Application of 2D-NMR with room temperature NMR probes for the assessment of the higher order structure of filgrastim.

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TitleApplication of 2D-NMR with room temperature NMR probes for the assessment of the higher order structure of filgrastim.
Publication TypeJournal Article
Year of Publication2017
AuthorsBrinson, RG, Ghasriani, H, Hodgson, DJ, Adams, KM, McEwen, I, Freedberg, DI, Chen, K, Keire, DA, Aubin, Y, Marino, JP
JournalJ Pharm Biomed Anal
Volume141
Pagination229-233
Date Published2017 Jul 15
ISSN1873-264X
Abstract

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 (1)H(N)-(15)N(H) 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, the applicability of the 2D-NMR method to fingerprint the HOS of filgrastim products is demonstrated 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.

DOI10.1016/j.jpba.2017.03.063
Alternate JournalJ Pharm Biomed Anal
PubMed ID28454057