Speakers: Brian Berridge (NIH), Andreas Baudy (Merck), Amy Pointon (AstraZeneca), Rhiannon Hardwick (BMS)
Organizers: Doris Zane (Gilead), Radha Sura (Gilead)
Date: 2022-10-21
Time: 8:30-13:00 Pacific Time
Registration fee: Free
Location: Online via zoom
Major Sponsor:
Vendor show vendors registered to date:
Registration: http://www.PBSS.org
Registration deadline:2022-10-20  (it will close sooner if the seating cap is reached)

About the Topic

MicroPhysiological systems (MPS) are complex in vitro models that mimic physiologically relevant functions of animal or human organs and tissues. MPS have the potential to predict both the efficacy and/or safety of new drugs. The intent of this workshop is to understand how MPS technologies, such as organ-on-a chip, are being applied during drug development, challenges to the adoption of MPS and regulatory considerations. This workshop will provide an introduction/overview to MPS, as well as a deeper dive into organ systems such as liver, cardiovascular and skin.

Microphysiological Systems in Drug Development- Opportunities and Challenges

B. R. Berridge, NIH

Concerns about the usefulness of animal studies in translational research generally but drug development more specifically have prompted the development of novel and innovative in vitro modeling platforms that offer opportunity to reduce our dependence on animal studies.  Complex in vitro modeling systems derived from human cells including spheroids, organoids and microphysiological systems are improving our ability to interrogate in vivo-relevant biology and pathobiology in non-animal systems.  Microphysiological systems are the current pinnacle of in vivo relevance in an in vitro system but with complexity comes challenges.  Though they continue to lack the systems-level biological complexity of a whole animal system, they can recapitulate tissue-level biology in meaningful ways.  These systems can be applied in a number of contexts to support drug development but require significant characterization, validation and qualification to engender the confidence in decision-making usually derived from animal studies.  Characterization and application of these systems will benefit from partnerships with usual purveyors of in vivo modeling platforms to ensure support for relevant decision-making.  Additionally, we’re likely to need a novel decision framework to support the use of novel modeling platforms.  This presentation will explore the opportunities, strengths and weaknesses of these rapidly evolving modeling systems.  We’ll additionally discuss approaches to building confidence and informing continued refinement of these technologies.

Increasing the Complexity of In Vitro Liver Models in Drug Development

Andreas Baudy, Merck

The liver is critical to consider during drug development because of its central role in the handling of xenobiotics, a process which often leads to localized and/or downstream tissue injury. Our ability to predict hu-man clinical safety outcomes with animal testing is limited due to species differences in drug metabolism and disposition, while traditional human in vitro liver models often lack the necessary in vivo physiological fidelity. To address this, increasing numbers of liver microphysiological systems (MPS) are being developed, however the inconsistency in their optimization and characterization often leads to models that do not possess critical levels of baseline performance that is required for many pharmaceutical industry applications.  In this presentation I will go over an industry guidance on best approaches to benchmark liver MPS based on 3 stages of characterization.  Additionally, I will describe the ideal MPS model, provide a perspective on currently best suited MPS contexts of use, highlight examples of the 5 major categories of advanced liver models, and go over the challenges that remain in the field.

Cardiovascular MPS and advance in vitro models: potential applications to cardiac safety

Amy Pointon, Safety Innovations, Clinical Pharmacology and Safety Sciences, AstraZeneca, Cambridge, UK

Cardiovascular safety finding encompass a range of perturbations covering ECG changes, haemodynamics and cardiac pathology.  Despite a comprehensive non-clinical cardiac safety screening cascade, potential safety signals are sometimes not detected until in vivo studies.  In order to improve translation, microphysiological platforms and advanced in vitro models designed to mimic specific physiological cardiac microenvironments are emerging.  These model systems offer us an opportunity to develop approaches that are suitable for the different context of uses throughout drug discovery and development.  As the cardiovascular system is composed of a complex set of biological process, one advanced model system is currently unlikely to fit all needs.  We will share some key characteristics an ideal cardiovascular safety model would have and consider how these flex depending on the context of use in which a model is being applied within and postulate which areas of cardiac safety could benefit most from these advanced model systems.  Two case studies of models developed/evaluated with different context of use will be shared, firstly the application of human cardiac 3D models for structural cardiotoxicity and secondly the potential application of MPS systems to define temporal pharmacokinetic-pharmacodynamic relationships. 

Collective Efforts of the IQ MPS Affiliate to Advance CIVM/MPS and Recommendations for Skin Model Development

Rhiannon N. Hardwick, Discovery Toxicology, Bristol Myers Squibb, San Diego, CA

Historically, drug discovery and development has relied primarily on assessing the efficacy, pharmacokinetics, pharmacodynamics, and safety of new molecular entities in 2D cell culture and animal models. This approach has proven useful over several decades and formed the foundational support for initiation of numerous clinical trials. However, considerable shortcomings have been identified, which has led to the continual search for more predictive, physiologically relevant models to limit clinical attrition due to lack of efficacy and/or safety issues. More recently, complex in vitro models (CIVM, e.g., spheroids, organoids, 3D tissues, etc.) and microphysiological systems (MPS, e.g., bioprinted tissues, organ-on-a-chip) have gained considerable interest among scientists and within the popular culture for their potential to reduce, refine, and perhaps in some cases, replace the use of animals in pharmaceutical testing. Yet despite the enthusiasm for such models, broad adoption across the industry with respect to use in decision-making within a pharmaceutical portfolio and regulatory submissions has been slow and cautious. The IQ MPS Affiliate was officially formed in 2018 as a subgroup of the International Consortium for Quality & Innovation in Pharmaceutical Development (IQ). This group of pharmaceutical scientists, with evolving membership over the years, has sought to identify opportunities and challenges in the implementation of CIVM/MPS while fostering the growth of these technologies. This presentation will focus on the collective efforts of the IQ MPS Affiliate including:  gaining a deeper understanding of the evolving use of CIVM/MPS within the pharmaceutical industry, sharing technical learnings between model developers and member companies, establishing a framework for collaboratively qualifying CIVM/MPS for specific contexts of use, facilitating dialogue between pharmaceutical scientists and global regulators on key aspects of CIVM/MPS in decision-making, and establishing recommendations for minimally expected functional capabilities of CIVM/MPS. The presentation will close with an example of the IQ MPS Affiliate efforts to provide technical recommendations for CIVM/MPS, highlighting the opportunities and future needs of skin models within pharmaceutical testing.

Brian Berridge is currently the Scientific Director of the Division of Translational Toxicology (DTT) at the NIH’s National Institute of Environmental Health Sciences.   He has responsibility for the scientific leadership and operational management of the intramural DTT which conducts hazard assessments of substances of public health concern, develops novel research methods and approaches as well as advances our understanding of toxicological mechanisms and modes of action.

Brian is an Oklahoma State University-trained veterinarian and American College of Veterinary Pathologists-boarded anatomic pathologist.  He has a PhD from Texas A&M University and post-doctoral training in comparative cardiovascular pathology from the Texas Heart Institute in Houston, TX.  Before joining NIH in 2018, Brian spent 17 years in the pharmaceutical industry at Eli Lilly and GlaxoSmithKline as a toxicologic pathologist and, subsequently, lead for animal research strategy at GSK.  While in the pharmaceutical industry, he led the collaborative IQ Consortium’s Microphysiological Systems Working Group which partnered with the NIH National Center for the Advancement of Translational Sciences to support the development and adoption of these innovative systems in drug development.  Since coming to NIH, he has championed and supported the expansion of complex in vitro modeling systems as a key research platform for the DTT and toxicology community more generally.  His major interest is in the effective use of both animal and non-animal modeling systems for the advancement of comparative and translational biomedical science.

Andreas R. Baudy, Ph.D. is an Assoc. Principal Scientist at Merck & Co., Inc. and a member of the ADME & Discovery Toxicology Department.  He received his B.S. in Biochemistry & Molecular Biology from the Pennsylvania State University in 2005 and PhD in Molecular Medicine from the George Washington University. He conducted post-doctoral studies at Genentech in the Biomedical Imaging Department developing imaging assays to support Translational Oncology.  

In 2013 he began work at Merck Research Laboratories in the Pharmacology department to develop high content imaging assays and soon after transferred to Safety Assessment.  Since then he has been conducting work on evaluating microphysiological systems and also leads a company-wide 3D Tissue Models group composed of multi-disciplinary scientists that aim to leverage advanced in vitro models to aid in drug development.

Amy Pointon is a Senior Director and Project Leader in Clinical Pharmacology and Safety Sciences at AstraZeneca.  She gained her PhD from the University of Leicester MRC Toxicology Unit, UK.  In 2009, she joined AstraZeneca, while at AstraZeneca, she has developed holistic cardiovascular safety strategies, in particular the development of in vitro approaches.  She is currently the cardiovascular safety target organ lead responsible for cardiovascular preclinical safety.

Rhiannon N. Hardwick, PhD, DABT, is a Scientific Associate Director in Discovery Toxicology at Bristol Myers Squibb, San Diego, CA, where she serves as a project toxicologist for discovery programs. She also leads a lab team with focus on the use of complex in vitro models and microphysiological systems in the identification and characterization of tox liabilities, as well as mechanistic in vitro and in vivo investigations. She is a Diplomate of the American Board of Toxicology, an active member of the Society of Toxicology and American College of Toxicology, on the Editorial Board for Toxicological Sciences, current Chair of the Cellular and Molecular Mechanisms of Toxicity Gordon Research Conference, and current Chair of the IQ Consortium Microphysiological Systems Affiliate. She maintains in active role in mentoring and outreach, is a guest lecturer for the University of Arizona College of Pharmacy and San Diego State University, and serves on the Washington State University College of Pharmacy and Pharmaceutical Sciences Industry Advisory Board. Dr. Hardwick completed her undergraduate studies at the University of Oklahoma as a McNair Research Scholar, graduate work at the University of Arizona College of Pharmacy under the guidance of Nathan J. Cherrington, and postdoctoral research at the University of North Carolina at Chapel Hill in the Curriculum in Toxicology.

Agenda

Note: This is an online meeting, The Zoom link will be sent to the registrants 1+ days before the event.