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.
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
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
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.
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, .
- pDNA: differentiate all isoforms to follow your process and verify final quality (raw material).
- 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
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.
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
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
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.
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.
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
Our teams develop the layout, workflow and design of your mRNA complete process including pDNA , LNP encapsultion based on your needs.
Learn More About mRNA Production
Webinars
IVT reactions are efficient for mRNA production, and new analytical tools can help you achieve high recovery and quality.
Learn how biopharmaceutical companies can apply proven strategies to overcome the hidden complexities in mRNA production.
Roundtable explores smart strategies to overcome challenges in mRNA process development
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.
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.
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.
