(151a) Cell Culture Scale-up and Technology Transfer for 12,000 L-Scale Therapeutic Antibody Manufacturing

Adalimumab (Humira), a therapeutic monoclonal antibody used for the treatment of rheumatoid arthritis and other immunological indications, has been commercially produced by Chinese Hamster Ovary (CHO) cell culture process. Due to increasing market demand, the production process has been scaled up from the current 3,000-L and 6,000-L scales in Worcester, MA to 12,000-L scale in Barcelonata, PR. Technology transfer considerations, including validation planning, equipment testing, process scale-up, and process improvement were assessed to ensure a successful operation. Comparability of oxygen mass transfer coefficients (kLa) and mixing blend times for all bioreactors was studied. A comprehensive comparison of in process and final product testing was performed at all scales. Product titer, and key product quality attributes including oligosaccharide profiles and product related acidic species were comparable at the 12,000 L scale of operations. Metabolic profiles and key nutrient consumption were also investigated at various cell culture scales. Several technology transfer issues occurred during the engineering runs but were quickly resolved. Overall, the case study shows that careful planning, detailed process mapping and quick troubleshooting are critical to the success of process transfer and scale up.