Optimal Economic Design and Operation of Single‐ and Multi‐column Chromatographic Processes

Abstract

Single-column chromatography is widely used in the biopharmaceutical industries, although multi-column alternatives in the form of simulated moving bed (SMB) processes are now emerging. It may be difficult, however, to determine which column alternative will be best suited for a given application, and this work sets out to address this issue. A systematic approach is presented that is based on a full economic appraisal of each process alternative based on an optimization of the net annual profit. Single-column processes with and without recycling are considered, as are both the SMB and the Varicol process. The cyclic steady state for the SMB and Varicol processes is determined directly by complete discretization. The approach is applied to a case study based on a linear isotherm where it is found that for this particular system, a recycling policy is not necessary for the single column. When comparing the single-column process with the multi-column alternatives, the single column is the most economical provided the life time of the project is short; however, the economic benefits of the more capital-intensive multi-column processes are greater if the life time of the project is over 5 years. The SMB process is found to perform marginally better than the Varicol process over 15 years; however, this may be because not all extra degrees of freedom for the Varicol process were considered.

Pharma 4.0 Continuous mRNA Drug Products Manufacturing

“…The volumetric flow rates in the SMB conduct the same relevant movement in respect to the stationary resin as that in a true moving bed chromatography [10,11] (see Figure 2). For the chromatography types considered, 20 min retention time is assumed for a workable separation yield to be achieved [20][21][22]. Having obtained the plasmid DNA precipitate, HIC-201 was engaged in order to achieve lysate purification of RNA impurities or denatured plasmid forms, lipopolysaccharides (LPS) and contained protein debris [23].…”

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

“…and separation-independent costs (wages, labor, maintenance, etc.) are taken into account and weighed by cost factors, which sometimes are inaccurate or difficult to characterize [183,184].…”

“…Such optimization algorithms are, e.g., IPOPT (Interior Point OPTimizer) [185], employed for liquid as gas phase SMB separations [65,67,[186][187][188][189][190]; commercial package gOPT from gPROMS with a single (or multiple) shooting-control vector parameterization, used in the two-level optimization of an existing Parex® unit [181], for ageing analysis [191], gas phase separation of propane/propylene [117], or for optimal economic design [184]; MUSCOD-II, a software package based on a multiple shooting code [192]; nondominated sorting genetic algorithm (NSGA) or jumping gene-based algorithms [193], such as NSGA-II-JG, applied by several groups to optimize SMB units, from p-xylene to chiral separations [45,66,182,[194][195][196][197][198][199][200] Netherlands). Nevertheless, the design, construction, and operation of a flexible lab-scale SMB unit, the FlexSMB-LSRE®, as detailed elsewhere [37,201], is addressed in this section as an example of a chiral separation development until the demonstration stage (proof-of-concept).…”