This webinar will cover “The Role of Model Master Files for Sharing, Acceptance, and Communication with FDA”, highlighted the desire for facilitating wider usage of models through implementation of MMF idea. The presentation will give some background, with a view to discuss what MMF is NOT, so people can get some idea on what might be considered as MMF!

Second part of the webinar will show-the utilization of PBPK modeling and simulation in organ impairment clinical trials.

This webinar is divided into three parts. First Amin is focused to extend our understanding, application and future discussions from a Recently published a report ((2024), Fang et al.) summarising the discussions of a symposium by the FDA and the Center for Research on Complex Generics (CRCG) to discuss the best practices for utilizing modeling approaches to support generic product development. The report, entitled ‘Role of Model Master Files for Sharing, Acceptance, and Communication with FDA”, highlighted the desire for facilitating wider usage of models through implementation of MMF idea. It was proposed that MMF can ensure best practices on application and ease the necessary cooperation among stakeholders. However, it was clear that perspectives on what constitutes MMF is widely variable within the modeling community. Hence, a subsequent workshop was scheduled for May 2024 to iron out the practical facets related to implementation of MMF. The presentation will give some background, with a view to discuss what MMF is NOT, so people can get some idea on what might be considered as MMF!

The second part (By Christine and Weize) of the webinar will focus on “Using Modeling and Simulation to Support Organ Impairment Clinical Trials”
The first part of this work was to conduct a retrospective analysis using a consistent PBPK modeling approach to determine the accuracy of organ impairment predictions using in-house compounds and recommend an internal strategy for OI PBPK application during drug development. Five compounds (and relevant metabolites) were examined retrospectively (5 with hepatic impairment studies, 1 with a renal impairment study) to better understand the utility of PBPK in supporting OI study design, dose selection, and drug labeling, and the learnings from the approach were subsequently used for prospective predictions.

Lastly, this work was to evaluate the feasibility of using PopPK or PBPK model-generated virtual controls to reduce or replace the enrollment of healthy control subjects in organ impairment studies. Dedicated organ impairment PK studies typically include a healthy control group matched for age, body weight, and gender to the enrolled organ impaired subjects to assess the unconfounded impact of organ dysfunction on drug disposition and exposure. However, enrolling a control group can be challenging due to ethical concerns, safety considerations, and restrictions due to matched demographics; therefore the model-based virtual control approach was explored to help reduce or replace the need of enrolling control subjects in OI PK studies.

Christine Bowman, Ph.D.

Christine Bowman is a Principal Scientist in the Drug Metabolism and Pharmacokinetics Department at Genentech, Inc. She is a DMPK project lead for discovery and development projects, and her research interests include improving in vitro to in vivo extrapolation with new in vitro methods and PBPK modeling. Prior to joining Genentech, Christine received her PhD from the University of California, San Francisco (PI: Dr. Leslie Benet) where she focused on improving hepatic clearance predictions.

Weize Huang, Ph.D.

Weize Huang obtained his PharmD and PhD degrees from the University of Washington - Seattle, where his PhD thesis focused on mechanistic PBPK modeling of renal disposition for drugs and metabolites. He is currently a principal scientist in the Clinical Pharmacology group at Genentech.

Amin Rostami, Ph.D.

The Institute of Scientific Information (ISI, Clativate) listed Amin as one of the world’s most highly cited researchers (under ‘Pharmacology & Toxicology’) in 2017. The work of Professor Rostami covers wide areas of drug development over the last 30 years, ranging from pharmaceutics (e.g. bioavailability and bioequivalence) to clinical pharmacology (e.g. mixture pharmacology of drug/metabolites), translational and systems pharmacology (e.g. quantitative proteomics of enzymes and transporter for in vitro to in vivo (IVIVE) scaling).

As the Director of Centre for Applied Pharmacokinetic Research (CAPKR) at the University of Manchester, Amin collaborates with many pharmaceutical companies with a view to transfer latest scientific applications into modern drug development. Amin was co-founder of two spin-off companies from the University of Sheffield (Simcyp Limited [now part of Certara Inc]) and Diurnal Limited [now part of Neurocrine Bioscience]). As a leader in the field of Physiologically-based Pharmacokinetics (PBPK) and Quantitative Systems Pharmacology (QSP), he is internationally recognized for his expertise in IVIVE to predict the behavior of drugs in human body and understanding the associated inter-individual variabilities. He was one of the founding editors of Pharmacometrics and System Pharmacology and serves on the Editorial Boards of several other journals.

As the Senior Vice President of Research & Development (SVP) and Chief Scientific Officer at Certara, he facilitates the incorporation and integration of the latest advances in translational modelling to bio-simulation platforms offered by Certara to its clients, with the aim of accelerating the development and regulatory approval of safer drug products and bringing them to the patients.