mRNA-based vaccines and therapeutics are of growing interest because of their high efficacy, rapid development timelines, and excellent safety profiles. Encapsulation of the mRNA in Lipid Nanoparticles (LNP) enables effective delivery of the mRNA to ensure protein translation. However, the large size and unique behavior of the LNP can create significant challenges in the design and implementation of the sterile filtration step used to ensure sterility of the final product. Filter capacities and LNP yields are significantly smaller than those for traditional biotherapeutics, and the fouling behavior does not follow traditional mechanisms. Experimental filtration studies were performed with an mRNA-LNP product developed by Moderna using a commercially available sterile filter. Filter performance data were obtained for both constant pressure and constant flux operation. The flux / pressure data were analyzed using the different classical fouling models (pore blockage, pore constriction, and cake filtration), with derivative plots used to identify unusual changes in fouling mechanisms over the course of the filtration process. The results provide important insights into the underlying mechanisms controlling sterile filtration of lipid nanoparticles, facilitating the design and operation of sterilizing grade filter operations in the production of mRNA vaccines and therapeutics.

Sterile filtration of lipid nanoparticles for mRNA vaccines and therapeutics

ACS Spring 2022

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