Role Of Membrane Chemistry And Filter Format In Tangential Flow Filtration Of mRNA And Lipid Nanoparticles

Ultrafiltration and diafiltration (UF/DF) via tangential flow filtration (TFF) is an important unit operation that is typically employed during multiple steps in RNA and lipid nanoparticle (LNPs) downstream processing. Optimization of RNA and LNP UF/DF processes to run at ambient temperature while maintaining product quality and minimizing processing time is critical. A longstanding question for TFF optimization of RNA and LNPs is filter format- whether to use a hollow fiber or flat sheet cassette. Here we take a deep dive into TFF optimization for RNA and LNPs using 100 kDa filters of different membrane chemistry (polysulfone (PS), polyethersulfone (PES), and regenerated cellulose (RC)) and format (hollow fibers (HFs) and flat sheet (FS) cassettes). Our data reveals how membrane chemistry and filter format can significantly impact process optimization for mRNA and LNPs.