机器学习驱动的培养条件和培养基成分优化以减轻单克隆抗体生产中的电荷异质性:当前进展与未来展望
Machine learning-driven optimization of culture conditions and media components to mitigate charge heterogeneity in monoclonal antibody production: current advances and future perspectives.
作者信息
Kavoni Hossein, Shahidi Pour Savizi Iman, Gopalakrishnan Saratram, Lewis Nathan E, Shojaosadati Seyed Abbas
机构信息
Biotechnology Department, Faculty of Chemical Engineering, Tarbiat Modares University, Tehran, Iran.
R&D Department, Behestan Innovation Factory, Tehran, Iran.
出版信息
MAbs. 2025 Dec;17(1):2547084. doi: 10.1080/19420862.2025.2547084. Epub 2025 Aug 14.
Charge heterogeneity in monoclonal antibodies (mAbs), caused by post-translational modifications, remains a substantial obstacle to ensuring consistent, stable, and effective therapeutics. Conventional optimization techniques, such as one-factor-at-a-time and design of experiments, often fail to capture the complex, nonlinear interactions between culture parameters (e.g. pH, temperature, duration) and medium components (e.g. glucose, metal ions, amino acids). This review highlights machine learning (ML) as a powerful approach for modeling these relationships and forecasting charge variant profiles in CHO cell-based mAb process development. We summarize supervised learning and regression methods used to link process conditions with charge heterogeneity and present case studies showing ML's role in reducing acidic and basic variants. We also discuss challenges related to data quality, model interpretability, scalability, and regulatory compliance. Finally, we propose a roadmap for adaptive, ML-driven optimization strategies for bioprocess development, aligned with Quality-by-Design principles.
翻译后修饰导致的单克隆抗体(mAb)电荷异质性,仍然是确保治疗药物一致性、稳定性和有效性的重大障碍。传统的优化技术,如一次一个因素法和实验设计,往往无法捕捉培养参数(如pH值、温度、持续时间)和培养基成分(如葡萄糖、金属离子、氨基酸)之间复杂的非线性相互作用。本综述强调机器学习(ML)是一种强大的方法,可用于在基于CHO细胞的单克隆抗体制备工艺开发中对这些关系进行建模和预测电荷变体谱。我们总结了用于将工艺条件与电荷异质性联系起来的监督学习和回归方法,并展示了机器学习在减少酸性和碱性变体方面作用的案例研究。我们还讨论了与数据质量、模型可解释性、可扩展性和法规合规性相关的挑战。最后,我们提出了一个与质量源于设计原则相一致的、用于生物工艺开发的自适应、机器学习驱动的优化策略路线图。
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