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Fully Integrated downstream process to enable Next Generation Manufacturing
  • +4
  • Irina Ramos,
  • Nikunj Sharda,
  • Ramon Villafana,
  • Kevin Hill-Byrne,
  • Kang Cai,
  • Joanna Pezzini,
  • Jon Coffman
Irina Ramos
AstraZeneca Medimmune

Corresponding Author:[email protected]

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Nikunj Sharda
AstraZeneca Medimmune
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Ramon Villafana
Inhibrx LP
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Kevin Hill-Byrne
PAK BioSolutions VA USA
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Kang Cai
AstraZeneca Medimmune
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Joanna Pezzini
PAK BioSolutions VA USA
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Jon Coffman
AstraZeneca Medimmune
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Next generation manufacturing (NGM) has evolved over the past decade to a point where large biopharmaceutical organizations are making large investments in the technology and considering implementation in clinical and commercial processes. There are many well-considered reasons to implement NGM. For the most part, organizations will not fund NGM unless the implementation benefits the funding organization by providing reduced costs, reduced time or additional needed capabilities. Productivity improvements gained from continuous purification are shown in this work, which used a new system that fully integrates and automates several downstream unit operations of a biopharmaceutical process to provide flexibility and easy implementation of NGM. The equipment and automation supporting NGM can be complicated and expensive. Biopharmaceutical Process Development considered two options: (1) design its own NGM system or (2) buy a pre-built system. PAK BioSolutions (Virginia, US), provides a turn-key automated and integrated system that can operate up to four continuous purification stages simultaneously, while maintaining a small footprint in the manufacturing plant. The PAK system provides significant cost benefits (~10x lower) compared to the alternative – integration of many different pieces of equipment through a Distributed Control System (DCS) that would require significant engineering time for design, automation and integration. Integrated and Continuous Biomanufacturing can lead to significant reductions in facility size, reduced manufacturing costs, and enhanced product quality when compared to the traditional batch mode of operation. The PAK system uses new automation strategies that robustly link unit operations. We present the optimized process fit, sterility and bioburden control strategy, and automation features (such as pH feedback control and in-line detergent addition) that enabled continuous operation of a 14 day end-to-end monoclonal antibody purification process at the clinical manufacturing scale.
03 Oct 2022Submitted to Biotechnology and Bioengineering
03 Oct 2022Submission Checks Completed
03 Oct 2022Assigned to Editor
10 Oct 2022Reviewer(s) Assigned
13 Nov 2022Review(s) Completed, Editorial Evaluation Pending
13 Nov 2022Editorial Decision: Revise Major
14 Feb 20231st Revision Received
14 Feb 2023Submission Checks Completed
14 Feb 2023Assigned to Editor
14 Feb 2023Review(s) Completed, Editorial Evaluation Pending
18 Feb 2023Reviewer(s) Assigned
12 Mar 2023Editorial Decision: Accept