In the biotechnology industry, process optimization and performance robustness studies are key to achieving efficient, reliable, and high yield cell culture processes. The use of undefined raw materials, specifically hydrolysates, often enhances the productivity of a culture, but it may also contribute to variability. It is therefore advantageous to remove these undefined materials and develop a capable process without them. Two versions of a fed-batch CHO cell culture process for commercial manufacture of a monoclonal antibody were developed, one with hydrolysates and one without, with a focus on maintaining appropriate product quality relative to the Phase I and II clinical material.

Process development was performed through sequential experiments studying the effects of various process parameters and medium components. Both processes were evaluated in 2L bioreactors and 250mL shake flasks. By performing separate optimization experiments for each process type, different production conditions were defined, demonstrating that the development of a hydrolysate-free process should be performed separately from experiments for a hydrolysate-containing process, and that removal of hydrolysate from a hydrolysate-containing process will not always provide a reliable measure of the potential hydrolysate-free performance of a given cell line.