Engineering Challenges of Continuous Biomanufacturing Processes (
            <scp>CBP</scp>
            )

Thiess, Holger; Zobel-Roos, Steffen; Gronemeyer, Petra; Ditz, Reinhard; Strube, Jochen

doi:10.1002/9783527699902.ch3

Cited by 7 publications

(5 citation statements)

References 88 publications

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“…From a pure process control point of view, both continuous and batch production processes have unique characteristics that make their control difficult. One of the most important differences between continuous bioprocessing and batch or even fed-batch operations is in their required level of control sophistication [39]. For a fed-batch process, the objective of process control is mainly to achieve a given feeding profile while ensuring that variables such as pH and temperature are kept in check.…”

Section: Pat Solutions and Robotics For Better Controlmentioning

confidence: 99%

Why Is Batch Processing Still Dominating the Biologics Landscape? Towards an Integrated Continuous Bioprocessing Alternative

et al. 2020

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Continuous manufacturing of biologics (biopharmaceuticals) has been an area of active research and development for many reasons, ranging from the demand for operational streamlining to the requirement of achieving obvious economic benefits. At the same time, biopharma strives to develop systems and concepts that can operate at similar scales for clinical and commercial production—using flexible infrastructures, such as single-use flow paths and small surge vessels. These developments should simplify technology transfer, reduce footprint and capital investment, and will allow to react readily to changing market pressures while maintaining quality attributes. Despite a number of clearly identified benefits compared to traditional batch processes, continuous bioprocessing is still not widely adopted for commercial manufacturing. This paper details how industry-specific technological, organizational, economic, and regulatory barriers that exist in biopharmaceutical manufacturing are hindering the adoption of continuous production processes. Based on this understanding, the roles of process systems engineering (PSE), process analytical technologies, and process modeling and simulation are highlighted as key enabling tools in overcoming these multi-faceted barriers in today’s manufacturing environment. Of course, we do recognize that there is also a need for a clear set of regulations to guide a transition of biologics manufacturing towards continuous processing. Furthermore, the role played by the emerging fields of process integration and automation as well as digitalization is explored, as these are the tools of the future to facilitate this transition from batch to continuous production. Finally, an outlook focusing on technology, management, and regulatory aspects is presented to identify key concerted efforts required to drive the broad adaptation of continuous manufacturing in biopharmaceutical processes.

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Section: Pat Solutions and Robotics For Better Controlmentioning

confidence: 99%

Why Is Batch Processing Still Dominating the Biologics Landscape? Towards an Integrated Continuous Bioprocessing Alternative

et al. 2020

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“…Continuous bioprocessing circumvents the aforementioned downstream bottleneck and batch scale-up problems by increasing the productivity and flexibility of each unit operation with a simultaneous increase in product quality resulting from continuous product processing (i.e., short hold times) [6,14,[21][22][23][24][25][26][27][28][29][30][31][32][33]. The FDA (U.S. Food and Drug Administration), EMA (European Medicinal Agency), ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use), and various industrial working groups have started to publish guidelines (ICH Q8 to Q11) to increase product quality during manufacturing and; therefore, promoting continuous bioprocessing [34][35][36][37][38][39].…”

Section: Critical View On Current Practicementioning

confidence: 99%

Accelerating Biomanufacturing by Modeling of Continuous Bioprocessing—Piloting Case Study of Monoclonal Antibody Manufacturing

et al. 2019

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An experimental feasibility study on continuous bioprocessing in pilot-scale of 1 L/day cell supernatant, that is, about 150 g/year product (monoclonal antibody) based on CHO (Chinese hamster ovary) cells for model validation is performed for about six weeks including preparation, start-up, batch, and continuous steady-state operation for at least two weeks stable operation as well as final analysis of purity and yield. A mean product concentration of around 0.4 g/L at cell densities of 25 × 106 cells/mL was achieved. After perfusion cultivation with alternating tangential flow filtration (ATF), an aqueous two-phase extraction (ATPE) followed by ultra-/diafiltration (UF/DF) towards a final integrated counter-current chromatography (iCCC) purification with an ion exchange (IEX) and a hydrophobic interaction (HIC) column prior to lyophilization were successfully operated. In accordance to prior studies, continuous operation is stable and feasible. Efforts of broadly-qualified operation personal as well as the need for an appropriate measurement and process control strategy is shown evidently.

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“…7,[21][22][23] Continuous bioprocessing circumvents the aforementioned downstream bottleneck and batch scale-up problems by increasing the productivity and flexibility of each unit operation with a simultaneous increase in product quality resulting from continuous product processing (i.e., short hold times). 4,9,16,[23][24][25][26][27][28][29][30][31][32][33][34] The Food and Drug Administration, European Medicinal Agency, International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) and various industrial working groups have started to publish guidelines (ICH Q8-Q11) to increase product quality during manufacturing, thereby promoting continuous bioprocessing. [35][36][37][38][39][40] Key technologies and concepts needed to realize the full potential of continuous production are process analytical technology (PAT) and quality-by-design (QbD) guidelines.…”

Section: Introductionmentioning

confidence: 99%

Process analytical technology as key‐enabler for digital twins in continuous biomanufacturing

Schmidt

Helgers

Lohmann

et al. 2022

J of Chemical Tech & Biotech

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Over the last few years rapid progress has been made in adopting well‐known process modeling techniques from chemicals to biologics manufacturing. The main challenge has been analytical methods as engineers need quantitative data for their workflow. Industrialization 4.0, Internet of Things, artificial intelligence and machine learning activities up to big data analysis have taken their share in solving fundamental problems like component‐ or at least group‐specific evaluation of spectroscopic data. Besides, concerning inline analytics methods included in process analytical technology concepts the key technology has been the generation of decisive validated digital twins based on process models. This review aims to summarize the methodology to achieve a holistic understanding of process models, control and optimization by means of digital twins using the example of recent work published in this field. © 2021 The Authors. Journal of Chemical Technology and Biotechnology published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry (SCI).

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Engineering Challenges of Continuous Biomanufacturing Processes ( CBP )

Cited by 7 publications

References 88 publications

Why Is Batch Processing Still Dominating the Biologics Landscape? Towards an Integrated Continuous Bioprocessing Alternative

Why Is Batch Processing Still Dominating the Biologics Landscape? Towards an Integrated Continuous Bioprocessing Alternative

Accelerating Biomanufacturing by Modeling of Continuous Bioprocessing—Piloting Case Study of Monoclonal Antibody Manufacturing

Process analytical technology as key‐enabler for digital twins in continuous biomanufacturing

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