CPSA 2004

This session will initiate a dialogue on biomarker discovery and
evaluation, setting the stage for two subsequent sessions which explore
these topics in greater detail. Two distinguished speakers will share
their experience and vision for how biomarker strategies and current
technology can be deployed to optimize the discovery and development of
novel therapeutic agents.

An Industrial Perspective on Biomarker Research: One Approach Taken
Stanley Hefta, Bristol-Myers Squibb

Biomarkers of Oxidative Stress
Ian Blair, University of Pennsylvania

Bradley Ackermann, Eli Lilly and Co.
Edward Brewer, Tandem Labs
Chandra Natarajan, Sanofi Aventis
Steve Unger, Bristol-Myers Squibb

The industry for the outsourcing of bioanalytical analysis from the pharmaceutical sector has been an arena of considerable change in recent years. Riding the crests and troughs of its R&D partners, the 1990s were a time of great growth for the outsourcing sector, but in a climate of weak pipelines, uncertain future of blockbuster drug candidates, and reduced pharmaceutical R&D budgets this sector has been required to reassess its operational strategies. This session will initiate a dialogue on outsourcing strategies and explore this topic from two perspectives -Ý"Big Pharma" and Contract Research Organizations.

The Impact of Value Enhancement Initiatives to Outsourcing Strategies
Roger Hayes, Schering Plough Research Institute

Outsourcing and Offshoring DMPK Studies - The Pros and Cons
Zamas Lam, Quest Pharmaceutical Services

Cost Benefit Analysis
Mickey O'Brien, Tandem Labs

High Throughput Analysis & Information Management Strategies
Discussion Leader: Eric A. Milgram, Advanced Chemistry Development

The purpose of this session will be to examine the challenges that arise due to operating in a high-throughput mode and to look at some solutions that have been developed to meet those challenges. For example, all high-throughput groups must develop solutions for keeping track of the large numbers of samples coming through the laboratory, developing generic sample treatment and analysis methods, and automating data collection and processing. Also, data quality standards have to be implemented with a tradeoff between minimizing the number of data items that a human must examine and maximizing the confidence of the results for the purpose of making a business decision. Most groups use a combination of both commercial and in-house developed hardware and software.

Flexible Automation Tools for Drug Metabolism: Workstation and Fully
Automated Approaches for in vitro and PK Studies
Tom Lloyd, H. Kandoussi and R. Talaat, Wyeth

Automatic Reduction of Analytical Data System
Kenneth Lewis, Eli Lilly and Company

High-Throughput LC-MS – A Total Package
Manish Soni, Aventis Pharmaceuticals

Current Strategies & Preferences for Metabolite identification
Discussion Leader: Jonathan Josephs, Bristol-Myers Squibb

The requirements for metabolite identification in drug discovery and
development range from the rapid in vitro identification of major
metabolic soft spots in early discovery through the exhaustive
determination of the extract structure of low concentration metabolites
formed in vivo in drug development studies. The session will cover a
number of strategies for meeting these challenges utilizing in vitro and
in vivo approaches for metabolite generation and the application of mass
spectrometry and NMR spectrometry as both on line and static techniques.

An Integrated Analytical Approach for Determination of Metabolic
Stability, Metabolic Soft-Spots and Rate of Metabolite Formation using
a Hybrid Linear Ion Trap/Fourier Transform Mass Spectrometer
Petia Shipkova, Mary F. Grubb, Jonathan Josephs, Robert A. Langish, Mark
Sanders, Bristol-Myers Squibb

Considerations for Metabolite Characterization Studies in Support of Drug Discovery
Kathleen A. Cox, Schering-Plough Research Institute

Nanoelectrospray as a Tool for Drug Metabolite Structure Elucidation
Gary D. Bowers, GlaxoSmithKline

SepNMR: A System for the Isolation and Preparation of Trace Components
from Mixtures for NMR Analysis
David J. Detlefsen, Jeffrey L. Whitney, Mark E. Hail, Novatia;
Feng Xu, Bristol-Myers Squibb

Biomarker Discovery
Discussion Leaders: Bradley L. Ackermann, Eli Lilly and Company
Sushmita M. Roy, SurroMed

This session will address emerging technologies used for biomarker
discovery with a focus on proteomics and metabolomics. Differential
profiling and structure identification will be demonstrated in the
context of biomarker discovery. The interplay of biochemistry, mass
spectrometry and bioinformatics will be addressed and experiences during
the process of technology development will be shared and discussed.

Molecular System Biology's Role in the Critcal Path Initiative
Stephen A. Martin, Beyond Genomics

Metabonomics: Applications in Safety Assessment and Biomarker Discovery
John Shockcor, Bruker BioSpin Corporation

Differential Protein and Metabolite Profiling for Biomarker Discovery
Mimi Roy, SurroMed

High Throughput ADME & Pharmaceutical Property Profiling
Discussion Leader: Jeffrey L. Dage, Eli Lilly and Company

High throughput can sometimes give people cause to doubt the quality or practicality of data. This has been showcased in recent articles in the Wall Street Journal "Drug Industry's Big Push Into Technology Falls Short, Testing Machines Were Built to Streamline Research – But May be Stifling" and the response in C&E news "Drug Discovery, As High-Throughput Screening Draws Fire, Researchers Leverage Science to Put Automation into Perspective." This session will focus on how automation and computational tools have been leveraged to produce high quality ADME and pharmaceutical profiling data. In addition and more importantly demonstrate the approaches associated with turning the data into informed decision-making and applying this knowledge across projects.

Introduction to Session
Jeff Dage, Eli Lilly and Company

Integrating ADME Screening Data into Discovery Decision-Making - The How and Why
James M. Grace, Eli Lilly and Company

Evolving Concepts in the Pharmaceutical Profiling Data Desired by Drug
Discovery Teams and the Methods of Collaborating for Project Impact
Edward H. Kerns, Wyeth

Decision-Making Strategies in Drug Discovery
Phillip S. Burton, ADMETRx, Inc.

Molecular Imaging Using MALDI and Ion Mobility-Mass Spectrometry: A New Paradigm for Proteomics
David H. Russell, Texas A&M University
Download abstract (PDF) 52 KB

Metabolic Profiles of Drug Toxicity and Disease
Richard Beger, Food and Drug Administration
Download abstract (PDF) 40 KB

Tissue Imaging - Localization of Drugs and Metabolites
Discussion Leader: Yunsheng Hsieh, Schering Plough Research Institute

The use of mass spectrometric techniques as an analytical tool has become standard in pharmaceutical research and development. Mass spectrometry is routinely applied throughout all phases of drug discovery and development, from the synthesis of new chemical entities (for structural characterization) to the analysis of lead compounds in clinical trials (for metabolite identification and pharmacokinetics). This session will discuss various MS-based imaging methodologies to provide useful information about the localization of a given target in biological tissues.

Mapping Small Molecules in Intact Tissue by Laser Microprobe Ion Trap Tandem Mass Spectrometry
Timothy Garrett and Richard Yost, University of Florida

Imaging Proteins in Tissues via MALDI Mass Spectrometry
Michelle L. Reyzer, Vanderbilt University

Imaging Mass Spectrometry for Probing the Brain
Stanislav Rubakhin, University of Illinois

Tissue Imaging Using MALDI Tandem Mass Spectrometry for Drug Candidates
Yunsheng Hsieh, Schering-Plough Research Institute

Biomarker Evaluation
Discussion Leaders: Bradley L. Ackermann, Eli Lilly and Company;
Sushmita M. Roy, SurroMed

This session will focus on strategies and techniques used in the difficult, yet essential, process of translating candidate markers into tools that truly guide pre-clinical and clinical pharmacology. The importance of cross-functional partnerships, emerging technologies, and iterative learning will be emphasized.

Quantitation of Peptides & Protein Biomarkers by MS
Brad Guild, Millennium

Analysis of Small Molecule Biomarkers
Tom Oglesby, Taylor Technologies

Establishing Pre-Clinical and Clinical PK/PD Relationships
Carl Garner, Eli Lilly and Company

The success of drug discovery research relies upon the quality of the corporate compound library. As compound stability can be affected by many factors, it is important to assess the quality of the library over time. Advances in analytical technologies made it possible. The discussion will be focused on assessing the quality of compound library with analytical technology.

Emerging Technologies and Applications
Discussion Leader: David S. Wagner, GlaxoSmithKline

The last few decades has generated extraordinary technological advancements in medicine, science, transportation, engineering, and communication. These technologies have changed the way in which we live our personal lives as well as scientists’ ability to conduct research. New technologies are constantly being developed world wide in universities and companies, and speculating which ones will transform science is challenging. Several emerging areas of technology that should have a profound impact on the pharmaceutical industry will be discussed. These advances incorporate instrumentation, nanotechnology, and novel sample preparation. Each technology will be highlighted exemplifying the potential and promise for the pharmaceutical industry.

HPLC Chip Technology
Tom A. van de Goor, Agilent Technologies

Ion/Ion Methods for Peptide and Protein Sequence Analysis: Electron Transfer Dissociation and Beyond
Joshua J. Coon, John E.P. Syka, Jeffrey Shabanowitz, Donald F. Hunt, University of Virginia
 
Microwave-Enhanced Proteomic Applications – Rapid and Efficient Techniques for Protein Analysis
J. Doug Ferguson, E. Keller Barnhardt, CEM Corporation