Physiologically-Based Pharmacokinetic Modeling to Support Pediatric Clinical Development: An IQ Working Group Perspective on the Current Status and Challenges

Pediatric drug development has historically lagged years behind adult programs due to ethical, logistical, and scientific barriers. This IQ Working Group publication demonstrates how physiologically-based pharmacokinetic (PBPK) modeling is reshaping that landscape by enabling smarter pediatric extrapolation, more confident first-in-children dose selection, and reduced reliance on extensive clinical trials. The paper reviews current applications of pediatric PBPK across therapeutic areas, from infectious disease to oncology, and outlines where PBPK offers distinct advantages over population PK, particularly in guiding dosing regimens, sampling strategies, DDI and food-effect assessment, and label extensions.

While pediatric PBPK has already accelerated access to therapies for children, the authors also highlight scientific gaps that must be addressed to unlock its full potential, especially for neonates and emerging treatment modalities. Critical needs remain around early-life absorption and GI physiology, tissue distribution (including CNS exposure), enzyme and transporter ontogeny, and the scarcity of clinical data for model qualification in the youngest patients. The publication calls for industry-wide collaboration to expand public datasets, integrate real-world data and microdose studies, and leverage modern machine learning techniques to advance pediatric PBPK and increase confidence in regulatory decision-making.