Customized NanoProducers Lipid Nanoparticle (LNP) Production and Formulation System

Customized NanoProducers

SYSTEMS FOR LIPID NANOPARTICLE (LNP) PRODUCTION AND FORMULATION

The number of parallel units depends on the application. Also, the number of pumps, flow meters, jets mixers and pipes can be adapted to the required conditions and scale. All IJM NanoProducers are built in a stainless steel frame on casters and are suitable for CIP cleaning procedures in pharmaceutical production. The IJM DoubleCore NanoProducer contains two parallel mixing units. Each unit consists of 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 IJM NanoProducer 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) NanoProducer. 

THE TECHNOLOGY

Impingement Jets Mixing Technology (IJM) enables the formulation and production of high­quality 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.

System for LNP formulation consisting of:

KNAUER high­pressure dosing pumps 80P

Coriolis flow meters

KNAUER IJM mixers

Inlet manifolds for lipid/ethanol mixture and API/buffer mixture

Outlet manifold for LNP solution

Back­seal washing system

Frame (stainless steel system 1.4301)

Installation & familiarization by KNAUER

A customized technical documentation which is order­ and article­related

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)

Customized NanoProducers

Number of impingement jets mixers: up to 8

Number of pumps:up to 16

Number of flow meters:up to 16

Number of valves:-

Process connection inlet**:Sanitary Clamp Connector (2 inlets)

Process connection outlet**:Sanitary Clamp Connector (1 outlet)

Volumetric flow rate:depending on configuration

Volumetric flow rate:depending on configuration

Maximum operating pressure***:50–70 bar (725–1015 psi)

Liquid temperature range:4–60 °C (39.2–140 °F)

Wetted materials:stainless steel, PEEK, titanium, FFKM, PTFE (GFP 55), aluminum oxide, ruby, sapphire, EPDM, zirconium oxide, POM, hastelloy

Software:CDS, 21 CFR part 11 and GAMP 5 compliant

Interfaces:pump: LAN, RS­232, pin header connectors; flow meter: RS­232 + FLOW­BUS™

Power supply:pump: 100–240 VAC single phase, 50/60 Hz; flow meter: 115/230 VAC single phase, depending on configuration

Power consumption (per device):pump: maximum 320 W; flow meter: 3 W; PC: 1000 W; monitor: 380 W; network switch: 50 W

Ambient conditions:temperature range: 4–40 °C; 39.2−104 °F; below 90 % humidity (non­condensing)

Dimensions (W x H x D):depending on configuration

Net weight (approx.):depending on configuration

API-predilution and quenching:depending on configuration

Customized technical documentation, order-and article-related:Yes

Factory acceptance test:Yes

Site acceptance test:Yes