MilliporeSigma - Viral Safety - 6

Viral Safety

Advances in Upstream Technologies Reduce Viral-Contamination Risks
"We are moving toward next-generation
expression systems for the manufacture of
recombinant therapeutic proteins and
vaccines with superior attributes, such as
improved product quality, higher productivity,
and shorter development timelines,"
asserted Dr. Mascarenhas.
Dr. Mascarenhas led a team of scientists that
developed a genetically engineered CHO
host cell line refractory to viral contamination. She and her colleagues have employed
genetic engineering to make the CHO line
resistant to the parvovirus, minute virus of
mice (MVM). This was accomplished by
modifying the major receptors used by
the virus to enter the cell. "Our goal was to
ensure that the cell lines were inherently
resistant to MVM contamination, as this is
the cell's last line of defense," she
explained.

Upstream suite in a mAb manufacturing plant. A major component
of a virus safety strategy is preventing viruses from entering the
upstream process.

In a peer-reviewed study, the group reported
that having recognized the role of sialic acid
in mediating virus entry into the cell, they
developed a cell line with modified sialic acid
glycan structures which lacked the ability to
bind MVM. The development of this cell line
has resulted in the first commercially available gene-editing approach for the creation
of MVM-resistant CHO cells: Centinel
Intelligent Virus Defense™ technology.
Dr. Mascarenhas explained that while a
majority of the known viral contaminants
in CHO lines were introduced through contaminated animal-derived components,

| October 1, 2017

MVM contamination continues to be a
threat, even in chemically defined processes.
Although it is impossible to completely
remove the risk of viral contamination, using
CHO cells that are resistant to one of the biggest threats to the industry should greatly
enhance even the most comprehensive
viral-mitigation programs in use.

Ensuring Product Quality
"Companies need to implement a multilayered approach for their viral risk mitigation
strategy," explained Kevin Kayser Ph.D., head
of upstream R&D at MilliporeSigma. "For example, we are constantly evaluating our raw
materials used in cell culture-media manufacturing. We establish robust procedures for
the selection and approval of vendors and
raw materials to aid in this risk mitigation."
According to Dr. Kayser, viral contaminants
ordinarily enter the process train from
various sources, such as cells (endogenous),
raw materials (serum), or manufacturing
processes.
"Companies cannot detect viral contamination at the level of one viral particle per liter,
yet it is known that this is sufficient to infect
a biologics manufacturing run, causing
contamination and loss of the product," Dr.
Kayser explained. "The industry's sampling
and detection methods aren't capable of this
low-level detection. We take the risk very
seriously, and use a variety of strategies to
mitigate against viral contamination risk."

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