A biopharmaceutical grade poloxamer designed with less hydrophobic contaminants and shown to resolve growth issues for mammalian cell lines was implemented in a commercial biopharmaceutical process and expected to improve protection of cells from hydrodynamic stress [[1]](#ref-0001). However, contrary to expected results, the cell growth and resultant titer further declined. This was not consistent with prior reports in literature [[2]](#ref-0002), which demonstrated that these hydrophobic contaminants present in P188 poloxamer contributed to low performance due to inefficiency in protecting cells from shear stress. An analytical screening tool as well as a novel, high shear stress bioreactor model was developed and used to determine that an overall higher poloxamer average molecular weight was actually the root cause of poor growth in this SP2/0 production cell line. This demonstrates an increased SP2/0 sensitivity to subtle differences in poloxamer molecular weight distribution.