Efficient Selection of Cell Clones with Higher Productivity in the Production of Recombinant Human Monoclonal Antibodies

Abstract

In order to optimize the production of recombinant human monoclonal antibodies (rhMAbs), it is important to select cell clones that will exhibit superior performance under manufacturing conditions. During this screening stage, many cell lines must be cultured and evaluated concurrently, and the culture conditions must be limited in order to streamline the process. Therefore, the culture conditions necessitated by mass screening often differ from those actually used during the production stage, with the result that some clones which appear efficient in the former do not prove successful in the latter. To rectify this problem, we sought a smaller-scale method for selecting cell clones. First, we evaluated the cultivation of rhMAb-producing Chinese hamster ovary (CHO) cells on tissue culture plates. The results showed that the culture plates exhibited culture characteristics (cell density, productivity) similar to those of Erlenmeyer flasks, which we used as a scaled-down model of manufacturing conditions. This indicated that the culture-plate procedure could be used to evaluate cell clones under manufacturing conditions. This novel scaled-down method using tissue culture plates instead of a bioreactor or flask could be a fast, simple and consistent technique for the selection of cell clones with superior performance under manufacturing conditions.