Pediatric Non-Clinical Drug Testing

ALAN M. HOBERMAN, PhD, DABT, Fellow ATS, is Executive Director of Site Operations and Toxicology at Charles River Preclinical Services, Horsham, PA. ELISE M. LEWIS, PhD, is Director of Reproductive and Neurobehavioral Toxicology at Charles River Preclinical Services, Horsham, PA.

• Preface ixAcknowledgments xiContributors xiii1. Introduction 1Elise M. Lewis, Luc M. De Schaepdrijver, and Timothy P. Coogan2. Overview of Pediatric Diseases and Clinical Considerations on Developing Medicines for Children 29Bert Suys and José Ramet3. Nonclinical Safety Assessment for Biopharmaceuticals: Challenges and Strategies for Juvenile Animal Testing 41Timothy P. Coogan4. FDA Approach to Pediatric Testing 59Robert E. Osterberg5. Pediatric Drug Development Plans 79Kimberly C. Brannen and Beatriz Silva Lima6. Application of Principles of Nonclinical Pediatric Drug Testing to the Hazard Evaluation of Environmental Contaminants 93Susan L. Makris7. Nonclinical Testing Procedures—Pharmacokinetics 115Loeckie L. de Zwart, Johan G. Monbaliu, and Pieter P. Annaert8. Preclinical Development of a Pharmaceutical Product for Children 129Graham P. Bailey, Timothy P. Coogan, and Luc M. De Schaepdrijver9. Juvenile Toxicity Study Design for the Rodent and Rabbit 141Alan M. Hoberman and John F. Barnett10. Dog Juvenile Toxicity 183Keith Robinson, Susan Y. Smith, and Andre Viau11. Use of the Swine Pediatric Model 213Paul C. Barrow12. Juvenile Immunodevelopment in Minipigs 231André H. Penninks, Geertje J.D. van Mierlo, Frieke Kuper, Cor J. Snel, Niels-Christian Ganderup, and André P.M. Wolterbeek13. Use of Primate Pediatric Model 255Gerhard F. Weinbauer, Gary J. Chellman, Allan Dahl Rasmussen, and Elvira Vogelwedde14. Approaches to Rat Juvenile Toxicity Studies and Case Studies: a Pharmaceutical Perspective 281Susan B. Laffan and Lorraine PosobiecAppendix 1 Maturation of Organ Systems in Various Species 301Appendix 2 Sample Juvenile Toxicity Testing Protocol 303Index 331

“Overall, this is a very useful book in bringing together many of the aspects associated with JA toxicology testing of pharmaceuticals for the first time, especially for those new to this growing field, with the chapters on study design considerations being especially useful.”  (British Toxicology Society New, 1 November 2012)“The book is an essential reference for international regulatory personnel, toxicologists, pharmacokineticists, scientists working in the pharmaceutical industry, academics and physicians and pharmacists concerned about the safe use of medicines in children.”  (Pharmaceutical Journal, 11 September 2012)“No other single resource combines pediatric drug development considerations with the most recent regulatory requirements and the approach to selecting and testing in nonclinical models. This is a unique and comprehensive reference that will inform and guide readers through the challenges and approaches to the safe and effective use of medications in children.”  (Doody’s, 17 August 2012)