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\begin{document}

\title{Online/At-line Monitoring of Product Titer \& Critical Product Quality
Attributes (CQAs) During Process Development}



\author[1]{Letha Chemmalil}%
\author[1]{Tanushree Prabhakar}%
\author[1]{June Kuang}%
\author[2]{Jay West}%
\author[1]{Zhijun Tan}%
\author[1]{Vivekh Ehamparanathan}%
\author[1]{Yuanli Song}%
\author[1]{Jianlin Xu}%
\author[1]{Julia Ding}%
\author[1]{Zheng Jian Li}%
\affil[1]{Bristol-Myers Squibb Co}%
\affil[2]{Bristol-Myers Squibb}%


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  \date{May 31, 2024}


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\begin{abstract}
Process analytical technology (PAT) has been defined by the Food and
Drug Administration (FDA) as a system for designing, analyzing, and
controlling manufacturing through timely measurements to ensure final
product quality. Based on quality-by-design (QbD) principles, real-time
data monitoring is essential for timely control of critical quality
attributes (CQAs) to keep the process in a state of control. To
facilitate next-generation continuous bioprocessing, deployment of PAT
tools for real-time monitoring is integral for process understanding and
control. Real-time monitoring and control of CQAs is essential to keep
the process within the design space, which is in alignment with the
guiding principles of QbD concepts. The contents of this manuscript are
pertinent to the online/at-line monitoring of upstream titer and
downstream product quality. We have demonstrated that Waters' PATROL
system can be utilized to measure product titer and CQAs directly from
bioreactors and downstream unit operations, respectively. We have
established that online titer assay results from fed-batch and
perfusion-based alternating tangential flow (ATF) bioreactors are
comparable to at-line and conventional offline results. The utility of
the PATROL system for online product quality measurements of down-steam
unit operations for real-time peak pooling has been demonstrated.%
\end{abstract}%



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\verb`PAT Manuscript_ PATROL.docx`  available at \url{https://authorea.com/users/297575/articles/426842-online-at-line-monitoring-of-product-titer-critical-product-quality-attributes-cqas-during-process-development}

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