An assessment of the impact of Raman based glucose feedback control on <scp>CHO</scp> cell bioreactor process development
Luke Gibbons, Francis Maslanka, Nikky Le, Al Magill, Pankaj Kumar Singh, Joseph K. McLaughlin, Fiona Madden, Ronan Hayes, Barry McCarthy, Christopher K. Rode, Jim O’Mahony, Rosemary Rea, Caitlin O'Mahony‐Hartnett
Abstract
Process analytical technology (PAT) tools such as Raman Spectroscopy have become established tools for real time measurement of CHO cell bioreactor process variables and are aligned with the QbD approach to manufacturing. These tools can have a significant impact on process development if adopted early, creating an end-to-end PAT/QbD focused process. This study assessed the impact of Raman based feedback control on early and late phase development bioreactors by using a Raman based PLS model and PAT management system to control glucose in two CHO cell line bioreactor processes. The impact was then compared to bioreactor processes which used manual bolus fed methods for glucose feed delivery. Process improvements were observed in terms of overall bioreactor health, product output and product quality. Raman controlled batches for Cell Line 1 showed a reduction in glycation of 43.4% and 57.9%, respectively. Cell Line 2 batches with Raman based feedback control showed an improved growth profile with higher VCD and viability and a resulting 25% increase in overall product titer with an improved glycation profile. The results presented here demonstrate that Raman spectroscopy can be used in both early and late-stage process development and design for consistent and controlled glucose feed delivery.