Compliance with Quality by Design (QbD) constitutes a major challenge in biopharmaceuticals. Monoclonal antibodies (mAbs) represent a significant biopharmaceutical product class, typically produced in mammalian cell cultures. A key quality attribute for mAb production is glycosylation. We examine how process intensification affects glycosylation via dynamic optimization using different problem formulations. We maximize process performance with simultaneous control of product quality. For these, we utilize a mechanistic dynamic model for mAb production in mammalian cell cultures including glycosylation presented by Ehsani et al. in Computer Aided Chemical Engineering (2017). To achieve target glycan distribution in the final product, we incorporate constraints for the acceptable glycosylation ranges into the dynamic optimization problem. As a result, we derive optimal supplementation profiles of nutrients and/or nucleotide sugars. This work successfully illustrates an example of how model-based dynamic optimization can be employed for implementation of the QbD approach in biopharmaceutics.

设计质量（QbD）的合规性构成了生物制药的主要挑战。单克隆抗体（mAb）代表重要的生物制药产品类别，通常在哺乳动物细胞培养物中产生。mAb产生的关键质量属性是糖基化。我们研究了过程强化如何通过使用不同问题公式的动态优化来影响糖基化。我们在控制产品质量的同时最大化过程性能。对于这些，我们利用机械动力学模型在哺乳动物细胞培养物中产生mAb，包括Ehsani等提出的糖基化。在计算机辅助化学工程专业（2017）。为了在最终产品中实现目标聚糖分布，我们将可接受的糖基化范围的约束条件纳入了动态优化问题。结果，我们得出了营养素和/或核苷酸糖的最佳补充概况。这项工作成功地说明了如何在生物制药中采用基于模型的动态优化来实现QbD方法的示例。