(204a) Bioprocessing of mRNA-Lipid Nanoparticles – New Insights from the Collaboration between Moderna and Penn State

The recent success of mRNA vaccines has generated increased interest in the use of Lipid Nanoparticles (LNP) for delivery of nucleic acids for both vaccines and gene therapies. However, the size and properties of the LNPs can lead to unique phenomena during manufacturing that are not typical of other biologics. A collaboration between Moderna and Penn State was established in 2021 to expand our fundamental understanding of the factors controlling the performance of sterile filtration of mRNA‐LNPs. This talk will provide an overview of this collaboration, highlighting the use of advanced microscopy techniques (both electron microscopy imaging and atomic force microscopy) to understand the nature of the mRNA-LNP deposits formed on the membrane surface during the sterile filtration process. Additional insights were provided by analysis of the fouling data using classical blocking models. Taken together, these results provide important information on the physical properties of the LNP that can be used to guide the development and application of sterile filtration processes for these important biotherapeutic products.