Challenges in process control for continuous processing for production of monoclonal antibody products

Rathore, Anurag S.; Nikita, Saxena; Thakur, Garima; Deore, Navnath

doi:10.1016/j.coche.2021.100671

Cited by 34 publications

(23 citation statements)

References 61 publications

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“…It should be noted that there are multiple surge tanks in the end‐to‐end integrated continuous process diagram, which are located before and after the multicolumn continuous chromatography operations to eliminate the cyclic discontinuity. The introduction of surge vessels adds safety, flexibility, and robustness to a fully continuous biomanufacturing line by providing a temporal buffer (Rathore et al, 2021; Thakur et al, 2021).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Process design of a fully integrated continuous biopharmaceutical process using economic and ecological impact assessment

Ding

Ardeshna

Gillespie

et al. 2022

Biotech & Bioengineering

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Continuous biomanufacturing is a promising alternative to current batch operation as it offers benefits in terms of improved productivity, product quality, and reduced footprint. This study aims to build a fully integrated continuous platform for monoclonal antibody (mAb) production incorporating novel technologies (like intensified seed expansion and continuous high cell density perfusion operations, single‐pass tangential flow filtration, and single‐use technologies) as well as media and buffer preparation steps. Economic assessment is performed on the basis of the total cost of goods (COGs), which is $102.2/g in the base‐case scenario with a bioreactor scale of 500 L. E‐factor is used as an environmental indicator and the result shows that 4865.6kg of process water and 11.1 kg of consumables are required to produce 1 kg mAbs. After the development and analysis of the benchmark process, scenario analysis is performed to assess the impacts of the bioreactor scale (60–2000 L) and upstream titers (1.12–2.08 g/L) on the process economics as well as on the environmental footprint. With the increase of bioreactor scale and mAb titer, the operating COGs per unit product decrease. Moreover, increasing the mAb titer is more favorable in terms of the ecological impacts. To investigate the production capacity, the upstream production is increased and the downstream bottlenecks are determined. It is found that only the multicolumn chromatographic (MCC) operations become the process bottleneck and the order of the MCC unit operation that becomes the process bottleneck depends on capacity utilization for that step. Finally, a new platform is built with the integration of membrane chromatography and the two designed processes are compared in terms of economic and ecological impacts.

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Section: Methodsmentioning

confidence: 99%

“…The structural similarities between different mAbs make this platform widely accepted and regarded as an industry benchmark. Thus, this platform is adopted in this study to construct the continuous process and the corresponding process line by providing a temporal buffer (Rathore et al, 2021;Thakur et al, 2021).…”

Section: Process Descriptionmentioning

confidence: 99%

Process design of a fully integrated continuous biopharmaceutical process using economic and ecological impact assessment

Ding

Ardeshna

Gillespie

et al. 2022

Biotech & Bioengineering

View full text Add to dashboard Cite

show abstract

“…The risk of product or process deviations in a continuous setup necessitates the use of robust and intelligent controllers that are capable of handling deviations in a fully automated manner. 181 Developing such integrated controllers has several challenges with respect to developing model predictive control strategies, control hardware, and software integration, and interfacing between the unit operation equipment and control system. However, a fully integrated closed-loop continuous mAb manufacturing process has not yet been reported in the open literature and, therefore, this is an active and open area of research.…”

Section: Design and Implementation Of The Control Systemmentioning

confidence: 99%

“…These recent advances lay a solid foundation for the implementation of a robust process control strategy in continuous biopharmaceuticals manufacturing. The risk of product or process deviations in a continuous setup necessitates the use of robust and intelligent controllers that are capable of handling deviations in a fully automated manner 181 . Developing such integrated controllers has several challenges with respect to developing model predictive control strategies, control hardware, and software integration, and interfacing between the unit operation equipment and control system.…”

Section: Integrated Advanced Process Controlmentioning

confidence: 99%

Recent advances in integrated process analytical techniques, modeling, and control strategies to enable continuous biomanufacturing of monoclonal antibodies

Chopda

Gyorgypal

et al. 2021

J of Chemical Tech & Biotech

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Continuous bioprocessing is significantly changing the biological drugs (or biologics) manufacturing landscape by potentially improving product quality, process stability, and overall profitability, as was similarly seen during the adoption of advanced manufacturing processes for small molecule drugs in the past decade. However, the implementation of continuous manufacturing for biological processes producing protein-based drug molecules, such as monoclonal antibodies (mAbs), is facing several new hurdles. The barriers to continuous bioprocessing can be overcome through improved process understanding via better predictive capabilities enabled by hybrid modeling that can also lead to robust process control. This review article summarizes the recent advances and ongoing obstacles faced during the use of advanced process analytical technologies (PAT), process modeling, and control strategies to enable continuous manufacturing of mAbs. In addition, this review also discusses the process strategies and future directions of advanced continuous manufacturing approaches that have been adapted by other industries and that could be implemented for mAbs production soon.

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“…Many scholars have explored job-shop production control. For example, Rathore et al [13] fully considered the constraints on zero waiting of jobs during processing and the operator's learning effect, constructed a mathematical model for zero-waiting flow shop scheduling problem, and solved the model with genetic algorithm (GA) / path relinking search algorithm, which involves elite retention strategy and local search operator. Taking minimal makespan as the object, Lage Junior and Godinho Filho [14] modelled the flow shop scheduling problem with machine allocation, job sequence, and initial processing time as decision variables, and solved the problem with the adaptive GAsymbiotic organisms search (SOS) algorithm, which contains mutualism, commensalism, and parasitism operators.…”

Section: Introductionmentioning

confidence: 99%

Application of Machine Learning and Rule Scheduling in a Job-Shop Production Control System

Zhao¹,

Zhang²

2021

Int. j. simul. model.

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As intelligent and precision manufacturing becomes the trend of industrial production, it is of practical significance to study the job-shop production control. However, the existing studies have not provided an evaluation mechanism to reasonably measure the control efficiencies of different plans. The desired control objectives are not easily achieved for job-shop production control problems with dynamic changes. Therefore, this paper probes into the dynamic job-shop production control problem based on deep reinforcement learning and rule scheduling. Firstly, a multi-objective optimization model was established for the production control system of dynamic job-shop. Then, deep reinforcement learning was introduced to job-shop production control system to transform the dynamic job-shop production control problem. After that, the authors proposed a dynamic job-shop production control method based on deep reinforcement learning, and explained the collaboration strategy for multiple subsystems. The proposed method was proved effective through experiments.

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Challenges in process control for continuous processing for production of monoclonal antibody products

Cited by 34 publications

References 61 publications

Process design of a fully integrated continuous biopharmaceutical process using economic and ecological impact assessment

Process design of a fully integrated continuous biopharmaceutical process using economic and ecological impact assessment

Recent advances in integrated process analytical techniques, modeling, and control strategies to enable continuous biomanufacturing of monoclonal antibodies

Application of Machine Learning and Rule Scheduling in a Job-Shop Production Control System

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