Mitigating Deficiencies in Evidence during Regulatory Assessments of Advanced Therapies: A Comparative Study with Other Biologicals
Mitigating Deficiencies in Evidence during Regulatory Assessments of Advanced Therapies: A Comparative Study with Other Biologicals
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DOI：
10.1016/j.omtm.2020.05.035
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发表时间：
2020-09-11
影响因子：
4.7
通讯作者：
Abou-El-Enein, Mohamed
中科院分区：
文献类型：
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作者：
Elsallab, Magdi;Bravery, Christopher A.;Abou-El-Enein, Mohamed
先进治疗药品 (ATMP) 包括细胞疗法、基因疗法和组织工程产品，为各种严重和衰弱疾病提供了多种新颖的治疗方法。迄今为止，几种先进疗法已获得针对多种适应症的营销授权。然而，部分产品的市场表现令人失望，导致其退出。产品上市时的质量、安全性和功效的现有证据对其市场成功起着至关重要的作用。为了评估先进疗法上市许可提交的证据是否充分，并将其与更成熟的生物产品进行比较，我们对 ATMP 和其他生物制品之间的监管提交进行了匹配比较。我们对监管反对意见和与预期数据要求的偏差进行了定量评估，分别作为证据充分性和监管灵活性的指标。我们的结果表明，无论产品类型如何，产品制造都充满挑战。先进疗法在提交的临床数据中显示出严重缺陷。提交的非临床数据包从监管灵活性中受益最多。此外，ATMP开发商需要在批准后阶段遵守更多承诺，这可能会增加市场表现的压力。减轻未来产品开发中观察到的此类缺陷，可以利用其市场成功的潜力。
Advanced therapy medicinal products (ATMPs) comprising cell therapy, gene therapy, and tissue-engineered products, offer a multitude of novel therapeutic approaches to a wide range of severe and debilitating diseases. To date, several advanced therapies have received marketing authorization for a variety of indications. However, some products showed disappointing market performance, leading to their withdrawal. The available evidence for quality, safety, and efficacy at product launch can play a crucial role in their market success. To evaluate the sufficiency of evidence in submissions of advanced therapies for marketing authorization and to benchmark them against more established biological products, we conducted a matched comparison of the regulatory submissions between ATMPs and other biologicals. We applied a quantitative assessment of the regulatory objections and divergence from the expected data requirements as indicators of sufficiency of evidence and regulatory flexibility, respectively. Our results demonstrated that product manufacturing was challenging regardless of the product type. Advanced therapies displayed critical deficiencies in the submitted clinical data. The submitted non-clinical data packages benefited the most from regulatory flexibility. Additionally, ATMP developers need to comply with more commitments in the post-approval phase, which might add pressure on market performance. Mitigating such observed deficiencies in future product development, may leverage their potential for market success.