Design and scale-up of an innovative purification process for monoclonal antibodies

Design and scale-up of an innovative purification process for monoclonal antibodies

Monoclonal antibodies are made using mammalian cells (usually CHO-cells) and subsequently purified with the help of multi-step (usually 3) chromatography. The entire production process is very expensive, with a significant proportion of the cost being incurred by the chromatography gels used, particularly by the first purification step based on a protein A chromatographic gel.

The aim of this project is to generate an alternative purification process, free of protein-based chromatographic phases, by using novel, substrate-specific chromatographic materials based on the instrAction technology. These are characterized by their higher stability and thus greater degree of robustness and safety manifested during the process. In the field of "small molecules" (chemically synthesized drug substance) purification, the instrAction chromatographic phases being used have already proven how efficiently they work on an industrial scale. In the field of protein purification, there are meaningful results for antibodies from natural non-recombinant sources (blood plasma). The purification process is to be used as a platform in the manufacture of recombinant antibodies, regardless of the antibody sub-class, and thus become an alternative standard process in the manufacture of monoclonal antibodies as active substances for clinical trial testing as well as for supplying the market.

Within the framework of the project and based on the results of a feasibility study, the scale-up capability of the process, which will be conclusively optimized during the project, will be demonstrated. Various different antibodies from the Sanofi-Aventis portfolio will be used to this end. Starting at the laboratory scale, the purification will be demonstrated up to the pilot-plant scale (10 -500 L fermenter, 0.4-32 L columns). In terms of capacity, yield, and quality, the process will be compared to the existing standard processes within Sanofi-Aventis.

Extending phase production at instrAction and the activities needed to achieve this, not only in the field of manufacturing safety and quality assurance, but also with regard to essential regulatory requirements, form a part of this project. Its medium- to long-term goals are to significantly reduce costs and improve the robustness of the manufacturing processes for monoclonal antibodies, concurrently reducing the costs of the drugs manufactured from them.

Keywords 

  • Innovative mAB purification
  • Protein A-free
  • Multimodal chromatography
  • Down-stream processing

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