AN2615: Multi-attribute quantification of LNP-mRNA therapeutics by FFF-MALS and DLS

Bringing effective and safe mRNA lipid nanoparticles therapeutics to market requires quantitation of multiple quality attributes throughout development, manufacturing, and quality control. Multi-angle light scattering (MALS) coupled to separation by field-flow fractionation (FFF) offers an automatable, high-precision, and simultaneous quantification of:

• LNP size distribution
• LNP particle concentration
• Lipid and mRNA concentration
• Size-dependent mRNA payload distribution

Here, we perform LNP characterization via FFF-MALS to quantify multiple attributes for two mRNA-LNP COVID-19 vaccines. We find that while the particles in the two vaccine samples span a similar size range, there are significant differences in the relative amounts of the different-sized particles and in how the mRNA drug substance is distributed across them. The approach is 21 CFR Part 11 compliantand can be used to evaluate batch-to-batch consistency, formulation stability, manufacturing, and storage conditions of mRNA lipid nanoparticles.