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.
Files
Metadata
Work Title | Pressure-dependent fouling behavior during sterile filtration of mRNA-containing lipid nanoparticles |
---|---|
Access | |
Creators |
|
Keyword |
|
License | In Copyright (Rights Reserved) |
Work Type | Article |
Publisher |
|
Publication Date | July 29, 2022 |
Publisher Identifier (DOI) |
|
Deposited | January 23, 2023 |
Versions
Analytics
Collections
This resource is currently not in any collection.