Preclinical Development Handbook

A clear, straightforward resource to guide you through preclinical drug development Following this book′s step–by–step guidance, you can successfully initiate and complete critical phases of preclinical drug development. The book serves as a basic,comprehensive reference to prioritizing and optimizing leads, toxicity, pharmacogenomics, modeling, and regulations. This single definitive, easy–to–use resource discusses all the issues that need consideration and provides detailed instructions for current methods and techniques. Each chapter was written by one or more leading experts in the field. These authors, representing the many disciplines involved in preclinical toxicology screening and testing, give you the tools needed to apply an effective multidisciplinary approach. The editor, with more than thirty years′ experience working with pharmaceutical and biotechnology companies, carefully reviewed all the chapters to ensure that each one is thorough, accurate, and clear. Among the key topics covered are: ∗ In vitro mammalian cytogenetics tests ∗ Phototoxicity ∗ Carcinogenicity studies ∗ The pharmacogenomics of personalized medicine ∗ Bridging studies ∗ Toxicogenomics and toxicoproteomics Each chapter offers a full exploration of problems that may be encountered and their solutions. The authors also set forth the limitations of various methods and techniques used in determining the safety and efficacy of a drug during the preclinical stage. This is a hands–on guide for pharmaceutical scientists involved in preclinical testing,enabling them to perform and document preclinical safety tests to meet all FDA requirements before clinical trials may begin.

Preface. 1 Preclinical Drug Development Planning ( Nirmala Bhogal, Robert Combes, and Michael Balls ). 2 Use of Project Teams in Preclinical Development ( Dorothy M. K. Keefe, Joanne M. Bowen, and Rachel J. Gibson ). 3 Relationship between Animal Models and Clinical Research: Using Mucositis as a Practical E xample ( Rachel J. Gibson, Joanne M. Bowen, and Dorothy M. K. Keefe ). 4 Bacterial Mutation Assay ( Premkumar Kumpati ). 5 In Vitro Mammalian Cell Mutation Assays ( C. Anita H. Bigger, Martha M. Moore, and Robert H. Heflich ). 6 In Vitro Mammalian Cytogenetic T ests ( R. Julian Preston ). 7 In Vivo Genotoxicity Assays ( Andreas Hartmann, Krista L. Dobo, and Hans–Jörg Martus ). 8 Repeat Dose Toxicity Studies ( Shayne Cox Gad ). 9 Irritation and Local Tissue Tolerance Studies in Pharmacetical S afety Assessment ( Shayne Cox Gad ). 10 Safety Assessment Studies: Immunotoxicity ( Jacques Descotes ). 11 Immunotoxicity Testing: ICH Guideline S8 and Related Aspects ( Hans–Gerd Pauels and John Taylor ). 12 Reproductive and Developmental Toxicology ( Ronald D. Hood and Robert M. Parker ). 13 Carcinogenicity Studies ( Shayne Cox Gad ). 14 Toxicokinetics: An Integral Component of Preclinical Toxicity S tudies ( Sonu Sundd Singh ). 15 In Vitro Toxicokinetics and Dynamics: Modeling and Interpretation of Toxicity Data ( Arie Bruinink ). 16 Toxicologic Pathology ( Paul B. Tchounwou and José A. Centeno ). 17 Secondary Pharmacodynamic Studies and In Vitro Pharmacological Profiling ( Duncan Armstrong, Jacques Migeon, Michael G. Rolf, Joanne Bowes, Mark Crawford, and Jean–Pierre Valentin ). 18 Current Practices in Safety Pharmacology ( Alan S. Bass, Peter K. S. Siegl, Gary A. Gintant, Dennis J. Murphy, and Roger Porsolt ). 19 Safety Assessment of Biotechnology–Derived T herapeutics ( Mary Ellen Cosenza ). 20 Preclinical Development of Protein Pharmaceuticals: An O verview ( Dipankar Das and Mavanur R. Suresh ). 21 The Pharmacogenomics of Personalized Medicine ( Ronald E. Reid ). 22 Genomics ( Dimitri Semizarov and Eric A. G. Blomme ). 23 Proteomics ( Juan Casado and J. Ignacio Casal ). 24 Toxicogenomics in Preclinical Development ( Eric A. G. Blomme, Dimitri Semizarov, and Jeffrey F. Waring ). 25 Toxicoproteomics: Preclinical Studies ( B. Alex Merrick and Maribel E. Bruno ). 26 Regulatory Considerations ( Evan B. Siegel and Duane B. Lakings ). 27 Regulatory Issues in Preclinical Safety Studies (U.S. FDA) ( Kenneth L. Hastings and William J. Brock ). 28 Selection and Utilization of CROs for Safety Assessment ( Joanne R. Kopplin and Ward R. Richter ). 29 Auditing and Inspecting Preclinical Research and Compliance with Good Laboratory Practice (GLP) ( N. J. Dent ). 30 Drug Impurities and Degradants and Their Safety Qualification ( Robin C. Guy ). 31 Bridging Studies in Preclinical Pharmaceutical Safety Assessment ( Shayne Cox Gad ). Index.