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Wednesday, June 16
7:30 am Continental Breakfast Break-Out Discussions
Choosing the Right Criteria and Assays for Testing High-Risk Biologicals
Moderator: Noël Dybdal, Ph.D., D.V.M., Associate Director, Principal Scientist, Safety Assessment, Genentech, Inc.
Correlating in vitro Data with Clinical Outcomes
Moderator: To be announced
Evaluating New Tools for Assessing Preclinical Safety
Moderator: Gary Gintant, Ph.D., Senior Group Leader, Department of Integrative Pharmacology, Global Pharmaceutical Research & Development, Abbott Laboratories
New Regulatory Landscapes for the Prospective Exclusion of Unacceptable Cardiovascular Risk: FDA and EMA Documents addressing the Development of New Antidiabetic Drugs for Type 2 Diabetes Mellitus
Moderator: J. Rick Turner, Ph.D., Senior Scientific Director, Cardiac Safety Services, Quintiles
The employment of automated algorithms for reading ECG intervals is receiving much current attention. There are strong opinions in favor and not in favor of this methodology. Attendees will be invited to share their experiences and thoughts.
8:30 Chairperson's Remarks
Ernest D. Bush, Ph.D., Vice President & Research Director , Cambridge Healthtech Associates
8:40 ASAT: The Netherlands Program to Develop Alternatives to Animal Testing for Drug Safety
Michael Liebman, Ph.D., President/Managing Director, Management, Strategic Medicine, Inc.
ASAT is a government-funded program that supports the development of alternative methods for evaluating drug safety beyond animal models. Althought it's ultimate goal is the elimination of animal testing, it is focused on optimizing the selection and utilization of animal models using computational and experimental methods. A critical component of the program centers on improving the ability to take pre-clinical testing results and move them successfully into man by early detection of side-effects and/or risk.
9:10 Moving the Safety Elephant: The Challenges in Getting from the Good Idea to Business as Usual
David Cook, Ph.D., Associate Director, Pharmacology and Toxcicology, Astra Zeneca R&D
The “elephant in the corner” when considering new approaches in drug safety is the fact that the assessment of drug safety is an activity driven by proscribed regulatory needs which are essential to ensure that volunteers and patients are not inappropriately exposed to potentially hazardous substances. Implementing creative options to the assessment of drug safety is therefore doubly challenging as it requires not only assessing new approaches for their potential value but doing so against a business background which is inherently very conservative. I will discuss my personal experiences in being a non-toxicologist entering the world of drug safety assessment and how a three stranded approach built on developing tools, approaches most importantly people can move the safety elephant.
9:40 Developing Cell Models and Assays with Improved Predictivity for Drug Toxicity TestingSponsored by
Stephen Minger, Ph.D., Head of R&D Cell Technologies, GE Healthcare
It is necessary to develop novel and better human-predictive cellular screening assay systems in order to reduce attrition and increase drug discovery productivity e.g. in the area of cardiovascular disease where toxicity is a major cause of drug withdrawal. Human embryonic stem cells can offer the drug discovery community physiologically relevant screening options. These cells can be both cultured and differentiated reproducibly into spontaneously contracting cardiomyocytes to scale and quality to satisfy appropriate screening paradigms. Characterisation of the cardiomyocytes in automated HCA assays and on platforms for high-throughput electrophysiological recordings indicate that they are suitable for predictive toxicology screening and comparable to cell models currently employed.
Sponsored by
9:55 Does Capture Compound Mass Spectrometry (CCMS) elucidate drug actions?
Friedrich Kroll, Ph.D., Head, Medicinal Chemistry, caprotec bioanalytics GmbH
The molecular basis of in-vivo effects of drugs is often difficult to clarify. Utilizing trifunctional probes that contain small drug molecules as their selectivity functions we are able to isolate and identify their known targets. In a case study of a toxic Parkinson drug and in contrast to its congener major drug/protein interactions with components of the respiratory chain and the fatty acid β-oxidation are discovered. Reproducible capture results of this kind illustrate that CCMS is a straight forward tool for the identification of drug’s potential off-targets and their MOA and thereby, assists to reengineer or to reject drugs at an earlier pre-clinical stage.
10:10 Networking Coffee Break, Poster and Exhibit Viewing
10:50 EXPERT PANEL: Casting the Right Safety Net: Exploring Creative Options for Predicting Drug Safety
Panelists:
David Cook, Ph.D., Associate Director, Pharmacology and Toxcicology, Astra Zeneca R&D
Michael Liebman, Ph.D., President/Managing Director, Management, Strategic Medicine, Inc.
Paul Watkins, M.D., Director, Hamner-UNC Institute for Drug Safety Sciences, University of North Carolina at Chapel Hill
Shama M. Kajiji, Ph.D., Director, Portfolio Franchise Management, Merck & Co.
Stefan Platz, Ph.D., D.V.M., Head of Toxicology/Pathology, F. Hoffmann-La Roche Ltd.
12:20 pm Sponsored by
Luncheon Presentation
New Systems for High-Throughput Cell Analysis and for Analysis of Beating Cardiomyocytes
Manfred Watzele, Ph.D., Director R&D, Roche Diagnostics GmbH
Yama A. Abassi, Senior Director of Assay Development and Cell Biology, ACEA Biosciences
Significant scientific advances of the last years, in particular in molecular and cell biology and biotechnology, are paving the way for major improvements in human toxicity testing. These advances can make toxicity testing quicker, less expensive, and more directly relevant to human exposures. They could also reduce the use of animals in safety testing by replacing animal tests with in vitro tests based on cells, cellular components and tissues, preferably of human origin. This becomes increasingly important in the political, ethical and legal context where both highest safety standards and the implementation of the so-called “3R principle” of Replacement, Refinement and Reduction of experimental animals by alternatives are highest priorities.
Pharmaceutical and biotechnology companies must show evidence of their compound’s biological activity and provide data indicating that the drug is reasonably safe and effective before initial administration into humans. Safety assessment or nonclinical testing is the first major step toward regulatory approval. While animal studies are still needed to detect changes in tissues and developmental processes, high amounts of synthesized and purified compounds are needed at a very early step of drug development. In vitro studies with cellular models are therefore the method of choice to save compounds and time for eliminating toxic compounds in that early phase
Roche Diagnostics GmbH has recently launched the xCELLigence System allowing for the dynamic monitoring of cellular events like cell proliferation, cell morphology/integrity or changes in adhesion/attachment of cells to substrate.
The system measures and integrates all cellular events in real-time in an impedance readout so that none of the cellular responses is lost.
We will show how cellular toxicity assays on hepatocytes can be optimized for optimum density and surface substrate ECM (extracellular matrix protein) coating using impedance measurements on the xCELLigence System. An optimum seeding density was required to obtain the highest sensitivity of toxicity detection. Compared to normal endpoint assays shorter assay times or higher sensitivity of detection was obtained using real-time impedance measurements.
Our newest generation instrument with an automated workflow for high throughput measurement of cellular receptors and toxicity screens. Options for different applications will be demonstrated.
Recently it has been reported that somatic cells can be reprogrammed by expression of four stem-cell related factors (Oct4, Sox2, c-myc, Klf4) into pluripotent, stem-cell like populations called induced pluripotent stem cells (iPS) (Takahashi K et al Cell 2007 131(5):861-72). More recently, the first studies demonstrating tissue-specific differentiation of patient-specific iPS lines in vitro have been published, indicating that iPS cells have comparable differentiation capacity as human ES cells but offer the unique perspective to study patient- and/or disease-specific cells. This offers the chance to screen for drugs and test for toxic side effects of drugs on human tissue specific cells. Especially cardiomyocytes derived from stem cells are now available from different suppliers and are of high interest in drug safety studies. We will present data how drug influence on beating cardiomyocytes can be measured on our new xCELLigence Cardio System in high throughput.
1:20 pm End of ConferenceSponsored by
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