Column Fouling of Biopharmaceutical Process Chromatographic Resins via PX2+

Column fouling of chromatographic resins is a common failure mode in downstream biopharmaceutical process operations.  Sensitive real-time fluorescence sensing has been shown to be an effective approach to detect column fouling and derive clean in place (CIP) or replacement approaches.  Pathak and colleagues developed a fluorescence-based real-time tool to monitor fouling during chromatographic operation.1, 2 This tool could detect changes in protein A ligand densities, foulant concentration accumulation, and foulant deposition during cation exchange chromatography.3  Real-time LIF (high-throughput) could be used in a standalone mode or in tandem with subsequent manual tedious sample preparation and analysis via SDS-PAGE.4  While full-spectrum fluorescence spectroscopy has been used to assess resin fouling, a single excitation-emission wavelength combination via a LED based photometer, such as our PX2+ equipped with an in-line front surface probe, affords an attractive compact and lower cost option for in situ in-line monitoring of the chromatographic bed.  Alternatively, a single use LIF flow cell at the column terminus could also be utilized for sensitive breakthrough detection of an auto-fluorescent protein.  Our LIF sensor technology has been used across various solid and liquid based biopharmaceutical applications in routine GMP operations.

  1. Pathak, M.; Lintern, K.;  Chopda, V.;  Bracewell, D. G.; Rathore, A. S., Fluorescence based real time monitoring of fouling in process chromatography. Sci Rep 2017, 7, 45640.
  2. Cole, K. D.; Gaigalas, A.; Almeida, J. L., Process Monitoring the Inactivation of Ricin and Model Proteins by Disinfectants Using Fluorescence and Biological Activity. Biotechnology Progress 2008, 24 (3), 784-791.
  3. Nweke, M. C.; Rathore, A. S.; Bracewell, D. G., Lifetime and Aging of Chromatography Resins during Biopharmaceutical Manufacture. Trends in Biotechnology 2018, 36 (10), 992-995.
  4. Grönberg, A.; Eriksson, M.;  Ersoy, M.; Johansson, H. J., A tool for increasing the lifetime of chromatography resins. mAbs 2011, 3 (2), 192-202.

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