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\begin{document}

\title{Synthesis of `Nereid', a new phenol-free detergent to replace Triton
X-100 in virus inactivation}



\author[1]{Jean-Baptiste Farcet}%
\author[2]{Johanna Kindermann}%
\author[2]{Michael Karbiener}%
\author[1]{Richard Scheinecker}%
\author[1]{Otto Kostner}%
\author[3]{Thomas Kreil}%
\affil[1]{Takeda}%
\affil[2]{Baxter AG Austria}%
\affil[3]{Takeda Austria Vienna}%


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  \date{May 16, 2024}


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\begin{abstract}
In the 1980-ies, virus inactivation steps were implemented into the
manufacturing of biopharmaceuticals in response to earlier unforeseen
virus transmissions. The most effective inactivation process for
lipid-enveloped viruses is the treatment by a combination of detergents,
often including Triton X-100 (TX-100). Based on recent environmental
concerns, the use of TX-100 in Europe will be ultimately banned, which
forces the pharmaceutical industry, among others, to switch to an
environmentally friendly alternative detergent with fully equivalent
virus inactivation performance as TX-100. In this work, a
structure-activity relationship study was conducted that ultimately led
to the synthesis of several new detergents. One of them, named `Nereid',
displays inactivation activity fully equivalent to TX-100. The synthesis
of this replacement candidate has been optimized to allow for the
production of several kg of detergent at lab scale, to enable the
required feasibility and comparison virus inactivation studies needed to
support a potential future transition. The 3-step, chromatography-free
synthesis process described herein uses inexpensive starting materials,
has a robust and simple work-up, and allows production in a standard
organic laboratory to deliver batches of several hundred grams with
\textgreater{}99\% purity.%
\end{abstract}%



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