Process development and optimization of fed-batch production processes for therapeutic proteins by CHO cells

Background In the biopharmaceutical industry, process development and optimization is key to produce high quality recombinant proteins at high yields. As technologies mature, pressure on cost and timelines becomes greater for delivering scalable and robust processes. Overall, process development should be viewed as a continuum from the early stages up to process validation. Here we outline a lean approach on upstream development during the initial phases to optimize yields while maintaining the desired product quality profiles. Early-stage process development was designed to lead to the establishment of a baseline process and to systematically include experiments with input parameters that have a high impact on performance and quality. At this stage, potential for pre-harvest titer and yield increases as well as product quality challenges were identified. Feed adjustments and systematic experiments with top, high, and medium impact parameters have then been performed to develop a robust and scalable process. This approach was applied to two early stage upstream processes.