Protein A resins have two major disadvantages, high cost and low resin stability. We evaluated the purification of the recombinant antibody rituximab using a non–Protein A purification scheme. This included a cation exchange (CEX) resin for capture purification, followed by anion exchange (AEX) resin for intermediate, and a hydroxyapatite (mixed mode) media for polish purification. Simultaneous purification was performed with a Protein A workflow. The CEX – AEX – mixed-mode resins workflow was economical and yielded >99% purity and 80% yield of rituximab. Host cell protein (HCP) levels were reduced by four logs and host cell cDNA (hcDNA) levels by 5 logs after the final purification step. A pharmacokinetic bridging assay suggests that the purified monoclonal antibody behaved in a similar way to a rituximab standard, showing no significant loss of structure or function throughout purification. We therefore propose that a non–affinity based purification workflow for rituximab provides better process economics and uncompromised results.