Managing Toxicology for the Future: Improving Predictive Power Through Integrated Technologies, 2nd Edition

Table of Contents

Chapter 1: Introduction: Industry Environment

• Focus of the Report
• The Pharmaceutical Industry: A Historical Perspective
• The Problem-The Increase in R&D Costs
• Industrialization of Drug Discovery
• The Trend Toward Pulling Risk Upstream
• The Three Bottlenecks of Pharmaceutical R&D
• Competitive Advantages of Early Safety Screening
• Adverse Drug Reactions and Drug-Drug Interactions
• References

Chapter 2: Technology Strategies

• Traditional Animal Studies
  • Preclinical Safety Testing-An Overview
  • Categories of Preclinical Animal Toxicity Testing
  • Preclinical Safety Testing for Biopharmaceuticals
  • Limitations of Preclinical Animal Testing
• Phase I-IV Clinical Studies
  • Clinical Development (Phase I-III Clinical Trials)
  • Post-Marketing Studies (Phase IV Studies)
  • The Product Quality Control Problem in Drug Development
• Improving Animal Studies
  • Telemetry Sensors
  • Liquid Chromatography and Mass Spectrometry
  • Non-mammalian Animal Models
  • Transgenic Animal Models
  • Imaging Technologies
• The "Omic" Triad
• Toxicogenomics
  • Reference Databases in Toxicogenomics
  • Toxicogenomics and Traditional Pathology
  • Maximizing the Benefit of Toxicogenomic Studies
• Toxicoproteomics
  • Key Technologies for Toxicoproteomics
  • Toxicoproteomic Applications
  • Maximizing the Benefit of Toxicoproteomics
• Metabonomics
  • Key Technologies for Metabonomics
  • Maximizing the Benefit of Metabonomics
• Predictive Toxicology
  • The Need for In Vitro and In Silico Models
  • In Vitro Toxicity Assays
  • In Vitro Drug-Metabolism Assays
  • Genotyping Assays for Drug-Metabolizing Enzymes
  • In Silico Approaches: Computational Models and Databases
  • Current In Silico Models for Toxicity
  • Current In Silico Models for ADME Properties
• Role of Drug Delivery in Toxicology
• References

Chapter 3: Business Strategies

• Platform Technology Companies
  • Animal Model Companies
  • ADME/Tox Assay Technology Companies
  • Toxicogenomics & Toxicoproteomics Companies
  • In Silico Predictive Toxicology Companies
  • Other Platform Technology Companies
  • The Absorption and Elimination of Platform Technology Companies
  • Internal Efforts-A Shift in Focus towards ADME/Tox
  • Pulling Risk Upstream
  • Public and Regulatory Pressures
• References

Chapter 4: A Case Study of Toxicity Impact-Product Withdrawals

• Introduction
  • Adverse Drug Reactions
  • Impact of ADRs and Drug Product Withdrawals
  • Medical Need vs. Risk
• Factors Influencing Increased Incidence of Drug Product Withdrawals
  • FDA Reform
  • Overall Risk Management Framework
  • Market Withdrawals and Clinical Trial Flaws
  • Other Factors Leading to the Recent Increase in Drug Withdrawals
• The Case Study-Baycol (Avastatin)
  • Baycol Overview
  • Baycol ADRs
  • Ramifications of Baycol ADRs and Market Withdrawal
  • Bayer's Reaction to the Baycol ADR
  • Conclusions from the Baycol Case Study
• Industry Response to ADR's and Drug Withdrawals
  • Estimates of Preventable ADR's
  • Collaborative Drug Therapy Management
  • Clinical Trial Design, Pharmacogenomics and Toxicity Biomarkers
• References

Chapter 5: Company Profiles