Abstract：
This study assesses the use of population pharmacokinetics (PopPK) in supporting pediatric dosing of novel biological drug products. The labeling for biologic drug products approved by the US Food and Drug Administration (FDA) from 2002 until 2021 was reviewed to identify those with a pediatric indication. For the drugs with a pediatric indication, the dosing regimen(s) based on age groups, dosing strategy, the use of PopPK to support the dose, and the types of pediatric clinical trials were reviewed. Data were collected from FDA\'s review documents and product labels on the Drugs@FDA website, and as needed, more clinical trial details were collected from PubMed and clinicaltrials.gov. The role of PopPK analyses in dosing was captured when mentioned in the label or review as playing a role in selecting the approved pediatric dose and/or in verifying the adequacy of the studied dose to support labeling. Between 2002 and 2021, FDA approved 169 biological products, and 78 of 169 (46%) products have an approved indication for which the label contains dosing recommendations for pediatric use. For the 78 products approved in pediatrics, there was a total of 180 clinical trials that included pediatric patients. Phase 3 pediatric trials commonly supported pediatric approval and dosing for the reviewed products (64%, 50/78 products; 56.1%, 101/180 trials). PopPK analyses were reported to play a critical role in dose selection, prediction, and verification for 40 of the 78 products (51%), including informing pediatric dosing in the absence of pediatric data (e.g., drugs approved under animal rule), comparing exposures to the exposure range observed in adults, and informing alternative dosing strategies in certain age or body weight groups. PopPK analyses have been applied in a variety of ways to inform pediatric dosing and support extrapolation from adult data or other pediatric age groups for biologics. Understanding and learning from these past cases on the use of pharmacometrics tools to support pediatric dosing of biological products can inform future pediatric development programs.
摘要：
这项研究评估了群体药代动力学（PopPK）在支持儿科给药新型生物药物产品中的应用。对2002年至2021年美国食品和药物管理局（FDA）批准的生物药物产品的标签进行了审查，以识别具有儿科适应症的产品。对于有儿科适应症的药物，基于年龄组的给药方案，给药策略，使用PopPK来支持剂量，并回顾了儿科临床试验的类型。数据是从FDA的审查文件和产品标签上的药品@FDA网站上收集的，根据需要，更多的临床试验细节从PubMed和临床试验收集.当在标签或审查中提到PopPK分析在给药中的作用时，它在选择批准的儿科剂量和/或验证研究剂量是否足够支持标签方面发挥作用。从2002年到2021年，FDA批准了169种生物制品。169种产品中的78种(46%)具有批准的适应症,标签中包含儿科使用的给药建议.对于儿科批准的78种产品，共有180项临床试验包括儿科患者.第三阶段儿科试验通常支持儿科批准和审查产品的给药(64%，50/78产品；56.1%，101/180试验)。据报道，PopPK分析在剂量选择中起关键作用，预测，以及对78种产品中的40种(51%)的验证，包括在没有儿科数据的情况下通知儿科给药(例如，根据动物规则批准的药物)，将暴露与成人观察到的暴露范围进行比较，并告知某些年龄或体重组的替代给药策略。PopPK分析已经以多种方式应用，以告知儿科剂量，并支持从成人数据或其他儿科年龄组的生物制剂推断。从这些过去的案例中了解和学习使用药物计量学工具来支持儿科给药的生物制品可以为未来的儿科发展计划提供信息。
