Integrating crystallization with experimental model parameter determination and modeling into conceptual process design for the purification of complex feed mixtures

Lucke, M.; Koudous, I.; Sixt, Maximilian; Huter, Maximilian; Strube, Jochen

doi:10.1016/j.cherd.2018.03.029

Cited by 12 publications

(12 citation statements)

References 91 publications

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“…Further, empirical models like quantitative structure-activity relationship (QSAR) are applied to predict the discontinuity point of proteins in presence of PEG molecules [35,36]. Moreover, model approaches derived from a mechanistic model approach for crystallization are described also for precipitation [60][61][62][63][64][65]. These models are built with population balances and contain detailed information about nucleation, birth, growth, and disruption of crystals or agglomerates.…”

Section: Modeling Of Precipitationmentioning

confidence: 99%

Accelerating Biologics Manufacturing by Modeling: Process Integration of Precipitation in mAb Downstream Processing

Lohmann

Strube

2020

Processes

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The demand on biologics has been constantly rising over the past decades and has become crucial in modern medicine. Promising approaches to cope with widespread diseases like cancer and diabetes are gene therapy, plasmid DNA, virus-like particles, and exosomes. Due to progress that has been made in upstream processing (USP), difficulties arise in downstream processing and demand for innovative solutions. This work focuses on the integration of precipitation using a quality by design (QbD) approach for process development. Selective precipitation is achieved with PEG 4000 resulting in an HCP depletion of ≥80% respectively to IgG. Dissolution was executed with a sodium phosphate buffer (pH = 5/50 mM) reaching an IgG recovery of ≥95%. However, the central challenge in process development is still an optimal process design, which is transferable for a broad molecular variety of new products. This is where rigorous modeling becomes vital in order to generate digital twins to support early-stage process development and reduce the experimental overhead. Therefore, a model development and validation concept for construction of a process model for precipitation is also presented.

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Section: Modeling Of Precipitationmentioning

confidence: 99%

Accelerating Biologics Manufacturing by Modeling: Process Integration of Precipitation in mAb Downstream Processing

Lohmann

Strube

2020

Processes

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“…f f perm f f f eed (63) The removal ratio, RR, is the mass load of contaminants in the concentrate stream of the regenerator as a fraction of the feed. It is assumed to be a variable in this work and is defined as given in Equation (64).…”

Section: Lr =mentioning

confidence: 99%

“…f f con cr con f f f eed c f f eed (64) In order to determine the area of the membrane required, A m , the permeate flow rate is divided by the water flux as given in Equation (65).…”

Section: Rr =mentioning

confidence: 99%

Process Design, Integration, and Intensification

Halwagi¹,

Dominic²

2019

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“…The raw plant material is ground to approximately 1 mm with a Crystallization is a typical final purification and isolation step preparing for formulation steps of plant-based or semi-synthetical processes, e.g., artemisinin [11][12][13][14][15][16][17][18][19][20][21][22][23]. The crystallization step itself is affected in various ways, based on mechanical and thermodynamic influences, e.g., [24]. The main driving force for crystallization is the solid-liquid equilibrium and, therefore, the solubility of the target component in a system.…”

Section: Raw and Purified Materialsmentioning

confidence: 99%

“…Even though seeding strategies prevent primary nucleation, secondary nucleation like breakage or attrition and agglomeration as counterpart affect the particle distribution. These effects are component-specific, and therefore have to be determined for the chosen artemisinin system [24,31]. Artemisinin forms two polymorphs, which means it grows in different crystal shapes.…”

Section: Raw and Purified Materialsmentioning

confidence: 99%

Systematic and Model-Assisted Process Design for the Extraction and Purification of Artemisinin from Artemisia annua L.—Part IV: Crystallization

et al. 2018

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In this study, process integration for crystallization of a priori purified Artemisia annua L. is investigated. For this total process, the integration operation boundaries and behavior of the crystals are studied. This is performed focusing on a conceptual process design study for artemisinin, aiming towards the development of a crystallization step under given parameters by process integration. At first, different crystallization systems consisting of ethanol-water or acetone-water mixtures are compared. In subsequent steps, the metastable zone width and the behavior of the crystals regarding agglomeration and breakage are checked. Furthermore, the sensitivities of process variables based on several process parameters are investigated. Additionally, the final process integration of crystallization as a combined purification and isolation step is studied.

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Integrating crystallization with experimental model parameter determination and modeling into conceptual process design for the purification of complex feed mixtures

Cited by 12 publications

References 91 publications

Accelerating Biologics Manufacturing by Modeling: Process Integration of Precipitation in mAb Downstream Processing

Accelerating Biologics Manufacturing by Modeling: Process Integration of Precipitation in mAb Downstream Processing

Process Design, Integration, and Intensification

Systematic and Model-Assisted Process Design for the Extraction and Purification of Artemisinin from Artemisia annua L.—Part IV: Crystallization

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