title: Near-infrared and two-dimensional fluorescence spectroscopy monitoring of monoclonal antibody fermentation media quality: aged media decreases cell growth.
abstract: In biomanufacturing processes, the influence of feedstock components on product yield and quality is considerable and often poorly understood. Here we describe the capabilities of near-infrared spectroscopy (NIRS) and two dimensional (2D)-fluorescence spectroscopy in detecting chemical changes over time in two types of culture media (one basal media and one feed media) used in the production of monoclonal antibodies (mAbs) by Chinese hamster ovary (CHO) cells. Both spectroscopies were able to detect compositional changes in basal media over storage period of 12 weeks. NIRS was more effective in detecting changes in feed medium composition. The impact of storage time in process performance was evaluated by using aged media components in mAb cultivations. The study suggests that basal media aging results in a decrease of the integral of viable cells (IVC) (cell growth over time), while product titer is not significantly affected. Feed media appears to be less sensitive to storage and no correlation between the age of the media and cell culture performance was detected. Results obtained provide a basis on which to further improve cell culture raw material quality assessment using vibrational (e.g. NIRS) and optical (e.g. 2D-fluorescence) spectroscopic methods.
authors.affiliation: Roche Diagnostics GmbH-Pharmaceutical Biotech Production & Development, Penzberg, Germany. christian.hakemeyer@roche.com
authors.forename: Christian
authors.initials: C
authors.lastname: Hakemeyer
authors.forename: Ulrike
authors.initials: U
authors.lastname: Strauss
authors.forename: Silke
authors.initials: S
authors.lastname: Werz
authors.forename: Francisca
authors.initials: F
authors.lastname: Folque
authors.forename: Jose C
authors.initials: JC
authors.lastname: Menezes
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D016466:CHO Cells; D018929:Cell Culture Techniques / Q000379:methods*; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media; D005285:Fermentation; D025341:Principal Component Analysis; D013050:Spectrometry, Fluorescence / Q000379:methods; D019265:Spectroscopy, Near-Infrared; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D003470:Culture Media
keywords: 2D-fluorescence spectroscopy; Aging effects; Media components; Monoclonal antibody cultivation; Near-infrared spectroscopy