Enable a reliable, swift scale-up to cGMP manufacturing for mRNA encapsulation with the high-end FDmiX technology. Discover how to master challenges, streamline production and allow for faster, more predictable development of nucleic acid delivery systems.

Lonza joined forces with two Engineering experts, FDX Fluid Dynamix (FDX) and the Fraunhofer Institute for Production Systems and Design Technology IPK to advance the encapsulation efficiency of mRNA-based therapies. The result of this collaboration is Lonza’s new platform using FDmiX - a cutting-edge mixing device that has the potential to revolutionize the way nucleic acids are encapsulated

Addressing challenges in nucleic acid-based therapies

mRNA therapies are currently developed for the prevention and treatment of various diseases (ranging from infectious diseases to cancers and genetic disorders). However, the transition from pre-clinical development to commercial manufacturing poses several challenges, particularly in achieving consistent and scalable encapsulation processes.

Why the mRNA encapsulation process matters

The size and properties of Lipid Nanoparticles (LNPs), including those encapsulating mRNA, DNA and other nucleic acids impact their biological function, so the formulation must be consistent throughout the process for therapeutic efficacy. This also keeps manufacturing as cost-effective as possible.

An efficient encapsulation process should:

  • Be economically viable
  • Be fast to minimize time in the facility
  • Be easily scalable
  • Deliver stable homogenous particles

We’re delighted that our new platform meets all of these requirements. Enabled by the FDmiX device, the platform offers seamless scale-up capabilities, ensuring predictable and efficient production from research to commercial scales.

Introducing Lonza’s LNP platform leveraging the FDmiX device

The in-licensed technology FDmiX uses a unique oscillating flow that enables 6-8 times faster and more robust mixing - resulting in consistent nanoparticle size and fewer filtration losses. This unique technology speeds up processing and ensures the LNPs stay stable and evenly mixed, whilst maintaining favorable critical quality attributes (CQAs) for both cargo and LNPs.

How do the components work?

Let’s take a closer look at the components of this technology.

Figure 1
The mixer (see Figure 1) consists of a base plate, into which an OsciJet nozzle and a mixing chamber are milled, as well as a lid (not shown). The base and lid are bolted together to ensure a tight sealing. To the left of the metal plate, the mixer is shown schematically.

One of the components to be mixed is introduced into the system at ① and then flows into the OsciJet nozzle. As it flows through the OsciJet nozzle, this stream starts to sweep left and right several hundred times per second.

The second component is introduced at ② perpendicular to the mixer and then meets the sweeping jet of the first component at ③. The high-frequency sweeping motion now ensures that the first component interacts quasi-abruptly with the second component and is then transported further into the mixing chamber.

The mixture then leaves the outlet ④ further downstream of the mixing chamber, where an optional inline dilution port can be added.

The new Lonza platform for GMP manufacturing

Lonza has qualified the FDmiX device and it is now readily available for use in GMP manufacturing.

Torsten Schmidt, Head of mRNA Business Unit, Lonza, commented: "This collaboration with FDX and Fraunhofer IPK allows us to offer a unique technology as part of our Lonza platform for the production of mRNA products from pre-clinical to commercial scales.”

During qualification, we found the following advantages:

  1. High stability due to favorable particle morphology and consistent particle size (e.g. 5 freeze-thaw cycles without visible impact on particle quality)
  2. Easy and predictable scale-up from research scale to manufacturing scale
  3. High encapsulation efficiency (>80 % across all tested conditions)
  4. Minimized time in the facility due to the combination of high flow rates and high mRNA/lipid concentrations (about 2 hours for encapsulating 100g of mRNA)

Overall, we demonstrated considerable process advantages as well as increased stability and homogeneity of LNPs - all while maintaining favorable CQAs.

Contact Us About LNP Encapsulation

Optimizing GMP Manufacturing of Lipid Nanoparticles

Discover Lonza's recent offering: next generation encapsulation of nucleic acids with FXmiX. Resulting in high manufacturability, stability, and homogeneity of Lipid Nanoparticles.

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