A best practice framework for applying physiologically-based pharmacokinetic modeling to pediatric drug development

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Pediatric Pharmacology
• Computational Biology

Background:

• Physiologically-based pharmacokinetic (PBPK) models are increasingly utilized in drug development.
• These models are valuable for projecting pediatric clinical trial doses.
• However, PBPK models are not yet fully integrated into regulatory submissions for pediatrics.

Purpose of the Study:

• To review the current application of PBPK models in pediatric drug development.
• To advocate for expanded integration of PBPK model-informed approaches in regulatory guidance for pediatrics.
• To present best practice standards for PBPK model development and regulatory interaction.

Main Methods:

• Literature review of PBPK model applications in pediatric drug development.
• Analysis of current regulatory landscape for PBPK models in pediatrics.
• Synthesis of emerging data supporting PBPK model integration.

Main Results:

• PBPK models show broad application in projecting pediatric drug doses and can reduce the need for clinical studies.
• There is a growing body of evidence supporting the expanded use of PBPK models in regulatory submissions.
• Best practice standards are proposed to facilitate further development and interaction.

Conclusions:

• PBPK modeling is a valuable tool for pediatric drug development and regulatory decision-making.
• Expanded integration of PBPK models into regulatory guidance is warranted.
• Collaboration among regulators, industry, and modelers is crucial for advancing PBPK modeling standards.