Practical Aspects of Using PBPK Modeling to Support Model-Informed Dosing in Pregnant Women and Children: A Hands-On Workshop for Non-Modelers

Friday, September 16, 2022

10:00 AM – 4:00 PM ET

Co-Chair(s)

Saskia N. de Wildt, MD, PhD

Professor of Clinical Pharmacology
Radboud University Medical Center
Ping Zhao, PhD

Senior Program Officer
Bill & Melinda Gates Foundation
Jolien Freriksen, PhD

Postdoc
Radboud University Medical Center

Speaker(s)

Nada Abla Geiser, PharmD, PhD

Associate Director, Drug disposition and PBPK modeling
Medicines for Malaria Venture
Lisa M. Almond, PhD

Senior Director of PBPK Consultancy
Certara UK (Simcyp Division)
Susan Cole, BSc

Expert Clinical Pharmacology Assessor
MHRA
Paola Coppola, MSc

AstraZeneca
Marika A. de Hoop-Sommen, PharmD

Radboud University Medical Center
Rick Greupink, BSc, MSc, PharmD, PhD

Assistant Professor
Radboud university medical center
Trevor N. Johnson, MSc, PhD

Principal Scientist
Certara
Amita Pansari, MPH

Senior Research Scientist
Simcyp Division, Certara UK Ltd
Damian Roelofsen, MSc

Junior Researcher
Radboud University Medical Center
Karen Rowland Yeo, PhD

SVP, Client & Regulatory Strategy
Simcyp - Certara
Joyce E.M van der Heijden, MSc

PhD candidate
Radboud University Medical Center
Hedwig van Hove, MSc

PhD candidate
Radboud University Medical Center
Xinyuan (Susie) Zhang, PhD

Daiichi Sankyo, Inc.

Session Description

Because drug dosing information in pediatrics and pregnant women is often insufficient or scarce, sub-optimal use of medicines is common in investigator driven trials and in clinical practice. Physiologically-based pharmacokinetic (PBPK) models of medicines verified using data from adult and non-pregnant subjects, coupled with virtual physiology models representing children and pregnant women have the potential to enhance dose selection in these situations through simulations. While PBPK modeling has gained momentum to support pediatric dose selection in commercial drug development, the opportunity for PBPK to support dose selection in investigator-initiated research or clinical care in both children and pregnant women has not been fully embraced. The underusage of PBPK is more pronounced in global health drug development.

A major roadblock to the use of PBPK in these settings is the perceptions of the complexity of the approach that require special modeling expertise, and the lack of confidence in application of PBPK by many healthcare providers who are in need of optimal dosing for children and pregnant women in real-life situations. The workshop intends to fill the translational gap between the modeling and simulation community and decision makers at the forefront of global drug development and clinical care.

Learning Objectives

Understand basics of PBPK modeling, its utility and impact in drug development, and key considerations when applying these models to evaluate drug dosing in children and pregnant women.
Use PBPK models, through hands-on simulations to evaluate the impact of physiological changes on a drug’s disposition, and the implication of dose modification in these populations.
Discuss the necessary framework for implementing of model-informed dosing paradigm in drug development and clinical care.

Session Schedule

10:00 AM - 10:05 AM ET
Welcome and Introduction
Saskia N. de Wildt, MD, PhD and Ping Zhao, PhD

Session 1: General and Pediatric

10:05 AM - 10:10 AM ET
Session 1 Introduction
Jolien Freriksen, PhD

10:10 AM - 10:25 AM ET
What You Should Know About Contemporary PBPK
Karen Rowland Yeo, PhD

10:25 AM - 10:40 AM ET
Quantifying Ontogeny: What You Should Know About Contemporary Pediatric PBPK
Trevor Johnson, PhD

10:40 AM - 10:55 AM ET
Demo
Jolien Freriksen, PhD

10:55 AM - 12:00 PM ET
Hands-On Breakout Room #1: Dose-Selection in Young Children
All Speakers

12:00 PM - 12:30 PM ET
BREAK

12:30 PM - 1:15 PM ET
Hands-On #1 Case Studies: Report-Back from Each Group
Jolien Freriksen, PhD and Trevor Johnson, PhD

Session 2: Pregnancy

1:15 PM - 1:17 PM ET
Session 2 Introduction
Rick Greupink, PhD

1:17 PM - 1:32 PM ET
Virtual Pregnancy: What You Should Know About Contemporary Pregnancy PBPK Model
Amita Pansari, MPH

1:32 PM - 2:35 PM ET
Hands-On Breakout Room #2: Dose-Selection in Pregnant Women During the 3rd Trimester
All Speakers

2:35 PM - 2:45 PM ET
BREAK

2:45 PM - 2:55 PM ET
Doravirine case: What is the Value of PBPK Predictions in the Absence of Clinical Data in Pregnant Women?
Jolien Freriksen, PhD

2:55 PM - 3:05 PM ET
Hands-On Breakout Room #2 Discussion
All Speakers

3:05 PM - 4:00 PM ET
Regulatory and Clinical Considerations: Update on Collaborations to Advance Model-Informed Dosing in Special Populations
Susan Cole, BS and Saskia N. de Wildt, MD, PhD