Pediatric drug development: current landscape, challenges, and future directions

Pediatric drug development has seen significant progress through the implementation of extrapolation strategies incorporating modeling and simulation (M&S) techniques. The ICH E11A guideline provides a systematic framework for pediatric extrapolation, advocating for comprehensive assessments of disease characteristics, pharmacology, and therapeutic outcomes to determine the appropriateness of such methodologies. At the 2025 Pharmaceuticals and Medical Devices Agency (PMDA) workshop, stakeholders emphasized the importance of adopting such strategies to address drug lag and loss observed in Japan, as well as the necessity of establishing flexible consultation mechanisms early in the development process. Here, to illustrate M&S capabilities, physiologically-based pharmacokinetic (PBPK) modeling was employed using physiological data from Japanese pediatric populations to simulate PKs, with validation across 14 drugs indicating predictive accuracy within a 0.5-2.0-fold range of observed PK parameters. These results provide a basis for further validation of this population. Ultimately this approach intends to support dosage and administration in preparation for pediatric clinical trials in Japan, as well as to reinforce the scientific justification. Moreover, PBPK modeling enhances theoretical insights into predicting PKs for special pediatric populations with unique disease conditions and assessing drug-drug interaction risks, which are not amenable to prospective clinical trials. Achieving further progress in this field necessitates multidisciplinary collaboration among industry, regulatory agencies, academia, and healthcare institutions, with each party fulfilling its respective responsibilities to collectively advance pediatric drug development.