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Published on: December 12, 2019
Toward end-to-end continuous biopharmaceutical manufacturing: Current advances and prospects
Seonbong Lee1, Taehyeon Kim2, Jimin Kang1
1Department of Biological Sciences and Bioengineering, Inha University, 100 Inha-ro, Michuhol-gu, Incheon 22212, Republic of Korea.
End-to-end continuous biopharmaceutical manufacturing requires integrating upstream and downstream processes. Overcoming interface mismatches is key for sustained, high-quality production with minimal pooling.
Area of Science:
- Biopharmaceutical Manufacturing
- Chemical Engineering
- Process Intensification
Background:
- Continuous manufacturing offers process intensification beyond individual unit operations.
- End-to-end continuity integrates upstream and downstream processing for long-duration operation with minimal pooling.
Purpose of the Study:
- To review progress in end-to-end continuous biopharmaceutical manufacturing.
- To frame continuity as a system-level integration and interface-engineering challenge.
- To identify barriers and solutions for achieving practical end-to-end continuity.
Main Methods:
- Systematic review of recent advancements in upstream and downstream bioprocessing.
- Analysis of integration case studies focusing on interface challenges.
- Discussion of enabling technologies like PAT and digital twins.
Main Results:
- Perfusion upstream processes enable high cell density but require strict parameter control.
- Continuous downstream operations (capture, polishing, viral clearance) are increasingly feasible.
- Interface mismatches between upstream and downstream operations are the primary barrier, necessitating synchronization and conditioning.
Conclusions:
- Achieving end-to-end continuity relies on robust interface engineering and platform integration.
- Addressing cyclic dynamics and feed variability is crucial for long-duration robustness.
- Coordinated advances in technology and validation are essential for practical implementation.
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