Drug Development

Herausgeber: Cayen, Mitchell N

• Gebundenes Buch

Produktbeschreibung

The focus of early drug development has been the submission of an Investigational New Drug application to regulatory agencies. Early Drug Development: Strategies and Routes to First-in-Human Trials guides drug development organizations in preparing and submitting an Investigational New Drug (IND) application. By explaining the nuts and bolts of preclinical development activities and their interplay in effectively identifying successful clinical candidates, the book helps pharmaceutical scientists determine what types of discovery and preclinical research studies are needed in order to support a submission to regulatory agencies.

Produktdetails

• Verlag: John Wiley & Sons / Wiley
• Seitenzahl: 654
• Erscheinungstermin: 9. August 2010
• Englisch
• Abmessung: 240mm x 161mm x 40mm
• Gewicht: 1144g
• ISBN-13: 9780470170861
• ISBN-10: 0470170867
• Artikelnr.: 29934072

Autorenporträt

MITCHELL N. CAYEN, PhD, is Principal of Cayen Pharmaceutical Consulting, LLC, a firm that advises pharmaceutical companies in nonclinical and clinical drug develop-ment, with specific focus on candidate drug selection, discovery, drug metabolism and pharmacokinetics, drug development strategies, and regulatory submissions. Previously, he was senior director of drug metabolism and pharmacokinetics at Schering-Plough Research Institute.

Inhaltsangabe

Contributors. Foreward. Preface. PART I INTRODUCTION. 1 Drug Discovery and
Early Drug Development (Mitchell N. Cayen). 1.1 The Drug Discovery and
Development Scene. 1.2 Drug Discovery. 1.3 Pre-FIH Drug Development. 1.4
The FIH Trial. 1.5 The Regulatory Landscape. 1.6 Contract Research
Organizations. 1.7 Concluding Remairs to Introductory Perspectives.
References. PART II LEAD OPTIMIZATION STRATEGIES. 2 ADME Strategies in Lead
Optimization (Amin A. Nomeir). 2.1 Introduction. 2.2 Absorption. 2.3
Distribution. 2.4 Metabolism. 2.5 Excretion. 2.6 Pharmacokinetics. 2.7
Prioritizing ADME Screens. 2.8 In Silico ADME Screening. 2.9 The Promise of
Metabolomics. 2.10 Conclusions. References. 3 Prediction of
Pharmacokinetics and Drug Safety in Humans (Peter L. Bullock). 3.1
Introduction. 3.2 Prediction of Human Pharmacokinetic Behavior. 3.3
Prediction of Drug Safety. 3.4 Conclusions. References. 4 Bioanalytical
Strategies (Christopher Kemper). 4.1 Introduction. 4.2 Basic Bioanalytical
Techniques and Method Development. 4.3 Bioanalytical Method Validation. 4.4
Special Issues with Ligand-Binding Assays. 4.5 Partial and
Cross-Validations. 4.6 Application of Validated Methods to Sample Analyses:
Some Perspectives. 4.7 Risk-Based Paradigms: Discovery and Development
Support. 4.8 Road to "First in Human". 4.9 International Perspectives. 4.10
Conclusions. References. PART III BRIDGING FROM DISCOVERY TO DEVELOPMENT. 5
Chemistry, Manufacturing and Controls: The Drug Substance and Formulated
Drug Product (Örn Almarsson and Christopher J. Galli). 5.1 Introduction.
5.2 Pre-NCE Activities and CMC Development. 5.3 CMC Consideration at the
NCE Stage. 5.4 NCE-to-GLP Transition (Bridging from Discovery to Pre-FIH
Development). 5.5 CMCs to Meet Clinical Trial Material Requirements. 5.6
CMC Strategic Considerations. 5.7 Case Studies. 5.8 Evolution of Drug
Development: Implications for CMCs in the Future. Resources. References. 6
Nonclinical Safety Pharmacology Studies Recommended for Support of
First-in-Human Clinical Trials (Duane B. Lakings). 6.1 Introduction and
Overview. 6.2 Timing of Safety Pharmacology Studies. 6.3 CNS Safety
Pharmacology. 6.4 Cardiovascular Safety Pharmacology. 6.5 Respiratory
System Safety Pharmacology. 6.6 Renal/Urinary Safety Pharmacology. 6.7
Gastrointestinal System Safety Pharmacology. 6.8 Autonomic Nervous System
Safety Pharmacology. 6.9 Other Systems. 6.10 Discussion and Conclusion.
References. PART IV PRE-IND DRUG DEVELOPMENT. 7 Toxicology Program to
Support Initiation of a Clinical Phase I Program for a New Medicine (Hugh
E. Black, Stephen B. Montgomery and Ronald W. Moch). 7.1 Introduction. 7.2
Toxicology Support of Discovery. 7.3 Goals of the Pre-FIH Toxicology
Program. 7.4 Importance of a Clinical Review of the Nonclinical
Pharmacology Data. 7.5 Take the Time to Plan Appropriately. 7.6 The Active
Pharmaceutical Ingredient. 7.7 Timely Conduct of In Vitro Assays. 7.8
Development of Validated Bioanalytical and Analytical Assays. 7.9 Planning
for the Conduct of Toxicity Studies. 7.10 GLP Toxicology Program. 7.11
Pre-IND Meeting. 7.12 Conclusion. References. 8 Toxicokinetics in Support
of Drug Development (Gary Eichenbaum, Vangala Subrahmanyam and Alfred
P.Tonelli). 8.1 Introduction. 8.2 Historical Perspectives. 8.3 Regulatory
Considerations. 8.4 Factors to Consider in the Design of Toxicokinetic
Studies. 8.5 Toxicokinetic Parameter Estimates and Calculations. 8.6
Interpretation of Toxicokinetic Data. 8.7 Role of Toxicokinetics in
Different Types of Toxicity Studies. 8.8 Role of Toxicokinetics in
Integrated Safety Assessment. 8.9 Conclusion. References. 9 Good Laboratory
Practices (Anthony B. Jones, Kathryn Hackett-Fields and Shari L.
Perlstein). 9.1 Introduction. 9.2 Hazard and Risk. 9.3 US GLP Regulations.
9.4 GLPs in the Bioanalytical Laboratory. 9.5 Moving Into the Future: A
Closing Overview. 9.6 Appendixes. References. PART V PLANNING THE
FIRST-IN-HUMAN STUDY AND REGULATORY SUBMISSION. 10 Estimation of Human
Starting Dose for Phase I Clinical Programs (Lorrene A. Buckley, Parag
Garhyan, Rafael Ponce and Stanley A. Roberts). 10.1 Introduction. 10.2
Characteristics of Well-Behaved Therapeutic Candidates. 10.3 Regulatory
Guidances for FIH-Enabling Preclinical Safety Assessment: General
Principles. 10.4 Nonclinical Pharmacokinetics and Pharmacodynamics for
Human Dose Projection. 10.5 Establishing the First-in-Human Dose. 10.6
Phase I Clinical Trial Support: Use of MABEL or Pharmacologically Active
Dose. 10.7 Support of Exploratory Clinical Studies. 10.8 Considerations in
the Design of Phase I Trials. 10.9 Interdisciplinary Partnerships. 10.10
Beyond the FIH Dose. 10.11 Concluding Perspective. 10.12 Four Case Studies.
References. 11 Exploratory INDs/CTAs (Mitchell N. Cayen). 11.1
Introduction. 11.2 Regulatory Background. 11.3 Experience and Various
Perspectives on ExpINDs or ExpCTAs. 11.4 Some Reactions and Perspectives on
the ExpIND/ExpCTA Initiative. 11.5 What Is an Ideal Candidate for an
ExpIND/ExpCTA? 11.6 Conclusions. References. 12 Unique Considerations for
Biopharmaceutics (Laura P. Andrews and James D. Green). 12.1 Introduction
and Background. 12.2 Selection of the Molecule: Contrasts to Small-Molecule
Considerations. 12.3 Production and Process Considerations in Pre-FIH
Development. 12.4 Bioanalytical Assay Considerations. 12.5 Objectives and
Implementation of Pre-FIH Safety Assessment Programs. 12.6 Post-IND
Considerations: Support of Phase II and III and Registration. 12.7 The
TeGenero Incident and Implications for Biopharmaceutic Nonclinical Safety
Evaluation Programs. 12.8 Conclusions. References. 13 Project Management
and International Regulatory Requirements for First-in-Human Trials
(Carolyn D. Finkle and Judith Atkins). 13.1 Introduction: Initiate Product
Development with the End in Mind. 13.2 Importance of Project Management.
13.3 FDA Input Early and Often. 13.4 IND Submission in the United States.
13.5 Global Clinical Trials. 13.6 Clinical Trial Application. 13.7
Conclusion. References. 14 First-in-Human Regulatory Submissions (Mary
Sommer, Mark Ammann, Ulf B. Hillgren, Kathleen J. Kovacs and Keith Wilner).
14.1 Introduction. 14.2 Submission Strategies. 14.3 First-in-Human
Dossiers. 14.4 United States: Investigational New Drug Application. 14.5
European Union: Clinical Trial Application. 14.6 Japan: Clinical Trial
Protocol Notification. 14.7 Emerging Regions. 14.8 Biopharmaceuticals. 14.9
Final Considerations. Appendix 1: Abbreviations and Acronyms. Appendix 2:
Definitions and Glossary of Terms. Appendix 3: Some Relevant Government and
Regulatory Documents. Appendix 4: Some Relevant Resources with Web Sites.
Index.