Detection and Quantification of Antibodies to Biopharmaceuticals

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
Jörgen Dahlström 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