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

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.

This is the peer reviewed version of the following article: [Pressure‐dependent fouling behavior during sterile filtration of mRNA‐containing lipid nanoparticles. Biotechnology and Bioengineering 119, 11 p3221-3229 (2022)], which has been published in final form at https://doi.org/10.1002/bit.28200. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions: https://authorservices.wiley.com/author-resources/Journal-Authors/licensing/self-archiving.html#3.

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Work Title Pressure-dependent fouling behavior during sterile filtration of mRNA-containing lipid nanoparticles
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Open Access
Creators
  1. Kevork Oliver Messerian
  2. Anton Zverev
  3. Jack F. Kramarczyk
  4. Andrew L. Zydney
Keyword
  1. Lipid nanoparticle (LNP)
  2. mRNA vaccine
  3. Sterile filtration
  4. Fouling
  5. Bioprocessing
License In Copyright (Rights Reserved)
Work Type Article
Publisher
  1. Biotechnology and Bioengineering
Publication Date July 29, 2022
Publisher Identifier (DOI)
  1. https://doi.org/10.1002/bit.28200
Deposited January 23, 2023

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Version 1
published

  • Created
  • Added Pressure-dependent_fouling_behavior.pdf
  • Added Creator Kevork Oliver Messerian
  • Added Creator Anton Zverev
  • Added Creator Jack F. Kramarczyk
  • Added Creator Andrew L. Zydney
  • Published
  • Updated Keyword, Publication Date Show Changes
    Keyword
    • Lipid nanoparticle (LNP), mRNA vaccine, Sterile filtration, Fouling, Bioprocessing
    Publication Date
    • 2022-11-01
    • 2022-07-29
  • Deleted Pressure-dependent_fouling_behavior.pdf
  • Added LNP-sterile filtration-ScholarSphere.pdf.pdf
  • Deleted LNP-sterile filtration-ScholarSphere.pdf.pdf
  • Added LNP-sterile filtration-ScholarSphere.pdf
  • Updated