Polymer-Coated Fiber Optic Sensor as a Process Analytical Tool for Biopharmaceutical Impurity Detection

Large-scale purification of monoclonal antibodies using Protein A affinity chromatography continues to be one of the dominant processes in the production of biopharmaceuticals. In order to reduce the processing cost, ensure the purity of the product, and enable safe resin reuse, it is important to (a) estimate the quality of these resins, and (b) quantify the process-related impurities. This article presents the possibility of using a sensitive, rugged optical system as a process analysis tool for the assessment of resin fouling by quantification of the impurities like Protein A, host cell proteins (HCPs), and histones present in the elute. We have developed a conducting polymer-coated fiber optic sensor to detect these impurities, a flow cell to bypass the column elute directly toward the sensor, and associated electronics to make it a portable device for onsite applications. Protein A impurities (3 to 100 ng/mL) have been measured in pure buffer samples, while HCPs (100 to 350 ng/mL) and histone impurities (5 ng/mL to 1~\mu \text{g} /mL approximately) were detected in composite elute samples. In comparison to enzyme linked immunosorbent assay (ELISA)-based techniques, this low-cost, user-friendly sensing device demonstrates fast detection and high sensitivity for real-time monitoring of all process-related impurities.