High-Throughput Raman Process Monitoring of Downstream Protein Purification

Raman spectroscopy is a proven tool for in-line process monitoring and control. It can be used to quantify concentrations of chemical compounds online and in real-time. High-performance Raman spectroscopy, made possible by Tornado Spectral Systems’ patented High-Throughput Virtual Slit (HTVS™), enhances Raman signal by increasing photon flux by 10x to 30x as compared to conventional Raman spectrometers. This significant advancement in technology enables faster measurements, lower limits of detection, and/or the use of intrinsically safe lower laser power, when needed. These additional gains in spectral quality and sensitivity uniquely enable success in difficult applications, such as fast measurements of proteins of interest during both upstream and downstream bioprocessing. Downstream processing refers to the recovery and the purification of biosynthetic pharmaceuticals from biological sources, such as a fermentation broth. Of particular interest is the production and purification of therapeutic monoclonal antibodies (mAb). This market is projected to reach a value of USD 350 billion by the end of 2027. The downstream portion of the process typically accounts for 50–80% of the production costs of mAb therapeutics (Farid, 2007; Gavara, Bibi, Sanchez, Grasselli, & Fernandez‐Lahore, 2015) in those cases where the mAb purification platforms involve at least two to three chromatographic and filtration steps (Fahrner et al., 2001; Low, O’Leary, & Pujar, 2007).