MilliporeSigma - Viral Safety - 23

Viral Safety

Keeping Up with Viral Safety Trends in Bioprocessing
due to its technical complexities and requirement for
Big Data bioinformatics. To address these concerns, the
Advanced Virus Detection Technologies Interest Group
(AVDTIG) was formed as a joint effort by regulatory and
industry scientists to share data and experiences using
advanced virus-detection technologies such as NGS.
"There are about 30 companies working in the AVDTIG
right now," said Dr. Wisher. "This year, the group is
publishing papers that will discuss best practices
for NGS methods and data analysis. They're also
developing a curated database of useful sequences
for viral safety studies as well as making a number of
standard purified virus preparations so that spiking
studies can be done to get a better idea of the
sensitivity of the technique."
Although regulatory agencies will not yet accept NGS
as a replacement for standard virus detection tests, the
technology is already impacting industry expectations
and standards. "Last month at a viral safety meeting,
Sanofi announced during a presentation that they
will be using NGS for screening cell lines and vaccines
and submitting that data along with all of the
conventional testing that was done for all new
products," said Dr. Wisher.

Viral Safety Testing in Quality by Design
Another trend in the industry, which has been
introduced and consistently encouraged by regulatory
authorities is the implementation of Quality by Design
(QbD) approach in process operations. The QbD
approach encourages an understanding of how raw

| October 1, 2017

materials and manufacturing processes impact the critical quality attributes of the product, i.e., attributes that
impact the safety, efficacy, and quality of a drug product.
Ultimately, a design space is defined, which represents
the operating range, within which the process meets
the critical quality attributes of the product. The
"absence of virus" can be considered a critical quality
attribute that impacts the safety of the drug product.
"The QbD approach enhances a manufacturer's understanding of their process and unit operations as well
as the impact of operating parameters on quality attributes," explained Dr. Raghunath. "Following QbD methodology, we have put together a knowledge base that
details the impact of various process conditions and
operating parameters on the viral clearance performance
of a downstream virus filter. The impact of parameters
that can typically change during the process, such as
pressure, conductivity, pH, protein concentration, and
membrane lots, on virus retention is reported. Understanding the effects of these parameters on quality
attributes like virus retention allows those parameters
to be controlled within a given range."
Using the principles of QbD for viral safety testing
results in a more thorough understanding of the design
space for viral clearance unit operations and the
appropriate controls that are needed to maintain the operating parameters. Key to the methodology is upfront
identification of risk factors and incorporation of testing
protocols to manage those risks, and NGS helps to
identify viral contamination risk. "When using novel
substrates in bioprocessing, extensive NGS character-

ization can be performed on several lots of the raw
materials to identify potential contaminants that may be
present," said Dr. Remington. "This can help focus testing
so that manufacturers have a rational testing strategy
for specific contaminants, and appropriate assays
can be designed."
Integrating sensitive new technologies for viral
detection into a QbD approach to biomanufacturing
provides confidence for both the manufacturer and
regulatory agency that the risks of virus entry to the
process are minimized, low levels of virus can be
detected, and the process parameters are controlled
to assure the expected levels of virus removal in the
downstream process, thereby assuring the integrity
and safety of the drug product. n

Traditional Testing
and Unknown Viruses

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Colette Coté, Ph.D.
Principal Scientist,
Focusing on the
BioReliance® Portfolio
of MilliporeSigma

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