Bioanalytical Aspects in Biological Therapeutics

Xiaohui Xu, PhD, is Director at Daiichi-Sankyo Inc. She is actively serving in the American Association of Pharmaceutical Scientists (AAPS) PK Assay Group and IQ Consortium Metabolite Working Group. She has extensive experiences in regulated bioanalytical field including global submissions, covering small molecules, biologics and new modalities. She has extensive publications and 2 book chapters. She received her Doctorate in Pharmaceutical Analysis from College of Pharmacy, the University of Georgia. Weifeng Xu, PhD, is Director at Merck & Co., Inc. He is an active member and leader in the AAPS and the European Bioanalysis Forum’s (EBF) immunogenicity community and has published multiple papers on immunogenicity assay development and validation. He is also co-leading the IQ Consortium Bioanalytical Considerations and Challenges for Cell Therapies subgroup. More recently Weifeng also became Bioanalytic lead to multiple vaccine projects within Merck including COVID-19 and pneumococcal to oversee all clinical immunogenicity assays.

Preface vii
Xiaohui Xu and Weifeng Xu

Foreword ix
Binodh DeSilva

Acknowledgments xiii

About the Editors xv

List of Contributors xvii

1 Overview of the Development of Biotherapeutics and the Role of Bioanalytical Sciences 1
Robert Dodge

2 Basic Immunology for Bioanalytical Testing of Biotherapeutics 23
Kang Chen and Weifeng Xu

3 Platform and Instrument Considerations in Bioanalytical Testing 51
Dominic Warrino and Franklin Spriggs

4 Pharmacokinetic Assays 67
Tong-Yuan Yang and Eric Wakshull

5 Recent Progress in Biomarker Bioanalysis and Target Engagement Assessment 87
Yan G. Ni, Lindsay E. King and Carmen Fernández-Metzler

6 Immunogenicity Risk Assessment for Biotherapeutics 141
Jochem Gokemeijer

7 Bioanalytical Strategy to Support Clinical Immunogenicity Assessment: Anti-drug Antibodies 159
Ying Wang and Michael Luong

8 Bioanalytical Scheme for Antidrug Neutralizing Antibody Assays 185
Weifeng Xu, Bonnie Wu and Jim McNally

9 Critical Reagents in Bioanalysis 209
Yang Xu, Agostinho Gomes Rocha, Shannon Chilewski, Krisna C. Duong-Ly, Kun Yang and Jonathan Haulenbeek

10 Statistical Aspects of Bioanalytical Testing 239
Arkady M. Gershteyn and Mark Ma

11 Bioanalytical Aspects in Biological Therapeutics: Biotransformation 277
Wenying Jian, Cong Wei and Jinping Gan

12 New Modalities: Multidomain Therapeutics and Gene Therapy Programs 309
Kelly Colletti and Mark Ma

13 Regulatory Aspects for Assay Development, Validation, and Sample Analysis 327
Amy Lavelle and Megan Wiberg

Index 355