Sanofi R&D, Chilly-Mazarin, France.
AstraZeneca R&D, Paris, France.
Clin Ther. 2019 Dec;41(12):2630-2642. doi: 10.1016/j.clinthera.2019.10.006. Epub 2019 Nov 5.
European policy makers have provided a number of incentives for the development of medicines for orphan diseases as early as 1999 through the Orphan Regulation and created obligations for medicines developers to investigate their products in children through the Paediatric Regulation adopted in 2006. This article describes the challenges that developers of orphan medicines are facing with pediatric indications, discusses the interplay between the Orphan Regulation and the Paediatric Regulation, and provides some recommendations on how to optimize drug development under the current European Union regulatory framework.
This article discusses the European Union's Orphan Regulation, Paediatric Regulation, and the implications of the intersection of the regulations on the development of orphan medicines for pediatric use.
Although these regulations have been successful in meeting their objectives separately, different regulatory frameworks entail separate governance, multiple assessments, varying approaches and priorities to unmet medical needs, and joined-up regulatory process coordination. Better integration of regulatory pathways would therefore be helpful in stimulating more global drug development of pediatric orphan medicines, including optimizing the interaction between both regulations, using innovative drug development approaches while considering alternatives to randomized clinical trials, better identification and prioritization of unmet medical needs in pediatrics, and ensuring the alignment of regulatory processes.
Rare diseases are categorized as "orphan diseases" because their occurrence in a small number of patients means that, regardless of the apparent high unmet medical need, there is limited public and market interest to justify the high development risk and significant investment to develop new treatments. However, unexplored potential within the area, as well as a conducive regulatory environment, can further support the development of medicines to treat rare diseases, including for children.
早在 1999 年，欧洲政策制定者就通过《孤儿药法规》为孤儿病药物的开发提供了多项激励措施，并通过 2006 年通过的《儿科法规》为药物开发者规定了在儿童中研究其产品的义务。本文描述了开发孤儿药面临儿科适应症的挑战，讨论了《孤儿药法规》和《儿科法规》之间的相互作用，并就如何在当前欧盟监管框架下优化药物开发提出了一些建议。
本文讨论了欧盟的《孤儿药法规》、《儿科法规》，以及法规交叉对儿科使用孤儿药开发的影响。
尽管这些法规在各自的目标上取得了成功，但不同的监管框架需要单独的治理、多次评估、对未满足的医疗需求的不同方法和优先事项，以及联合监管程序协调。因此，更好地整合监管途径将有助于刺激儿科孤儿药的更全球化药物开发，包括优化这两项法规之间的相互作用，在考虑替代随机临床试验的情况下，采用创新药物开发方法，更好地确定和优先考虑儿科的未满足医疗需求，并确保监管程序的一致性。
罕见病被归类为“孤儿病”，因为它们在少数患者中发生，这意味着，无论明显的高未满足医疗需求如何，公众和市场的兴趣有限，无法证明开发新疗法的高风险和重大投资是合理的。然而，该领域内未被探索的潜力以及有利的监管环境可以进一步支持治疗罕见病的药物的开发，包括儿童用药。
