Pressure-dependent fouling behavior during sterile filtration of mRNA-containing lipid nanoparticles

Kevork Oliver Messerian, Anton Zverev, Jack F. Kramarczyk, Andrew L. Zydney

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


The COVID-19 pandemic has generated growing interest in the development of mRNA-based vaccines and therapeutics. However, the size and properties of the lipid nanoparticles (LNPs) used to deliver the nucleic acids can lead to unique phenomena during manufacturing that are not typical of other biologics. The objective of this study was to develop a more fundamental understanding of the factors controlling the performance of sterile filtration of mRNA-LNPs. Experimental filtration studies were performed with a Moderna mRNA-LNP solution using a commercially available dual-layer polyethersulfone sterile filter, the Sartopore 2 XLG. Unexpectedly, increasing the transmembrane pressure (TMP) from 2 to 20 psi provided more than a twofold increase in filter capacity. Also surprisingly, the effective resistance of the fouled filter decreased with increasing TMP, in contrast to the pressure-independent behavior expected for an incompressible media and the increase in resistance typically seen for a compressible fouling deposit. The mRNA-LNPs appear to foul the dual-layer filter by blocking the pores in the downstream sterilizing-grade membrane layer, as demonstrated both by scanning electron microscopy and derivative analysis of filtration data collected for the two layers independently. These results provide important insights into the mechanisms governing the filtration of mRNA-LNP vaccines and therapeutics.

Original languageEnglish (US)
Pages (from-to)3221-3229
Number of pages9
JournalBiotechnology and bioengineering
Issue number11
StatePublished - Nov 2022

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology


Dive into the research topics of 'Pressure-dependent fouling behavior during sterile filtration of mRNA-containing lipid nanoparticles'. Together they form a unique fingerprint.

Cite this