Assessment of the Higher Order Structure (HOS) of monoclonal Antibodies (mAbs) by NMR and Orthogonal Techniques

Donna Baldisseri Ph.D.

January 28th 5pm EST

Amgen 360 Binney St, Cambridge, MA 02141

Happy Hour Sponsored by Bruker Biospin

This will be a hybrid event. The speaker will be on line but we would like to get the community to get together in person. We highly encourage members to join us at Amgen.

Abstract

The analytical comparability of biologic products and their biosimilars ensures product quality and is required for regulatory approval. In this study, Nuclear Magnetic Resonance  (NMR) spectroscopy was used to evaluate the HOS of Humira (adalimumab) and its biosimilars under normal and photo-stressed conditions. Under normal conditions, 1D and 2D NMR spectra showed strong structural similarity among all products. However, photo-stressed samples exhibited distinct structural differences which included increased methionine oxidation and localized conformational changes and which were seen to be influenced by Closed Container Systems (CCS) and formulation. These changes correlated with findings from size-exclusion chromatography, capillary isoelectric focusing, and mass spectrometry (MS), which revealed size and charge heterogeneity, as well as site-specific methionine oxidation in the heavy chains.  In contrast, circular dichroism spectral analysis showed minimal variation in secondary structures. These results underscore the utility of NMR as a sensitive tool for comparative structural analysis of monoclonal antibodies and their biosimilars, particularly under stress conditions, and highlight the impact of formulation and CCS on product stability.

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