GMP 良好生产规范

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GMP 是 《药品生产质量管理规范》（Good Manufacturing Practice）的英文缩写，是药品生产和质量管理的基本准则，旨在确保药品安全、有效、质量可控.



GMP is the abbreviation for Good Manufacturing Practice, which is the fundamental principle for drug production and quality management, aimed at ensuring the safety, effectiveness, and controllable quality of drugs

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GMP 的核心目标

✅ 防止污染、交叉污染、混淆和差错

通过系统化的管理，确保每一批药品都符合预定用途和注册要求。

The core objective of GMP✅  Prevent pollution, cross contamination, confusion, and errorsThrough systematic management, ensure that each batch of drugs meets the intended use and registration requirements.

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GMP 的基本原则（五大要素）

要素

核心内容

1. 人员（People）

- 所有人员需培训合格后上岗<br>- 明确职责，关键岗位（如质量负责人）需资质认证<br>- 健康管理（如定期体检）

2. 厂房与设施（Premises）

- 洁净区划分（A/B/C/D级）<br>- 空气净化系统（HVAC）<br>- 合理布局（人流、物流分开）<br>- 防止交叉污染设计

3. 设备（Equipment）

- 设备需验证（IQ/OQ/PQ）<br>- 定期维护与校准<br>- 清洁规程明确，防止残留

4. 物料与产品（Materials & Products）

- 原辅料、包装材料需检验合格<br>- 严格仓储管理（先进先出、状态标识）<br>- 成品放行前必须完成全项检验

5. 文件与记录（Documentation）

- “没有记录就没有发生”<br>- 所有操作必须有标准操作规程（SOP）<br>- 记录真实、及时、完整、可追溯

Basic Principles of GMP (Five Elements)
Core Content of Elements
1. Personnel - All personnel must be trained and qualified before taking up their posts<br>- Responsibilities must be clearly defined, and key positions (such as quality managers) require qualification certification<br>- Health management (such as regular physical examinations)
2. Premises - Cleanroom division (A/B/C/D levels)<br>- Air purification system (HVAC)<br>- Reasonable layout (separation of people and logistics)<br>- Design to prevent cross contamination
3. Equipment - Equipment needs to be validated (IQ/OQ/PQ)<br>- Regular maintenance and calibration<br>- Clear cleaning procedures to prevent residue
4. Materials&Products - Raw materials and packaging materials must be inspected and qualified<br>- Strict warehouse management (first in, first out, status identification)<br>- Full inspection must be completed before the release of finished products
5. Documentation - "No record, no occurrence"<br>- All operations must have standard operating procedures (SOP)<br>- Records must be truthful, timely, complete, and traceable

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GMP 的核心体系与流程1. 质量管理体系（QMS）

• 由质量管理部门独立行使职权。
• 质量受权人（QP）负责最终产品放行。
  

2. 验证与确认（Validation）

• 工艺验证：证明生产工艺能持续稳定生产出合格产品。
• 清洁验证：证明设备清洁后无交叉污染风险。
• 分析方法验证：确保检验方法准确可靠。
• 计算机化系统验证（CSV）：如LIMS、MES系统。
  

3. 变更控制（Change Control）

• 任何变更（工艺、设备、原料、场地）必须评估、审批、验证。
• 防止“随意改动”。
  

4. 偏差管理（Deviation）

• 实际结果偏离规定时，必须调查根本原因。
• 采取纠正与预防措施（CAPA）。
  

5. 纠正与预防措施（CAPA）

• 针对偏差、投诉、召回、审计发现等问题，系统性改进。
  

6. 产品年度质量回顾（PQR）

• 每年对所有产品进行质量趋势分析，评估体系有效性。
  

7. 供应商管理

• 对原辅料、包材供应商进行审计和批准。
  

The core system and process of GMP
1. Quality Management System (QMS)
The quality management department independently exercises its powers.
The Quality Authorized Person (QP) is responsible for the final product release.
2. Validation and Confirmation
Process validation: Prove that the production process can continuously and stably produce qualified products.
Cleaning verification: Prove that there is no risk of cross contamination after the equipment is cleaned.
Validation of analytical methods: Ensure the accuracy and reliability of the testing methods.
Computerized System Validation (CSV): such as LIMS and MES systems.
3. Change Control
Any changes (process, equipment, raw materials, site) must be evaluated, approved, and verified.
Prevent 'arbitrary modifications'.
4. Deviation management
When the actual results deviate from the regulations, the root cause must be investigated.
Take Corrective and Preventive Action (CAPA).
5. Corrective and Preventive Action (CAPA)
Systematically improve issues such as deviations, complaints, recalls, and audit findings.
6. Product Annual Quality Review (PQR)
Conduct quality trend analysis on all products annually to evaluate the effectiveness of the system.
7. Supplier Management
Audit and approve suppliers of raw materials and packaging materials.

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GMP 检查与认证

• 检查依据：NMPA组织飞行检查、日常监督检查。
• 检查重点：
  • 数据完整性（Data Integrity）
  • 偏差与变更控制
  • 清洁与防止交叉污染
  • 人员培训与资质
  • 记录真实性
    
• 处罚措施：
  
  • 警告
  • 限期整改
  • 罚款
  • 暂停生产
  • 吊销《药品生产许可证》
  • 刑事责任（如数据造假）
    

GMP inspection and certification
Inspection basis: NMPA organizes flight inspections and daily supervision inspections.
Key inspection points:
Data Integrity
Deviation and Change Control
Cleaning and preventing cross contamination
Personnel training and qualifications
Record authenticity
Punishment measures:
Warning
Deadline rectification
fine
Suspend production
Revocation of Drug Production License
Criminal liability (such as data falsification)

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国际GMP 体系对比

体系

地区/组织

特点

中国GMP

中国 NMPA

借鉴欧盟，强调全过程控制

EU GMP

欧盟 EMA

全球最严格，附录多，强调质量文化

cGMP

美国 FDA

“c”为current，强调动态合规，FDA检查严厉

PIC/S

国际药品认证合作组织

成员国互认，标准与EU GMP基本一致

WHO GMP

世界卫生组织

发展中国家参考标准，用于国际采购

✅ 中国GMP已与EU、PIC/S等基本接轨，出口药品需满足目标国GMP要求。

Comparison of International GMP SystemsRegional/organizational characteristics of the systemChina GMP and NMPA draw inspiration from the European Union, emphasizing full process controlEU GMP, EU EMA are the strictest in the world, with multiple appendices and emphasis on quality cultureCGMP US FDA "c" is current, emphasizing dynamic compliance and strict FDA inspectionsPIC/S International Pharmaceutical Certification Cooperation Organization member countries mutually recognize each other, and the standards are basically consistent with EU GMPWHO GMP World Health Organization Reference Standard for Developing Countries, Used for International Procurement✅  China's GMP has been basically aligned with EU, PIC/S, etc., and exported drugs must meet the GMP requirements of the target country.

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GMP 新趋势与挑战

趋势

说明

数据完整性（ALCOA+）

数据应满足：可归因、清晰、同步、原始、准确 + 完整、一致、持久、可用

连续制造（Continuous Manufacturing）

GMP需适应新生产模式

智能制造与数字化

MES、LIMS、AI在GMP中的应用与合规

供应链全球化

原料药境外生产监管挑战

质量文化（Quality Culture）

从“合规驱动”转向“文化驱动”

New Trends and Challenges in GMP
Trend Explanation
Data integrity (ALCOA+): Data should meet the following criteria: attributable, clear, synchronous, original, accurate+complete, consistent, persistent, and usable
Continuous Manufacturing GMP needs to adapt to new production modes
Application and Compliance of Intelligent Manufacturing and Digital MES, LIMS, AI in GMP
Global supply chain, challenges in overseas production supervision of active pharmaceutical ingredients
Quality Culture Shifts from Compliance Driven to Culture Driven