Early Drug Development: Strategies and Routes to First-in-Human Trials / Edition 1

Hardcover (Print)
Used and New from Other Sellers
Used and New from Other Sellers
from $139.95
Usually ships in 1-2 business days
(Save 17%)
Other sellers (Hardcover)
  • All (7) from $139.95   
  • New (6) from $142.96   
  • Used (1) from $139.95   

Overview

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.

Read More Show Less

Editorial Reviews

From the Publisher
"As such, it may serve both as an introduction for newcomers but also as a reference for the more experienced ... The reader will find valuable advice on how to find the best strategy towards entry into the clinic." (ChemMedChem, 2011)
Read More Show Less

Product Details

  • ISBN-13: 9780470170861
  • Publisher: Wiley
  • Publication date: 8/30/2010
  • Edition description: New Edition
  • Edition number: 1
  • Pages: 654
  • Sales rank: 1,122,980
  • Product dimensions: 6.10 (w) x 9.40 (h) x 1.60 (d)

Meet the Author

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.

Read More Show Less

Table of Contents

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. 

Read More Show Less

Customer Reviews

Be the first to write a review
( 0 )
Rating Distribution

5 Star

(0)

4 Star

(0)

3 Star

(0)

2 Star

(0)

1 Star

(0)

Your Rating:

Your Name: Create a Pen Name or

Barnes & Noble.com Review Rules

Our reader reviews allow you to share your comments on titles you liked, or didn't, with others. By submitting an online review, you are representing to Barnes & Noble.com that all information contained in your review is original and accurate in all respects, and that the submission of such content by you and the posting of such content by Barnes & Noble.com does not and will not violate the rights of any third party. Please follow the rules below to help ensure that your review can be posted.

Reviews by Our Customers Under the Age of 13

We highly value and respect everyone's opinion concerning the titles we offer. However, we cannot allow persons under the age of 13 to have accounts at BN.com or to post customer reviews. Please see our Terms of Use for more details.

What to exclude from your review:

Please do not write about reviews, commentary, or information posted on the product page. If you see any errors in the information on the product page, please send us an email.

Reviews should not contain any of the following:

  • - HTML tags, profanity, obscenities, vulgarities, or comments that defame anyone
  • - Time-sensitive information such as tour dates, signings, lectures, etc.
  • - Single-word reviews. Other people will read your review to discover why you liked or didn't like the title. Be descriptive.
  • - Comments focusing on the author or that may ruin the ending for others
  • - Phone numbers, addresses, URLs
  • - Pricing and availability information or alternative ordering information
  • - Advertisements or commercial solicitation

Reminder:

  • - By submitting a review, you grant to Barnes & Noble.com and its sublicensees the royalty-free, perpetual, irrevocable right and license to use the review in accordance with the Barnes & Noble.com Terms of Use.
  • - Barnes & Noble.com reserves the right not to post any review -- particularly those that do not follow the terms and conditions of these Rules. Barnes & Noble.com also reserves the right to remove any review at any time without notice.
  • - See Terms of Use for other conditions and disclaimers.
Search for Products You'd Like to Recommend

Recommend other products that relate to your review. Just search for them below and share!

Create a Pen Name

Your Pen Name is your unique identity on BN.com. It will appear on the reviews you write and other website activities. Your Pen Name cannot be edited, changed or deleted once submitted.

 
Your Pen Name can be any combination of alphanumeric characters (plus - and _), and must be at least two characters long.

Continue Anonymously

    If you find inappropriate content, please report it to Barnes & Noble
    Why is this product inappropriate?
    Comments (optional)