Measurement of High Protein Concentrations by Optical Rotation: A Case Study for Monitoring of Monoclonal Antibody Drug Downstream Processes

Title:Measurement of High Protein Concentrations by Optical Rotation: A Case Study for Monitoring of Monoclonal Antibody Drug Downstream Processes

Volume: 22 Issue: 12

Author(s): Hidenori Inaba*, Kosuke Wakabayashi, Ikuo Tsujimoto, Noriko Yoshimoto and Shuichi Yamamoto

Affiliation:

• Graduate School of Science and Technology for Innovation, Faculty of Engineering, Yamaguchi University, 2-16-1 Tokiwadai, Ube-shi, Yamaguchi 755-8611, Japan
• Downstream Bioprocess Science, Chemical and Biotechnological Technology Labs., Astellas Pharma Inc., 5-2-3 Tokodai, Tsukuba-shi, Ibaraki 300-2698, Japan

Keywords: Biopharmaceuticals, antibody, cell culture process, purification process, concentration measurement, optical rotation, in-line/on-line monitoring, process analytical technology.

Abstract:

Background: Recent advancements in cell engineering and bioreactor engineering have enabled high monoclonal antibody (mAb) concentrations in harvested solutions for the downstream process (DSP).

Methods: As many unit operations such as capture chromatography, polish chromatography, membrane filtration, virus inactivation, virus filtration, and concentration by ultrafiltration are involved in DSP, it is crucial to monitor the process carefully in order to perform reliable and stable DSP operations. One of the most important signals (process parameter) to be monitored is the protein concentration CP. Although various methods are available, most of them are not suited for measuring high CP. In this paper, we have developed a method for measuring very high CP by optical rotation (OR).

Result: Linear correlations were confirmed between OR and Cp in the range CP = 0 to 80 g/L for mAbs with high repeatability and small variation coefficients. This method was applied to the monitoring of CP in the opaque (colored) solution during the cell culture. The CP by OR was in good agreement with those by the standard Protein A HPLC method.

Conclusion: Monitoring of high CP by OR is expected to be an efficient process analytical tool (PAT) for DSP.

Cite this article as:

Inaba Hidenori *, Wakabayashi Kosuke, Tsujimoto Ikuo, Yoshimoto Noriko and Yamamoto Shuichi, Measurement of High Protein Concentrations by Optical Rotation: A Case Study for Monitoring of Monoclonal Antibody Drug Downstream Processes, Current Protein & Peptide Science 2021; 22 (12) . https://dx.doi.org/10.2174/1389203722666211210121258

DOI https://dx.doi.org/10.2174/1389203722666211210121258	Print ISSN 1389-2037
Publisher Name Bentham Science Publisher	Online ISSN 1875-5550