Toxicogenomics and Predictive Toxicology: Market and Business Outlook

Table of Contents

Chapter 1. Introduction

1.1 Overview

1.2 Impact of Toxicology Issues on Drug Development

• Adverse Drug Reactions

1.3 Toxicology Background

• Effects of Toxicants

Chapter 2. The Role of Toxicology in Drug Development

2.1. The Drug Development Process

2.2 Traditional Approaches versus Predictive Toxicology

• Toxicity Testing in the Drug Development Process
• Traditional Approaches
• Animal Models
• Genotoxicity Tests
• Limits of Traditional Approaches
• Predictive Toxicology

2.3 Potential Benefits of Predictive Toxicology

• Reduce Adverse Drug Reactions
• Reduce Cost of Drug Development
• Reduce Length of Time of Drug Development
• Improve Drugs
• Reduce Animal Testing
• Increase Sensitivity
• Improve Other Industries
• Reduce Potential Lawsuits
• Provide Biomarkers
• Reduce Regulatory Requirements
• Rescue Failed Drugs

Chapter 3. Toxicogenomics

3.1 Overview

3.2 Background

• Genes and Genomics
• The Genome Structure
• Gene Expression
• Advantages of Genomics Approaches

3.3 Measuring Gene Expression

• DNA Microarrays
• Companies Selling Microarray Products for Toxicology Testing
• RNA Splicing

3.4 Applications of Toxicogenomics

• In Vitro Applications
• Predictive Versus Mechanism-Based Investigations

3.5 Toxicogenomics Data

• National Center for Toxicogenomics
• Standardization and Comparison of Toxicogenomics Data
• Toxicogenomics Data Analysis
• Proprietary Toxicogenomics Databases
• Public Toxicogenomics Databases

3.6. Collaborations in Toxicogenomics Research

• The Toxicogenomics Research Consortium
• HESI Collaborative Research Program

3.7. Case Study: Using Microarrays to Detect Kidney Toxicity

Chapter 4. Technologies for Predictive Toxicology

4.1. Metabolomics/Metabonomics

• Profiling Metabolites
• Detecting Metabolites
• Growth of Metabolomics
• Advantages of Metabolomics
• Future of Metabolomics
• Selected Companies Active in Metabolomics

4.2. Toxicoproteomics

• Primary Technologies for Toxicoproteomics
• In-House Approaches
• Selected Companies Providing Toxicoproteomic
• Products and Services

4.3. Pharmacogenomics

• Drug Metabolism
• Selected Companies Active in Pharmacogenomics

4.4. In Silico Predictive Toxicology

• Applications and Limitations in Predictive Toxicology
• In Silico Methods
• Programs and Companies Active in Predictive
• In Silico Toxicology
• Limitations and Appropriate Uses of In Silico Methods

4.5. New Animal Models

• Types of Animal Toxicity Tests
• Limitations of Toxicology Testing
• Companies Offering Approaches to Improving Current
• Animal Models
• Zebrafish
• Caenorhabditis elegans

4.6. Novel In Vitro Assays: Animal on a Chip

• Applications
• Three-Dimensional Tissue Models
• Animal on a Chip--Companies and Approaches
• Stem Cells

Chapter 5. Business and Strategic Issues

5.1 Overview

5.2 Potential Applications of Predictive Toxicology Throughout Drug Development

5.3 Cost Factors Driving the Adoption of New Toxicology Approaches

• Cost of the Assay Itself
• Cost of Drug Failures
• Primary Areas of Growth in Predictive Toxicology and
• Toxicogenomics

5.4. Factors Limiting Growth of New Toxicology Approaches

• Unknown Mechanisms of Drug Toxicity
• Regulatory Pressures That Promote Extremely Conservative
• Approaches to Toxicology Testing
• Drug Toxicity Research Primarily Takes Place Within
• Pharmaceutical Companies

5.5. Key Players

• Government
• Pharmaceutical Industry
• Biotechnology Industry
• Academia
• Vendors
• Healthcare Providers and Patients

5.6. Regulatory Issues

• U.S Regulatory Agencies Concerned with Safety/Toxicology-Related Issues
• United States
• Global Regulations
• Europe

5.7. Unmet Needs and Opportunities in Technology Development

• Biomarkers
• Data Quality and Analysis
• Databases
• Demonstrated Accuracy
• Heart Rhythm Abnormalities

5.8. Toxicology Technology Evaluations Using SWOT Analysis

• Comparison of Rodent Versus Zebrafish Models
• Cross Comparison of Toxicogenomics Versus Proteomics
• Versus Metabolomics

5.9. Conclusion

Chapter 6. Expert Interviews

• Dave Craford, Affymetrix
• Jacques Retief, Affymetrix
• Jim Neal, Iconix Pharmaceuticals, Inc.
• Thomas J. Colatsky, Icoria
• Peter Lord, Johnson & Johnson Pharmaceutical Research and Development
• Weida Tong, FDAs National Center for Toxicological Research
• Michael L. Shuler, Cornell University
• William B. Mattes, Gene Logic Inc.
• Donna Mendrick, Gene Logic Inc.

Appendix

References

Glossary

Index