王佳域 柳鹏程 陈巧云 李明 黄倩倩 陈锦敏 孙骏

摘 要 目的：研究江蘇省大、中、小型药品生产企业的药物警戒工作现状，为不同规模企业的药物警戒工作开展提供参考。方法：通过问卷调查及检索相关网站，对江苏省内108家企业的药物警戒工作现状进行考察，调查不同规模企业的药物警戒情况（组织机构、人员及培训、药物警戒文件、计算机系统）、药品安全性监测情况（个例报道、定期安全性更新报告、上市后安全性研究）和药品风险管理情况（信号管理、风险管理计划、风险控制措施、药品安全性沟通），并分别提出建议。结果与结论：不同规模企业在组织机构设置（独立设置专门机构）方面无显著差异（P=0.60），大部分企业在独立设置药物警戒专门机构上的比例均不足五成，在人员及培训（负责人专职情况、专职人员数、其中医学及临床药学类人员数）、文件（制定培训管理制度、委托管理与重点监测相关规程）和计算机系统3个方面存在显著差异（P<0.05）;不同规模企业在个例报告的主要收集途径上无显著差异，但大型企业2019年自主报告数量（P<0.01）、针对定期安全性更新报告设有质量控制流程的比例（P=0.01）、近5年开展过上市后安全性研究的比例（P<0.01）均显著高于中、小型企业;大型企业（70.00%）和中型企业（84.38%）认为“缺乏技术指导原则”是影响信号管理的重要因素的比例高于小型企业（53.57%）（P=0.01）;大型企业（60.00%）和中型企业（50.00%）在近5年内开展过风险管理计划的比例高于小型企业（30.36%）（P=0.04）;大型企业（50.00%）在近5年内采取过说明书修订措施的比例高于中型企业（37.50%）和小型企业（25.00%）（P=0.05）;大型企业（70.00%）和中型企业（59.38%）针对药店药师实施沟通活动的比例高于小型企业（32.14%）（P<0.01）。整体而言，大型企业在药物警戒体系、药品安全性监测、药品风险管理等方面优于中、小型企业。大型企业在主动开展风险管理计划方面、中型企业在专职负责人方面、小型企业在药物警戒体系等方面均有一定程度欠缺。因此，笔者建议大型企业以有效管控品种风险为目标，主动加强风险管理;中型企业继续提升主体责任意识，加强药物警戒工作的资源投入力度;小型企业应切实提高重视程度，重点改善药物警戒体系及具体工作的合规性。

关键词 药物警戒;药品上市许可持有人;药品生产企业;企业规模;现状

ABSTRACT   OBJECTIVE： To study the current situation of pharmacovigilance work in large， medium and small-scale pharmaceutical manufacturers in Jiangsu Province， and to provide reference for the pharmacovigilance development of drug manufacturers with different scales. METHODS： The situation of pharmacovigilance work in 108 manufacturers in Jiangsu province was investigated through a questionnaire survey and related websites. The pharmacovigilance work （organization， personnel and training， document， computer system）， drug safety monitoring （case report， regular safety update report， post-marketing safety research） and drug risk management （signal management， risk management plan， risk control measures， drug safety communication） of different manufacturers were investigated to put forward the suggestions. RESULTS & CONCLUSIONS： There was no significant difference in the organizational structure （independently established specialized agencies） among manufacturers of different scales （P=0.60）. Most of the manufacturers had less than 50% of the proportion in the independent establishment of specialized institutions for pharmacovigilance. There was significant difference in personnel and training （situation and number of full-time staff in charge， medical and clinical pharmacy personnel number）， document （formulating training management system， entrusted management and key monitoring procedures）， computer system （P<0.05）. There was no difference in the main collection ways of case reports among manufacturers of different scales; however， the number of independent reports in 2019 （P<0.01）， the proportion of quality control process for regular safety update reports （P=0.01）， and the proportion of carrying out post-marketing safety research in recent five years （P<0.01） in large-scale manufacturers were all significantly higher than small- and medium-scale manufacturers. The proportions of large-scale manufacturers （70.00%） and medium-scale manufacturers （84.38%）， which considered “lack of technical guidelines” as an important factor affecting signal management， were higher than that of small-scale manufacturers （53.57%） （P=0.01）; the proportions of large-scale manufacturers （60.00%） and medium-scale manufacturers （50.00%）， which had carried out risk management plans in the past five years， were higher than that of small-scale manufacturers （30.36%） （P=0.04）; the proportion of large-scale manufacturers （50.00%）， which adopted the measures in recent 5 year， was higher than medium-scale manufacturers （37.50%） and small-scale manufacturers （25.00%）; the proportions of large-scale manufacturers （70.00%） and medium-scale manufacturers （59.38%）， which carried out communication for pharmacists， were higher than small-scale manufacturers （32.14%） （P<0.01）. Large-scale manufacturers outperformed small- and medium-scale manufacturers in terms of pharmacovigilance system， drug safety monitoring and drug risk management. Large-scale manufacturers had a certain degree of lack of initiative on performing risk management plans， medium-scale manufacturers on full-time staffs in charge， and small-scale manufacturers on pharmacovigilance system. So， it is recommended that large-scale manufacturers take effective control of variety risk as the goal and actively risk management; medium-scale manufacturers should continuously enhance the awareness of responsibility and improve the investment of resources on pharmacovigilance work; small-scale manufacturers should pay more attention to improving the pharmacovigilance system and the compliance of specific work.

KEYWORDS   Pharmacovigilance; Holder of drug marketing authorization; Drug manufacturers; Manufacturer scale;Current situations

近年来，以落实药品生产企业主体责任为目的的政策与举措不断出台[1-2]，企业在药品不良反应监测方面的意识和能力已有大幅提升，但其当前工作仍以“被动监测”药品不良反应/事件为主，主动监测及风险管理较为薄弱，同时大多数企业尚未建立贯穿药品全生命周期、以风险管理为核心的监测体系——药物警戒体系[3]。新修订《药品管理法……