mRNA Production | Sartorius

mRNA Development and Manufacturing

Be Prepared for the Hidden Complexity in Your mRNA Process

Messenger RNAs (mRNAs) are a fast-emerging class of biotherapeutics. While they hold considerable promise, the field is still in its infancy. mRNA therapies offer a new opportunity for targeted treatment of challenging diseases and flexible manufacturing, as demonstrated by the rapid development of mRNA vaccines against COVID-19. The clinical potential of mRNA extends beyond vaccines to other advanced therapies, such as protein replacement, gene therapy, and cancer immunotherapy.

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Webinar | mRNA Process - From IVT to Final Filtration 

IVT reactions are efficient for mRNA production, and new analytical tools can help you achieve high recovery and quality.    

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Take Control of Your mRNA Process

The journey to develop new mRNA process can be complex, with hidden barriers along the way. With Sartorius, you have a partner that can empower you to

  • Master your mRNA process
  • Enhance your purity without compromising your yield
  • Define optimal manufacturing  strategy and facility design

Define a Process for Your Unique mRNA

Download this interactive guide to navigating the challenges and finding solutions for your pDNA, mRNA and LNP processes.

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Process Understanding

Master Your mRNA Process

The right analytical strategy for process optimization, in-process control and quality control is essential. A solid understanding of process performances, covering the wide spectrum of pDNA, mRNA and LNP steps can:  

  • Shorten process development times
  • Provide rapid and accurate quality control assays
  • Make processes even more robust
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Each RNA Drug is Unique

New types of RNA are emerging; their lengths, size and folding patterns varies, the targeted final doses are evolving.  The In Vitro Transcription, commonly use for the production of mRNA, is a complex enzymatic reaction.  Fast and efficient tracking of pDNA, mRNA and associated impurities is critical for success, while keeping cost-of-goods minimal. As a result, each mRNA process is unique and must be thoroughly optimized.  

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Monitor and Optimize Your Process With mRNA and pDNA-Specific Analytics 

PATFIX platform is an at -line HPLC system, combined with the monolith technology. Specifically set for  non HPLC expert to run analytics in process lab in only 5-15 minutes,  .

  1.  pDNA: differentiate all isoforms to follow your process and verify final quality (raw material).  
  2.  mRNA : quantify, monitor your IVT components and  impurities (i.e dsRNA, truncated RNA)  

Powerful data analytics software is used to monitor and understand the parameters affecting your process and to optimize experimental design. Modelling allows iterative optimization of the process. Simca and PATfix® enhance control and follow-up during production.

Sartorius Solutions

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CIMac™ Analytical Columns

PATfix® HPLC system

MODDE® DOE Software

MODDE® can help improve the efficiency of your process development process by making every experiment count.

SIMCA® MVDA Software

mRNA Product Quality

A Purification Process as Unique as Your mRNA

As a new and rapidly evolving field, mRNA processes are lacking standardization. New forms or mRNA are emerging, like saRNA or circRNA, and the application of mRNA beyond vaccines requires higher doses, meaning more stringent purity requirements. As a result, there is not a one-fits-all solution to purify mRNA.

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Reach Required Purity for Each RNA Drug

Superior solutions are required for the purification of pDNA, mRNA and LNP (Lipo-Nano Particles), as these are large molecules that can be shear sensitive and may be similar to process-related impurities, such as dsRNA or truncated RNA for the mRNA process.   

With multiple production platforms (saRNA, cirRNA, mRNA), with any new contruct, processes vary – as do the impurities that may be introduced. This impedes the development of a fit for purpose purification platform

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Monolith Purification Visual

Unique Molecules Call For Diverse Solutions

Sartorius comprehensive toolbox and expertise in pDNA, mRNA and LNP purification allows to quickly and confidently maximize quality and yield:

  • The ready-to-use HiP2 platform process achieves high purity and homogeneity of pDNA in two chromatography steps (CIMmultus DEAE and CIMmultus C4HLD), and can be combined with our  Single -Use -line  hollow fiber for a maximum recovery.
  • A comprehensive toolbox of 4   chromatography monolithic columns, from affinity to reverse phase, and our unique Hydrosart TFF cassettes is dedicated to mRNA purification, enabling, to target impurity levels  of even high RNA content doses.
  • Our broad offering of TFF consumable allows the gentle purification of LNPs, to maximize yields.

Sartorius Solutions

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Chromatography Development Services

Monolithic Chromatography

Hollow Fiber TFF

TFF Cassettes

mRNA Commercial Production

Optimizing Facility Set-up at Commercial Scale

The manufacturing process is at the core of the facility design. A robust and cost-efficient process flow has to be implemented in a fit-for-purpose facility, while allowing enough flexibility to quickly adapt to changes.

Key considerations are scale, single- vs multi-product, current titers vs future state titers, localized vs centralized manufacturing, and in-house vs outsourced pDNA manufacture. 

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Understanding Your Challenges

Facility scale for mRNA production is rather small compared to mAbs and may integrate pDNA production and encapsulation. Facility design at scale is complex and may include decisions about vertical integration and segregation of appropriate areas.  

For mRNA production, RNAse contamination should be avoided as it degrades RNA and contributes to shorter shelf life and lower quality.

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From DNA Template to Encapsulation - Find Your mRNA Production Strategy

We design a bioprocess with maximum flexibility in mind to facilitate changing requirements and tailor our offering around your business scenario. Integrated solutions can bridge gaps between engineering firms and scientific solutions to recommend optimal facility design.

End-to-end closed single-use processing solutions with aseptic connections and disconnections prevent RNAse contamination.

Sartorius Solutions

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Bioprocess Development Engineering

We provide a unique implementation methodology for your bioprocess using SU technologies and hybrid solutions for your type & scale of process.

Flexsafe Pro Mixer for Single Use Mixing

Flexsafe® Pro Mixer

The Fast, Flexible, and Intelligent Single-Use Mixer for All Mixing Steps in cGMP Bioprocessing. Mix Smarter - Not Harder.

Frozen Storage

Aseptic Disconnections

Sartorius offers multiple disconnection technologies, with proven sterility assurance, to accommodate your specific process requirements.

Aseptic Connections

Sartorius brings together multiple technologies and vast experience, with more than 1.2 million sterile connections supplied every year.

Extractables and Leachables Testing 

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Solutions for End to End Bioprocessing with Integrated Automation

Our teams develop the layout, workflow and design of your mRNA complete process including pDNA , LNP encapsultion based on your needs.

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Learn More About mRNA Production

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Application Note

Take Control of Your mRNA Production Process With Powerful Analytics

Unlock new insights to streamline mRNA process development, product quantification, and sample characterization.

Application Note

pDNA Isoform Monitoring Supports Robust mRNA Production

Our application note reveals how to quickly implement innovative tools for developing and maintaining robust pDNA production processes.

Webinars

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From IVT to Final Filtration - Get the Most From Your mRNA Process

IVT reactions are efficient for mRNA production, and new analytical tools can help you achieve high recovery and quality.    

Watch Webinar

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Are You Ready for Hidden mRNA Production Challenges?

Learn how biopharmaceutical companies can apply proven strategies to overcome the hidden complexities in mRNA production.

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The Hidden Complexity in the Development of Your mRNA Process

Roundtable explores smart strategies to overcome challenges in mRNA process development

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Part – 1: Increase pDNA Purity and Yields

In part one you will learn how to achieve higher yields in the plasmid DNA by ensuring the quality and purity of the raw materials and taking other steps to optimize the production process.

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Part - 2: Break Down the mRNA Bottleneck with Rapid Analytical Strategies

In part two of the 'Your mRNA process, Simplified' webinar series, we continue to explore how improved processes, analytics, and tools can help meet the unprecedented demand for mRNA.

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Part - 3: Select the Right Purification Approach for Your Process

In this final webinar of the series, Sartorius purification experts demonstrate the flexibility that can be achieved with an mRNA purification toolbox featuring monolithic chromatography.

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Article

Production & Purification of mRNA

PDF | 440.8 KB
Article

The Rise of mRNA: New Era, New Challenges

PDF | 444.1 KB
Article

Rethinking Chromatography

PDF | 1.1 MB
Article

Mastering mRNA Manufacturing

PDF | 482.9 KB
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Monitor, Control, and Optimize Your mRNA Process

Affinity-based chromatographic isolation is useful for mRNA production, but IVT productivity requires high oligo dT binding capacity.

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Poster

Effect of Mg Ç+ Ion Concentration on IVT Reaction Kinetics Determined

PDF | 318.7 KB
Poster

Extraction of mRNA From IVT Mixtures With CIMmultus® Oligo dT Column

PDF | 243.9 KB

Plasmid DNA (pDNA) Production

Discover the steps required to purify plasmid DNA and how our solutions can improve your workflow.

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Consult Our Experts

Consult Our Experts