A decade of marketing approval of gene and cell-based therapies in the United States, European Union and Japan: An evaluation of regulatory decision-making
A decade of marketing approval of gene and cell-based therapies in the United States, European Union and Japan: An evaluation of regulatory decision-making
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DOI：
10.1016/j.jcyt.2018.03.038
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发表时间：
2018-06-01
期刊：
影响因子：
4.5
通讯作者：
Hoekman, J.
中科院分区：
文献类型：
--
作者：
Coppens, D. G. M.;de Wilde, S.;Hoekman, J.
随着基因和细胞疗法（GCT）的发展，人们对临床进展有着广泛的期望。然而，确定收益和风险是高度不确定的。我们通过比较美国（US）、欧盟（EU）和日本的监管评估程序，研究了不同司法管辖区之间GCT批准决策的差异。通过比较批准和上市后风险管理考虑的产品特征、证据和非证据因素，对18个评估程序的队列进行了分析。产品特性差异很大，只有三种产品在多个司法管辖区销售。在所有获批的GCT中，几乎有一半获得了孤儿药认定。总体而言，在美国和欧盟申请中，临床获益的确证性证据或适应症是明显的，而在日本，批准仅基于非确证性证据。由于科学不确定性和安全性风险，欧盟和日本要求开展大量上市后风险管理活动。欧盟和日本当局在审批决策时经常考虑未满足的医疗需求。这些意见强调了这两个管辖区实施的立法的效果，这些立法促进了对许可证发放采取适应性做法。在美国，最近对两种嵌合抗原受体-T细胞（CAR-T）产品的评估表明，在最近的改革下，GCT批准的趋势是更宽松的方法，而不是以前批准的二元决策方法。表明目前三大监管机构都愿意承担风险，批准具有科学不确定性和安全性风险的GCT，敦促其准确关注上市后风险管理。
There is a widely held expectation of clinical advance with the development of gene and cell-based therapies (GCTs). Yet, establishing benefits and risks is highly uncertain. We examine differences in decision-making for GCT approval between jurisdictions by comparing regulatory assessment procedures in the United States (US), European Union (EU) and Japan. A cohort of 18 assessment procedures was analyzed by comparing product characteristics, evidentiary and non-evidentiary factors considered for approval and post-marketing risk management. Product characteristics are very heterogeneous and only three products are marketed in multiple jurisdictions. Almost half of all approved GCTs received an orphan designation. Overall, confirmatory evidence or indications of clinical benefit were evident in US and EU applications, whereas in Japan approval was solely granted based on non-confirmatory evidence. Due to scientific uncertainties and safety risks, substantial post-marketing risk management activities were requested in the EU and Japan. EU and Japanese authorities often took unmet medical needs into consideration in decision-making for approval. These observations underline the effects of implemented legislation in these two jurisdictions that facilitate an adaptive approach to licensing. In the US, the recent assessments of two chimeric antigen receptor-T cell (CAR-T) products are suggestive of a trend toward a more permissive approach for GCT approval under recent reforms, in contrast to a more binary decision-making approach for previous approvals. It indicates that all three regulatory agencies are currently willing to take risks by approving GCTs with scientific uncertainties and safety risks, urging them to pay accurate attention to post-marketing risk management.