t2 and t1 (h) and IVCD (cell h mL1 ) is the integral viable cell density. On the contrary, the previous intensified process showed an “apparent” 2.5-fold decrease in q p at the end of culture because of the presumed limited protein solubility at higher concentrations. Optimizing amino acid composition of CHO cell culture media for a fusion. high integral viable cell density (IVCD) and high specific productivity. IVCD is representative of overall cell culture health, where batches with high IVCD values promoted cell growth more than batches with low values and it was measured using a Cedex automated cell counter (Roche Diagnostics Co., Mannheim, Germany). In all VCD conditions, q p was maintained. The selection of clonally-derived Chinese hamster ovary (CHO) cell lines with. We studied different viable cell densities (VCDs) inside the bioreactor (one to five-fold) and found a corresponding two-fold modulation of monomer levels. decreased integrated viable cell density (IVCD), increased cell death, and higher specic productivity with increased glucose concentration. To overcome this limitation and maintain the cell-specific productivity (q p) in culture, we explored a perfusion process where recombinant protein was continuously removed from the bioreactor to maintain low product concentration and consequently, minimize protein aggregation. Furthermore, results indicated that a maximum product concentration was reached beyond which no additional soluble protein accumulated in culture even when doubling the integrated viable cell density with the intensified process, suggesting additional secreted protein was precipitating. from a major biopharmaceutical company, changes to IVCD and cell-specific protein. We identified that protein aggregates increased with accumulated protein concentration inside the bioreactor. Following three days of static culture on the ChemStress plate. Integral viable cell concentration (IVCD), understood as the concentration of viable cells that were working during the time the cell culture lasted, was calculated as area under curve by trapezium. We studied a poorly-behaved bispecific scaffold that increasingly aggregated (up to 62% high molecular weight species, HMW) as a function of culture time in a fed-batch and intensified cell culture processes. Secreted recombinant proteins can aggregate during cell culture.
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