Bioprocess Technologies and Engineering, Biopharmaceutical Development, AstraZeneca, Gaithersburg, Maryland, USA.
Molecular Biology and Protein Sciences, Inhibrx, La Jolla, California, USA.
Biotechnol Bioeng. 2023 Jul;120(7):1869-1881. doi: 10.1002/bit.28384. Epub 2023 Apr 6.
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 needed to support NGM can be complicated and expensive. Biopharmaceutical Process Development considered two options as follows: (1) design its own NGM system or (2) buy a prebuilt system. PAK BioSolutions offers 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 system provides significant cost benefits (~10× lower) compared with the alternative-integration of many different pieces of equipment through a Distributed Control System 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 with the traditional batch mode of operation. The 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), which enabled continuous operation of a 14-day end-to-end monoclonal antibody purification process at the clinical manufacturing scale.
下一代制造（NGM）在过去十年中不断发展，以至于大型生物制药公司正在对该技术进行大量投资，并考虑将其应用于临床和商业流程。实施 NGM 有很多经过深思熟虑的原因。在大多数情况下，除非实施能够通过降低成本、缩短时间或提供额外所需的能力使资助组织受益，否则组织不会资助 NGM。这项工作展示了从连续纯化中获得的生产力提高，它使用了一种新系统，该系统完全集成和自动化了生物制药工艺的几个下游单元操作，从而提供了灵活性和易于实施 NGM。支持 NGM 所需的设备和自动化可能很复杂且昂贵。生物制药工艺开发考虑了以下两个选项：（1）设计自己的 NGM 系统，或（2）购买预制系统。PAK BioSolutions 提供了一个交钥匙的自动化集成系统，该系统可以同时运行多达四个连续的纯化阶段，同时在制造工厂中保持较小的占地面积。与通过需要大量工程时间进行设计、自动化和集成的分布式控制系统集成许多不同设备的替代方案相比，该系统提供了显著的成本优势（~10 倍）。与传统的批处理操作模式相比，集成和连续生物制造可以显著减少设施规模、降低制造成本和提高产品质量。该系统使用新的自动化策略，这些策略可稳健地连接单元操作。我们介绍了优化的工艺拟合、无菌和生物负荷控制策略以及自动化功能（例如 pH 反馈控制和在线添加洗涤剂），这些功能使临床制造规模下 14 天端到端单克隆抗体纯化过程的连续运行成为可能。
