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Reducing Batch Times in Cell Culture Media Production

Background/Requirement - Culture Media Production

A large, multi-national biotechnology company approached High Shear Mixer Manufacturer Quadro to help them find a way to improve their production of cell culture media base solutions.

The preparation of media, buffers and reagents for the manufacture and production of protein pharmaceuticals involves the mixing of extremely high-quality water (WFI) with crystal, powder or liquid ingredients, using a validated recipe.

Cell culture media base provides the proper nutrients necessary for growth of selected cells such as those required for the purpose of producing and isolating nucleic acids, while inhibiting the growth of others.

The cell culture media base for this application required the incorporation of two powdered ingredients including a very fine, free-flowing powder and a fine, poor flowing powder into WFI without lumps, agglomerates or the generation of foam. This last requirement was difficult as both powders tended to foam when added to water. The batch size was 2800L.

The company was using a bottom-mounted magnetic mixer to blend the incorporated powders. Powders were added into the top of the tank by inverting totes above the vessel, causing rafting/floating. Batch times exceeded 10 hours as the agitation produced by the mixers was not enough to fully wet and deagglomerate the ingredients. Conventional vortexing mixing methods used to incorporate powdered ingredients also tend to have foaming issues with a percentage of the powdered ingredient becoming trapped in the foam, and not incorporated into the solution.

Quadro's Approach to Reducing Batch Times

To solve the manufacturer's problem, a Quadro Ytron® ZC In-line Powder Disperser was installed. The Quadro Ytron® ZC High Shear Mixer is specifically designed to disperse extremely difficult-to-wet powders into a liquid stream in a single-pass. Powder incorporation is achieved by the presence of significant vacuum in the reactor housing generated by the liquid seal created between the rotor and stator. This vacuum ensures that powders from the hopper above are drawn into the reactor head, where the particles are subjected to intense mechanical shearing prior to hydration into the liquid stream. The result is a homogeneous dispersion of the powders without "fish-eyes" or lumps, and minimal foaming.

Quadro ZC Powder Disperser

The ZC Disperser was set up in re-circulation in a vessel with a centrifugal pump feeding the liquid to the Disperser. The ZC was also designed for clean-in-place and did not require disassembly or an external method for cleaning.

ZC Powder Disperser Advantages

  • Rapid incorporation & dispersion of solids during the liquid fill cycle.
  • Improved product consistency from batch to batch.
  • Less air entrainment.
  • Simple and straightforward cleaning.

Summary

By improving dispersion and wetting of the powdered ingredients, batch times were reduced from 10+ hours to less than 1 hour with the ZC Powder Disperser.

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Posted by Matt Baumber

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