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. Robust physiologically-based pharmacokinetic (PBPK) models have the potential to enhance dose selection in these situations. While PBPK modeling has gained momentum to support pediatric dose selection in commercial drug development, the opportunity for PBPK modeling to support dose selection in investigator-initiated research or clinical care in both children and pregnant women has not been fully explored. Furthermore, the use of PBPK modeling in global health drug development is underused. A major roadblock to the use of PBPK in these settings is the gap between the modeling and simulation community and healthcare professionals who make recommendations for dosing in children and pregnant women in real-life scenarios.
The objectives of this LinkedIn Live session are to describe how PBPK modelling can be used to support dose finding in clinical and research scenarios and discuss the necessary framework for implementation.
Mark R. Lovern, PhD
Sr. Vice President, Integrated Drug Development
Mark has over 15 years of experience applying modeling and simulation toward optimally informing drug development decision-making. Mark’s work history has been split between pharmaceutical companies such as GSK and UCB, and companies that support the biopharmaceutical industry. He has also taught over 50 technical training workshops on modeling tools and methodology. His most recent therapeutic area experience has been with infectious disease and autoimmune disorders.
Karen Rowland Yeo, PhD
Senior Vice President, Client & Regulatory Strategy
Since 2002, Karen has led projects relating to the extrapolation of in vitro data to predict in vivo pharmacokinetics in humans. This has included development and implementation of the models into the Simcyp Simulator. Her specific research interests include physiologically based pharmacokinetic modeling and prediction of drug-drug interactions.
Senior Program Officer, Bill & Melinda Gates Foundation
Ping obtained his BS in Pharmacy from Beijing Medical University in China in 1994, and his PhD in Pharmaceutics from University of Washington in Seattle, WA, USA in 2002. Since then, Ping has worked in pharmaceutical and biotech industries as a DMPK scientist and a clinical pharmacologist (Pfizer, Sonus and Amgen). In 2008, he joined the Office of Clinical Pharmacology at US Food and Drug Administration (FDA). Over 9 years at FDA, he became an Expert Reviewer by leading the agency’s first PBPK (physiologically-based pharmacokinetic modeling) Program, reviewing more than 200 PBPK submissions in IND/NDA/BLAs, championing PBPK regulatory research, drafting the agency’s first PBPK guidance, and liaising with other regulatory agencies (UK, Europe, and Japan) on harmonizing the assessment of PBPK analyses. In 2017, Ping joined the Bill & Melinda Gates Foundation in Seattle, WA. In his role as a Senior Program Officer of Quantitative Sciences, Ping designs and oversees the investments that apply quantitative pharmacology models to support research and development programs addressing global health concerns, especially in women and young children. Through these investments, he fosters collaborations among grantees to advance PBPK research, broaden PBPK applications, and advocate the recognition of sound model predictions as quality evidence in product development and clinical practice. Ping remains active in clinical pharmacology. He published more than 80 peer-reviewed articles and is currently an associate editor for the journal Clinical Pharmacology and Therapeutics-Pharmacometrics and Systems Pharmacology.
Saskia de Wildt
Professor of Clinical Pharmacology, Radboud University
Professor Saskia de Wildt is Chair of Clinical Pharmacology and pediatric intensivist at Radboud University, the Netherlands. She has published over 190 peer-review international papers and received over 8 million euros in Principal Investigator research funding. Her research, largely supported by grants from ZonMW, EU and the Bill and Melinda Gates Foundation, aims to individualize drug therapy in children and pregnant women. In leadership roles as WP lead for Strategic Feasibility Advice and director of the Dutch trialnetwork PEDMED-NL, she contributes to IMI2 project Conect4children (140 million euros) which to build EU pediatric clinical trial infrastructure. She is also director of the Dutch and International Pediatric Formulary consortium.
Clinical Pharmacology Assessor, MHRA
Susan Cole is an Expert Pharmacokinetics Assessor and leads the Clinical Pharmacology group in the Innovative Medicine Group at the MHRA, the UK Regulatory Agency. Prior to joining the MHRA in 2012, Sue worked for 26 years at Pfizer in the UK in the field of Drug Metabolism and Pharmacokinetics. While in industry, Sue fulfilled a number of roles including: Head of the Preclinical Pharmacokinetics and Modeling group and as a Clinical Pharmacologist.
In the past, Sue was a member of the Pharmacokinetics Working Party, the Modeling and Simulation Working Group and the Scientific Advice Working Party at the European Medicines Agency and contributed to the guideline: Reporting of PBPK modeling and simulation. Sue is currently the lead investigator at the MHRA on a project with Bill and Melinda Gates Foundation: Evaluating physiologically-based pharmacokinetic (PBPK) modeling and simulations to inform drug dosing in pregnant women.