Application of Raman spectroscopy in monoclonal antibody producing continuous systems for downstream process intensification |
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Authors: | Denizhan Yilmaz Hamidreza Mehdizadeh Dunie Navarro Amar Shehzad Michael O'Connor Philip McCormick |
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Affiliation: | 1. Global Technology & Engineering, Pfizer Global Supply, Pfizer Inc., Peapack, New Jersey;2. Bioprocess Research & Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Chesterfield, Missouri;3. Bioprocess Research & Development, Biotherapeutics Pharmaceutical Sciences, Pfizer Inc., Andover, Massachusetts |
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Abstract: | Monoclonal antibodies (mAbs) are biopharmaceuticals produced by mammalian cell lines in bioreactors at a variety of scales. Cell engineering, media optimization, process monitoring, and control strategies for in vitro production have become crucial subjects to meet increasing demand for these high value pharmaceuticals. Raman Spectroscopy has gained great attention in the pharmaceutical industry for process monitoring and control to maintain quality assurance. For the first time, this article demonstrated the possibility of subclass independent quantitative mAb prediction by Raman spectroscopy in real time. The developed model estimated the concentrations of different mAb isotypes with average prediction errors of 0.2 (g/L) over the course of cell culture. In situ Raman spectroscopy combined with chemometric methods showed to be a useful predictive tool for monitoring of real time mAb concentrations in a permeate stream without sample removal. Raman spectroscopy can, therefore, be considered as a reliable process analytical technology tool for process monitor, control, and intensification of downstream continuous manufacturing. The presented results provide useful information for pharmaceutical industries to choose the most appropriate spectroscopic technology for their continuous processes. |
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Keywords: | CHO cell culture multivariate modeling process analytical technology process monitoring Raman spectroscopy |
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