Integrated solutions for preparing cell culture media

Updated on : 02/20/2023 - Mixing and grinding intelligently combined

Preparing cell cultures involves a process in which cells are grown under well controlled conditions. In basic medical and biological research, processes such as metabolism and cell division can be studied in this way. This provides scientists with crucial insight in the search for vaccines, therapies and cures. Furthermore, in today’s biologicals production cells are used to produce new and innovative pharmaceuticals. It’s most important that these cells generate high-quality drug in a validated process constantly.

The foundation for optimising cell activity and growth curves lies in creating the ideal breeding environment – and therefore in the recipe and correct formulation of ingredients for the culture medium. The quality of the culture medium is strongly determined by the particle size and the homogeneous dispersion of the ingredients in dry powder. Over the past 20 years, Hosokawa Alpine has specialized in an integrated process that meets the demanding conditions and high pharmaceutical standards of cell culture media production. The universal system starts immediately after formulation and takes into account all process steps from pre-mixing, grinding and post-mixing through to packaging. The Hosokawa Alpine core technologies of mixing and grinding are thus cleverly combined to achieve the best results.

Fine grinding of challenging materials

For the preparation of cell culture media there is a virtually endless choice in recipes with different bulk densities, particle sizes or flow properties. Once the right mixture is found, various parameters become important, as Hermann Schmidt, Operations Director Pharma & Lab Division at Hosokawa Alpine, explains. “On the one hand, the mixing ratio must be replicable to guarantee exact results. In addition, there must be no contamination in the mixing process itself - unwanted contact with oxygen, moisture or germs in the environment must be avoided.”

Throughout the manufacturing process, a high degree of automation not only ensures safety and reliability, but also makes it possible to produce a wide variety of media and batch sizes on one system. This flexibility must be guaranteed because new batches with different formulations are produced daily for the preparation of cell cultures. The micronisation takes place in Hosokawa Alpine’s UPZ fine impact mill. With its variety of grinding inserts, this mill type can create product finenesses from 90 % < 150 µm up to < 20 µm.

“In the production of cell culture media, the pin discs are ideal for finely micronised and homogeneous products. Due to the combination of the fitting process parameters, the fine product features a steep particle size distribution and good mixing properties”, as Hermann Schmidt explains. Another suitable solution for the formulation of special cell culture media is the cryogenic processing by Hosokawa Alpine Contraplex pin mill, which enables gentle micronisation of sensitive raw materials.

UPZ fine impact mill, mounted on a Nauta conical screw mixer

Highest mixing accuracy without contamination

The quality of the ingredients is additionally ensured by short processing times under controlled, cool conditions. Hosokawa’s mixers and mills are designed to minimize impact and contamination of the media. One example of this is the Nauta conical screw mixer. In accordance with the cGMP hygiene standard, the Nauta mixer is equipped with a cover welded in one piece to the vessel as well as flushable seals. Spray balls are positioned at strategic locations for wet cleaning. These wet all surfaces and nozzles, ensuring thorough cleaning from top to bottom. The Hosokawa Alpine process for the production of dry media for cell cultures has become an industry standard and a guarantee for high quality media.

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