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. 

Customized NanoProducers脂質納米顆粒(lnp)生產和配方系統

并聯單元的數量取決于應用程序。此外，泵、流量計、射流混合器和管道的數量可以適應所需的條件和規模。所有IJM NanoProducer建立在一個不銹鋼框架上的腳輪，適合在制藥生產的CIP清洗程序。IJM DoubleCore NanoProducer包含兩個并行混合單元。每個機組由四個泵組成。濃縮活性藥物成分(API)溶液首先稀釋，然后與有機相混合。最后，混合物在第三個混合器中被淬火。兩個裝置都可以獨立運行。根據客戶的要求，IJM NanoProducer可以配置多達8個并行混合單元。每個單元包括兩個泵輸送脂質和API流，兩個流量計用于流量控制和一個噴射混合器。根據配置，API的預稀釋和淬火（quenching）可以在撞擊射流混合(IJM)NanoProducer以外的一個工藝步驟中對所有單元的組合流進行。

THE TECHNOLOGY

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.

技術

撞擊射流混合技術(IJM)可以配制和生產攜帶API的高質量脂質納米顆粒(例如用于mRNA疫苗)。活性藥物成分與脂類的封裝過程是基于撞擊射流混合技術，即兩股流在射流混合室中高速碰撞。其中一條流包含有機溶劑中的脂類，另一條流包含水中的API。

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.

高速的混合降低了脂質的溶解度，從而形成了均勻的納米顆粒。納米粒子的質量取決于流體的流動穩定性、混合器的幾何形狀和流體速度。作為步，混合物被淬火（quenched）以阻止粒子生長。

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 API/buffer mixture

Outlet manifold for LNP solution

Back-seal washing system

Frame (stainless steel system 1.4301)

Installation & familiarization by KNAUER

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)

LNP配方系統包括:

KNAUER高壓給料泵80P

Coriolis 流量計

KNAUER IJM混合器

用于脂質/乙醇混合物和API/緩沖混合物的入口歧管

LNP溶液的出口歧管

Back-seal清洗系統

框架(不銹鋼系統1.4301)

KNAUER的安裝和熟悉

與訂單和產品相關的定制技術文檔

安裝前、安裝中、安裝后的客戶服務

毛細管定制和標簽

FAT (KNAUER Berlin工廠驗收測試)

SAT(客戶現場驗收測試)

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, RS-232, pin header connectors; flow meter: RS-232 + FLOW-BUS™

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 (non-condensing)

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

撞擊射流混合器數量:8

泵的數量:16

流量計數量:16個

閥門數量:-

工藝連接入口**:Sanitary Clamp Connector(2個入口)

工藝連接插座**:Sanitary Clamp Connector(1個出口)

容積流速:具體配置

容積流速:具體配置

工作壓力***:50–70 bar (725–1015 psi)

液體溫度范圍:4-60°C(39.2-140°F)

濕性材料:不銹鋼，PEEK，鈦，FFKM, PTFE (GFP 55)，氧化鋁，紅寶石，藍寶石，EPDM，氧化鋯，POM，哈氏合金

軟件:CDS, 21 CFR part 11和gamp5兼容

接口:泵:LAN, RS-232，引腳頭連接器;流量計:RS-232 + flow - bus™

電源:泵:100-240伏單相，50/60赫茲;流量計:115/230伏單相，具體配置

功耗(每臺設備):泵:320w;流量計:3w;電腦:1000 W;監控:380 W;網絡交換機:50w

環境條件:溫度范圍:4-40°C;39.2?104°F;濕度低于90%(不凝結)

尺寸(寬×高×深):具體配置

凈重(約):具體配置

API-預稀釋和淬火（quenching）:具體配置

與訂單和產品相關的定制技術文檔:是

工廠驗收測試:是的

現場驗收測試:是的