Microdosing in Translational Medicine: Pros and Cons

Table of Contents

Chapter 1. Introduction: The Quest for Early Human Data

• 1.1 A Quicker and Safer Way to Develop New Drugs is Needed
• 1.2 The Basic Dilemma: Extrapolating from Animals to Humans
• 1.3 Better Software Will Help, But Solutions for Judging Effects on Humans are Needed Now
• 1.4 The Concept of Microdosing

Chapter 2. Microdosing and Clinical Pharmacology

• 2.1 The Benefit of Early Human Pharmacodynamic Information
• 2.2 Expected Relations between Microdoses and Clinically Effective Doses
• 2.3 Microdosing Known Compounds to Assess Investigational Drug Effects
• 2.4 Bioanalytical Support: Constraints and Perspectives
  • Accelerator Mass Spectrometry
  • Tandem Liquid Chromatography/Mass Spectroscopy
  • Positron-Emission Tomography
• 2.5 Using Microdosing-Type Analytical Methods in Safety Pharmacology

Chapter 3. Microdosing Studies as a Strategic Tool

• 3.1 Microdosing as a Tool to Weigh Drug Development Options
• 3.2 A Fruitful Marriage with in silico Optimization Techniques and "-omics"
• 3.3 Option for Studies in Unconventional Populations

Chapter 4. Microdosing as a Regulatory Challenge and Opportunity

• 4.1 The EMEA Position Paper on Microdosing
• 4.2 The FDA Exploratory IND Guideline
• 4.3 Other Regulatory Guidelines for Studies Using Radioactive Drugs
• 4.4 Benefits in Costs, Time, and Logistics
• 4.5 The Ethical Aspect: Reducing the Burden on Volunteers and the Use of Animals

Chapter 5. Practical Experience and Planning-Stage Projects with Microdosing

• 5.1 Proof of Concept through In Vitro and Animal Studies
• 5.2 Collaborative Industry and Public/Private Efforts
  • The Consortium for Resourcing and Evaluating AMS Microdosing
  • Azidothymidin Study by Radiant Research and Vitalea Sciences
  • The EU Microdose AMS Partnership Programme (EUMAPP)
• 5.3 Pharmaceutical Companies as Sponsors of Microdosing Studies
  • GlaxoSmithKline
  • Servier
  • Speedel Pharmaceuticals
  • Tripep
  • Neurocrine Biosciences
  • Industry Opinions on the Acceptance of Microdosing

Chapter 6. Expert Roundtable Commentaries

• Dr. Ali Arjomand, President and COO, Accium Biosciences
• Dr. Stephen Dueker, President, Vitalea Science
• Dr. Jon Ruckle, Medical Director, Early Phase Research, Radiant Research
• Dr. Lloyd Stevens, Business Support Manager, Pharmaceutical Profiles
• Prof. Dr. Colin Garner, CEO, Xceleron

• Question 1: Do you see possibilities for modifying current microdosing protocals to make them more predictive?
• Question 2: Do you see additional potential in evaluating other parameters relevant to drug development, such as drug interactions?
• Question 3: How do you estimate the potential of isotopes other than 14C?
• Question 4: How do you see the relationship between AMS and LC/MS/MS developing?
• Question 5: What role do you see for imaging technologies, expecially PET, in microdosing studies?
• Question 6: Could human microdosing be accepted to such an extent that it becomes a routine screening tool for drug leads in a streamlined clinical development process?
• Question 7: Could you comment on the potential feedback loops between human microdosing studies, the various "-omics," and in silico methods?
• Question 8: Do you see opportunities for microdosing in formal preclinical study programs?
• Question 9: With EMEA and FDA guidelines in place, how do you think the scenery will develop geographically during the next few years?
• Question 10: What are your optimistic and pessimistic estimates for the dollar volume of the microdosing market by 2010 and 2015?
• Question 11: What share of this market do you estimate your company will capture by 2010 and 2015?

Chapter 7. Conclusion: Cambridge Healthtech Associates' Scenario for Microdosing in Drug Development

• 7.1 Today's Outlook Depends on Where You Are in the Drug Development Process
• 7.2 Along the Way: Getting Over Nonscientific and Noneconomic Factors
• 7.3 An Exciting New Tool

Appendix A.

• Companies Offering Microdosing Services

Appendix B.

• Cambridge Healthtech Associates - Microdosing Survey - April 2006-04-24

References

Company Index with Web Addresses