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02858nam a2200445Ia 4500 |
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10.1016-j.chroma.2022.463078 |
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220706s2022 CNT 000 0 und d |
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|a 00219673 (ISSN)
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|a Binary separation control in preparative gradient chromatography using iterative learning control
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|b Elsevier B.V.
|c 2022
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|z View Fulltext in Publisher
|u https://doi.org/10.1016/j.chroma.2022.463078
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|a Purification of biopharmaceuticals has shifted toward continuous and integrated processes, in turn bringing along a need for monitoring and control to maintain a desired separation between the target pharmaceutical and any impurities it may carry. In this study, a cycle-to-cycle control of the retention volumes of two compounds in a chromatographic, ion exchange purification step was developed, allowing the process to maintain the desired retention volumes in the separation. The controller made use of a model-based, multivariate iterative learning control (ILC) algorithm that used a quadratic-criterion objective function for optimal set point control, along with feed-forward control based on direct model inversion for preemptive control of set point changes. The model was calibrated using 3 experiments, allowing for fast setup. The controller was tested by introducing three different disturbances to a sequence of otherwise identical ion exchange separation processes: a change in the salt concentration of the elution buffer, a change in set point, and a change in the pH of the elution buffer. It was capable of correcting for all disturbances within at most 3 cycles, proving its efficacy. The successful application of ILC for separation control in biopharmaceutical purification paves the way for the development of further ILC-based control strategies within the field, as well as combination with other control strategies. © 2022
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|a Binary separation
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|a Biopharmaceuticals
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|a Control strategies
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|a Controllers
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|a Feed-forward control
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|a Feed-forward control
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|a Ion exchange
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|a Ion-exchange
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|a Ions
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|a Iterative learning control
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|a Iterative learning control
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|a Iterative methods
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|a Learning algorithms
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|a Model based controls
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|a Model-based control
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|a Preparative chromatography
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|a Preparative chromatography
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|a Preparative gradient chromatography
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|a Purification
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|a Separation
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|a Separation control
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|a Separation control
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|a Setpoints
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|a Two term control systems
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|a Andersson, N.
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|a Espinoza, D.
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|a Nilsson, B.
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|t Journal of Chromatography A
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