(194a) Standing Wave Design of a Non-Isocratic Three-Zone Simulated Moving Bed for Continuous Purification of Therapeutic Proteins

Protein therapeutics is the fastest growing segment of new pharmaceutical products. Production of protein drugs usually involves many challenging purification steps, resulting in higher production costs than those of low molecular weight drugs. Conventional manufacturing of therapeutic proteins involves multiple batch purification processes, which can take many days or weeks to complete. For insulin production from recombinant E. coli, more than 10 weeks are required to produce high-purity insulin. Continuous capture and purification of therapeutic proteins can reduce manufacturing time, minimize proteolytic degradation of the target proteins, increase protein yield and purity, and reduce purification costs. A three-zone, open-loop, non-isocratic simulated moving bed with different adsorption conditions (pH, displacer concentration, ionic strength, solvent strength, or a combination of these factors) can achieve a much higher adsorbent productivity and a lower purification cost than the corresponding batch stepwise elution chromatography. Monoclonal antibody capture on Protein A is used as an illustrative example. The batch and continuous processes with the same adsorbent volume are compared for two cases: separation of a target protein from a non-adsorbing impurity (Case 1), and separation of a target protein from a competing impurity and a non-adsorbing impurity (Case 2). For both cases, the SMBs can achieve ~100% purity and 99+% yield. The SMB for Case 1 has an order of magnitude higher productivity and product concentration and the SMB for Case 2 has two orders of magnitude higher productivity and product concentration than the optimal batch stepwise elution process.