One of the primary challenges in robust manufacturing of vaccines is rapid feedback on biophysical properties that represent critical quality attributes (CQAs) or are otherwise important determinants of process yield and performance. In the absence of real-time measurements of these quantities, the process must be sampled for at-line or off-line characterization, leading to delayed response. Often process engineers must rely on indirect process parameters for timely—but uncertain—feedback, rather than direct product attributes, to determine process endpoints, deviations from product specifications, or optimal pool cutoffs. Lack of real-time technology for measuring product attributes also contributes to extended timelines for process development.

This webcast focuses on real-time multi-angle light scattering (RT-MALS), a novel process analytical technology that measures key quality attributes of macromolecules and nanoparticles. For vaccines based on viruses, virus-like particles or lipid nanoparticles, RT-MALS determines average size and particle concentration, which are used to control downstream purification and concentration of viruses or consistent lipid nanoparticle production. For vaccines comprising polymers such as polysaccharides, RT-MALS measures molecular weight and rms radius for controlling depolymerization and similar processes. We will review the technology of RT-MALS and its applications in vaccine production and process development. Applications to production of viral and non-viral vectors for gene therapy are also relevant.