necessary in order to minimize the lag phase in the bioreactor to within five days following initial seeding when the cells start to grow 24 hours after seeding and achieve a density between 5 u00d7 10 5 to 9 u00d7 10 5 a continuous supply of fresh medium is provided and spent medium is removed on a continuous basis the rate of medium exchange commences at approximately 0 5 reactor volume day and is increased to 4 reactor volumes day when cell density reaches about 2 to about 4 u00d7 10 6 cells ml in this continuous state of perfusion cell densities of about 8 u00d7 10 6 are achieved which is a consequence of delivering nutrients and removing waste products on a continuous basis therefore perfusion typically achieves about 10 to about 20 fold higher cell density than the average daily cell density obtained in spinners where cells are grown in a batch mode the configuration of the reactor that permits retention of cells while maintaining continuous perfusion is presented in fig2 the principle involves an external hollow fiber filtration device with a piping module that recirculates cells back into the reactor from the retentate side of the filter membrane while spent medium is withdrawn from the permeate side use of a hollow fiber filter with a 0 1 micron pore size for the.