Sterilizing-Grade Filtration Of mRNA Encapsulated Lipid-Nanoparticles

Constant pressure (VMAX) testing was conducted on a range of sterilizing grade Cytiva and competitor polyethersulfone (PES) membrane filters to determine their throughputs, in liters per square meter (L/m2) and flux, in liters per square meter per hour (LMH). Testing was conducted at two pressures, 40 and 10 psig using an mRNA-LNP suspension to compare their performance under typical process conditions. The data showed that Cytiva Supor™ Prime had the highest throughput and flux of all filter membranes tested at both test pressures. Cytiva Supor™ EX ECV and Cytiva Fluorodyne™ EX EDF membranes showed equivalent or better throughputs and fluxes at both pressures compared to competitor filter membranes. The data also shows that both Supor™ Prime and Fluorodyne™ EX EDF will remove all incident Brevundimonas diminuta bacteria from the mRNA-LNP suspension produced at both high (30 psi) and low (10 psi) test pressures. Analysis of the uncapped mRNA-LNP filtrates showed that the CQAs of mean particle diameter, PDI and EE% were all within specification for an mRNA-LNP product formulation. The analytics and constant pressure VMAX testing conducted on the capped mRNA-LNPs showed that the CQAs of capped material were also unaffected by filtration through either the Cytiva or competitor sterilizing-grade filter membranes.