Approach 灵活的监管方式
• Regulators evaluate risk, based on: 监管机构在以下基础上评估风险: – Product and process design (Q8) 产品和工艺设计(Q8) – Measures to evaluate and manage risks (Q9) 评估和管理风险的措施(Q9) – Quality system implementation(Q10) 实施质量体系(Q10) • Regulators determine risk and modify level of oversight according for: 监管机构确定风险以及调整管理水平是根据: – Submissions 提交资料 – Post-approval change review 批准后变更回顾 – GMP inspections GMP 检查
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ICH Q9 “Quality Risk Management” “质量风险管理” 质量风险管理” 质量风险管理
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Q9 Overarching Principles 总体原则
• “The evaluation of the risk to quality should be based on scientific knowledge and ultimately link back to the protection of the patient; and 评估质量风险应基于科学知识并最终同对病人的保护联系起来。 • The level of effort, formality, and documentation of the quality risk management process should be commensurate with the level of risk.” 投入的努力程度、管理的正式程度及文件管理水平应与风险水平相适 应。
“Systems” thinking
and methods!
“系统”的思维和方法
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Severity and Probability Risk 严重程度和概率 风险
Increasing Probability of Occurrence 发生概率的递增
High Risk
Medium Risk Low Risk
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Q8 Concepts 概念
• Information from pharmaceutical development studies is the basis for risk management (using Q9) 药物开发研究过程中所获得的信息是风险评估的基础（用Q9）。 – Identify critical parameters, which carry risk 识别有风险的重要参数 • This assessment helps define the “design space” 这项评估有助于定义“设计空间” – Multidimensional combination and interaction of input variables (e.g., material attributes) and process parameters that have been demonstrated to provide assurance of quality 已被证明可以保证质量的输入变数（如原料）和工艺参数的多维 结合及其相互作用。