Nourafkan, E;
Yang, Z;
Maamra, M;
Kis, Z;
(2025)
Advancing continuous encapsulation and purification of mRNA vaccines and therapeutics.
European Journal of Pharmaceutical Sciences
, 212
, Article 107183. 10.1016/j.ejps.2025.107183.
(In press).
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Abstract
The messenger RNA (mRNA) platform technology is advancing the deployment of vaccines and therapeutics to combat various diseases. The COVID-19 pandemic highlighted the urgent need for large-scale mRNA vaccine production, exposing supply constraints and driving demand for more cost-effective and scalable manufacturing solutions. To address these challenges, integrated and continuous mRNA manufacturing processes provide significant advantages over traditional batch methods, including increased efficiency, reduced labor requirements, a smaller manufacturing footprint, and faster production. Here, we present the first continuous process integrating: 1) continuous flow encapsulation of mRNA into lipid nanoparticles (LNPs), 2) real-time in-line particle size and polydispersity index (PDI) monitoring using spatially-resolved dynamic light scattering, 3) single-pass tangential flow filtration (SP-TFF) purification of mRNA-LNPs. The continuously produced and SP-TFF purified mRNA-LNP critical quality attributes are: 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 the final pH of 7. During the TFF purification, an increase in average mRNA-LNP size and formation of bleb compartments on the particle's surface was also observed. Additionally, a 90 % recovery of mRNA-LNPs was achieved using regenerated cellulose (RC) membrane SP-TFF with an overall concentration factor of 10X. This study lays the foundations for faster and more efficient manufacturing of high-quality mRNA vaccines and therapeutics.
| Type: | Article |
|---|---|
| Title: | Advancing continuous encapsulation and purification of mRNA vaccines and therapeutics |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ejps.2025.107183 |
| Publisher version: | https://doi.org/10.1016/j.ejps.2025.107183 |
| Language: | English |
| Additional information: | © 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) |
| Keywords: | Continuous manufacturing, Lipid nanoparticles, Microfluidic mixing, Real-time in-line monitoring, Tangential flow filtration, mRNA |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10210980 |
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