Precision and Robustness of 2D-NMR for Structure and Assessment of Filgrastim Biosimilars

Published

February 5, 2016

Author(s)

Houman Ghasriani, Derek Hodgson, Robert G. Brinson, Ian McEwen, Lucinda F. Buhse, Steven Kozlowski, John Marino, Yves Aubin, David Keire

Abstract

The higher order structure of biotherapeutics is a critical quality attribute (CQA) that can be evaluated by nuclear magnetic resonance (NMR) spectroscopy at atomic resolution. NMR spectral "fingerprinting" can directly establish drug substance structural consistency across manufacturing changes or for comparing a biosimilar to an innovator reference product. Here, an inter-laboratory comparability study was performed on a US approved innovator product (filgrastim) and three unapproved, foreign-sourced filgrastim products using isotope-edited 2D-NMR at natural abundance. Due to its marketplace relevance, filgrastim was selected to establish standard protocols for the 2D-NMR method with the goal of general applicability to other protein therapeutics. Spectra acquired on the same samples on six different spectrometers, at four different field strengths in four different laboratories show highly similar "fingerprints" when analyzed using combined chemical shift difference (CCSD) or whole spectral point-by-point comparisons. The data demonstrate the high precision and robustness of NMR measurements for structure assessment.

Citation

Nature Biotechnology

Volume

34

Issue

2

Pub Type

Journals

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DOI Link

Keywords

2D-NMR fingerprint, G-CSF, Multivariate Analysis, biosimilars, follow-on, subsequent entry biologics

Citation

Ghasriani, H. , Hodgson, D. , Brinson, R. , McEwen, I. , Buhse, L. , Kozlowski, S. , Marino, J. , Aubin, Y. and Keire, D. (2016), Precision and Robustness of 2D-NMR for Structure and Assessment of Filgrastim Biosimilars, Nature Biotechnology, [online], https://doi.org/10.1038/nbt.3474 (Accessed April 15, 2024)