Process Analytical Technology for Real-Time Monitoring of Pharmaceutical Bioconjugation Reactions

Abstract

Process analytical technology (PAT) is increasingly being explored within pharmaceutical production and process development, with a particular emphasis in the vaccine and biologics space. PAT aims to provide increased process understanding and control through real-time monitoring of critical quality attributes and key process parameters as well as detection of process deviations. Downstream purification in pharmaceutical manufacturing processes can be complex and requires copious analytical characterization. Herein, we showcase the successful implementation of PAT for monitoring bioconjugation reactions related to both vaccine and biologic pharmaceutical manufacturing processes. Specifically, we explore a variety of PAT-based techniques and their utility for monitoring polysaccharide–protein and protein–small molecule bioconjugation reactions. PAT applications using at-line multiangle light scattering, in situ fluorescence spectroscopy, in situ viscosity, and at-line hydrophobic interaction chromatography are shown to each provide distinct, real-time analytical information to enhance the understanding and characterization of bioconjugation reactions.