Module232025

5/7/2025

Variability in PK and PD across paediatric populations by size, age, maturation complexity identifying the optimal dose for an investigational medicine. • Clear strategy on how to select the optimal dose for a trial protocol or product label is essential to maximize the safety, effectiveness and tolerability of medicines for paediatric use.

Dose selection

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• Understanding of dose/exposure – Response (in relations to safety, tolerability, biological activities and effectiveness) is essential  No requirement to establish a E-R curve in peadiatrics and does not preclude the use of exposure matching for dose selection  Aim to target exposures in children to those known to be efficacious/safe in adults  Most biologically active dose in oncology/rare diseases  Dose ranging data may be needed – clinical endpoint/biomarker response  Incorporation of realistic level of variability per each age group • Modelling and simulation approaches increasingly used  PBPK-PD modelling is increasingly used to predict drug effects. • Need some paediatric PK data for confirmation of dose selection assumptions  Population PK modelling using sparse sampling  The proposed dosing regimen should be re-evaluated through simulation techniques

Dose selection

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