Impingement jets mixing technology (IJM) enables the formulation and production of high-quality lipid nanoparticles carrying API (e.g. for mRNA vaccines). The encapsulation process of active pharmaceutical ingredients with lipids is based on impingement jets mixing technology, where two streams collide at high velocity in a jet mixing chamber. One of the streams contains the lipids in organic solvents and the other stream the API in water.
The mixing at high velocity reduces the solubility of the lipids so that homogenous nanoparticles are formed. The quality of nanoparticles depends on the streams‘ flow stability, the mixer geometry and the fluid velocities. As a final step, the mixture is quenched to stop particle growth.
The number of parallel units depends on the application. Also, the number of pumps, flow meters, jet mixer and pipes can be adapted to the required conditions and scale. All skids are built in a stainless steel frame on casters and are suitable for CIP cleaning procedures in pharmaceutical production. The Small Production Scale Unit IJM Skid contains two parallel mixing units. Each unit contains four pumps.
Concentrated Active Pharmaceutical Ingredient (API) solution is diluted first and then mixed with the organic phase. Finally, the mixture is quenched in a third mixer. Both units can be operated independently.
The Large Production Scale Units can be configured with up to eight parallel mixing units depending on the customer requirements. Each unit consists of two pumps to deliver lipid and API streams, two flow meters for flow control and one jet mixer. Depending on the configuration, the predilution of the API and quenching can be performed for the combined flow of all units in one process step outside the Impingement Jets Mixing (IJM) Skid.
KNAUER'S Impingement Jets Mixing (IJM) technology was developed for the production of mRNA-based coronavirus vaccines, where the mixers play the important role of encapsulating the API (mRNA) within a lipid nanoparticle (LNP). This is an essential step that makes mRNA therapies bioavailable, tolerable and efficacious.
mRNA encapsulation should occur at a high encapsulation efficiency and with a homogenous particle size distribution. Each different mRNA therapy uses a unique mRNA strand and therefore requires different encapsulation conditions - in order to achieve efficient encapsulation for each new therapy the mixing conditions and the lipid formulation used need to be carefully tested and selected.
In short: Pre-clinical research and development (R&D) is needed to determine the optimum conditions for the encapsulation of an API, such as mRNA.
R&D before scale-up allows the correct conditions to be found using a smaller, more economical system and these conditions can then be used at later stages of production - reducing costs and improving time-to-market.
This is exactly what KNAUER's new system, the NanoScaler, was built to do.
System for LNP formulation consisting of:
• KNAUER high-pressure dosing pumps 80P
• Coriolis flow meters
• KNAUER IJM mixers
• Inlet manifolds for lipid/ethanol mixture and mRNA/buffer mixture
• Outlet manifold for LNP solution
• Back-seal washing system
• Frame (stainless steel system 1.4301)
• Installation & familiarization by KNAUER
In addition, we offer for our customers:
• A customized Technical documentation which is order- and article-related
• Customer Service before, during and after the set up
• Capillary customization and labeling
• FAT (Factory Acceptance Test at KNAUER Berlin)
• SAT (Site Acceptance Test at customer site)
“I am delighted that we have been able to successfully deliver all our systems for vaccine production on time. It makes our team proud that we are helping to combat COVID-19 in this way.”
Lilit Avagyan, Business Development Manager
KNAUER supplies small desktop devices to users in research and development as well as complete IJM-Skids for pilot and production scale for the pharmaceutical industry.
The pilot scale unit is ideal for the production of small batches of LNP with a maximum product throughput of approx. 1.0 L/min.
Our production scale units can be equipped with 2 up to 8 impingement jets mixers reaching a product throughput of up to 4.0 L/min.
We have put together a detailed comparison of the skids. Of course, all skids can be configured to your needs.
Depending on the process the end user must consider the legal situation of patents and intellectual property.
KNAUER is designing the customized hardware solution on customers' request, process and chemistry are not inlcuded.
Technical information are subject to change.