Safety of Biologics, Including Biosimilars: Perspectives on Current Status and Future Direction
Safety of Biologics, Including Biosimilars: Perspectives on Current Status and Future Direction
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DOI：
10.1007/s40264-018-0684-9
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发表时间：
2018-11-01
期刊：
影响因子：
4.2
通讯作者：
Trifiro, Gianluca
中科院分区：
文献类型：
--
作者：
Ingrasciotta, Ylenia;Cutroneo, Paola M.;Trifiro, Gianluca
近年来，高度创新和昂贵的生物制剂的上市改善了对自身免疫性疾病、癌症和慢性肾衰竭等高负担疾病的管理。一些广泛使用的生物制剂最近失去了或即将失去专利，从而为世界范围内越来越多的生物仿制药的营销开辟了道路，这些产品在质量、安全性和有效性方面与已获得许可的参考产品相似，从而可能节省制药支出。关于生物仿制药和参考产品之间的可互换性的许多争论仍在进行中，因为担心切换可能引起潜在的免疫原性，这可能导致缺乏效果和毒性。如果判断参考产品和相关生物仿制药是可互换的，那么用生物疗法成功治疗的患者理论上可以接受生物仿制药以控制成本。然而，监管机构对生物仿制药的可互换性和自动替代的立场存在很大差异。生物仿制药的获益-风险概况经常受到临床医生的质疑，因为上市前关于临床疗效和安全性的信息有限，尽管生物仿制药是基于与参考产品的可比性练习来获得生物仿制药批准的。然而，在欧洲首个生物仿制药获批后的10多年时间里，没有证据表明生物仿制药和原研药在安全性方面存在差异。在这种情况下，通过分析自发报告数据库和索赔数据库，对生物制剂和生物仿制药的上市后安全性进行评估是至关重要的。生物制剂药物警戒的一个重要问题是可追溯性，在自发性药物不良反应报告中指出品牌名称和批号，但这一要求并不经常得到解决。本综述旨在概述生物制剂的特点和潜在挑战，重点是上市后环境。
In recent years, marketing of highly innovative and costly biologics improved the management of high-burden diseases such as autoimmune diseases, cancers, and chronic renal failure. Several widely prescribed biologics have recently lost or will shortly lose their patents, thus opening avenues to the marketing of a growing number of biosimilars worldwide, which are products similar in terms of quality, safety, and efficacy to already licensed reference products, thus allowing for potential savings in pharmaceutical expenditure. Numerous debates about the interchangeability between biosimilars and reference products are still ongoing, owing to concerns about potential immunogenicity raised by switching, which may cause a lack of effect and toxicity. Patients successfully treated with biologic therapy may theoretically receive biosimilars to contain costs, if reference product and related biosimilar are judged as interchangeable. However, the positions of regulatory agencies on the interchangeability and automatic substitution of biologics with biosimilars are very different. The benefit-risk profile of biosimilars has been often questioned by clinicians owing to the limited amount of pre-marketing information on clinical efficacy and safety, despite biosimilarity being based on a comparability exercise with the reference product to gain the biosimilar approval. Nevertheless, after more than 10years of marketing from the first biosimilar approval in Europe, no proof of differences in terms of the safety profile of biosimilars and originators has been reported. In this context, post-marketing evaluation of both biologics and biosimilars safety profiles through analyses from spontaneous reporting databases and claims databases is crucial. An important issue for the pharmacovigilance of biologics concerns the traceability, indicating the brand name and batch number in spontaneous adverse drug reaction reports, but this requirement is not frequently addressed. This review aims to provide an overview of the characteristics and potential challenges in the safety profile assessment of biologics with a focus on the post-marketing setting.