Pareto-optimal reversed-phase chromatography separation of three insulin variants with a solubility constraint.

摘要: Abstract With the shift of focus regulatory bodies, from fixed process conditions towards flexible ones based on understanding, model-based optimization is becoming an important tool for development within biopharmaceutical industry. In this paper, a multi-objective study separation three insulin variants by reversed-phase chromatography (RPC) presented. The decision variables were load factor, concentrations ethanol and KCl in eluent, cut points product pooling. addition to purity constraints, solubility constraint total concentration was applied. function mobile phase, main aim investigate effect maximal productivity. Multi-objective performed with without constraint, visualized as Pareto fronts, showing optimal combinations two objectives productivity yield each case. Comparison constrained unconstrained fronts showed that former diverges when becomes active, because increase decreasing almost halted. Consequently, we suggest operating point at which outlet reaches limit most suitable one. According results optimizations, C4 adsorbent (0.41 kg/(m3 column h)) less than half C18 (0.87 kg/(m3 column h)). This partly caused higher selectivity between adsorbent, but reason difference how affects processes. Since elution one, also higher, allowing pool concentration. An alternative method finding suggested evaluated, it shown give very satisfactory well-mapped fronts.