Near-infrared and two-dimensional fluorescence spectroscopy monitoring of monoclonal antibody fermentation media quality: Aged media decreases cell growth

• Published in: Biotechnology journal Vol. 8; no. 7; pp. 835 - 846
• Main Authors: Hakemeyer, Christian, Strauss, Ulrike, Werz, Silke, Folque, Francisca, Menezes, Jose C.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01-07-2013; WILEY‐VCH Verlag
• Subjects: 2D-fluorescence spectroscopy; Aging; Aging effects; Animals; Antibodies, Monoclonal - metabolism; Cell Culture Techniques - methods; CHO Cells; Cricetinae; Cricetulus; Culture Media; Fermentation; Media components; Monoclonal antibody cultivation; Near-infrared spectroscopy; Principal Component Analysis; Spectrometry, Fluorescence - methods; Spectroscopy, Near-Infrared; Time Factors; Media components; 2D-fluorescence spectroscopy; Monoclonal antibody cultivation; Aging effects; Near-infrared spectroscopy
• ISSN: 1860-6768; 1860-7314
• DOI: 10.1002/biot.201200355

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.
The effect of raw materials variability on product titer and quality in bio‐manufacturing is considerable and often poorly understood. A strategy to identify compositional changes over time in two media components (one basal and one feed media) using fast, multiparametric, fingerprinting techniques, i.e. near‐infrared and two‐dimensional fluorescence spectroscopies is presented. The study suggests that basal media aging results in a decrease of the integral of viable cells (IVC) i.e. cell growth over time.