Brinson Robert G, Ghasriani Houman, Hodgson Derek J, Adams Kristie M, McEwen Ian, Freedberg Darón I, Chen Kang, Keire David A, Aubin Yves, Marino John P
Institute for Bioscience and Biotechnology Research, National Institute of Standards and Technology and the University of Maryland, 9600 Gudelsky Drive, Rockville, MD 20850, United States.
U.S. Food & Drug Administration, Center for Drug Evaluation and Research, Division of Pharmaceutical Analysis, 645 S. Newstead Avenue, St. Louis, MO 63110, United States; Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, Health Canada, 251 Sir Frederick Banting Drive, Ottawa, ON K1A 0K9, Canada.
J Pharm Biomed Anal. 2017 Jul 15;141:229-233. doi: 10.1016/j.jpba.2017.03.063. Epub 2017 Apr 4.
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 H-N 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.
生物治疗药物的高阶结构（HOS）是一项关键质量属性，可通过核磁共振（NMR）光谱在原子分辨率下进行评估。HOS的NMR光谱图谱可用于确定生物制品在整个生产变更过程中的HOS一致性，或用于比较生物类似药与创新型参比产品。之前一项使用非格司亭药品开展的实验室间研究表明，二维（2D）-NMR H-N异核相关光谱法是一种高度稳健且精确的方法，可使用高灵敏度NMR“冷探头”在天然丰度下绘制生物治疗药物的HOS图谱。在此，使用较低灵敏度的室温NMR探头证明了2D-NMR方法在对非格司亭产品的HOS进行指纹识别方面的适用性。结合化学位移偏差和主成分分析来说明2D-NMR方法在室温探头上实施时的性能和实验室间精密度。
