GT 267-004 is a nonabsorbed, nonantibiotic, high molecular weight anionic polymer that is undergoing clinical evaluation as a Clostridium difficile toxin sequestrant. The active pharmaceutical ingredient (API) is a mixed salt form that consists of approximately 30 to 50% potassium and 70 to 50% sodium as the counterions on the polymer. The initial polymerization process results in an aqueous polymer solution with the polymer in the 100% sodium form. This article describes the use of two innovative approaches, electrodialysis (ED) and ion exchange using ion exchange resins (IXR), to convert the single-salt polymer to the mixed-salt form. Electrodialysis experiments were conducted using a stack of five cells, each of which contained two cation and one anion exchange membranes. The electrodialysis was run in batch mode with a sodium chloride solution as the concentrate stream and a potassium chloride solution as the diluate stream. The ED process was monitored on-line by measuring the conductivity of the streams. Yield loss of the API through the ED membranes was minimal. The ED process was found to be fast, efficient, and reproducible. The ion exchange experiments were conducted using a strong acid cation resin in the potassium form. By using a fixed bed column mode, an appropriate amount of ion exchange was carried out to produce the mixed-salt API in the effluent stream. The resin bed could be regenerated using KCl solution and reused for subsequent batches of polymer solution. The recovery of the API in the product solution was excellent. The ion exchange route was used to synthesize radio-labeled API for clinical trials.