Please circulate and post School of Pharmacy Faculty of Medicine The Chinese University of Hong Kong Seminar on How “How to Improve the Widespread Use of Modeling and Simulation in Drug Discovery and Development” Presented by Dr. Michael B. Bolger Chief Scientist Simulations Plus, Inc. Lancaster, CA & Adjunct Professor of Pharmaceutical Sciences USC School of Pharmacy, Los Angeles Date: Wednesday, 14 October 2009, 4:30 p.m. – 5:30 p.m. Venue: Pharmacy Conference Room, 6/F, Choh-ming Li Basic Medical Sciences Building, The Chinese University of Hong Kong Abstract For decades, industries like aerospace and automotive have utilized modeling, simulation, and computer assistance in product design. Life science industries have been much slower to adopt modeling and simulation technology, probably due in part to the complexities of living systems. It is well known that product development failures due to pharmacokinetic issues were common in the 1980s and 90s. In order to address these issues, in 1996 we started development of software tools for modeling and simulation of the ADMET characteristics of candidate drug molecules. Simultaneously we developed tools for estimation of biopharmaceutical properties and for gastrointestinal simulation and physiologically-based PKPD modeling. This type of technology and an increased f awareness of ADMET i in the h ti l industry has issues i th pharmaceutical i d t h resulted i a d lt d in decrease i th percentage of d in the t f drug f il due to failures d t pharmacokinetic issues. The talk will present case studies using GastroPlusTM and ADMET PredictorTM that demonstrate the value of modeling and simulation in pharmaceutical development. We will discuss the evolution of the Advanced Compartmental Absorption and Transit (ACAT) model, the early incorporation of saturable gut metabolism and transport, the integration of estimated biopharmaceutical properties for a purely in silico simulation of Cp vs. time profile, and our development of a flexible framework for physiologically-based PK/PD in a variety of species and human age groups. We will briefly describe our current developments in oral cavity, pulmonary, and ocular delivery. Biographical Sketch Upon completion of his doctorate in Pharmaceutical Chemistry from the University of California at San Francisco in 1978 he joined the faculty of Pharmaceutical Sciences at the University of Southern California (USC) School of Pharmacy where he conducted research and teaching in medicinal chemistry and the computational aspects of drug discovery and development for 23 years. From 1987-1993, simultaneous with his academic duties, he was a founder and Director of Medicinal Chemistry at CoCensys Inc. There, he studied the chemistry and use of novel neuroactive steroids for treatment of anxiety, epilepsy, and sleep disorders. Drug candidates emanating from seven of his patents have been tested in Phase I and II clinical trials for petite mal epilepsy, sleep disorders, and migraine. As a faculty member at USC School of Pharmacy, his research was supported by several NIH basic science research grants and he published over 50 peer-reviewed publications. Currently, as Chief Scientist at Simulations Plus, Inc. (Lancaster, CA), he oversees a team of scientist / programmers at in the development of software programs (ADMET Predictor/Modeler, ClassPharmer, GastroPlus, DDDPlus, and MembranePlus) for estimation of biopharmaceutical properties, simulations of absorption and bioavailability, automated generation QSP/AR model building, in vitro dissolution, and cell culture permeability simulation. He was elected to the rank of Fellow of the American Association for the Advancement of Science in 1996.