Uncovering new poloxamer attributes which significantly impact mammalian cell growth performance

Abstract

A problem with the supply of raw materials has significantly affected the production of a commercial recombinant biopharmaceutical. The substance known as poloxamer (P188), historically used to protect mammalian cells from shear stress, was found to be the reason for reduced viable cell density and IgG titer. To address the issue, a small-scale model was developed and analytical methods were evaluated to screen incoming lots of the material. After contacting the poloxamer supplier, it was discovered that they had created a new preparation of poloxamer intended for cell culture applications, with the goal of eliminating hydrophobic contaminants that reduce its effectiveness (Guth et al., 2017) [1]. However, contrary to expectations, the new preparation resulted in even lower cell growth and titer. This finding was inconsistent with previous reports, which had suggested that hydrophobic contaminants contributed to low performance due to inefficiency in protecting cells from shear stress (Peng et al., 2016) [2]. The team developed an analytical screening tool and a novel high shear stress bioreactor model to investigate the issue. They found that the overall higher average molecular weight of poloxamer was actually the root cause of poor growth in the SP2/0 production cell line, demonstrating the increased sensitivity of SP2/0 cells to subtle differences in poloxamer molecular weight distribution.