Application of 2D-NMR with Room Temperature NMR Probes for the Assessment of the Higher Order Structure of Filgrastim
Robert G. Brinson, Houman Ghasriani, Derek Hodgson, Adams Kristie, Ian McEwen, Kang Chen, Yves Aubin, John P. Marino
The higher order structure (HOS) of biotherapeutics is a critical quality attribute that can be evaluated by nuclear magnetic resonance (NMR) spectroscopy at atomic resolution. NMR spectral mapping of HOS can be used to establish HOS consistency of a biologic across manufacturing changes or to compare a biosimilar to an innovator reference product. A previous inter-laboratory study performed using filgrastim drug products demonstrated that two-dimensional (2D)-NMR 1HN-15NH heteronuclear correlation spectroscopy is a highly robust and precise method for mapping the HOS of biologic drugs at natural abundance using high sensitivity NMR cold probes. Here, we demonstrate applicability of the 2D-NMR method to fingerprint the HOS of filgrastim products using lower sensitivity, room temperature NMR probes. Combined chemical shift deviation and principal component analysis are used to illustrate the performance and inter-laboratory precision of the 2D-NMR method when implemented on room temperature probes.
, Ghasriani, H.
, Hodgson, D.
, Kristie, A.
, McEwen, I.
, Chen, K.
, Aubin, Y.
and Marino, J.
Application of 2D-NMR with Room Temperature NMR Probes for the Assessment of the Higher Order Structure of Filgrastim, Journal of Pharmaceutical and Biomedical Analysis, [online], https://doi.org/10.1016/j.jpba.2017.03.063
(Accessed February 25, 2024)