Tuesday, October 21, 2025 – Main Conference Day 1Tuesday, 21 October 2025 - JT (Japan Time, GMT+09:00)

This presentation explores the application of modeling and simulation to enhance the analysis and design of pharmaceutical manufacturing processes, with a focus on cell cultivation for monoclonal antibodies (mAbs) and cell therapies. We present the development and implementation of mechanistic and hybrid modeling approaches that provide a deeper understanding of cell culture dynamics and support model-based decision-making throughout process development. y leveraging predictive simulations, our approach has shown the potential to deliver tangible benefits, including a theoretical reduction of labor costs by up to 38%. These real-world impacts are demonstrated through actual case studies that highlight how digital techniques can contribute to efficient process development. The presentation concludes by addressing the required time and cost associated with modeling and simulation, and discusses the key factors that must be considered to maximize their impact in bioprocess development.

Despite the many benefits MS offers, non-MS LC-based analytics remains the industrial standard for process analytical technology (PAT) applications as MS is often perceived to be too complex to implement for biologics production. For upstream process development, MS can provide insight on complex isoforms, indicative of modifications at the glycans and sequence level which can be critical quality attributes (CQAs) for final drug product release. Waters' Bioprocess Walk-up Solution is an automated at-line LC-MS-based platform purposefully designed to streamline sample-to-result turnaround time from weeks to hours, allowing bioprocess engineers to monitor product CQAs for informed process decision making. In this case study, Waters collaborated with Chitose to implement the use of BioAccord^TM LC-MS system as at-line PAT for mAb production in CHO-MK¹ cells to accelerate process decision making during upstream process development through timely measurement of product CQAs. The presentation will cover:

• High productivity of CHO-MK¹ cells in a very short culture period as shown by the results from a study based on design of experiments (DOE) principles using an Ambr® 15 system and the establishment of the optimal culture conditions using an Ambr® 250 system.
• Streamlined LC-MS workflow from sample preparation to data acquisition and processing directly on crude samples sampled daily from Ambr® 15 and 250 systems, followed by seamless data transfer to JMP® software for multi-variate data analysis (MVDA).
• Daily turnaround time of comprehensive data packages from spent media metabolites (amino acids, vitamins, metabolites, etc.) to product titer, glycoforms etc.

[1] The CHO-MK¹ host cell line, which is banked as a host cell bank to produce biopharmaceuticals, is CHITOSE’s CHO host cell line that was developed for industrial applications from the primary cell culture of a healthy Chinese hamster ovary tissue. Chitose Laboratory Corp. provides stable cell line development services to generate pre-master cell banks expressing innovative proteins using their high-yield, fast-growing CHO-MK¹ host cells and their original CS CHO expression vector.