FTA法与FMECA法在药品质量偏差调查中的应用

Application of FTA Method and FMECA Method in Drug Quality Deviation Investigation

目的:为我国制药企业开展药品质量风险防控提供新的思路和方法。方法:以某制药企业于2014年4月生产的某中药注射剂在热原项目检验结果的偏差调查为例,采用故障树分析法(FTA)和故障模式、影响及危害分析法(FMECA)对可能导致该偏差的所有影响因素(包括人、机、料、法、环)进行分析,并建立系统化的药品质量偏差调查和风险评估模式。结果与结论:分析表明,导致该批次中药注射剂在热原检查结果中出现偏差的直接原因,是实验用家兔实验间隔休息时间不符合规定,其根本原因是化验室为节约成本导致购入家兔数量不足(即"料"因素管理系统存在漏洞);此外,还发现实验操作的供试液配制和注射环节缺少复核、可追溯性差,配制环节存在引入热原和浓度错误的风险,注射环节存在操作误差的风险(即"法"因素管理系统存在漏洞)。经分别采取修订《实验室动物购入、管理制度》、强化培训与完善监督机制,以及增设供试液配制和注射操作步骤全程双人复核及视频监控、修订相关文件和记录等措施,有效防止了由于实验物料不符合规定引起检验结果出现偏差事件的再次发生,并避免了因检验过程中缺少复核等必要操作导致偏差的产生。可见,运用FTA和FMECA法可有效增强偏差调查的方向性,从而提升偏差调查过程的系统性和科学性,该模式具有实践推广价值。

OBJECTIVE： To provide new idea and method for the prevention and control of drug quality risk in pharmaceutical enterprises in China. METHODS： Taking the deviation investigation of pyrogen test for a TCM injection produced by a pharmaceutical enterprise in Apr. 2014 as an example. Influential factors （including staff, machine, material, method, environment） which could induce the deviation were analyzed by Fault tree analysis （FTA） method and Failure mode, effects and criticality analysis （FMECA） method. Both systematic drug quality deviation investigation and risk assessment model were established. RESULTS ＆ CONCLUSIONS： The direct reason for deviation of pyrogen test is that the experimental interval does not conform to requirements; root reason is that cost saving of laboratory leads to insufficient quantity of rabbits （i.e. there are loopholes in the management system of material element）. In addition, it is found that preparation and injection process of test solution lack of check and have poor traceability; preparation process has pyrogen and concentration error risk, and injection process has operating errors risk （i.e. there are loopholes in the element management system）. By revising Laboratory Animal Purchase and Management System, strengthening training and improving monitoring mechanism, adding recheck and video monitoring for preparation and injection steps of test solution by two persons, revising related documents and records, and other measures, this kind of deviation, which are caused by material not meeting the requirements, are effectively prevented from happening again. And, such deviations, which are caused by absence of recheck and other necessary operations in the process of inspection, are also effectively prevented from happening again. FMECA and FTA can effectively enhance the directionality of deviation investigation so as to improve the systematic and scientific property of investigation process. This mode has practical value