Abstract

Monoclonal antibody (MAb) production has adopted an accepted technology platform for downstream processing (1). The need for more economic processes has been addressed by increasing MAb titers in fermentation and aiming toward greater bioreactor volumes to increase productivity. Consequently, cost pressures are now passed on to downstream process groups. Membrane and chromatography resin savings are more important for MAb processes than ever before, with highly productive cell cultures generating large volumes of process fluid to purify (2).

Traditionally, protein A resins have a comparably high share among the costs of consumables in MAb processing. Protein A ligands for chromatography need to be alkaline stable, highly discriminating, with low ligand leaching levels, which requires substantial effort in development of these affinity media. Large feed streams also require higher downstream capacities and increase demands on labor and plant equipment, which of course increases the investment.

Debottlenecking the downstream platforms is a current concern in regard to both process capacity and cost. Only after that may manufacturers take full advantage of high titers and large bioreactor volumes. One possible approach to this challenge is to use more efficient resins, and high-capacity protein A resins seem promising.

In silico simulation of a typical MAb process can assist in detailed examination of the particular factors influencing protein A chromatography costs. Applying design of experiments (DoE), Costioli et al. reported (among other things) on the cost-effectiveness of overloading conditions for high- titer cell cultures (3). Such a study is supposed to extend derived results by two factors — resin capacity and the number of protein A runs per fermentation batch — and how they affect the cost of protein A chromatography as a unit operation. That is not linked to protein A resin price alone, but also to the cost of hardware. Identifying important factors that could provide savings in protein A chromatography was a goal of our DoE study.

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