This work examined the use of single-pass tangential flow filtration (SPTFF) to concentrate cell culture harvest. Conventional tangential flow filtration (TFF) is routinely used in biotechnology and related industries to concentrate protein solutions and exchange them into the final formulation buffer. However, several pump passes and a recirculation skid are required to achieve the target concentration in conventional TFF. Thus, it is impractical to implement TFF for inline concentration of protein solutions during the manufacture of biologic products. New developments in the biotechnology industry have focused on using ultrafiltration in a single pump pass (also known as SPTFF) to concentrate protein solutions in a single pump pass as an inline concentration step. There is thus a potential utility for this technology to overcome manufacturing bottlenecks. While there is limited work in literature describing the use of SPTFF for concentration of in-process protein pools, no work has been reported on the use of SPTFF for concentration of cell culture harvest and the challenges faced in this situation. This work examines the utility of using a 30 kDa ultrafiltration membrane in the SPTFF mode to concentrate cell culture harvest for six different biologic assets in order to determine its feasibility over a wide range of biologic cell culture harvest streams. Cell culture harvest provided unique challenges to SPTFF that were overcome using a synthetic adsorptive hybrid filter technology. In particular, the hydraulic conditions necessary to achieve a targeted concentration factor varied from lot-to-lot for the same molecule. This caused difficulty in implementing a given set of operating conditions for the same molecule because of process instability. To address these challenges, we used high capacity adsorptive filters that effectively reduced both particulates and soluble contaminants during primary recovery to improve the SPTFF performance. The adsorptive filter mainly removed process related impurities, specifically HCP and DNA that prematurely fouled the ultrafiltration membrane and changed the capacity of SPTFF. The adsorptive filter also eradicated cell-culture lot-to-lot performance variability with SPTFF by offering a relative standard deviation of <10%. The use of SPTFF by simultaneously coupling the clarification with the concentration was successfully demonstrated. This is the first work to report the use of SPTFF to concentrate cell culture harvest for six different biologic assets, overcoming challenges using adsorptive filtration, and demonstrate debottlenecking for manufacturing.