Real-Time In Situ Monitoring of CRM-197 and Polysaccharide Conjugation Reaction by Fluorescence Spectroscopy

Abstract

Aims: Process analytical technology (PAT) is increasingly being adopted within the pharmaceutical industry to build quality into a process. Development of PAT that provides real-time in situ analysis of critical quality attributes are highly desirable for rapid, improved process development. Conjugation of CRM-197 with pneumococcal polysaccharides to produce a desired pneumococcal conjugate vaccine is a significantly intricate process that can tremendously benefit from real-time process monitoring. Methods: In this work, a fluorescence-based PAT methodology is described to elucidate CRM-197-polysacharide conjugation kinetics in real time. Results & conclusion: In this work, a fluorescence-based PAT methodology is described to elucidate CRM-197-polysacharide conjugation kinetics in real time.

An Automated, Highly Selective Reaction Monitoring Instrument Using Molecular Rotational Resonance Spectroscopy

“…A wide variety of analysis techniques have been utilized for the online characterization of chemical reactions . Optical spectroscopic techniques such as Raman, mid-infrared, near-infrared, ultraviolet, and fluorescence are valued because of their ability to perform rapid in situ measurements for reaction characterization; however, they are limited in the structural information that they are able to provide and in their ability to resolve mixtures. − Chemometric models can partially overcome the resolution problem . However, unavoidable process variations can invalidate many of the underlying assumptions of these models to require their continuous and time-consuming maintenance including recalibration .…”