2025
2025
Join our flash talk presentation
Speaker: Mojca Tajnik Sbaizero, Process Development Manager, Sartorius BIA Separations
Date and Time: Part of flash talk series on Tuesday, November 11, 2025 | 4:00 PM–5:00 PM
Title: Advancing Biopharmaceutical Manufacturing: New Techniques for LNP-Based Therapeutics
Abstract
The development of lipid nanoparticle (LNP)-based biopharmaceuticals is revolutionizing nucleic acid delivery technologies, yet it faces significant challenges in manufacturing and characterization. Innovative solutions to enhance drug product integrity, recovery rates, and product characterization will be presented, offering a comprehensive overview of the manufacturing from plasmid DNA (pDNA) to RNA-LNP therapeutics. The process initiates with GMP-compliant pDNA processing using the Alkalizator system, followed by chromatographic purification with monoliths to yield pure linear pDNA. This pDNA undergoes transcription into mRNA during the in vitro transcription (IVT) reaction, further refined through targeted capture and polishing using a monolith toolbox adaptable to various RNA formats.
A novel purification method for encapsulating purified RNA into LNPs is introduced, replacing traditional tangential flow filtration (TFF) and dialysis techniques. Under optimized conditions, LNPs are loaded onto CIMmultus OH column immediately after encapsulation and subsequent neutralization. The purification process effectively removes ethanol and unencapsulated RNA, demonstrating higher recoveries, more uniform particles due to lower size distribution, and elevated activity in terms of protein production, assessed by cell-based assay measuring luciferase reporter protein. Total mRNA recovery and LNP activity are significantly improved using this novel process compared to existing filtration methods.
PATfix platforms ensure rigorous product quality monitoring, in particular the PATfix LNP Switcher characterizes multi-cargo LNPs for applications in CAR-T, CRISPR, and vaccine formulations. This end-to-end platform exemplifies process intensification, chromatographic innovation, and integrated analytics, advancing the development of scalable, high-purity RNA-LNP therapeutics for next-generation biopharmaceuticals.
In conclusion, the novel chromatographic process using CIM demonstrates superior activity and uniformity of RNA-LNP particles compared to traditional methods. By integrating monolithic technology at each stage from RNA production to LNP integrity assessment, consistent product quality and overall process performance and efficiency are ensured, supporting the development of safe and effective LNP-based therapies.
Location: Berlin, Germany
