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A multi‐faceted approach to analyzing glucose heat‐degradants and evaluating impact to a CHO cell culture process
Author(s) -
Moore Brandon,
Grinnell Chris,
Boumajny Boris,
Chen Rachel,
Frenkel Ruth,
Vilmorin Phil,
Sosic Zoran,
Khattak Sarwat
Publication year - 2020
Publication title -
aiche journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.958
H-Index - 167
eISSN - 1547-5905
pISSN - 0001-1541
DOI - 10.1002/aic.16295
Subject(s) - chemistry , formic acid , chromatography , toxicity , chinese hamster ovary cell , 5 hydroxymethylfurfural , high performance liquid chromatography , biochemistry , organic chemistry , fructose , receptor
Glucose solutions are commonly heated before use in medical and biotech applications to maintain cleanliness, however the resulting degradants can be toxic. This study examines two approaches to evaluating the heat degradants resulting from holding a 40% glucose solution at 55°C for 5 weeks: first, chemical changes to the solution were identified and quantified via analytical testing, and second the toxicity of the heat‐degraded 40% glucose solution was evaluated empirically by using it as a feed stock for a fed‐batch CHO‐cell‐based protein therapeutic manufacturing process. Colorimetric analysis quantified a color change during heating, and liquid chromatography assays measured an increase in the concentrations of two unknown degradants along with the commonly identified glucose impurity 5‐hydroxymethylfurfural (5‐HMF). Solution pH decreased over time, corresponding with an increase in formic acid concentration as measured via GC–MS. Despite this, cell culture toxicity was not observed, and protein productivity and product quality were maintained.