Smart Manufacturing Implementation of a Continuous Downstream Precipitation and Filtration Process for Antibody Purification

Recently, continuous bioprocessing has gained momentum in biomanufacturing and can alleviate many of the hurdles faced in batch or semi-batch operations. Moreover, the parallel development of smart manufacturing (SM) allows the rapid small-scale prototyping and large-scale implementation of continuous bioprocesses. With this background, this paper presents the laboratory- scale implementation of a continuous precipitation-filtration process that can ultimately be used for therapeutic protein capture purification. The experimental setup includes four static mixers, four peristaltic pumps, one hollow fiber dewatering filtration module, and multiple pressure sensors and weigh scales. The system also includes an in-line advanced microscopic particle imaging probe that provides real-time images and derived metrics of the precipitate particle morphologies and a fiber optic 880 nm optical absorbance probe. A polyclonal human serum antibody mixture (hIgG) (10 g/L) was used as a stand-in for a monoclonal antibody therapeutic along with 7% w/v polyethylene glycol (PEG, volume exclusion agent) and 10 mM zinc chloride (cross-linking agent) as the precipitants to demonstrate the principles of operation and control of a precipitation-based process using SM technology. An integrated input/output (I/O) system was used to acquire pressure, flow rate, and weigh scale data and also to communicate with the pumps to change flow rates in real-time. Edge computers communicate with the I/O system and the imaging probe and host the software layer. The software layer enables real-time data acquisition, data-driven and first-principles model predictions, closed-loop control of precipitate particle morphology using pump flow rate of PEG, and cloud communications with the Clean Energy Smart Manufacturing Innovation Institute Smart Manufacturing Innovation Platform. The paper presents the initial results obtained with this integrated system, demonstrating the potential of SM strategies to enhance the production of life-saving biopharmaceutical products.

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Work Title Smart Manufacturing Implementation of a Continuous Downstream Precipitation and Filtration Process for Antibody Purification
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Embargoed
Creators
  1. Sambit Ghosh
  2. Matthew Mergy
  3. Mirko Minervini
  4. Jacinta Okpanum
  5. Steven M. Cramer
  6. B. Wayne Bequette
  7. Andrew L. Zydney
  8. Todd M. Przybycien
Keyword
  1. Smart manufacturing
  2. Biopharmaceuticals
  3. Continuous bioprocessing
  4. Precipitation
  5. Process control
  6. Antibodies
License In Copyright (Rights Reserved)
Work Type Article
Publisher
  1. Smart and Sustainable Manufacturing Systems
Publication Date October 6, 2023
Publisher Identifier (DOI)
  1. https://doi.org/10.1520/SSMS20230003
Deposited January 29, 2024

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Version 1
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  • Created
  • Added Smart_Manufacturing-final.pdf
  • Added Creator Sambit Ghosh
  • Added Creator Matthew Mergy
  • Added Creator Mirko Minervini
  • Added Creator Jacinta Okpanum
  • Added Creator Steven M. Cramer
  • Added Creator B. Wayne Bequette
  • Added Creator Andrew L. Zydney
  • Added Creator Todd M. Przybycien
  • Published
  • Updated Keyword, Description Show Changes
    Keyword
    • Smart manufacturing, Biopharmaceuticals, Continuous bioprocessing, Precipitation, Process control, Antibodies
    Description
    • <p>Recently, continuous bioprocessing has gained momentum in biomanufacturing and can alleviate many of the hurdles faced in batch or semi-batch operations. Moreover, the parallel development of smart manufacturing (SM) allows the rapid small-scale prototyping and large-scale implementation of continuous bioprocesses. With this background, this paper presents the laboratory- scale implementation of a continuous precipitation-filtration process that can ultimately be used for therapeutic protein capture purification. The experimental setup includes four static mixers, four peristaltic pumps, one hollow fiber dewatering filtration module, and multiple pressure sensors and weigh scales. The system also includes an in-line advanced microscopic particle imaging probe that provides real-time images and derived metrics of the precipitate particle morphologies and a fiber optic 880 nm optical absorbance probe. A polyclonal human serum antibody mixture (hIgG) (10 g/L) was used as a stand-in for a monoclonal antibody therapeutic along with 7 % w/v polyethylene glycol (PEG, volume exclusion agent) and 10mMzinc chloride (cross-linking agent) as the precipitants to demonstrate the principles of operation and control of a precipitation- based process using SM technology. An integrated input/output (I/O) system was used to acquire pressure, flow rate, and weigh scale data and also to communicate with the pumps to change flow rates in real-time. Edge computers communicate with the I/O system and the imaging probe and host the software layer. The software layer enables real-time data acquisition, data-driven and first-principles model predictions, closed-loop control of precipitate particlemorphology using pump flow rate of PEG, and cloud communications with the Clean Energy Smart Manufacturing Innovation Institute Smart Manufacturing Innovation Platform. The paper presents the initial results obtained with this integrated system, demonstrating the potential of SM strategies to enhance the production of life-saving biopharmaceutical products.</p>
    • <p>Recently, continuous bioprocessing has gained momentum in biomanufacturing and can alleviate many of the hurdles faced in batch or semi-batch operations. Moreover, the parallel development of smart manufacturing (SM) allows the rapid small-scale prototyping and large-scale implementation of continuous bioprocesses. With this background, this paper presents the laboratory- scale implementation of a continuous precipitation-filtration process that can ultimately be used for therapeutic protein capture purification. The experimental setup includes four static mixers, four peristaltic pumps, one hollow fiber dewatering filtration module, and multiple pressure sensors and weigh scales. The system also includes an in-line advanced microscopic particle imaging probe that provides real-time images and derived metrics of the precipitate particle morphologies and a fiber optic 880 nm optical absorbance probe. A polyclonal human serum antibody mixture (hIgG) (10 g/L) was used as a stand-in for a monoclonal antibody therapeutic along with 7% w/v polyethylene glycol (PEG, volume exclusion agent) and 10 mM zinc chloride (cross-linking agent) as the precipitants to demonstrate the principles of operation and control of a precipitation-based process using SM technology. An integrated input/output (I/O) system was used to acquire pressure, flow rate, and weigh scale data and also to communicate with the pumps to change flow rates in real-time. Edge computers communicate with the I/O system and the imaging probe and host the software layer. The software layer enables real-time data acquisition, data-driven and first-principles model predictions, closed-loop control of precipitate particle morphology using pump flow rate of PEG, and cloud communications with the Clean Energy Smart Manufacturing Innovation Institute Smart Manufacturing Innovation Platform. The paper presents the initial results obtained with this integrated system, demonstrating the potential of SM strategies to enhance the production of life-saving biopharmaceutical products.</p>
  • Updated