Medios de cultivo celular

La instalación adecuada: la clave del rendimiento celular

Los cultivos celulares requieren medios específicos. El arte de propiciar la vitalidad celular y buenas curvas de crecimiento reside en la fórmula y en la correcta combinación de los ingredientes. Una vez determinada esta mezcla, el procesamiento adecuado desempeña un papel decisivo. El medio seco debe ser homogéneo tanto en el tamaño de partícula como en la proporción de la mezcla, de forma que no solo se disuelva rápidamente, sino que, además, tenga la misma composición en cada dosis individual. El procesamiento cuidadoso e higiénico de los medios de cultivo celular garantiza su alta calidad. Al mismo tiempo, las instalaciones de producción deben ser flexibles y eficientes para poder producir nuevos lotes a diario. Esto incluye, por supuesto, una limpieza fácil y rápida.

Vertical design of the equipment

High degree of flexibility for a large number of formulations

A great challenge in preparing cell culture media lies in the virtually endless choice in recipes with a wide range of components, different bulk densities, particle sizes or flow properties. This requires a universal system that takes into account all of the process steps from formulation, pre-mixing, grinding and post-mixing through to packaging.

The technology from the Hosokawa Group starts immediately after formulation, integrating the core technologies of mixing and grinding into a seamless process. This ensures the production of high-quality media. After formulation, the materials are poured into the pre-mixer. The homogenised material is then dosed into the UPZ fine impact mill. This can be mounted on the post-mixer. That is where collection then occurs, and if necessary further materials can be added. After a further homogenisation step, the end product is packed into the contamination-free packaging unit. The vertical design of the equipment arrangement provides a high degree of flexibility for a large number of formulations:

Closed loop inert system
Temperature-controlled grinding (down to -40°C)
High mixing accuracy
Closed packaging
Integrated cleaning

Procesos centrales de mezcla y molienda de un solo proveedor
Molienda fina refrigerada en el molino de impacto fino de Hosokawa Alpine
Mezcla cuidadosa y al mismo tiempo intensa en el mezclador cónico Nauta®
Limpieza integrada y automática de la instalación
Máximo grado de automatización

Highest mixing accuracy without contamination

Gentle yet intensive mixing in the Nauta conical mixer

The Nauta conical screw mixer from our Dutch partner Hosokawa Micron B.V. extremely efficient due to its convective technology. This allows it to gently combine the mixture with maximum accuracy but without damaging the structure.

To avoid cross-contamination between batches and in accordance with cGMP hygiene standards, the Nauta mixer is equipped with a semi or full convex cover (welded in one piece to the vessel), flushable seals and a special internal design. Cleaning is carried out by means of removable or stationary spray balls that wet all of the internal surfaces including the nozzles.

Key advantages of the Nauta mixer:

Maximum mixing accuracy
Gentle mixing without damaging the product
Flexible batch sizes between 15 and 100%
Hygienic design for an outstanding cleaning process
No separation during discharge

Fine grinding of challenging materials

Cryogenic fine grinding in the Hosokawa Alpine fine impact mills

The fine impact mill UPZ is used for fine and ultra-fine grinding and covers a range from approximately 20 to 1500 μm. A variety of grinding inserts are available for this type of mill, depending on the product and the required grain size. The aeration effect of the rotor ensures a cool grinding process and a fine-grained end product with good flow properties. In the production of cell culture media, the UPZ mill is typically equipped with pin discs for finely ground and homogeneous products up to 90% < 20 - 150 μm. The ground product has a steep particle size distribution and is easily mixed.

A suitable solution for the formulation of special cell culture media is the Contraplex CW II pin mill with counter-rotating pin discs and the option of low-temperature grinding with LN₂ cooling (down to -40°C).

Key advantages of the Hosokawa Alpine fine impact mills:

Steep particle size distribution
Grinding under low temperatures
Hygienic design for an outstanding cleaning process

Integrated, automatic system cleaning

Clinically clean and flexible in use

Systems for preparing cell cultures must be flexible and efficient if new batches with different recipes are to be manufactured every day. That is why cleaning options play a decisive role in the selection of suitable process equipment.

Hosokawa mixers and mills are designed to prevent contamination. The vertical, aseptic design with a high-quality surface finish and the conical mixing vessels with a fixed connection to the mill guarantee maximum product recovery.

However, some contamination can simply not be avoided, even if all of the necessary precautions are taken. For this reason, spray nozzles are positioned at strategic locations for wet cleaning of the production line. This wets everything and guarantees a thorough cleaning from top to bottom.

The spray nozzles clean the surfaces using a combination of impact and releasing action: from the pre-mixer and the mill to the post-mixer and the packaging unit. After the wet cleaning process, all of the components are dried from top to bottom with hot air, utilising the stack effect.

The highest degree of automation

Reliable automation under pharmaceutical standards

The production line is controlled by a fully automatic control system that meets the highest pharmaceutical standards such as FDA, cGMP and GAMP.

Soluciones fiables mediante sistemas integrados

El factor decisivo es el procesamiento en un proceso continuo, desde la mezcla previa hasta el envasado. Es esencial un enfoque integrado de la solución del proceso. De este modo se evita el contacto indeseado con el oxígeno, la humedad y los gérmenes del entorno. Los tiempos de procesamiento cortos en condiciones acondicionadas y refrigeradas garantizan la calidad de los ingredientes. Un alto grado de automatización en el proceso (especialmente en la limpieza y el secado) proporciona seguridad y flexibilidad y permite la producción de una amplia variedad de medios en una instalación, ya sea en tamaños de lote de unos pocos kilogramos o a una escala de toneladas. Por ejemplo, el proceso de Hosokawa Alpine para la producción de medios secos para cultivos celulares ya se ha convertido en un estándar de la industria y en una garantía de medios de alta calidad.