Chemical Engineering October 2021 - 16

cific post-translational modifications
can be obtained in one analytical run
through the use of HRMS as an additional
detector.
However, once the sterile sampling
and analysis are in place, data handling
is needed to provide feedback
in order to properly control the fermenter,
which means there's a lot
of software involved and it all has to
act together, notes Cook. Thermo
Scientific's Chromeleon Chromatography
Data System (CDS) software
can help streamline these laboratory
workflows. It delivers compliance
tools, networking capabilities,
instrument control, automation, data
processing and more. The enterprise
solution is designed for tracking, accountability
and quality assurance
(QA) and quality control (QC).
908 Devices' Knopp agrees that
analysis is a critical part of the bioprocess.
" In addition to the growing
biologics pipeline, there are initiatives
from the FDA [U.S. Food and Drug
Admin.] regarding quality by design
where they want you to understand
the importance of monitoring and
controlling each and every process
parameter and the critical quality attributes
of each biologic, " he says.
" This puts a lot of pressure on the
processor and analytical technologies
and creates a major drive toward
process integration, automation,
control and the ability to use
these analytical technologies inline. "
" Historically, there has been a hinderance
in taking these instruments
out to the process due to the large
size, complexity and expertise required
to run mass spectrometers
and interpret the data, " says Knopp.
" However, we are taking an approach
that is more analogous to the
computer industry in order to bring
it down from centralized mainframes
to desktops, laptops and mobile devices
by making simple and easy-touse
desktop and hand-held mass
spectrometer-based devices that are
more accessible. "
The company's REBEL desktop
device sits beside the bioreactor and
is capable of providing a quantitative
list of amino acids, dipeptides, watersoluble
vitamins and amines within
seven minutes (Figure 3). This allows
users to combine that informa16
tion
with other standard biochemical
markers and make decisions much
faster, shaving weeks off process
development cycles.
Knopp says bioprocessors are
showing enthusiasm at the prospect
of taking a laboratory-grade answer
from a mass spectrometer, moving it
out to their workplace and receiving a
comprehensive panel of analyses that
they would historically have to send
to a third-party laboratory and suffer a
long turnaround for results. " They can
analyze the information by looking at
the output on the screen and we've
made some recent integrations that
allow them to take that data into other
software programs they are using
to perform data analysis, enabling
them to look at trends and correlations
within their process, " he says.
That information can then be used to
provide insight into the process that
helps improve the efficiency and quality
of the process and end product,
and allows them to adjust their process
as needed in near real time.
Digitalization and modeling
As bioprocesses become more automated
and integrated with various
instruments and software programs,
they are accumulating more data that
should be used to further drive optimization
of the process, says Zeta's
Mayer. " Bioprocessing is no different
from other chemical processes in that
processors need to support all the
data in the automation system, get it
into a historian and turn the data into
actionable information, " he says. " This
is where digitalization and modeling
will begin to play a very important role
and why demand for this is growing. "
Zeta is currently working on a project
that uses digitalization and modeling
for predictive control of bioreactors,
says Mayer. " In theory, this
is simple: You mimic the process by
applying a mathematical model that
traces the entire process from the
early stages to the quality at the end.
If you have this model, you can use
it for optimizing the process and exploring
different ideas you'd like to try
to improve efficiency or quality. Simply
put, you get a map of the process and
exploit it for some optimum you'd like
to achieve, " he explains.
" We wanted to have the ability
908 Devices
FIGURE 3. 908 Devices' REBEL desktop device sits
beside the bioreactor and is capable of providing a
quantitative list of amino acids, dipeptides, water
soluble vitamins and amines within seven minutes.
This allows users to combine that information with
other standard biochemical markers and make
decisions much faster, shaving weeks off process
development cycles
to control bioreactors based on a
model, " he says. The company recently
began a project with two large
pharmaceutical companies in order
to explore the potential business
and commercial benefits behind the
bioreactor-modeling concept. By the
end of 2021, Zeta expects to have
a working prototype that would allow
the
pharmaceutical companies to
experiment with options, such as:
" I want to reduce my fermentation
time by 8%. What parameters can
be changed to meet that goal without
sacrificing quality? " or " How can
I combine unit operations and optimize
operations such as fermentation,
screening and downstream processes
to run one after the other to
get an overall optimum instead of a
local optimum? "
There are many different ideas on
how this technology may be applied
to improve operations and optimize
the process, but processors have
to know early enough in the process
development phase to create
an accurate model in order to take
the model through all the validation
steps, says Mayer. " This is one of
the reasons this technology has not
yet been applied in the bioprocessing
industry, so we are working on
this project as a proof of concept to
show end users that modeling control
does provide value. "
Overcoming future challenges
As the upstream part of the process
continues to evolve, the downstream
side faces its own set of challenges,
says Patrick Farquet, head renewables
and bio-based applications
with Sulzer Chemtech (Winterthur,
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