Robustness of steady state recycling chromatography with an integrated solvent removal unit

Siitonen, Jani; Mänttäri, Mika; Seidel‐Morgenstern, Andreas; Sainio, Tuomo

doi:10.1016/j.chroma.2015.03.007

Cited by 8 publications

(5 citation statements)

References 40 publications

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“…The analysis presented here allows us, for a specific system (with a given isotherm and given selectivity and kinetic rate constant), to identify the most favorable process, either IP or SP. Such selection should be followed by a detailed process optimization, where the optimal SMB operating conditions are determined following an approach similar to what is proposed in earlier literature. ,,,− With that approach, the N min constraint implemented here is relaxed, and also SMB operating conditions that correspond to rather small numbers of theoretical stages are considered. This is done under the separation requirement that the products’ purity fulfills an assigned specification, and implies that the operating point in the m j space moves away from the vertex of the complete separation region, thus resulting in smaller values of ( m 3 – m 2 ), as shown by Kaspereit and collaborators. , …”

Section: Effect Of Additional Design Parametersmentioning

confidence: 99%

Optimizing the Yield of a Pure Enantiomer by Integrating Chiral SMB Chromatography and Racemization. Part 2: Theory

Breveglieri

Otgonbayar

Mazzotti

2021

Ind. Eng. Chem. Res.

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We address the purification of the target enantiomer of a chiral compound from its racemic mixture, through simulated moving bed (SMB) chromatography either as a standalone or combined with the recycle and racemization of the undesired enantiomer. We carry out a comparative assessment of the two processes with focus on the role of the racemization kinetics, on the effect of the selectivity of the chiral stationary phase, and of the upstream symmetric synthesis of the racemate. The analysis is general thanks to the methods adopted for the optimal design of the integrated process (with racemization) and for the sizing of the SMB unit, as well as for the use of the four generalized Langmuir adsorption isotherms. In this way, we determine quantitative criteria that show that the standalone SMB process outperforms the integrated process when the performance of the racemization catalyst or the chiral stationary phase is poor and the racemic feed is inexpensive.

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Section: Effect Of Additional Design Parametersmentioning

confidence: 99%

Optimizing the Yield of a Pure Enantiomer by Integrating Chiral SMB Chromatography and Racemization. Part 2: Theory

Breveglieri

Otgonbayar

Mazzotti

2021

Ind. Eng. Chem. Res.

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“…Next, the two processes, each operated at its own optimal conditions, are compared. This analysis is conducted with reference to the polishing of a mAb of industrial relevance and accounts, in addition to yield, purity and productivity (Pirrung & Ottens, 2017), also for the important concept of process robustness, which is a major concern particularly in biopharmaceutical applications (Müller Späth et al, 2010; Siitonen et al, 2015). This has been quantified using a rigorous model‐based sensitivity analysis of the process performance with respect to its operating process parameters.…”

Section: Introductionmentioning

confidence: 99%

Analysis and optimal design of batch and two‐column continuous chromatographic frontal processes for monoclonal antibody purification

Shi

Vogg²,

Lin

et al. 2021

Biotech & Bioengineering

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The increasing demand for efficient and robust processes in the purification of monoclonal antibodies (mAbs) has recently brought frontal chromatography to the forefront. Applied during the polishing step, it enables the removal of high molecular weight aggregates from the target product, achieving high purities. Typically, this process is operated in batch using a single column, which makes it intrinsically subjected to a purity‐yield tradeoff. This means that high purities can only be achieved at the cost of lowering the product yield and vice versa. Recently, a two‐column continuous implementation of frontal chromatography, referred to as Flow2, was developed. Despite being able of alleviating the purity‐yield tradeoff typical of batch operations, the increase in the number of process parameters complicates its optimal design, with the risk of not exploiting its full potential. In this study, we developed an ad hoc design procedure (DP) suitable for the optimization of both batch frontal chromatography and Flow2 in terms of purity, yield, and productivity. This procedure provided similar results as a multiobjective optimization based on genetic algorithm but with lower computational effort. Then, batch and Flow2 operated at their optimal conditions were compared. Besides showing a more favorable Pareto front of yield and productivity at a specified purity, the Flow2 process demonstrated improved robustness compared to the batch process with respect to modifications in the loading linear velocity, washing buffer ionic strength and loading time, thus providing an appealing operation for integrated processes.

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“…In the second, a longer column might be adopted to provide satisfactory separations, but it would obviously lead to a higher column pressure and stricter requirement on equipment. Hence, some indirect methods were developed to extend the effective length of the column …”

Section: Introductionmentioning

confidence: 99%

“…As shown in Figure , a single‐column recycling chromatography offers an easy way to simulate a longer column without increasing the column pressure. During operation, the solute band is circulated back through the pump and then reinjected into the same column to improve the separation.…”

Section: Introductionmentioning

confidence: 99%

A twin‐column recycling chromatography with solvent gradient for reinforcing the isolation of minor impurities

et al. 2018

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A twin‐column recycling chromatography with solvent gradient was developed to isolate the minor impurities in the drugs. Two columns were connected through two 6‐port valves, and the solute band was diverted from one column into another by switching the valves. During the circulation of the solute band, a modifier was constantly added to the middle between the two columns so that the eluotropic strength of the downstream liquid was reduced. Thereby, the front of the band moved slower than the tail, bringing about a band compression effect to offset the band broadening so as to improve the separation and enhance the concentration of fraction without reducing the feeding amount. Such modified scheme was successfully used to purify a proprietary intermediate, displaying great advantages over the conventional scheme without solvent gradient in terms of recovery and fraction concentration. © 2018 American Institute of Chemical Engineers AIChE J, 65: 702–711, 2019

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Robustness of steady state recycling chromatography with an integrated solvent removal unit

Cited by 8 publications

References 40 publications

Optimizing the Yield of a Pure Enantiomer by Integrating Chiral SMB Chromatography and Racemization. Part 2: Theory

Optimizing the Yield of a Pure Enantiomer by Integrating Chiral SMB Chromatography and Racemization. Part 2: Theory

Analysis and optimal design of batch and two‐column continuous chromatographic frontal processes for monoclonal antibody purification

A twin‐column recycling chromatography with solvent gradient for reinforcing the isolation of minor impurities

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