PROCESS FOR CELL CULTURING BY CONTINUOUS PERFUSION AND ALTERNATING TANGENTIAL FLOW

A method for the production of a biological substance during the reduction of the degree of aggregation of aggregating cells in a cell culture to a level wherein no more than 5% of the cells comprise aggregates of at least 5 cells, wherein: a cell culture comprising cell culture medium and a suspension of cells that easily or inherently forms aggregates during culturing and which are able to produce the biological substance, are maintained in a continuous perfusion culturing system; cell culture medium is added to the cell culture; the cell culture is circulated inside a filter module comprising hollow fibers resulting in an outflow of liquid having a lower cell density than the cell culture, the flow inside the filter module being an alternating tangential flow, wherein no more than 5% of the cells in the culture form aggregates in suspension of at least 5 cells during the continuous perfusion culturing, whereby said cells produce the desired biological substance.