Optimal Design of a Size-Exclusion Tandem Simulated Moving Bed for Insulin Purification

Abstract

A tandem simulated moving bed (SMB) was developed previously for the purification of insulin from two impurities in two sequential steps. In this study, an efficient optimization tool based on the standing wave design is developed to find the optimal tandem SMB for insulin purification. Both system parameters (total number of columns, zone configuration, column diameter, and column length for each ring) and operating parameters (zone flow rates and switching time for each ring) are optimized to achieve the lowest purification cost. In the production range of interest, equipment cost dominates. For this reason, the optimal design has eight or fewer columns in each ring. The optimal design also has a small column length and a large column diameter, as the stationary phase for insulin purification is compressible and has a zone linear velocity limit. Splitting strategies and constraints on the column diameter and column length have significant effects on the optimal design. If there is a limit on the column diameter, optimization of the splitting strategy and column length can result in 24 and 25% savings, respectively, in total purification costs. Finally, if the limit on linear velocity is removed, a lower purification cost can be achieved by using longer columns with smaller diameters. The method developed in this study can be applied to other size-exclusion systems or linear isotherm systems.

Simulated Moving Bed Chromatography: From Concept to Proof‐of‐Concept

“…To account for these discrepancies, one can apply different compensation strategies that will approximate the experimental results to the ones predicted beforehand, e.g., the asynchronous port shift in Licosep SMB units [210,211], simplified by the switching time-compensating strategy [37], or more detailed approaches, such as the one developed under the scope of the triangle theory assumptions [203,212] or the SWT methodology [209,213]. The flush of dead-lines with pure product to avoid contamination is also described in the literature [204,205,214].…”

Enhanced performance of a tandem simulated moving bed process for separation of paclitaxel, 13-dehydroxybaccatin III, and 10-deacetylpaclitaxel by making a difference between the adsorbent particle sizes of the two subordinate simulated moving bed units

“…One of the well-established processes for complete separation of a ternary bioproduct mixture is a tandem simulated moving bed (SMB) process, which consists of two four-zone SMB units in series [1][2][3][4]. Between these two subordinate SMB units, the first SMB unit (or Ring I) fulfills the task of separating the highest-affinity or the lowest-affinity component from the other two components.…”

“…The unresolved two components in Ring I are then loaded again into a second SMB unit (or Ring II) for further separation. Such a tandem SMB process has been studied intensively in several previous publications for purification or separation of a ternary mixture containing a variety of valuable biochemicals [1][2][3][4].…”

“…One of the important criteria for evaluating the performance of the aforementioned tandem SMB process is the productivity [1][2][3][4][5], which is defined as the amount of a ternary feed-mixture that can be processed per unit time per unit bed volume (BV) while meeting the requirements for product purities. According to the literature [2,[5][6][7], the productivity is largely affected by the adsorbent particle size, which is known to have a considerable effect on both pressure drop and mass-transfer efficiency.…”

Standing wave optimization of SMB using a hybrid simulated annealing and genetic algorithm (SAGA)

“…In addition, the SWAT results were obtained in an order of magnitude faster than procedures such as grid search (Lee et al 2005b;Mun et al 2003). However, a potential source of error (lack of robustness) in SWAT was the use of a deterministic branch-and-bound algorithm to solve for the SMB configuration.…”