(141a) Stepwise Bulk Process for Enhanced Productivity and Stability of mRNA Vaccines

The current manufacturing process for mRNA vaccines utilizing the microfluidic technique offers advantages in regulating the size and homogeneity of the lipid nanoparticles (LNP) that form the core components of mRNA vaccine. However, for large-scale production, the capacity of the microchannel-based approach is limited due to difficult scale-up. Additionally, microchannels are susceptible to sedimentation and blockages, necessitating periodic replacement.

We developed a novel stepwise bulk method (SBM) for the manufacturing of mRNA vaccines that is simple, robust, and easily scalable. The new process comprises a series of reactors, each designed to perform specific functions such as mRNA binding and encapsulation. Due to its resistance to clogging and ease of control, this manufacturing process is expected to offer significantly improved productivity. We investigated LNP formation according to the EtOH volume fraction, lipid composition, and N/P ratio to verify the process. Through measurements of size, PDI, encapsulation efficiency, and luciferase luminescence, we confirmed that our method achieves comparable performance to Pfizer's mRNA vaccine produced by the microfluidic method. Finally, we verified that the properties of LNP are maintained as the production scale increases. This new process is expected to contribute to the control of infectious diseases and the development of LNP-based cancer vaccines and therapeutics.