Advancing continuous encapsulation and purification of mRNA vaccines and therapeutics

Jun 27, 2025European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

Improving continuous production and purification of mRNA vaccines and treatments

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mRNA Technology on OpenScience ↗PubMed ↗DOI ↗

Abstract

Continuous mRNA manufacturing achieved 90% recovery of lipid nanoparticles (LNPs) with a 10X concentration factor.

Continuous flow encapsulation of mRNA into LNPs provides advantages over traditional batch methods.
Key quality attributes of the produced mRNA-LNPs include 95.5% encapsulation efficiency and 86.2% mRNA integrity.
Real-time monitoring of particle size and polydispersity index (PDI) was implemented during the manufacturing process.
An increase in average mRNA-LNP size and surface bleb formation was observed during purification.
The final product had a pH of 7 and low residual ethanol content of 0.003%.

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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.

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Advancing continuous encapsulation and purification of mRNA vaccines and therapeutics

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