Cell Culture Optimization of An Antibody Platform to Manufacture Dual Variable Domain Immunoglobulins

Upstream process development of early stage monoclonal antibodies ideally fits to a standard platform process to facilitate rapid transfer of a project into a GMP environment to generate Phase I drug substance. The application of an antibody platform process was challenged with the development of an antibody-like molecule, a dual variable domain immunoglobulin (DVD-Ig). During upstream process development of a specific DVD-Ig, minimal modifications to the antibody platform process were implemented to ensure a robust DVD-Ig manufacturing process while maintaining project timelines. In addition, as the biopharmaceutical industry begins to eliminate complex media components by the implementation of chemically defined media in upstream development, the historical platform process requires reevaluation and optimization. Significant differences were observed between three media platforms for cell growth (4-fold difference in the integral of viable cell density) and DVD-Ig productivity (20-fold difference in cell specific productivity). mRNA levels were measured to investigate the possible mechanisms responsible for the observed cell specific productivity differences.