Systematic Development of a Size Exclusion Chromatography Method for a Monoclonal Antibody with High Surface Aggregation Propensity (SAP) Index.

Autor:	Knihtila R; Dragonfly Therapeutics, Waltham, MA 02451, USA., Song Y; GlaxoSmithKline, Waltham, MA 02140, USA., Chemmalil L; BMS Process Development Analytical Group, 38 Jackson Rd, Devens, MA 01434, USA. Electronic address: letha.chemmalil@BMS.com., Ding J; BMS Process Development Analytical Group, 38 Jackson Rd, Devens, MA 01434, USA., Mussa N; Ultragenyx Pharmaceutical Inc., Novato, CA 94949, USA., Li ZJ; BMS Analytical Development & Analytical Attribute Science in Biologics, 38 Jackson Rd, Devens, MA 01434, USA.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2021 Jul; Vol. 110 (7), pp. 2651-2660. Date of Electronic Publication: 2021 Apr 02.
DOI:	10.1016/j.xphs.2021.03.023
Abstrakt:	Size Exclusion Chromatography (SEC) has been widely used to assess aggregate content in bio-pharmaceutical drugs such as monoclonal antibodies (mAbs), and is routinely used during method development and release testing. Electrostatic interactions between protein analytes and SEC column resin are commonly observed besides the primary mode of size separation during SEC method development, which needs to be minimized. An effective method to minimize electrostatic interactions is through increasing mobile phase (MP) salt concentration. However; increasing salt concentration in MP will induce increased hydrophobicity of proteins and increased hydrophobic interactions between protein and stationary phase, as demonstrated for mAb-A in this paper, a protein with high surface aggregation propensity (SAP) score and an isoelectric point near mobile phase pH. In this work, a systematic, Design of Experimental approach was taken to identify optimal SEC method conditions including column type, buffer composition, ionic strength, pH and additives. The optimized method was demonstrated to be robust towards small changes in method operation conditions and was qualified for use in product release and stability studies. Additionally, biophysical and computational studies were performed to elucidate the role of MP additives, which supports the use of arginine as an essential additive to minimize undesirable hydrophobic interactions between proteins and stationary phase. (Copyright © 2021 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu