Raman spectroscopy as a real-time in situ analyzer for cell culture bioprocesses

5^th European Biosimilars Congress

June 27-29, 2016 Valencia, Spain

Alexander Pitters, Maryann Cuellar, Pat Wiegand, Sean Gilliam, Ian R Lewis and Bruno Lenain

Kaiser Optical Systems, France
Kaiser Optical Systems, Inc., USA

Scientific Tracks Abstracts: J Bioanal Biomed

Abstract :

Production of recombinant proteins using mammalian cell lines is a commonly used bioprocess in the biopharmaceutical field. Improvements in cell media and process control have been important in realizing improvements in cell viability and productivity, but there are many opportunities to further advance cell culture bioprocesses. A key factor toward further advancing cell culture bioprocesses is incorporation of in situ process analytical technologies (PAT) to enable in-process control. Molecular techniques - such as Raman spectroscopy - are widely used for PAT applications because they provide in situ information in real-time. Raman spectroscopy is a vibrational spectroscopic technique that provides a chemical and physical â�?�?fingerprintâ�? of a sample. The Raman spectroscopy â�?�?fingerprintâ�? provides simultaneous, in situ measurements of multiple bioprocess assays within a cell culture or fermentation bioprocess. Raman spectroscopy enables a more thorough bioprocess understanding and real-time control of nutrients and metabolites. Representative examples show how Raman spectra were used to generate multi-component qualitative and quantitative predictive models. We demonstrate real-time prediction and process control of glucose, lactate, glutamine, glutamate, ammonium, and viable cell density. When combined with PID, closed-loop, or other feedback controls, in situ Raman measurements can optimize feeding strategies and improve yield and titer. Recent feedback control studies underscore the capability of Raman to not only provide in situ chemical information, but also control protein quality. We provide customer examples in how Raman-controlled glucose feeding can optimize post-translational target protein glycosylation and Raman-controlled lactate accumulation can improve titer. Together, these studies demonstrate the value of Raman spectroscopy as an in situ bioprocess analyzer from process development to GMP manufacturing.

Biography :

Alexander Pitters is a Life-Science Engineer (M.Sc. - University of Technology and Economics Berlin), worked at Max Planck Institute for Molecular Genetics in Berlin as a Biologic-Technical Assistant, at Procter&Gamble Brussels Innovation Centre as a Process Development Engineer, and at Bayer Technology Services in Berkeley as a PAT-Biologics Engineer. He joined Kaiser as an Applications Scientist to analyze data, create chemometric models and develop business within the pharmaceutical industry.

Email: pitters@kosi.com