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The messenger RNA (mRNA) platform technology is being advanced for the deployment of vaccines and therapeutics to combat a wide range of diseases. During the COVID-19 pandemic, the urgent need for large-scale mRNA vaccine production was highlighted, and significant supply constraints were exposed, thereby increasing the demand for more cost-effective and scalable manufacturing solutions. To address these challenges, integrated and continuous mRNA manufacturing processes are being explored, as they offer notable advantages over traditional batch methods, including enhanced efficiency, reduced labor requirements, a smaller manufacturing footprint, and accelerated production timelines.
In this study, a fully continuous process is presented, in which three key steps are integrated: (1) continuous flow encapsulation of mRNA into lipid nanoparticles (LNPs), (2) real-time in-line monitoring of particle size and polydispersity index (PDI) using spatially resolved dynamic light scattering, and (3) single-pass tangential flow filtration (SP-TFF) for purification of mRNA-LNPs. The continuously produced and SP-TFF purified mRNA-LNPs are characterized by critical quality attributes including 95.5 ± 4 % encapsulation efficiency, 105 ± 6 nm average particle size, 0.1 ± 0.02 PDI, 0.003 % residual ethanol content, 0.4 ± 0.05 % fraction of unloaded LNPs, 86.2 ± 3 % mRNA integrity, and a final pH of 7. During TFF purification, an increase in average mRNA-LNP size and the formation of bleb compartments on the particle surface were observed. A 90 % recovery of mRNA-LNPs was achieved using regenerated cellulose (RC) membrane SP-TFF, with an overall concentration factor of 10X. Through this work, a foundation is established for the faster and more efficient manufacturing of high-quality mRNA vaccines and therapeutics.
- Nourafkan, E
- Yang, Z
- Maamra, M
- Kis, Z
- Department of Biochemical Engineering, University College London, Marshgate Building, London E20 2AE, UK
