Chromatography Based Near-Real-Time Measurements & Timely Control of Product Titer, Product Quality and Cell Culture Nutrients

PAT has been defined by the FDA as a system for designing, analyzing, and controlling manufacturing through timely measurements of CQAs to ensure the desired final product quality. Based on the QbD principles, online data monitoring is essential for the timely control of CPPs and CQAs to keep the process in the desired state of control. To facilitate next-generation continuous bioprocessing, the deployment of PAT tools for real-time monitoring is essential for process understanding and control to keep the process within the design space to align with the guiding principles of QbD. The highlight of this presentation pertains to the emerging PAT tools we developed for monitoring online upstream titer and nutrients, as well as upstream and downstream product quality, with the option to perform timely process control. For the measurement of titer from bioreactors and CQAs from downstream unit operations, a 1D-LC system interfaced with a process sample manager is utilized. A 2D-LC/1D-LC system interfaced with an inline sampling device is used for various applications, including online measurements of product titer, product quality and online amino acid quantitation of bioreactor samples. A sequential injector analyser system interfaced with a sampling device and 1D-LC is being leveraged for complex glycan analyses, peptide mapping, etc., requiring extensive sample preparations.

Presented by Letha Chemmalil, Scientific Associate Director at Bristol Myers Squibb

Dr Letha Chemmalil is serving as Scientific Associate Director at Bristol Myers Squibb in the Global Process Analytical Sciences & Technology group within the Biological Product Development division. Her prior affiliations include working for major biopharmaceutical companies such as Amgen, Genzyme, Seron, Wyeth, and others. Letha is an expert in creating new analytical methods, characterizing proteins using mass spectrometry (LC/MS and MALDI-TOF MS), and characterizing the physical properties of proteins using CD, DSC, FTIR, fluorescence spectroscopy, and other techniques. Her academic background spans the disciplines of chemistry and chemical engineering. Letha’s passion for process analytical technology (PAT) evolved in response to hearing stories shared by industry practitioners in reference to the lack of rapid analytical methods for real-time monitoring and timely control of CQAs. Roundtable discussions at various PAT consortiums also highlighted the deficit of reliable online analytical tools for supporting QbD driven process development and continuous bioprocessing. Letha believes that the majority of the offline analytical methods can be performed in the online mode with an appropriate interface. The continuous evolution of chromatographic systems and column chemistry enables a significant reduction in analysis time. With such a paradigm shift, online chromatographic methods have the potential to surpass the spectroscopic methods that are calibrated against the chromatographic method for predictive model building.

Followed by Accelerating Upstream Bioprocess Development Through Data-Driven Decisions

Cell line development scientists and upstream bioprocess engineers aim to optimize biotherapeutics production processes to maximize drug product quality, yield, and manufacturing efficiency. Currently, information on critical processes and product attributes required for informed decision making is often insufficient and not readily available. This has a negative impact on the process’s robustness, throughput, and outcome.

Direct measurement of cell culture media and product quality attributes (PQAs) has recently been offered thanks to the Waters BioAccord™ LC-MS system with dedicated workflows for process analytics of biopharmaceuticals. The BioAccord™ LC-MS system can be directly coupled to multi parallel bioreactor systems, like the Sartorius Ambr® 15 or 250 HT platforms, for accelerated process development.

With this all-in-one solution, process engineers can get direct access to the data they need to stay in charge: they can improve the quality and yield of the drug substance, lower the amount of impurities in the process and the product, and create more reliable processes that lower the risk of batch failure. This ultimately results in accelerated drug product development and manufacturing release from months or weeks to days, saving time and resources but, more importantly, enabling faster delivery of safer treatments to patients.

Please join us as Magnus Wetterhall presents how the Waters BioAccord™ LC-MS system offers enhanced capabilities for direct measurements of critical product quality attributes in cell line and process development. Nick Pittman will follow up on how you can use the same BioAccord™ LC-MS system to perform the most comprehensive cell culture media analysis to gain valuable insights and execute more informed decisions with your own high-quality data.

Presented by Magnus Wetterhall, Global Marketing Manager, Bioprocessing at Waters Corporation

Magnus Wetterhall joined Waters Corporation in 2022 as a Global Marketing Manager – Bioprocessing. He has more than 25 years of experience in upstream & downstream bioprocessing, advanced mass spectrometry, biomarker discovery, protein characterization, working at start-ups and large biotech companies, as well as academics. Magnus earned his M.Sc. and Ph.D. in analytical chemistry at Uppsala University, Sweden. He serves as the Global Marketing Manager at Waters Corporation in the Bioprocessing Team, where he is dedicated to delivering analytical solutions to advance upstream and downstream bioprocesses.

Nick Pittman Global Marketing Manager – Biopharmaceuticals at Waters Corporation

Nick Pittman joined Waters Corporation in 2013 as a biopharmaceutical specialist. He earned his master’s degree in chemistry at the University of Birmingham in Birmingham, England, UK. He serves as the Global Marketing Manager at Waters Corporation in the Biopharmaceuticals Team, where he explores how to provide technology that meets the varied analytical challenges of bioprocess scientists.

Sponsored by Waters Corporation

Waters Corporation, a global leader in analytical instruments, consumables, and software, has pioneered chromatography, mass spectrometry, and thermal analysis innovations serving the life, materials, and food sciences for more than 60 years. We ensure the efficacy of the medicines we take, the safety of the food we eat and the water we drink, and the quality of the products we use every day. With more than 7,800 employees worldwide, Waters operates in over 35 countries, including 14 manufacturing facilities, and has products available in more than 100 countries. Together with our customers, in labs around the world, we deliver scientific insights to improve human health and well-being, helping to ensure we leave the world better than we found it.