In the present study, the optimal medium perfusion rate to be used for the continuous culture of a recombinant CHO cell line in a packed-bed bioreactor made of Fibra-Cel disk carriers was detd. A first-generation process had originally been designed with a high perfusion rate, in order to rapidly produce material for pre-clin. and early clin. trials. It was originally operated with a perfusion of 2.6 vvd during prodn. phase in order to supply the high cell d. (.apprx.2.5*107 cell ml-1 of packed-bed) with sufficient fresh medium. In order to improve the economics of this process, a redn. of the medium perfusion rate by -25% and -50% was investigated at small-scale. The best option was then implemented at pilot scale in order to further produce material for clin. trials with an improved second-generation process. With a -25% redn. of the perfusion rate, the volumetric productivity was maintained compared to the first-generation process, but a -30% loss of productivity was obtained when the medium perfusion rate was further reduced to -50% of its original level. The protein quality under reduced perfusion rate conditions was analyzed for purity, N-glycan sialylation level, abundance of dimers or aggregates, and showed that the quality of the final drug substance was comparable to that obtained in ref. conditions. Finally, a redn. of -25% medium perfusion was implemented at pilot scale in the second-generation process, which enabled to maintain the same productivity and the same quality of the mol., while reducing costs of media, material and manpower of the prodn. process. For industrial applications, it is recommended to test whether and how far the perfusion rate can be decreased during the prodn. phase - provided that the product is not sensitive to residence time - with the benefits of reduced cost of goods and to simplify manufg. operations. [on SciFinder (R)]