In the production of biopharmaceuticals, high and consistent product quality is key. However, in current downstream processes, real-time process monitoring and control play a minor roll in assuring the product quality. Instead, industry widely relies on offline analytics to ensure product quality (e.g. product content, concentration of co-eluting contaminants, host cell proteins) and to define important process parameters. This approach is however time-demanding and may introduce unwanted variability into the process.
In 2004, US Food and Drug Administration (FDA) introduced the Process Analytical Technology (PAT) initiative, which aims to promote (near) realtime process monitoring and control. The research group MAB works on chemometric methods for realtime monitoring. A special focus is set on:
- Process monitoring by spectroscopy in conjunction with chemometrics
- Realtime process control based on the obtained information
- Root-cause investigations
N. Brestrich, T. Hahn, J. Hubbuch, Application of spectral deconvolution and inverse mechanistic modelling as a tool for root cause investigation in protein chromatography, Journal of Chromatography A 1437 (2016), p. 158–167.
N. Brestrich, A. Sanden, A. Kraft, K. McCann, J. Bertolini, J. Hubbuch, Advances in inline quantification of co-eluting proteins in chromatography: Process-data-based model calibration and application towards real-life separation issues, Biotechnology and Bioengineering 112 (2015), p. 1406-1416.
N. Brestrich, T. Briskot, A. Osberghaus, J. Hubbuch, A tool for selective inline quantification of co-eluting proteins in chromatography using spectral analysis and partial least squares regression, Biotechnology and Bioengineering 111 (2014), p. 1365-1373.