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Raman spectroscopic based chemometric models to support a dynamic capacitance based cell culture feeding strategy

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Abstract

Multiple process analytical technology (PAT) tools are now being applied in tandem for cell culture. Research presented used two in-line probes, capacitance for a dynamic feeding strategy and Raman spectroscopy for real-time monitoring. Data collected from eight batches at the 15,000 L scale were used to develop process models. Raman spectroscopic data were modelled using Partial Least Squares (PLS) by two methods—(1) use of the full dataset and (2) split the dataset based on the capacitance feeding strategy. Root mean square error of prediction (RMSEP) for the first model method of capacitance was 1.54 pf/cm and the second modelling method was 1.40 pf/cm. The second Raman method demonstrated results within expected process limits for capacitance and a 0.01% difference in total nutrient feed compared to the capacitance probe. Additional variables modelled using Raman spectroscopy were viable cell density (VCD), viability, average cell diameter, and viable cell volume (VCV).

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Acknowledgements

The authors thank the Manufacturing Operations and Manufacturing Sciences teams at the Biogen Hillerod site. A grateful thanks to the Irish Research Council for funding. Also, thanks to Barry McCarthy, Ronan Hayes and the Janssen department—BioTherapeutic Development.

Funding

Irish Research Council. Grant Number: EPSPG/2015/150.

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Authors and Affiliations

  1. Janssen Sciences Ireland UC, BioTherapeutic Development, Ringaskiddy, Cork, Ireland

    Carl Rafferty & Caitlin O’Mahony-Hartnett

  2. Cork Institute of Technology, Biological Sciences, Cork, Ireland

    Carl Rafferty, Jim O’Mahony & Rosemary Rea

  3. Janssen Sciences Ireland UC, Product Quality Management, Cork, Ireland

    Barbara Burgoyne

  4. Janssen Supply Group, Advanced Technology Center of Excellence, Raritan, NJ, USA

    Karin M. Balss & Olav Lyngberg

  5. Biogen, Global Process Analytics, Research Triangle Park, NC, USA

    Dan Hill

  6. Janssen Research and Development Malvern, DPDS, BioTherapeutic Development, Malvern, PA, USA

    Eugene Schaefer

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  1. Carl Rafferty
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Correspondence to Carl Rafferty.

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Rafferty, C., O’Mahony, J., Rea, R. et al. Raman spectroscopic based chemometric models to support a dynamic capacitance based cell culture feeding strategy. Bioprocess Biosyst Eng 43, 1415–1429 (2020). https://doi.org/10.1007/s00449-020-02336-2

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