雷保环 徐梦丹 邓剑雄 杨悦 陈文戈 朱鑫

中圖分类号 R95 文献标志码 A 文章编号 1001-0408（2021）08-0904-07

DOI 10.6039/j.issn.1001-0408.2021.08.02

摘 要 目的：为药品上市许可持有人（MAH）有效利用药品不良反应（ADR）报告数据，对生产质量风险进行主动监测与控制、开展药品生产风险管理提供技术方法。方法：通过建立三维风险矩阵、风险趋势模型，设计研发了基于ADR报告数据的MAH生产线风险预警系统，并根据某企业的ADR报告数据对系统的主要功能进行实例应用分析。结果：初步建立了MAH生产线风险预警系统，其主要框架包括数据来源与处理、模型构建（三维矩阵模型包括可能性指标、严重程度指标和敏感性指标等3个维度，风险趋势模型则根据产品生产批号编制原则设置）、结果输出与分析等三大模块，主要包含系统配置、生产线信号检测、可视化统计预警、ADR报告管理、标准数据管理等五大功能模块。通过某企业ADR报告数据的应用分析显示，该系统可实现对其生产线风险及时、主动地检测及预警，能较直观地反映其高风险生产线、品种及批号，与该企业品种的实际安全性情况相吻合。结论：该系统可帮助MAH利用ADR报告数据及时、主动地监测药品生产质量风险，排查高风险生产线、高风险品种、高风险批号的风险因素，辅助决策风险排查方向。

关键词 药品不良反应报告;药品上市许可持有人;生产线;风险预警系统

Development and Application of MAH Production Line Risk Warning System Based on ADR Report Data

LEI Baohuan1，XU Mengdan1，2，DENG Jianxiong3，YANG Yue4，CHEN Wenge5，ZHU Xin6（1. School of Clinical Pharmacy， Guangdong Pharmaceutical University， Guangzhou 510006， China; 2. NMPA Key Laboratory for Pharmacovigilance Technology Researoh and Evaluation， Guangzhou 510006; 3. Guangdong Pharmacological Society， Guangzhou 510080， China; 4. School of Pharmacy， Tsinghua University， Beijing 100084， China; 5. School of Mechanical and Electrical Engineering， Guangdong University of Technology， Guangzhou 510090， China; 6. Guangzhou Pinyi Technology Co.， Ltd.， Guangzhou 510095， China）

ABSTRACT   OBJECTIVE： To provide technical methods for marketing authorization holder （MAH） to effectively use the data of adverse drug reaction （ADR）， actively monitor and control the production quality risk， and carry out drug production risk management. METHODS： Through establishing three-dimensional risk matrix and risk trend model， the risk early warning system of MAH production line based on ADR report data is designed and developed; the main functions of the system were applied and analyzed according to the actual ADR report data of a certain company.  RESULTS： MAH production line risk warning system was established preliminarily. The main framework included data source and and processing module， model construction module （three-dimensional matrix model included possibility index， severity index and sensitivity index， risk trend model was set according to the principle of product production batch number preparation）， and result output & analysis module. Five major functional modules included system configuratio， production line signal detection， visual statistical early warning， ADR report management and standard data management. The application and analysis of ADR report data of a certain company showed that the system could realize detection and warning of the companys production line risk， which intuitively reflected its high-risk production lines， varieties and batch numbers. It was consistent with the actual safety situation of the companys varieties. CONCLUSIONS： The system can help MAH make use of ADR report data to actively monitor drug production quality risks in a timely manner， investigate risk factors for high-risk production lines， high-risk varieties and high-risk batch numbers， and assist in decision-making on the direction of risk investigation.

KEYWORDS   Adverse drug reaction report; Marketing authorization holder; Production line; Risk warning system

近年来，我国每年药品不良反应（ADR）报告的上报数量呈快速增长趋势，ADR报告数量由2009年的63万份增长至2019年的近151.4万份，增长率约为140%[1-2]。……