The biopharmaceutical industry is transitioning from currently deployed
batch-mode bioprocessing to a highly efficient and agile next generation
bioprocessing with the adaptation of continuous bioprocessing, which
reduces the capital investment and operational costs. Continuous
bioprocessing, aligned with FDA’s quality-by-design (QbD) platform, is
designed to develop robust processes to deliver safe and effective
drugs. With the deployment of knowledge based operations, product
quality can be built into the process to achieve desired critical
quality attributes (CQAs) with reduced variability. To facilitate next
generation continuous bio-processing, it is essential to embrace a
fundamental shift-in-paradigm from “quality-by-testing” to
“quality-by-design”, which requires the deployment of process
analytical technologies (PAT). With the adaptation of PAT, a systematic
approach of process and product understanding and timely process control
are feasible. Deployment of PAT tools for real-time monitoring of CQAs
and feedback control is critical for continuous bioprocessing. Given the
current deficiency in PAT tools to support continuous bioprocessing, we
have integrated Agilent 2D-LC with a post-flow-splitter in conjunction
with the SegFlow automated sampler to the bioreactors. With this
integrated system, we have established a platform for online
measurements of titer and CQAs of monoclonal antibodies (mAbs) as well
as amino acid concentrations of bioreactor cell culture.
Next Generation Cell Culture Tools Featuring Micro‐ and Nanotopographies for Biological Screening (Adv. Funct. Mater. 3/2022)
