In situ and real time Ramancombined with chemometric modelling: A robust Tool for upstream bioprocessing control

Alexander Pitters, Kaiser Optical Systems SARL , Saint Priest, France (alexander.pitters@endress.com)

Cell cultures are complex bioprocesses where living cells are cultivated under highly controlled conditions. To ensure a healthy progression of the cell cultures, the understanding and monitoring of the biomanufacturing processes are crucial key factors. Raman spectroscopy’s real-time and in situ measurement capabilities combined with chemometric modelling can play a fundamental role during process development and for production monitoring.

Kaiser Optical Systems has proven records of using Raman technology on major bioprocesses such as mammalian cell cultures and microbiological fermentation. Scalability, stability, and robustness make the Kaiser Raman technology a key to understand, optimize and automate bioprocesses thus enabling higher reliability and performances in compliance with GMP environment.

From lab (2L) to manufacturing scale (2000L), Kaiser technology transferability allows to monitor accurately critical chemical (glucose, glutamate, lactate, ammonium) and physical (osmolality, viable and total cell density (VCD &TCD)) parameters [1-3]. Recently, Generic glucose models have been reported to monitor multiple media and cell lines (figure below, a) [4-5]. Several industrial studies have also demonstrated that the understanding and monitoring of critical quality attributes through process automation improved the harvest titer by 60%[2-3]. Figure below (b & c) shows the glucose concentration automation allowing to increase drastically the Viable Cell Density [3].

Figure showing (a) Generic glucose model prediction for multiple media and cell lines[4]. Raman (b) glucose and (c) VCD prediction and automation for in-line obtained data (black trace) against off-line reference measurements (red circles)[3].