Continuous Purification for mRNA Vaccine Production: Replacing Chromatography with Adsorptive Membranes

This project focuses on continuous purification of messenger ribonucleic acid (mRNA) vaccine production via adsorptive membranes.
Categories
Drug substance
Equipment and Supplies
Talent/ Pipeline development
Active Immunization Countermeasures

Industry Need

  • Continuous vaccine production via purification of mRNA can accelerate manufacturing and reduce costs of production.   
  • Current resin-based chromatography for purification of mRNA vaccines is diffusive and slow, with long residence times 
  • Replacing the current method with adsorptive membranes (convective and fast, with short residence times could  
  • Reduce the residence times of the recovery process 
  • Facilitate continuous processing 
  • Retain a higher percentage of folded mRNA due to the reduced treatment tR 
  • Significantly reduce the equipment footprint 


Approach

Rensselaer aims to purify labile mRNA quickly at high yield and purity in a continuous production mode to increase quality and reduce production time and cost. The team’s approach is to replace resin-based chromatography with adsorptive membranes.  


The project will purify mRNA from a synthetic in vitro transcription (IVT) feed using an affinity membrane process and comparing the performance with commercial affinity chromatography bead column.  


The project will also demonstrate the affinity membranes can purify mRNA with similar purity and yield but a faster rate with smaller equipment setup by  

  • Optimizing affinity chemistry for mRNA biding to and elution from pre-selected membranes  
  • Scaling-up from sheet to hollow fiber affinity membranes  
  • Comparing performance (fiber membrane vs affinity chromatography resin vs monolith platform) 


Impacts

This project will increase quality, reduce production time and cost by speeding up as well as facilitating continuous production and purification of mRNA vaccines for other virus infections by converting from chromatographic to membrane-based separations.

Value Statement/Outcomes

This project replaces slow, diffusion-limited resin chromatography with convective adsorptive membranes, targeting a massive 80–90% reduction in residence times for mRNA purification. By slashing processing duration, the system is projected to increase the recovery of functional, folded mRNA by 15–20% while enabling a 60–70% reduction in equipment footprint compared to traditional columns. This shift to high-velocity hollow fiber membranes transforms downstream processing into a compact, continuous operation that significantly lowers the cost-per-dose and accelerates pandemic response speeds.

Outputs/Deliverables

Demonstrate that microporous affinity synthetic polymer membranes can be used in the purification of mRNA vaccines

Publications

Banik, R., Neuman, T. G., Hao, Z., Al Sharabati, M., Zhao, W., Anderson, D. G., Przybycien, T., Kilduff, J., & Belfort, G. (2025). Convection rather than diffusion for fast efficient mRNA vaccine purification. Separation and Purification Technology, 354, 129310. https://doi.org/10.1016/j.seppur.2024.129310

Posters

Belfort, G., Presenter, ARP-08 Continuous Purification for mRNA Vaccine Production: Replacing Chromatography with Adsorptive Membranes, NIIMBL National Meeting, Washington, D.C., July 28, 2022.

Additional Project Information (Members Only)

Login to the NIIMBL member portal to access additional project information, including presentations, progress updates, reports, and more.

Not yet a member? Learn more about which level of NIIMBL membership is right for you and your organization.

Project Lead

Rensselaer Polytechnic Institute

Rensselaer Polytechnic Institute