Integration of a complete downstream process for the automated lab-scale production of a recombinant protein

Gomis-Fons, Joaqúın; Löfgren, Anton; Andersson, Niklas; Nilsson, Bernt; Berghard, Lotta; Wood, Susanne G.

doi:10.1016/j.jbiotec.2019.05.013

Cited by 20 publications

(16 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…17 However, this process step was left out of the scope of this article since a larger process scale would have been needed to run an ultrafiltration process, as shown in previous work. 18 Notice that the omission of this step does not affect the present results focusing on the ICB and the control strategies since these are intended for the chromatography steps.…”

Section: Downstream Materialsmentioning

confidence: 98%

“…Gomis-Fons et al 18 This software communicates with UNICORN and sends instructions sequentially in an order determined by the process and selected by the user. For this case, the software was modified so that it could be continuously run without the need of manual labor, for which certain control strategies, discussed in detail in Section 3.1.3, were developed.…”

Section: Andmentioning

confidence: 99%

“…The different purification steps were integrated with each other in a process based on the concept of integrated column sequence (ICS). 9,10,18 This is an automated process, where all the steps are done in a single chromatography unit, and what elutes from one column is loaded directly to the next one, without any manual work.…”

Section: Continuous and Integrated Downstream In A Single Chromatogmentioning

confidence: 99%

“…An automatic way of pooling the eluates based on the absorbance has been already implemented in Orbit in previous work. 18 In this process, the absorbance values at which the pooling begins/ends (absorbance cut-off limits) were constant. In the present work, a feed-forward control feature was introduced.…”

Section: Adaptive Poolingmentioning

confidence: 99%

See 3 more Smart Citations

Model‐based design and control of a small‐scale integrated continuous end‐to‐end mAb platform

Gomis-Fons

Schwarz

Zhang

et al. 2020

Biotechnology Progress

Self Cite

View full text Add to dashboard Cite

A continuous integrated bioprocess available from the earliest stages of process development allows for an easier, more efficient and faster development and characterization of an integrated process as well as production of small-scale drug candidates. The process presented in this article is a proof-of-concept of a continuous end-to-end monoclonal antibody production platform at a very small scale based on a 200 ml alternating tangential flow filtration perfusion bioreactor, integrated with the purification process with a model-based design and control. The downstream process, consisting of a periodic twin-column protein A capture, a virus inactivation, a CEX column and an AEX column, was compactly implemented in a single chromatography system, with a purification time of less than 4 hr. Monoclonal antibodies were produced for 17 days in a high cell density perfusion culture of CHO cells with titers up to 1.0 mg/ml. A digital twin of the downstream process was created by modelling all the chromatography steps. These models were used for real-time decision making by the implementation of control strategies to automatize and optimize the operation of the process. A consistent glycosylation pattern of the purified product was ensured by the steady state operation of the process. Regarding the removal of impurities, at least a 4-log reduction in the HCP levels was achieved. The recovery yield was up to 60%, and a maximum productivity of 0.8 mg/ml/day of purified product was obtained.

show abstract

Section: Downstream Materialsmentioning

confidence: 98%

Section: Andmentioning

confidence: 99%

Section: Continuous and Integrated Downstream In A Single Chromatogmentioning

confidence: 99%

Section: Adaptive Poolingmentioning

confidence: 99%

See 2 more Smart Citations

Model‐based design and control of a small‐scale integrated continuous end‐to‐end mAb platform

Gomis-Fons

Schwarz

Zhang

et al. 2020

Biotechnology Progress

Self Cite

View full text Add to dashboard Cite

show abstract

“…The supervisory control and data acquisition system Orbit software (Nilsson et al, 2017) was used to store the generated data, analyze them, and control the hardware. This system has been used in previous studies (Andersson et al, 2017; Gomis‐Fons et al, 2019; Löfgren et al, 2018). Orbit was modified so that the real‐time controller could be implemented and to allow online monitoring of process attributes.…”

Section: Introductionmentioning

confidence: 99%

An integrated continuous downstream process with real‐time control: A case study with periodic countercurrent chromatography and continuous virus inactivation

Löfgren

Gomis-Fons

Andersson

et al. 2021

Biotech & Bioengineering

Self Cite

View full text Add to dashboard Cite

Integrated continuous downstream processes with process analytical technology offer a promising opportunity to reduce production costs and increase process flexibility and adaptability. In this case study, an integrated continuous process was used to purify a recombinant protein on laboratory scale in a two‐system setup that can be used as a general downstream setup offering multiproduct and multipurpose manufacturing capabilities. The process consisted of continuous solvent/detergent virus inactivation followed by periodic countercurrent chromatography in the capture step, and a final chromatographic polishing step. A real‐time controller was implemented to ensure stable operation by adapting the downstream process to external changes. A concentration disturbance was introduced to test the controller. After the disturbance was applied, the product output recovered within 6 h, showing the effectiveness of the controller. In a comparison of the process with and without the controller, the product output per cycle increased by 27%, the resin utilization increased from 71.4% to 87.9%, and the specific buffer consumption was decreased by 21% with the controller, while maintaining a similar yield and purity as in the process without the disturbance. In addition, the integrated continuous process outperformed the batch process, increasing the productivity by 95% and the yield by 28%.

show abstract

Overview of cloning in lactic acid bacteria: Expression and its application of probiotic potential in inflammatory bowel diseases

Vivekanandan,

Kasimani,

Kumar

et al. 2024

Biotech and App Biochem

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) imposes a significant impact on the quality of life for affected individuals. However, there was a current lack of a systematic summary regarding the latest epidemic trends and the underlying pathogenesis of IBD. This highlights the need for a thorough examination of both the epidemiological aspects of IBD and the specific mechanisms by which lactic acid bacteria (LAB) contribute to mitigating this condition. In developed countries, higher incidences and death rates of IBD have been observed, influenced by a combination of environmental and genetic factors. LAB offer significant advantages and substantial potential for enhancing IBD treatment. LAB's capabilities include the production of bioactive metabolites, regulation of gut immunity, protection of intestinal mechanical barriers, inhibition of oxidative damage, and restoration of imbalanced gut microbiota. The review suggests that screening effective LAB using cell models and metabolites, optimizing LAB intake through dose‐effect studies, enhancing utilization through nanoencapsulation and microencapsulation, investigating mechanisms to deepen the understanding of LAB, and refining clinical study designs. These efforts aim to contribute to comprehending the epidemic trend, pathogenesis, and treatment of IBD, ultimately fostering the development of targeted therapeutic products, such as LAB‐based interventions.

show abstract

Integration of a complete downstream process for the automated lab-scale production of a recombinant protein

Cited by 20 publications

References 20 publications

Model‐based design and control of a small‐scale integrated continuous end‐to‐end mAb platform

Model‐based design and control of a small‐scale integrated continuous end‐to‐end mAb platform

An integrated continuous downstream process with real‐time control: A case study with periodic countercurrent chromatography and continuous virus inactivation

Overview of cloning in lactic acid bacteria: Expression and its application of probiotic potential in inflammatory bowel diseases

Contact Info

Product

Resources

About