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

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.