Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics

Published

January 1, 2019

Author(s)

Robert G. Brinson, John P. Marino, Frank Delaglio, Luke W. Arbogast, Ryan M. Evans, Anthony J. Kearsley, Yves Aubin, Gregory Pierens, Xinying Jia, David Keizer, Jonas Stahle, Goran Widmalm, Chad Lawrence, Patrick Reardon, John Cort, Koichi Kato, Stuart Parnham, Andreas Blomgren, Torgny Rundlof, Kang Chen, David Keire, Thea Suter-Stahel, Gerhard Wider, Donna Baldisseri, Julie Wu, Mats Wikstrom, Medhi Mobli

Abstract

Of the top ten drugs on the global market in 2016, seven of them are biologics with a combined market value of over US$60 billion. Moreover, around 2,800 biopharmaceuticals, many of them monoclonal antibodies (mAbs), are in some stage of clinical development. With increasing interest in using mAbs as a platform for biopharmaceuticals has emerged the need for new analytical techniques that can more precisely assess the critical quality attributes (CQAs) of these large and very complex drugs. One CQA, higher order structure (HOS), is unique to biopharmaceuticals and essential for establishing consistency in biopharmaceutical manufacturing, detecting process-related product variations and comparing the structure of one biologic to another. Recently, two-dimensional nuclear magnetic resonance spectroscopy (2D-NMR) methods have been introduced that allow for the precise comparison of the HOS between two proteins, including monoclonal antibodies (mAb). Here, an inter-laboratory comparison involving 26 industrial, government and academic laboratories worldwide was performed as a benchmark using a standard mAb from NIST, to facilitate the translation of the 2D-NMR method into routine use for biopharmaceutical development. From over 400 spectral maps acquired on thirty-nine different NMR spectrometers ranging from 500 MHz to 900 MHz, chemometric analyses demonstrate reliable spectral fingerprints for the assessment of HOS, providing the measurement reproducibility and assurance needed by industry and regulatory agencies to enable adoption of 2D-NMR for the thorough assessment of the higher order structure of protein therapeutics, including mAbs.

Citation

mAbs

Volume

11

Issue

1

Pub Type

Journals

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DOI Link

Keywords

2D-NMR, higher order structure, NISTmAb, biomanufacturing

Citation

Brinson, R. , Marino, J. , Delaglio, F. , Arbogast, L. , Evans, R. , Kearsley, A. , Aubin, Y. , Pierens, G. , Jia, X. , Keizer, D. , Stahle, J. , Widmalm, G. , Lawrence, C. , Reardon, P. , Cort, J. , Kato, K. , Parnham, S. , Blomgren, A. , Rundlof, T. , Chen, K. , Keire, D. , Suter-Stahel, T. , Wider, G. , Baldisseri, D. , Wu, J. , Wikstrom, M. and Mobli, M. (2019), Enabling adoption of 2D-NMR for the higher order structure assessment of monoclonal antibody therapeutics, mAbs, [online], https://doi.org/10.1080/19420862.201 (Accessed October 12, 2025)