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\begin{document}

\title{Online/At-line Measurement, Analysis and Control of Product Titer \&
Critical Product Quality Attributes (CQAs) During Process Development}



\author[1]{Letha Chemmalil}%
\affil[1]{Bristol-Myers Squibb Co}%


\vspace{-1em}



  
  \date{June 18, 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
or near-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 and align with the
guiding principles of QbD. The contents of this manuscript are pertinent
to the online/at-line monitoring of upstream titer and downstream
product quality with timely process control. We demonstrated that a UPLC
system interfaced with a process sample manager (UPLC-PSM) can be
utilized to measure titer and CQAs directly from bioreactors and
downstream unit operations, respectively. We established online titer
measurements from fed-batch and perfusion-based alternating tangential
flow (ATF) bioreactors as well as product quality assessments of
downstream operations for real-time peak collection. This integrated,
fully automated system for online data monitoring with feedback control
is designed to achieve desired product quality.%
\end{abstract}%



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\textbf{Hosted file}

\verb`PAT Manuscript.docx`  available at \url{https://authorea.com/users/297575/articles/467495-online-at-line-measurement-analysis-and-control-of-product-titer-critical-product-quality-attributes-cqas-during-process-development}

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