Australian Research Council Training Centre for Biopharmaceutical Innovation, Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, Queensland, Australia.
Patheon Biologics-a part of Thermo Fisher Scientific, Brisbane, Queensland, Australia.
Biotechnol Bioeng. 2018 Dec;115(12):2893-2907. doi: 10.1002/bit.26812. Epub 2018 Oct 18.
Rapid advances in intensifying upstream processes for biologics production have left downstream processing as a bottleneck in the manufacturing scheme. Biomanufacturers are pursuing continuous downstream process development to increase efficiency and flexibility, reduce footprint and cost of goods, and improve product consistency and quality. Even after successful laboratory trials, the implementation of a continuous process at manufacturing scale is not easy to achieve. This paper reviews specific challenges in converting each downstream unit operation to a continuous mode. Key elements of developing practical strategies for overcoming these challenges are detailed. These include equipment valve complexity, favorable column aspect ratio, protein-A resin selection, quantitative assessment of chromatogram peak size and shape, holistic process characterization approach, and a customized process economic evaluation. Overall, this study provides a comprehensive review of current trends and the path forward for implementing continuous downstream processing at the manufacturing scale.
生物制品生产的上游工艺不断强化，下游工艺却成为生产方案的瓶颈。生物制造商正在寻求连续的下游工艺开发，以提高效率和灵活性、降低占地面积和产品成本，并改善产品一致性和质量。即使在实验室试验成功后，在生产规模上实施连续工艺也不容易实现。本文综述了将每个下游单元操作转化为连续模式的具体挑战。详细介绍了开发实用策略以克服这些挑战的关键要素。这些要素包括设备阀门的复杂性、有利的柱高径比、Protein-A 树脂的选择、色谱峰大小和形状的定量评估、整体工艺特性分析方法以及定制的工艺经济性评估。总的来说，本研究全面综述了当前的趋势和在生产规模上实施连续下游工艺的前进道路。
