Mechanisms and Control of Impurities in Continuous Crystallization: A Review

Darmali, Christine; Mansouri, Shahnaz; Yazdanpanah, Nima; Woo, Meng Wai

doi:10.1021/acs.iecr.8b04560

Cited by 45 publications

(32 citation statements)

References 167 publications

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“…Impurity rejection in these cases can be enhanced by fine-tuning the filtration and washing steps after the crystallization. 7 If the impurity concentration in the solid phase remains high after this process, impurity incorporation is not the result of surface adsorption or deposition and the user proceeds to Stage 5.…”

Section: Impurities In Crystallizationmentioning

confidence: 99%

A Structured Approach To Cope with Impurities during Industrial Crystallization Development

Urwin

Levilain

Marziano

et al. 2020

Org. Process Res. Dev.

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The perfect separation with optimal productivity, yield, and purity is very difficult to achieve. Despite its high selectivity, in crystallization unwanted impurities routinely contaminate a crystallization product. Awareness of the mechanism by which the impurity incorporates is key to understanding how to achieve crystals of higher purity. Here, we present a general workflow which can rapidly identify the mechanism of impurity incorporation responsible for poor impurity rejection during a crystallization. A series of four general experiments using standard laboratory instrumentation is required for successful discrimination between incorporation mechanisms. The workflow is demonstrated using four examples of active pharmaceutical ingredients contaminated with structurally related organic impurities. Application of this workflow allows a targeted problem-solving approach to the management of impurities during industrial crystallization development, while also decreasing resources expended on process development.

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Section: Impurities In Crystallizationmentioning

confidence: 99%

A Structured Approach To Cope with Impurities during Industrial Crystallization Development

Urwin

Levilain

Marziano

et al. 2020

Org. Process Res. Dev.

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show abstract

“…In one study, continuous crystallization of a full-length therapeutic mAb was carried out using a laboratory-scale stirred tank (with a cooled tubular reactor in bypass) and resulted in a space-time yield of up to 12 g/l.h (Hekmat et al, 2017). Approaches to and the scientific understanding of controls over the crystallization-purification process in continuous crystallization were recently described in a review (Darmali et al, 2019).…”

Section: Continuous Formulationmentioning

confidence: 99%

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Tripathi

Shrivastava

2019

Front. Bioeng. Biotechnol.

400

243

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Infectious diseases, along with cancers, are among the main causes of death among humans worldwide. The production of therapeutic proteins for treating diseases at large scale for millions of individuals is one of the essential needs of mankind. Recent progress in the area of recombinant DNA technologies has paved the way to producing recombinant proteins that can be used as therapeutics, vaccines, and diagnostic reagents. Recombinant proteins for these applications are mainly produced using prokaryotic and eukaryotic expression host systems such as mammalian cells, bacteria, yeast, insect cells, and transgenic plants at laboratory scale as well as in large-scale settings. The development of efficient bioprocessing strategies is crucial for industrial production of recombinant proteins of therapeutic and prophylactic importance. Recently, advances have been made in the various areas of bioprocessing and are being utilized to develop effective processes for producing recombinant proteins. These include the use of high-throughput devices for effective bioprocess optimization and of disposable systems, continuous upstream processing, continuous chromatography, integrated continuous bioprocessing, Quality by Design, and process analytical technologies to achieve quality product with higher yield. This review summarizes recent developments in the bioprocessing of recombinant proteins, including in various expression systems, bioprocess development, and the upstream and downstream processing of recombinant proteins.

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“…These impurities may be artificially added surfactants or additives, or they may be by-products or catalyst residues in the synthesis process, or they may come from the solvents used in the production process [101]. During the crystallization process, the explanation of impurities precipitation with crystals is divided into the following three mechanisms: (1) impurities are adsorbed on the surface of the crystal; (2) impurities are embedded inside the crystal lattice; (3) solvent entrapment [102]. The traditional method to improve the purity of crystal products is recrystallization, but it is a process at the expense of yield, which will make the production process more cumbersome.…”

Section: Purity Improvementmentioning

confidence: 99%

Application of PAT-Based Feedback Control Approaches in Pharmaceutical Crystallization

Gao

Zhang

et al. 2021

Crystals

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Crystallization is one of the important unit operations for the separation and purification of solid products in the chemical, pharmaceutical, and pesticide industries, especially for realizing high-end, high-value solid products. The precise control of the solution crystallization process determines the polymorph, crystal shape, size, and size distribution of the crystal product, which is of great significance to improve product quality and production efficiency. In order to develop the crystallization process in a scientific method that is based on process parameters and data, process analysis technology (PAT) has become an important enabling platform. In this paper, we review the development of PAT in the field of crystallization in recent years. Based on the current research status of drug crystallization process control, the monitoring methods and control strategies of feedback control in the crystallization process were systematically summarized. The focus is on the application of model-free feedback control strategies based on the solution and solid information collected by various online monitoring equipment in product engineering, including improving particle size distribution, achieving polymorphic control, and improving purity. In this paper, the challenges of feedback control strategy in the crystallization process are also discussed, and the development trend of the feedback control strategy has been prospected.

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Mechanisms and Control of Impurities in Continuous Crystallization: A Review

Cited by 45 publications

References 167 publications

A Structured Approach To Cope with Impurities during Industrial Crystallization Development

A Structured Approach To Cope with Impurities during Industrial Crystallization Development

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Application of PAT-Based Feedback Control Approaches in Pharmaceutical Crystallization

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