STUDIES OF PROTEIN OXIDATION AS A PRODUCT QUALITY ATTRIBUTE IN A SCALE-DOWN MODEL FOR CELL CULTURE PROCESS DEVELOPMENT

Abstract

High throughput mini-bioreactors (HTBRs), 50-mL bioreactors employing noninvasive optical sensor technology were previously validated and compared to benchscale bioreactors on the basis of dissolved oxygen (DO), pH and viable cell density (VCD) profiles (Xudong et al. 2006). To establish HTBRs as a valid scale-down model for cell culture process development and optimization, the ability to preserve product quality attributes across scales is essential. Experiments to evaluate and compare the effect of varying DO levels on product quality in HTBRs, traditional lab-scale systems and bench-scale bioreactors were conducted. Relative protein carbonyl concentration was measured as an indicator of oxidative damage. The effect of which is experimentally significant for the conditions tested. Although a trend of increasing protein carbonyl content in response to increasing DO was conserved across scales, observed differences in measured levels of protein carbonyl content between scales was evident.