Throughput-scalable manufacturing of SARS-CoV-2 mRNA lipid nanoparticle vaccines
Sarah J. Shepherd, Xuexiang Han, Alvin J. Mukalel, Rakan El‐Mayta, Ajay S. Thatte, Jingyu Wu, Marshall S. Padilla, Mohamad‐Gabriel Alameh, Neha Srikumar, Daeyeon Lee, Drew Weissman, David Issadore, Michael J. Mitchell
Abstract
Lipid nanoparticles (LNPs) are a potent delivery technology that have made it possible for the recent clinical breakthroughs in mRNA therapeutics and vaccines. A key challenge to the broader implementation of mRNA therapeutics and vaccines is the development of technology to produce precisely defined LNP formulations, with throughput that can scale from discovery to commercial manufacturing and meet the stringent manufacturing standards of the pharmaceutical industry. To address these challenges, we have developed a microfluidic chip that incorporates 1×, 10×, or 256× LNP-generating units that achieve scalable production rates of up to 17 L/h of precisely defined LNPs. Using these chips, we demonstrate that LNP physical properties and potency in vivo are unchanged as throughput is scaled. Our chips are fabricated out of silicon and glass substrates, which have excellent solvent compatibility, compatibility with pharmaceutical manufacturing, and can be fully reset and reused. SARS-CoV-2 mRNA-LNP vaccines formulated by our chips triggered potent antibody responses in a preclinical study. These results demonstrate the feasibility of directly translating microfluidic-generated LNPs to the scale necessary for commercial production.