Intelligent process development — An in-line Raman-assisted automatic cell culture process development platform

IF 3.5 3区工程技术 Q2 ENGINEERING, CHEMICAL

AIChE Journal Pub Date : 2025-04-10 DOI:10.1002/aic.18851

Zhijun Zhang, Zhe Lang, Gong Chen, Mingyue Fang, Hang Zhou, Weichang Zhou

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引用次数: 0

Abstract

In the competitive biopharmaceutical industry, rapid cell culture process development is crucial for establishing a high-yield bioprocess. Traditional clone selection and process optimization methods are laborious and time-consuming due to multiple iterative rounds. To enhance efficiency, real-time metabolite monitoring and parameter control are vital. We propose an intelligent process development (IPD) platform utilizing Raman spectroscopy-based process analytical technology (PAT) for real-time monitoring and feedback control. The IPD platform automates optimization, incorporating a cell-specific growth rate (μ)-based temperature downshifting strategy and a dynamic feeding approach. Compared to traditional fed-batch (TFB), the IPD strategy increased the clone's titer by 44% (1490 vs. 1034 mg/L). To meet large-scale manufacturing demands, we adapted the Raman-based IPD process into a TFB process with comparable titer, compatible with facilities lacking PAT or automation. This approach was validated with an alternative clone, demonstrating the IPD's ability to enhance productivity through a single automated round, accelerating development.

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智能过程开发-一个在线拉曼辅助的自动细胞培养过程开发平台

在竞争激烈的生物制药行业中，快速的细胞培养工艺开发是建立高产生物工艺的关键。传统的克隆选择和工艺优化方法由于需要多次迭代，费时费力。为了提高效率，实时代谢物监测和参数控制至关重要。我们提出了一个智能过程开发（IPD）平台，利用基于拉曼光谱的过程分析技术（PAT）进行实时监测和反馈控制。IPD平台采用基于细胞特异性生长速率（μ）的温度降速策略和动态进料方法进行自动化优化。与传统的分批补料（TFB）相比，IPD策略使克隆滴度提高了44% （1490 vs 1034 mg/L）。为了满足大规模生产需求，我们将基于拉曼的IPD工艺调整为具有相当滴度的TFB工艺，与缺乏PAT或自动化的设施兼容。该方法通过另一种克隆进行了验证，证明了IPD通过单次自动化循环提高生产率的能力，从而加速了开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

AIChE Journal 工程技术-工程：化工

CiteScore

7.10

自引率

10.80%

发文量

411

审稿时长

3.6 months

期刊介绍： The AIChE Journal is the premier research monthly in chemical engineering and related fields. This peer-reviewed and broad-based journal reports on the most important and latest technological advances in core areas of chemical engineering as well as in other relevant engineering disciplines. To keep abreast with the progressive outlook of the profession, the Journal has been expanding the scope of its editorial contents to include such fast developing areas as biotechnology, electrochemical engineering, and environmental engineering. The AIChE Journal is indeed the global communications vehicle for the world-renowned researchers to exchange top-notch research findings with one another. Subscribing to the AIChE Journal is like having immediate access to nine topical journals in the field. Articles are categorized according to the following topical areas: Biomolecular Engineering, Bioengineering, Biochemicals, Biofuels, and Food Inorganic Materials: Synthesis and Processing Particle Technology and Fluidization Process Systems Engineering Reaction Engineering, Kinetics and Catalysis Separations: Materials, Devices and Processes Soft Materials: Synthesis, Processing and Products Thermodynamics and Molecular-Scale Phenomena Transport Phenomena and Fluid Mechanics.