A single-source reference with a broad and holistic overview of nonclinical studies, this book offers critical training material and describes regulations of nonclinical testing through guidelines, models, case studies, practical examples, and worldwide perspectives. The book: Provides a complete overview of nonclinical study organization, conduct, and reporting and describes the roles and responsibilities of a Study Director to manage an effective study Covers regulatory and scientific concepts, including international testing and Good Laboratory Practice (GLP), compliance with guidelines, and animal models Features a concluding chapter that compiles case studies / lessons learned from those that have served as a Study Director for many years Addresses the entire spectrum of nonclinical testing, making it applicable to those in the government, laboratories and those actively involved in in all sectors of industry

A single-source reference with a broad and holistic overview of nonclinical studies, this book offers critical training material and describes regulations of nonclinical testing through guidelines, models, case studies, practical examples, and worldwide perspectives. The book:* Provides a complete overview of nonclinical study organization, conduct, and reporting and describes the roles and responsibilities of a Study Director to manage an effective study* Covers regulatory and scientific concepts, including international testing and Good Laboratory Practice (GLP), compliance with guidelines, and animal models* Features a concluding chapter that compiles case studies / lessons learned from those that have served as a Study Director for many years* Addresses the entire spectrum of nonclinical testing, making it applicable to those in the government, laboratories and those actively involved in in all sectors of industry

Foreword ixEdwin I. Goldenthal, PhD, ATSPreface xiContributors xiii1 Introduction to the Study Director 1Mary Ellen Cosenza, PhD, MS, DABT, RAC2 Good Laboratory Practice Regulations: Roles of the Study Director, Management, and Quality Assurance Unit 7Barbara Randolph, BS, MT (ASCP), MBA, RQAP (GLP)3 International Guidelines and Regulations of Nonclinical Studies 27Bert Haenen, PhD, ERT, Linda Blous, Msc, and Anne Harman Chappelle, PhD, DABT4 Facilities, Operations, Laboratory Animal Care, and Veterinary Services 43Susan A. MacKenzie, VMD, PhD, DABT, Gregory W. Ruppert, BA, and David G. Serota, PhD, DABT5 Regulatory Inspections 73Russell James Eyre, PhD, DABT, Lijie Fu, PhD, MPH, Fellow ATS, and Eric Austin, PhD, DABT6 Project Management and the Role of a Study Director 83Debra Kirchner, PhD, DABT, Parthena Martin, PhD, DABT, and Brenda Frantz, BS7 Managing Multi-site Studies: Roles of the Principal Investigator and the Study Director 95Suzanne R.T. Wolford, PhD, DABT8 Prestudy Preparation, the Protocol, Data Interpretation, and Reporting 107Carol S. Auletta, DABT, MBA, RAC9 Study Conduct 131Lisa Biegel, PhD, Heather Dale, PhD, and Mark Morse, PhD, DABT10 In Vitro Toxicology Models 145Gertrude-Emilia Costin, PhD, MBA, and Hans Raabe, MS11 Analytical Chemistry and Toxicology Formulations 171Eric S. Bodle, PhD, and Nutan Gangrade, PhD12 Statistical Design and Analysis of Studies 191John W. Green, PhD13 Clinical Pathology 225Niraj K. Tripathi, BVSc, MVSc, PhD, DACVP, Lila Ramaiah, BSc, DVM, PhD, DACVP, and Nancy E. Everds, DVM, DACVP14 Effective Incorporation and Utilization of Biomarkers in Nonclinical Studies 245Michael R. Bleavins, PhD, DABT15 Pathology: Necropsy and Gross Pathology 259Charles B. Spainhour, VMD, PhD, DABT16 Histopathology in Toxicity Studies for Study Directors 275Kevin Keane, DVM, PhD, Fellow IATP17 Toxicokinetics and Bioanalysis 297Anthony L. Kiorpes, PhD, DVM, DABT18 The Planning, Conduct, and Interpretation of Safety Pharmacology Studies: The Role of the Study Director in Safety Pharmacology Investigations 313Simon Authier, DVM, MSc, MBA, PhD, DSP, Michael J. Curtis, PhD, FHEA, FBPharmacolS, DSP, and Michael K. Pugsley, PhD, FBPharmacolS, DSP19 Genetic Toxicology Studies 333Robert R. Young, MS, Mark Powley, PhD, Timothy E. Lawlor, MA, and Marilyn J. Aardema, PhD20 Carcinogenicity Studies 355Reem Elbekai, BPharm, PhD, DABT, and Catherine M. Kelly, BS21 Contemporary Practices in Core Developmental, Reproductive, and Juvenile Toxicity Assessments 371Ali Said Faqi, DVM, PhD, DABT, Fellow ATS22 Immunotoxicology in Nonclinical Studies 393Florence G. Burleson, PhD, and Stefanie C.M. Burleson, PhD23 Nonclinical Safety Assessment of Biotechnology-Derived Products: Considerations and Challenges 405Barbara Mounho, PhD, DABT24 Gene and Cell Therapy Products 427Peter Working, PhD, DABT, Fellow ATS25 Vaccines: Preventive and Therapeutic Product Studies 439Deborah L. Novicki, PhD, DABT, Jayanthi J. Wolf, PhD, Lisa M. Plitnick, PhD, and Melanie Hartsough, PhD26 Toxicology Studies Conducted for Pesticides and Commodity Chemicals 465Elliot Gordon, PhD, DABT, and Linda A. Malley, PhD, DABT27 Medical Devices 485Gregory A. Kopia, PhD, and John F. Dooley, PhD28 Lessons from the Front Lines 505Christopher P. Chengelis, PhD, DABT, and C. Steven Godin, PhD, DABTIndex 519