Tavares Diana, Chien Hsiao-Tzu, Sheean Maria Elzbieta, Theunissen Peter, van Meer Peter, Van Malderen Karen
Paediatric Medicines Office, European Medicines Agency, Amsterdam, Netherlands.
Medicines Evaluation Board, Utrecht, Netherlands.
Front Med (Lausanne). 2025 Feb 10;12:1537001. doi: 10.3389/fmed.2025.1537001. eCollection 2025.
Juvenile Animal Studies (JAS) may be warranted to ensure the safe clinical use of medicines for children. The ICH S11 guideline was developed to guide the need for and design of JAS, and proposes a weight-of-evidence (WoE) approach. We evaluated how the introduction of the guideline shaped the non-clinical strategy for paediatric medicines in the European Union. Our review included Paediatric Investigation Plans (PIPs) for 127 products approved between 2020 and 2023, along with the associated regulatory assessment and final non-clinical plans. Although in 12 of selected PIPs a JAS was already ongoing or completed at the time of submission, in all other cases (115/127), the PIP was submitted before the initiation of JAS. In 75% (86/115) of these procedures the discussions based on the ICH S11 WoE approach led to an agreement on the proposed non-clinical strategy. In approximately a quarter of PIPs, there was disagreement on the outcome of the WoE analysis leading to the addition (3%), modification (10%), or removal (11%) of JAS. Our review indicates that the implementation of ICH S11 facilitates science-driven discussions about the necessity and design of JAS within the broader non-clinical strategy. A thorough consideration of developmental aspects of the product's pharmacological target, the clinical relevance of notable toxicity findings, and the clinical context of the medicine's use fosters effective dialogue and improves regulatory alignment. The WoE approach in ICH S11 ensures that relevant safety information is generated to support paediatric drug development while balancing the principles of non-clinical replacement, reduction and refinement (the 3Rs).
开展幼年动物研究（JAS）对于确保儿童用药的临床安全使用可能是必要的。国际人用药品注册技术协调会（ICH）S11指南旨在指导JAS的必要性及设计，并提出了证据权重（WoE）方法。我们评估了该指南的引入如何塑造了欧盟儿科药物的非临床策略。我们的审查包括2020年至2023年期间批准的127种产品的儿科研究计划（PIP），以及相关的监管评估和最终非临床计划。虽然在选定的12个PIP中，在提交时JAS已经在进行或已经完成，但在所有其他情况下（115/127），PIP是在JAS启动之前提交的。在这些程序的75%（86/115）中，基于ICH S11 WoE方法的讨论导致就提议的非临床策略达成一致。在大约四分之一的PIP中，对WoE分析结果存在分歧，导致增加（3%）、修改（10%）或取消（11%）JAS。我们的审查表明，ICH S11的实施有助于在更广泛的非临床策略中围绕JAS的必要性和设计进行科学驱动的讨论。对产品药理靶点的发育方面、显著毒性发现的临床相关性以及药物使用的临床背景进行全面考虑有助于进行有效的对话并改善监管一致性。ICH S11中的WoE方法可确保生成相关安全信息以支持儿科药物开发，同时平衡非临床替代、减少和优化（3R）原则。
