Magnetic bead-based downstream processes for biologics

The increasing demand for biopharmaceuticals, such as monoclonal antibodies (mAbs), which can target a variety of diseases, has placed a significant pressure on the manufacturing field to reduce the manufacturing costs and increase the capacity, flexibility and product quality. Process intensification of cell culture process, based on medium renewal i.e. perfusion mode, is one of the solutions to meet this demand. Culture intensifications has notably increased the volumetric productivity, and enabled very high cell densities (>200 x 1E6 cells/mL) as well as the product titres exceeding concentrations of 25 g/L. The created cell mass represents however a severe challenge for the following cell clarification and downstream operations. Pocess intensification is not only burdensome for the cell clarification but also for the capture step. Separation using magnetic beads has been used for decades as analytical tool and has recently gained interest in manufacturing as an alternative to traditional downstream operations. Using magnetic particles coupled with e.g. protein A ligand combines the advantage of the high affinity for mAbs with the favourable properties of magnetic beads such as rapidity, gentleness to the cells, and the capacity to process whole cell broth without clarification.
The purpose of the present work is to develop separation processes using magnetic beads. The first application was mAb purification based on magnetic separation as alternative to cell clarification followed by column chromatography capture. In an article, we showed that magnetic separation is highly qualified to be used in non-clarified cell suspension with density larger than 100 x 1E6 cells/mL. In another article, we demonstrated that the technique can be used at pilot scale.
Furthermore, the application of magnetic beads for the purification process of other types of biologics is currently under development, such as cell separation as advanced therapy medicinal products (ATMPs), or separation based on ion exchange.