Techniques for the facile characterization of the critical quality attribute (CQA) of higher order structure (HOS) of biologic drugs are critical for establishing consistency in drug manufacturing, detecting process-related drug product variations and comparing a biosimilar to an innovator reference product. Recently, two-dimensional nuclear magnetic resonance (2D-NMR) methods have been introduced for HOS assessment of biopharmaceutical samples, including monoclonal antibody (mAb) drugs, at atomic resolution. Here, an inter-laboratory study was performed using samples of the Fab domain derived from the NISTmAb standard. A total of 451 spectral maps were acquired on thirty-nine different NMR spectrometers ranging from 500 MHz to 900 MHz in twenty-six different laboratories. These spectral maps from all instruments could be correlated directly to HOS through precision metrics of combined chemical shift deviation and similarity metrics through principal component analysis. Results from the study demonstrate the chemometric-structural relationships and provide a pathway for harmonized implementation of 2D-NMR methods within the biopharmaceutical laboratory for drug discovery, process development, and quality control.

Establishing a pathway for robust implementation of higher order structure assessment of monoclonal antibodies therapeutics by 2D-NMR

255th National Meeting (2018)

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