Using NMR Spectroscopy to Obtain the Higher Order Structure of Biopharmaceutical Products

作者：Aubin Yves; Jones Christopher; Freedberg Daron I

来源：Biopharm International, 2010, 28-34.

The higher order structure of complex biological therapeutics such as polysaccharide-containing vaccines, recombinant proteins, and monoclonal antibodies is an important quality attribute of biopharmaceutical products. The relationship between higher order structure and product efficacy is a crucial issue in comparability studies, be they assessments of manufacturing changes or follow-on biologics. Several biophysical methods, such as circular dichroism, fluorescence, and bioassays, are typical for assessing structure but none provide information at high resolution. Nuclear magnetic resonance (NMR) spectroscopy is a well-established technique for biomolecular structure determination, albeit underused in characterizing biotherapeutics. NMR is misperceived as too expensive or complicated and therefore is excluded from the methods toolbox to assess higher order structure. In this paper, we show simple applications of NMR that provide detailed information on higher order structure. We also address the complexity and cost of including NMR in the process and quality control environments.

• 出版日期2010-8