• “Systems Approach” “系统化方法”
• Quality System 质量体系 • Facilities and Equipment System
设施和设备系统 • Materials System 物料体系 • Production System 生产体系 • Packaging and Labeling System 包装和标签体系 • Laboratory Control System 实验室控制体系
/AboutFDA/CentersOffices/CDER/ucm095598.htm
What type of inspection can be done? 可以进行什么类型的检查？
• Full Inspection Option 全面检查方案 – Quality System plus (at least) three other systems 质量体系加（至少）三个其他系统
• Facilities设施 Major considerations when evaluating aseptic processing operations… 对无菌工艺操作评估需要重要考虑的因素…
• Building Management System (BMS) 建筑管理系统（BMS）
• Environmental Controls (Temp, RH, DP) 环境控制（温度、湿度、压差）
China - June 2011
Inspections… 检查 …
• Are FACT finding in nature 是事实性的调查结果
• Require EVIDENCE 需要证据
• Are REGUALTORY in nature 实质上是一种监管 – What is said could end up in court 所说的内容可能最终会在法庭上裁决
The Law says… 法律规定...
“to assure that such drug meets the requirements of this Act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.” • “并保证符合其声称或据称的鉴别和含量、质量和纯度特征的现行药 品生产质量管理规范操作和管理。”
• Qualification of System 系统确认
• Maintenance/Calibration of system and sensors 系统和传感器的维护/校准
Facilities and Equipment System 设施和设备系统
• Equipment设备
– Qualification 确认
• Accomplish necessary, additional questions/concerns listed in the inspection assignment (“For Cause” Inspection) 要完成必要的检查、其它问题/额外关注点见“追因”检查的检查任务 分配
The Law says... 法律规定...
• Complaints 投诉 – Procedures define responsibilities 建立规程明确责任 – Investigation Reports 调查报告
Quality System cont. 质量体系 续
• Deviations (Non-Conformances) / OOS 偏差（不合格项）/ 超规 – SOPs define responsibilities 建立SOP明确责任 – Investigation Reports 调查报告 – Conclusions – Final Disposition 结论-最后处置
• Explain how to identify and document inspection observations 讲解如何确定和记录检查到的内容
Compliance Program Guidance Manual 符合性项目指南手册
7356.002 “Drug Manufacturing Inspections” “药品生产检查”
• Initial 初始确认 • Re-evaluation -- after changes 再确认-变更发生后
*(Change Control Documentation) *(变更控制文件)
– Preventive Maintenance / Calibration 预防性维护/校准
• Accomplish what is necessary per the established, supporting Compliance Policy Guidance Manual 检查执行的程度依据 符合性方针指导手册 – 7356.002 “Drug Manufacturing Inspections” 7356.002 “药品生产检查” • “Systems Approach” “系统化方法”
• Require ORGANIZATION and TIME MANAGEMENT 需要组织和时间管理
Objectives of Inspection 检查的目标
• Conduct the inspection in accordance with FD&C Act and Current Good Manufacturing Practice (CGMP) Regulations 检查的执行依据《联邦食品，药品和化妆品法》(FD&C Act) 及现行 药品生产管理规范(CGMP) 条例
Packaging
& Labeling 包装和标签
Records 记录
• Tools for control of highly-variable parts of the manufacturing process…HUMANS 用以控制生产过程中具有高变化性的那一部分...人类
• “If you didn’t document it, then it didn’t happen…” “没有记录，就没有发生…”
The CGMP Regulation CGMP 法规
• CGMP for Finished Pharmaceuticals 对于成品药的现行药品生产管理规范（CGMP） 21 CFR Parts 210 and 211 – Establish “what to” do, not “how to” 确定 “要做什么, 而不是“如何做” • Minimal standards 最低标准 • Maximum flexibility 最大的灵活性 • Specific enough to address problems 具体到足以解决问题 – e.g., Penicillin contamination control 例如，青霉素污染控制 • Technology neutral 技术中立 • Scalable 可扩展性
Quality System 质量体系
• Annual Product Reviews (APRs) 年度产品回顾（APR） – Summary综述 – Specific information required by 21 CFR 211 21 CFR 211要求的具体信息 – Trends – “Snapshot 趋势 – “快照”
Conducting an FDA Inspection
执行FDA检查
Douglas A. Campbell
Compliance Officer – Senior Policy Advisor CDER / Office of Compliance 药品审批研究中心 / 执法办公室
Division of Manufacturing and Product Quality International Compliance Branch
• Change Control 变更控制 – Associated documentation referenced throughout the inspection (record review) 在整个检查引用的相关文件 (记录评审)
Facilities and Equipment System 设施和设备系统
Conducting an FDA Inspection: Objectives 进行FDA检查的目标
• “Systems Approach” “系统化方法” – 6 systems overview 6大系统概述 – Type of coverage: 覆盖类型: • Records we audit/review 记录审计/审评的内容 • Operations/practices 操作/规范
• Abbreviated Inspection Option 简化检查方案 – Quality System plus one other system 质量体系加一个其他系统
Materials 物料
Facilities &
Equipment 设施及设备
Production 生产
Laboratory 实验室
The CGMP Regulation CGMP法规
• Current Good Manufacturing Practice for Finished Pharmaceuticals 对于成品药的现行药品生产管理规范（CGMP） 21 CFR Parts 210 and 211
– Substantive实质性 • Force and effect of law 法律效力