Monitoring of Nutrients, Metabolites, IgG Titer, and Cell Densities in 10 L Bioreactors Using Raman Spectroscopy and PLS Regression Models

ℹ️ We are pleased to announce the first publication resulting from the #ClimbIn project, now available in the journal Pharmaceutics MDPI. This work is the outcome of a collaborative effort between Morandise RUBINI, Martin Soucé, Igor Chourpa from Département NMNS UPR 4301/CBM - CNRS UPR4301/Université de Tours; Anaïs Berger, Thomas Saillard, Sylvain Arnould, Murielle Vergès from Servier; Julien Boyer, Jordane Poulain (Lallemand), Sylvie Roussel from Ondalys ; Julien Louet, Fabien Chauchard-Rios from INDATECH - Chauvin Arnoux Group.

🔎 In this study, we investigate the potential of Raman spectroscopy, which presents significant advantages within the Process Analytical Technology (PAT) framework by enabling real-time monitoring of bioprocesses and control of critical process parameters (CPPs), thereby ensuring consistent product quality defined by critical quality attributes (CQAs). A key challenge in this context is the development of analyte-specific calibration models. To address this, we propose an approach aimed at improving model specificity and demonstrate the applicability of Raman spectroscopy in an industrial environment. Specifically, we developed multivariate data analysis (MVDA) models for 10 L fed-batch CHO cell cultures. These models showed strong performance in predicting parameters, including nutrients (glucose, glutamine), metabolites (lactate, glutamate), cell densities (total and viable), and IgG concentration (titer).

🤝 The authors gratefully acknowledge funding from Bpifrance as part of the #ClimbIn project (DOS0162921/00), as well as support from the Université de Tours, #CPERFEDER, the Région Centre-Val de Loire, LabEx MAbImprove, and the Philippe Maupas Foundation.

📌 The open-access article is available at: https://www.mdpi.com/1999-4923/17/4/473