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Analysis of chemometric models applied to Raman spectroscopy for monitoring key metabolites of cell culture
Authors:Carl Rafferty  Kjell Johnson  Jim O'Mahony  Barbara Burgoyne  Rosemary Rea  Karin M. Balss
Affiliation:1. BioTherapeutic Development, Janssen Sciences Ireland UC, Cork, Ireland;2. Stat Tenacity, Saline, Michigan;3. Biological Sciences, Cork Institute of Technology, Cork, Ireland;4. Product Quality Management, Janssen Sciences Ireland UC, Cork, Ireland;5. Advanced Technology Center of Excellence, Janssen Supply Group, New Jersey
Abstract:The Food and Drug Administration (FDA) initiative of Process Analytical Technology (PAT) encourages the monitoring of biopharmaceutical manufacturing processes by innovative solutions. Raman spectroscopy and the chemometric modeling tool partial least squares (PLS) have been applied to this aim for monitoring cell culture process variables. This study compares the chemometric modeling methods of Support Vector Machine radial (SVMr), Random Forests (RF), and Cubist to the commonly used linear PLS model for predicting cell culture components—glucose, lactate, and ammonia. This research is performed to assess whether the use of PLS as standard practice is justified for chemometric modeling of Raman spectroscopy and cell culture data. Model development data from five small-scale bioreactors (2 × 1 L and 3 × 5 L) using two Chinese hamster ovary (CHO) cell lines were used to predict against a manufacturing scale bioreactor (2,000 L). Analysis demonstrated that Cubist predictive models were better for average performance over PLS, SVMr, and RF for glucose, lactate, and ammonia. The root mean square error of prediction (RMSEP) of Cubist modeling was acceptable for the process concentration ranges of glucose (1.437 mM), lactate (2.0 mM), and ammonia (0.819 mM). Interpretation of variable importance (VI) results theorizes the potential advantages of Cubist modeling in avoiding interference of Raman spectral peaks. Predictors/Raman wavenumbers (cm−1) of interest for individual variables are X1139–X1141 for glucose, X846–X849 for lactate, and X2941–X2943 for ammonia. These results demonstrate that other beneficial chemometric models are available for use in monitoring cell culture with Raman spectroscopy.
Keywords:bioprocess  cell culture  chemometric analysis  monitoring  process analytical technology  Raman spectroscopy
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