Real-time monitoring and control of downstream vaccine production processes by RT-MALS

In the development and manufacturing operations of vaccine production processes, it is common to employ offline analytics to monitor product quality attributes (PQAs). Offline analytics and the need to relate PQAs to process conditions impose various complications, delays and extra burdens when developing and marketing a vaccine product. Recently, real-time multi-angle light scattering (RT-MALS) has been shown to overcome many of these difficulties by providing timely and relevant PQA data, monitored directly inline or online with downstream processes such as purification, homogenization or formulation. Such real-time data, available immediately to the process developer or operator on time scales of seconds to minutes, help accelerate process development and ensure reliable, consistently reproducible process endpoints or pooling. RT-MALS monitors fundamental PQAs of vaccine antigen and adjuvant molecules, as well as delivery nanoparticles, such as molar mass, size and particle concentration. This talk will describe the science and technology of RT-MALS, with examples from unit operations such as preparative chromatography, tangential flow filtration, depolymerization and RNA-LNP formulation.