RESULTS

Current platform purification process for Bayer recombinant protein therapeutics

To reduce the cost of development and the time to clinic, the downstream process development team at Bayer recently established a platform purification process for Bayer's complex recombinant protein therapeutics (see Figure 1b). An older generation purification process is also included in Figure 1 for comparison (see Figure 1a). Not only does the current process have fewer unit operations, but it also uses more modern separation technologies, resulting in significantly higher yield and shorter process times, thus reducing the cost of goods.

Following the MA capture step, an immunoaffinity column was used to provide the majority of purification power of the entire process. Because of the products' sensitivity to non-neutral pH, elution from the immunoaffinity column was achieved with a high concentration of chaotropic salt instead of a pH change. As a result, the eluate was of very high conductivity and a dilution step, in some cases more than 10-fold, was needed before proceeding to the next unit operation. To further remove trace amount of impurities, one or two polishing columns were included after immunoaffinity. The second Q-MA step was a flow-through step designed specifically for removal of residual DNA. To ensure good product recovery, the MA polishing step operated under fairly high salt concentration (> 20 mS/cm at 5 °C), under which no HCP or viral clearance was observed. A viral filtration step provided robust non-enveloped virus clearance and enhanced the pathogen safety profiles of the products. Lastly, a ultrafiltration/diafiltration (UF/DF) step concentrated and formulated the drug substance for frozen storage.

The salt tolerance of Sartobind STIC may provide the opportunity to further improve the process by potentially adding HCP and/or viral clearance capability from high-salt feed streams, reduce the need for dilution, and reduce the number of unit operations.