Flow Cytometry in Drug Discovery and Development

This book covers the unique application of flow cytometry in drug discovery and development. The first section includes two introductory chapters, one on flow cytometry and one on biomarkers, as well as a chapter on recent advances in flow cytometry. The second section focuses on the unique challenges and added benefits associated with the use of flow cytometry in the drug development process. The third section contains a single chapter presenting an in depth discussion of validation considerations and regulatory compliance issues associated with drug development.

Preface xi Foreword xiii Acknowledgments xv Contributors xvii Part I Introduction 1 Philip Marder and Virginia Litwin 1 Introduction to Flow Cytometry 3 Elizabeth Raveche, Fatima Abbasi, Yao Yuan, Erica Salerno, Siddha Kasar, and Gerald E. Marti 2 Recent Advances in Flow Cytometry: Platforms, Tools, and Challenges for Data Analysis 23 Paul J. Smith, Roy Edward, and Rachel J. Errington 3 Introduction to Biomarkers 55 Ole Vesterqvist and Manjula P. Reddy Part II Flow Cytometry In The Drug Development Process 69 Virginia Litwin and Philip Marder 4 HTS Flow Cytometry, Small-Molecule Discovery, and the NIH Molecular Libraries Initiative 71 Larry A. Sklar and Bruce S. Edwards 5 A Multiparameter Approach to Cell Cycle Analysis as a Standard Tool in Oncology Drug Discovery 99 Carmen Raventos-Suarez and Byron H. Long 6 Flow Cytometry in Preclinical Toxicology/Safety Assessment 123 David McFarland and Kristi R. Harkins 7 Use of Flow Cytometry to Study Drug Target Inhibition in Laboratory Animals and in Early-Phase Clinical Trials 151 David W. Hedley 8 CD4 T Cell Assessments in Evaluation of HIV Therapeutics 169 Thomas N. Denny, Raul Louzao, John Wong, and Brooke Walker 9 Monitoring the Cellular Components of the Immune System During Clinical Trials: A Translational Medicine Approach 189 Virginia Litwin and James Andahazy 10 Immunogenicity Testing Using Flow Cytometry 205 Denise M. O.Hara and Valerie Theobald 11 Pharmacokinetics by Flow Cytometry: Recommendations for Development and Validation of Flow Cytometric Method for Pharmacokinetic Studies 225 Yuanxin Xu and Susan M. Richards Part III Validation And Regulatory Compliance 241 Virginia Litwin and Philip Marder 12 Regulatory Compliance and Method Validation 243 Carla G. Hill, Dianna Y. Wu, John Ferbas, Virginia Litwin, and Manjula P. Reddy 13 Instrument Validation for Regulated Studies 267 John Ferbas and Michelle J. Schroeder Part IV Future Directions 279 Virginia Litwin and Philip Marder 14 Probability State Modeling: A New Paradigm for Cytometric Analysis 281 C. Bruce Bagwell 15 Phospho Flow Cytometry: Single-Cell Signaling Networks in Next-Generation Drug Discovery and Patient Stratification 303 Peter O. Krutzik, Sean C. Bendall, Matthew B. Hale, Jonathan M. Irish, and Garry P. Nolan Index 335