(436a) Strategies to Increase Yield in Ternary Separation for Insulin Purification | AIChE

(436a) Strategies to Increase Yield in Ternary Separation for Insulin Purification

Authors 

Chung, P. - Presenter, Purdue University
Chin, C. Y. - Presenter, PureVision Technology


Increasing process yield in the purification of lispro insulin from a ternary mixture is important for reducing separation cost. A general rate model with a modified reversed phase modulator isotherm was developed to predict the separation of lispro insulin from two structurally-similar low-affinity and high-affinity impurities in reversed phase chromatography. Excellent agreement was observed between the simulated and experimental chromatograms. Transient column profiles were obtained from the simulations to illustrate the competitive adsorption, displacement, and tag-along mechanisms in protein migration. The overlap between the insulin adsorption wave and the desorption wave of the low affinity impurity was found to be the major cause for yield loss. The degree of overlap depended on dimensionless loading volume, dimensionless gradient shape, and the ratio of intraparticle diffusion rate to convection rate. Keeping the values of these dimensionless groups constant, one could ensure successful scale-up of this process. Strategies to increase yield for ternary separation were developed based on theoretical analysis and verified with simulations. New processes with increased yield were developed by modifying the gradient shape, reducing the loading amount, increasing column length, decreasing velocity, and decreasing extra-column dead volume.