Chromatography Based Near-Real-Time Measurements & Timely Control of Product Titer, Product Quality and Cell Culture Nutrients
23rd February 2023 | 10:00am EST / 7:00am PST / 3:00pm GMT / 4:00pm CET | Letha Chemmalil, Scientific Associate Director at Bristol Myers Squibb |WATCH FOR FREE
PAT has been defined by the FDA as a system for designing, analyzing, and controlling the manufacturing through timely measurements of CQAs to ensure desired final product quality. Based on the QbD principles, online data monitoring is essential for timely control of CPPs and CQAs to keep the process in a desired state of control. To facilitate next-generation continuous bioprocessing, 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. Highlight of this presentation is pertaining 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, 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’s areas of expertise include, analytical method development and protein characterization utilizing Mass Spectrometry (LC/MS & MALDI-TOF MS) and Biophysical Characterization (CD, DSC, FTIR, Fluorescence Spectroscopy, etc.). Her academic background is spanning in the disciplines of Chemistry and Chemical Engineering. Letha’s passion for Process analytical technology (PAT) was 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. Round table 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 majority of the offline analytical methods can be performed at the online mode with an appropriate interface. Continuous evolution of chromatographic systems and column chemistry enable significant reduction in analysis time. With such paradigm shift, online chromatographic methods have the potential to surpass the spectroscopic methods that are calibrated against chromatographic method for predictive model building.