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Solid-state NMR characterization of lyophilized formulations of monoclonal antibody therapeutics.

Published

Author(s)

Jacqueline Perodeau, Luke Arbogast, Andrew Nieuwkoop

Abstract

Monoclonal antibodies (mAbs) are an important and growing class of biotherapeutic drug. Methods development for characterization of critical quality attributes, including higher order structure (HOS), of mAbs remains an area of active inquiry. Recently, solution-state nuclear magnetic resonance (NMR) spectroscopy has received increased attention and a means for reliable, high-resolution HOS characterization of aqueous based preparations of mAbs. While mAbs are predominantly formulated in solution, up to 20 % are prepared as solid amorphous powders and techniques for robust characterization of HOS in the solid state remain limited. We propose here, the use of solid-state NMR (ssNMR) fingerprinting to inform directly on the HOS of solid preparations of mAbs. Using lyophilized samples of the NISTmAb reference material prepared with different formulation conditions, we demonstrate the proof-of-concept for recording 1H-13C cross-polarization (hC-CP) buildup spectral series at natural isotopic abundance mAb samples. We further demonstrate that hC-CP buildup series are sensitive to differences in formulation and how using Principal Component Analysis (PCA), samples can be differentiated from one another and provide structural details about important molecular interactions in solid phase protein formulations. Results from this study contribute to establishing the foundation for the use of ssNMR for HOS characterization of solid-phase biotherapeutics.
Citation
Molecular Pharmaceutics
Volume
20
Issue
3

Keywords

Monoclonal antibodies, nuclear magnetic resonance, principal component analysis, higher order structure

Citation

Perodeau, J. , Arbogast, L. and Nieuwkoop, A. (2023), Solid-state NMR characterization of lyophilized formulations of monoclonal antibody therapeutics., Molecular Pharmaceutics, [online], https://doi.org/10.1021/acs.molpharmaceut.2c00676, https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=935251 (Accessed May 26, 2024)

Issues

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Created January 26, 2023, Updated March 9, 2023