1. Introduction
A general concern in cell-based manufacturing of recombinant proteins,
including vaccines, is the potential contamination of the cell culture
with viruses, which has had severe consequences for patients and
manufacturers (Barone et al., 2020; Berting, Farcet, & Kreil, 2010).
With the pandemic emergence of SARS-CoV-2, the exposure of
biomanufacturing cell lines to a new virus has become a possibility, and
to safeguard biomedicines it is important to understand whether the
virus is even capable of infecting bioproduction cell lines, and if so,
whether the event would be detected by adventitious agent tests (AAT)
that are part of biomanufacturing quality control.
This study investigated four widely used biomanufacturing cell lines,
i.e. CHO and Vero, as well as the two human cell lines HEK-293 and
HT-1080, for their susceptibility to infection with SARS-CoV-2.
In addition, adventitious virus testing (AAT) as routinely performed for
in-process control testing per regulatory guidance (US Food and Drug
Administration, 1993; ICH, 1997), was evaluated for its ability to
detect SARS-CoV-2 infection if it were to occur. As MRC-5 cells are part
of the AAT detector cell line panel (Figure 1), these cells were also
tested for their susceptibility to SARS-CoV-2.