Are high purity antibodies produced by cell culture techniques? Why?

The detailed reasons for this are summarized below by QI Bio, an expert in cell biology products:

Currently, a variety of expression systems are available for heterologous expression of recombinant antibodies, but the industrialization of antibody drugs has always been based on the process of large-scale cultivation of animal cells. After nearly 30 years of development, the animal cell culture process used in the industry for recombinant antibody production has increased by more than 50-fold in terms of both cell culture density and antibody expression level. In the flow-addition process, the cell density can reach 1~2×107 cells/mL, the average daily yield is more than 200mg/L/day (up to 700mg/L/D), the volumetric yield of the final fluid can reach 3-5g/L (up to 13g/L), and the volume of culture can be up to 20,000L (Lonza, Portsmouth/NH-facility); the volume of perfusion culture can reach 20,000L (Lonza, Portsmouth/NH-facility); and the volume of culture can reach 20,000L (Lonza, Portsmouth/NH-facility). -The cell density in the perfusion culture process is up to 2×108cell/ml, and the antibody volumetric yield is up to 25~40g/L (Percivia XD? Perfusion System). The rapid improvement of the above industry technology level stems from both the breakthrough of upstream cell line construction technology and the maturation of cell mass culture process. In particular, the latter comprehensive media development, process optimization, combined with the use of new bioreactors, to achieve high-density, high-expression culture of animal cells, to meet the clinical demand for antibody drugs "kilogram-scale" production capacity.

The in vitro culture of animal cells involves the depletion of physical parameters of the bioreactor (temperature, pH, DO, DCO2, etc.), nutrients in the culture medium (glucose, glutamine, amino acids, vitamins, etc.), and the accumulation of their own metabolites (lactic acid, ammonia, recombinant proteins, etc.), as well as the changes in physiological and biochemical parameters (cell density, activity, energy-load, etc.). As the "cell factory" for recombinant antibody production, changes in the above process parameters directly affect the activity of the cell line and the yield of recombinant antibody production. For example, when lactate (58 mM), osmolality (382 mOsm/kg), and ammonia (5.1 mM) parameters exceed their corresponding thresholds, cell activity and antibody yield will decrease significantly. At present, the industry has conducted in-depth research on cell culture process parameters, and the control of the following parameters in large-scale animal cell culture has also become a standard practice

With the development and application of histological technologies, the development of current cell culture processes has moved from the simple optimization of process parameters into the depth of systematic histological studies, and the metabolic network of production cells and the mechanism of recombinant antibody synthesis have become increasingly clear. The differences in antibody yield of production cell lines under different process conditions have been able to be analyzed and explained at different levels, such as genome, proteome, and metabolome. This provides new clues for future large-scale cell culture process development. Meanwhile, with the deepening of the "QbD" concept in the industry, more and more "process analytical technologies" (Process analytical technologies) have been applied to the cell culture process, aiming to ensure that the protein drug can be produced by strengthening the monitoring of key process parameters. Process analytical technologies are increasingly being applied to the cell culture process, with the aim of ensuring the final quality of protein drugs by strengthening the monitoring of key process parameters. For example, media testing, culture process monitoring, and multi-batch data analysis. In the future, the development of large-scale cell culture processes based on recombinant antibody expression will move towards stabilizing production capacity and improving quality.