Detection and Quantification of Antibodies to Biopharmaceuticals – Practical and Applied Considerations

MICHAEL G. TOVEY, PhD, INSERM Director of Research in the Laboratory of Biotechnology and Applied Pharmacology, Ecole Normale Superieure de Cachan, France. He is an Associate Editor of the Journal of Interferon and Cytokine Research and author of more than two hundred articles on interferon, cytokines, and biotechnology.

INTRODUCTION : A PERSPECTIVE ix Michael G. Tovey CONTRIBUTORS xxi PART I RISK-BASED STRATEGIES 1 1 Principles of Risk Assessment and Monitoring of Antibody Responses to Biopharmaceuticals 3 Eugen Koren, Erik Foehr, and Charles A. O'Neill PART II REGULATORY REQUIREMENTS 13 2 Immunogenicity of Therapeutic Proteins: A Regulatory Perspective 15 Susan Kirshner 3 Guidance on Immunogenicity Assessment of Biologically Derived Therapeutic Proteins: A European Perspective 37 Meenu Wadhwa and Robin Thorpe 4 Japanese Regulatory Perspective on Immunogenicity 57 Takao Hayakawa and Akiko Ishii-Watabe PART III PRINCIPAL TECHNOLOGIES EMPLOYED FOR THE QUANTIFICATION OF ANTI-DRUG ANTIBODIES 81 5 Enzyme Immunoassays and Radioimmunoassays for Quantification of Anti-TNF Biopharmaceuticals and Anti-Drug Antibodies 83 Klaus Bendtzen and Morten Svenson 6 Confirmatory Immunogenicity Assays 103 Eric Wakshull and Daniel Coleman 7 The Use of Pharmacodynamics as a Surrogate Marker for the Detection of Anti-Drug Neutralizing Antibodies 119 Florian Deisenhammer 8 Cell-Based Assays for the Detection of Neutralizing Antibodies to Interferon Beta (IFN-beta) and Tumor Necrosis Factor Alpha (TNF-alpha) Inhibitors 133 Anthony Meager 9 Detection of Neutralizing Antibodies against Interferon Beta by Real-Time RT-PCR 157 Francesca Gilli and Antonio Bertolotto 10 Competitive Ligand-Binding Assays for the Detection of Neutralizing Antibodies 175 Bonnie W. Wu, George R. Gunn III, and Gopi Shankar 11 The Use of Surface Plasmon Resonance for the Detection and Characterization of Antibodies 193 Steven J. Swanson and Daniel Mytych 12 Hypersensitivity Reactions to Biopharmaceuticals: Detection and Quantification of Drug-Specific IgE Antibodies 211 Jorgen Dahlstrom and Lennart Venemalm PART IV ASSAY STANDARDIZATION AND VALIDATION 233 13 Standardization and Validation of Immunoassays 235 Daniel Kramer 14 Standardization and Validation of Cell-Based Assays for the Detection of Neutralizing Anti-Drug Antibodies 243 Deborah Finco-Kent and Amy Grenham 15 Standardization of Neutralizing Antibody Unitage by Bioassay Design: Constant Antigen and Constant Antibody Methodology 269 Sidney E. Grossberg, Yoshimi Kawade, and Leslie D. Grossberg PART V STATISTICAL CONSIDERATIONS 287 16 Cut Points and Performance Characteristics for Anti-Drug Antibody Assays 289 Viswanath Devanarayan and Michael G. Tovey 17 Dilutional Linearity for Neutralizing Antibody Assays 309 David Lansky and Carrie Wager PART VI ADAPTATION OF ANTI-DRUG ANTIBODY ASSAYS TO CHALLENGING CONDITIONS 319 18 Detection of Antibodies to Biopharmaceuticals in the Presence of High Levels of Circulating Drug 321 Arno Kromminga and Michael G. Tovey 19 Antibody Assays in Animal Research 331 Vera Brinks, Francesca Gilli, Melody Sauerborn, and Huub Schellekens 20 Immunogenicity of Microbial Digestive Enzymes for Oral Replacement Therapy in Pancreatic Exocrine Insufficiency 343 Claudia Berger and Uwe Niesner PART VII NOVEL TECHNOLOGIES FOR THE QUANTIFICATION OF NEUTRALIZING ANTIBODIES 369 21 Measurement of Biologically Active Drug as an Approach to Detection of Anti-Drug Neutralizing Antibodies 371 Yao Zhuang and Shalini Gupta 22 A Novel One-Step Cell-Based Assay for Quantification of Neutralizing Antibodies to Biopharmaceuticals 383 Christophe Lallemand and Michael G. Tovey INDEX 399