Utrecht Institute for Pharmaceutical Sciences-UIPS, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht, the Netherlands.
Drug Saf. 2012 May 1;35(5):417-27. doi: 10.2165/11597850-000000000-00000.
The characteristics of biopharmaceuticals may require a tailored approach to their safety management. However, information on what tools and methods are employed to assess the safety of biopharmaceuticals post-authorization is lacking.
This study investigates determinants that contribute to the post-authorization management of biopharmaceuticals.
A cohort study was performed including all centrally approved biopharmaceuticals for which a Direct Healthcare Professional Communication (DHPC) was issued during 1997-2009. Safety-related regulatory actions were defined as updates of the summary of product characteristics through type II variations. Determinants of these actions were identified based on publicly available data. Urgent variations, defined as variations accompanied by a DHPC, were compared with other, 'non-urgent', safety-related variations.
We identified 133 variations relating to 15 products, 24 urgent and 109 other variations. For 55% of urgent variations, spontaneous reports were the sole source of regulatory action, post-approval studies accounted for 33%, and 12% were based on other sources or combinations of sources. For the non-urgent variations, spontaneous reports were the sole source for 36%, post-approval studies for 28%, and 36% were based on other sources or combinations. Overall, most variations included safety issues categorized as 'infections and infestations' (33.1%), 'general disorders and administration site conditions' (25.6%), and 'neoplasms' (14.3%).
Determinants of urgent and non-urgent safety-related regulatory actions of biopharmaceuticals are largely similar. Spontaneous reports are an important pillar for both urgent and non-urgent actions and remain an important tool in the post-authorization safety management of biopharmaceuticals.
生物制药的特点可能需要针对其安全性管理采用定制方法。然而，关于在获得批准后用于评估生物制药安全性的工具和方法的信息却很缺乏。
本研究调查了促成生物制药获得批准后管理的决定因素。
进行了一项队列研究，纳入了所有在 1997 年至 2009 年期间获得中央批准的、发布了直接医疗保健专业人员沟通（DHPC）的生物制药。通过 II 类变更更新产品特性摘要的安全性相关监管行动被定义为安全相关行动。根据公开数据确定这些行动的决定因素。将紧急变更（定义为伴有 DHPC 的变更）与其他“非紧急”安全性相关变更进行比较。
我们确定了与 15 种产品相关的 133 种变化，其中 24 种为紧急变化，109 种为其他非紧急变化。对于 55%的紧急变化，监管行动的唯一来源是自发报告，批准后研究占 33%，12%基于其他来源或来源组合。对于非紧急变化，自发报告是唯一来源的占 36%，批准后研究占 28%，36%基于其他来源或来源组合。总体而言，大多数变化包括被归类为“感染和寄生虫病”（33.1%）、“一般疾病和给药部位状况”（25.6%）和“肿瘤”（14.3%）的安全问题。
生物制药紧急和非紧急安全性相关监管行动的决定因素基本相似。自发报告是紧急和非紧急行动的重要支柱，并且仍然是生物制药获得批准后安全性管理的重要工具。
