Cell cultures require specific media. The art of producing good cell vitality and growth curves lies in the recipe and the correct formulation of the ingredients. Once this mixture has been found, correct processing plays a decisive role. The dry medium must be homogeneous both in its particle size and in the mixing ratio so that it not only dissolves quickly but also contains the same, correct composition in each individual dose. Gentle and hygienic processing of the cell culture media ensures high quality. At the same time, the production systems also have to be flexible and efficient so new batches can be produced every day. To achieve this an easy and quick cleaning process is required.
One major 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 includes 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.
In the pre-mixer, the components of the media recipe are evenly distributed and this mixture is not segregated even when dosing onto the mill. In the mill, the various materials are crushed to a uniform grain size and conveyed directly to a second mixer. Here, even the smallest proportions of the mixture can be added to finalise the product. This mixer can be used to achieve high-quality homogenisation of the entire batch that is maintained throughout the packaging process.
This means that in the final step, the contamination-free packaging unit can produce a uniform product quality from the first to the last container. The vertical design of the machine arrangement allows the product to be guided easily and reduces the cleaning effort. Since no conveyor systems are required, there is also less equipment needed.
In addition, this machine arrangement produces a maximum material yield as well as a high degree of flexibility for a variety of formulations:
- Inert system with closed loop (saving 95% nitrogen)
- Temperature-controlled grinding (down to -40°C)
- High mixing accuracy
- Closed processing, from infeed to packaging
- Integrated cleaning
The Nauta conical screw mixer from our Dutch partner Hosokawa Micron B.V.works extremely quickly and efficiently thanks 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, the Nauta mixer has been systematically designed according to hygiene standards and GMP specifications.
Key advantages of the Nauta mixer:
- Maximum mixing accuracy
- Continuous, highly homogeneous product quality
- Gentle mixing that preserves the structure
- Flexible batch sizes between 15 and 100%
- Hygienic design for an outstanding cleaning process
- Continuous, homogeneous product upon discharge
- Highly energy-efficient mixed concept
Hosokawa Alpine's fine grinding solutions are also excellent for processing adhesive or bridging products. For temperature-sensitive cell culture media components, the highest product quality is also guaranteed.
The UPZ fine impact mill covers a range from about 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.
In the production of cell culture media, the UPZ mill is typically equipped with pin discs for finely ground and homogeneous products from 20 to 150 μm. The ground product has a steep particle size distribution, which allows for excellent mixing.
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). Since the nitrogen is supplied here in loop gas operation, nitrogen consumption is reduced by 95% compared to throughput gas operation. This also increases the product quality: The product has better storage options and there is no contamination from the ambient air. Oxidation or moisture ingress is also prevented.
Key advantages of the Alpine fine impact mill:
- Steep particle size distribution
- Grinding under low temperatures
- Hygienic design for an outstanding cleaning process
- Shortened throughput times and downtimes
Systems for preparing cell cultures need to 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.
Thanks to the automated cleaning of the Hosokawa Micron Group systems, continuous and reproducible cleaning results can be achieved. System downtimes are also reduced, as are errors – regardless of whether they are operating or cleaning errors. Compared to manual cleaning, this kind of system cleaning is easier to plan. All of this means that using Hosokawa equipment saves resources, both in terms of personnel and material.
The vertical, aseptic design with a high-quality surface finish and the conical mixing vessels with a fixed connection to the mill also guarantee maximum product recovery.
In order to remove the very last product residue from the system, spray nozzles are used for wet cleaning. Their positioning ensures cleaning validation even at critical points. After the wet cleaning, all of the components are dried with hot air.
An automated process makes cleaning validation possible for the equipment.
The production line is controlled by a fully automatic control system that meets pharmaceutical standards such as FDA, cGMP and GAMP. The system canrun autonomously up to the packaging stage, requiring no intervention during the production process and taking the burden off the operator. Automation also enables predictive maintenance.
- The Hosokawa Micron Group plant configuration can be used both in the laboratory and in production, as the processes are identical across the various plant sizes. This results in a safe scale-up from the laboratory plant to production. With parallel operation of laboratory and production plant, a change from laboratory sample to production scale is possible within a few minutes. This means maximum utilization of the main plant
- Demand-driven product planning
- Fast, flexible product development with short times from product development to production
- Wider range of formulations
- Reliable product quality in a wide range of batch sizes
As a total supplier, we shorten the project duration by approx. 10-30% compared to projects where components from different suppliers have to be coordinated.
Hermann Schmidt, Operations Director Pharma & Lab, Hosokawa Alpine
The decisive factor is processing in one continuous process – from premixing to packaging. An integrated approach to process solutions is essential. It prevents unwanted contact with oxygen, moisture and germs in the environment. Short processing times under cool, controlled conditions ensure the quality of the ingredients. A highdegree of automation in the process – especially when cleaning and drying – creates reliability and flexibility and enables the production of a wide variety of media on one line, whether in batch sizes of just a few kilograms or on a tonne scale.
The Hosokawa Alpine process for the production of dry media for cell cultures is now an industry standard and a guarantee for high quality media.
The established production processes offer investment security and customers can concentrate entirely on their product and formulation
without having to deal with the details of the system.