An Introduction to Bioanalysis of Monoclonal Antibodies

Ramani, Varun; Bhardwaj, Sanjeev; Ismaiel, Omnia A.

doi:10.1007/978-3-030-97193-9_2

Varun Ramani³,
Sanjeev Bhardwaj⁴ &
Omnia A. Ismaiel⁵

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 57))

748 Accesses

Abstract

Therapeutic monoclonal antibodies are one of the largest and fastest growing class of large-molecule biotherapeutics. Accurate and reliable quantification of these biotherapeutics in biological matrix is mandatory for their pharmacokinetic and pharmacodynamic assessments. Bioanalytical assays thus play an integral role in determining safety and efficacy of therapeutic monoclonal antibodies. Both immunoassays and liquid chromatography with tandem mass spectrometry (LC-MS/MS) based bioanalytical assays have been used to follow disposition of these biotherapeutics. This chapter provides an introductory overview of the therapeutic monoclonal antibodies, bioanalytical assays used for their pharmacokinetics and immunogenicity assessments, and regulatory considerations for the bioanalytical assays.

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Abbreviations

ADA:: Anti-drug antibody
ADC:: Antibody drug conjugate
ADCC:: Antibody-dependent cellular cytotoxicity
Anti-ID Ab:: Anti-idiotype antibodies
C1q:: Complement 1
CDC:: Complement-dependent cytotoxicity
CDR:: Complementarity determining region
DTT:: Dithiothreitol
EMA:: European Medicines Agency
Fab:: Fragment antigen binding region of the mAb
Fc:: Crystallizable fragment region of mAb
FcRn:: Neonatal Fc receptor
FDA:: US Food and Drug Administration
IAA:: Iodoacetic acid
IAM:: Iodoacetamide
IM:: Intramuscular
IgG:: Immunoglobulin G
IV:: Intravenous
LBA:: Ligand binding assay
LC-MS/MS or LCMS:: Liquid chromatography with tandem mass spectrometry
LLOQ:: Lower limit of quantitation
mAb:: Monoclonal antibody
PD:: Pharmacodynamics
PK:: Pharmacokinetics
RES:: Reticuloendothelial system
SC:: Subcutaneous
scfv:: Single-chain variable fragment
SIL-IS:: Stable isotopically labeled internal standard
TNF-α:: Tumor necrosis factor α
TCEP:: Tris (2-carboxyethyl) phosphine hydrochloride
VEGF-A:: Vascular endothelial growth factor type A

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Authors and Affiliations

Inhibrx, La Jolla, CA, USA
Varun Ramani
Janssen Biotherapeutics, Spring House, PA, USA
Sanjeev Bhardwaj
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Zagazig University, Ash Sharqiyah, Egypt
Omnia A. Ismaiel

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Varun Ramani
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Sanjeev Bhardwaj
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Omnia A. Ismaiel
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Drug Disposition and Design/DDT, Biopharma R&D, EMD Sereno Research and Development Institute, Billerica, MA, USA
Seema Kumar

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Ramani, V., Bhardwaj, S., Ismaiel, O.A. (2022). An Introduction to Bioanalysis of Monoclonal Antibodies. In: Kumar, S. (eds) An Introduction to Bioanalysis of Biopharmaceuticals. AAPS Advances in the Pharmaceutical Sciences Series, vol 57. Springer, Cham. https://doi.org/10.1007/978-3-030-97193-9_2

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DOI: https://doi.org/10.1007/978-3-030-97193-9_2
Published: 24 August 2022
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