Medical Design Briefs - January 2023 - 12

Therapeutic Cell Production
ly do all the steps in production and are
fully automated (toti-function SUS devices).
One of the most commercially
successful is toti-function SUS devices
designed for automated production of
CAR-T cell cancer therapies. Although
limited to one specific process, these are
truly modern marvels.
However, they don't necessarily produce
the best or most cells. Recent comparability
studies from the NIH show
surprising results.1 Although the exposure
to air is assumed to be minimal, it is
not clear how well exposures to suboptimal
transients of the critical process parameters
temperature, CO2
, and O2
are
avoided. Other variables inherent to
each fixed SUS platform might also be
suboptimal and significantly influence
the final cell product.
This is the challenge with standardized
live cell process automation. Whether it
is one step, or a few steps, or all the steps
in production, an automated process
that doesn't degrade one kind of cell may
degrade others. Automating too early in
development is a risk. Only clinical trials
can tell whether the cell product works.
Developers need flexibility until clinical
trials prove successful, and canned automation
is not usually flexible.
In development, only comparability
studies can tell whether a process
change, such as automation, improves,
or hurts product quality. Thus, unifunction
SUS devices and multifunction SUS
devices impose less risk because they do
not automate the entire process, but
then upstream and downstream steps
may still be left exposed to air.
Despite the runaway commercial success
of automated toti-function SUSs,
the obvious up-front limitation is that
most cell production processes do not fit
in these devices.
Even if one does fit, will that cell product
be clinically effective, or will nonobvious
inherent limitations compromise
the potency? Certain CAR-Ts are effective,
thankfully, but the verdict is still out
with other cells.
New Category Challenges Dogma
and Terminology
Alternatives are starting to appear that
achieve all the objectives: complete closure,
complete avoidance of air, and virtually
no limits or constraints up-front or
over time. Some are difficult to describe
because they do it in a different way. One
12
Attention is now shifting to adopting more modern equipment and methods to consistently produce
the best cells. (Credit: BioSpherix, Ltd.)
example is the Xvivo System model X2
from BioSpherix.
Unlike closed SUS devices, the X2
modular closed system is not constrained
to any particular process but can accommodate
any entire cell production process
- large or small, simple or complex,
centralized or distributed, manual
or automated.
With interconnected glove chambers,
from the outside it looks like an isolator.
However, looks don't tell the whole
story. Isolator dogma brings with it preconceived
notions: HVAC connections,
filtered air blowing through, thick
heavy gloves, etc. Like a modern automobile,
it's important to look under the
hood to find out if it is old gas or new
electric.
Unlike any other isolator, the Xvivo
system is infinitely configurable with unprecedented
plug-and-play modularity.
It assembles from a comprehensive library
of modular chambers, cochambers,
and subchambers, interconnecting
in all different ways to efficiently close
by form and fit around the workflow of
any different entire production process,
including all analytic, processing, and
automation equipment.
The X2 modular closed system is not constrained to any particular process but can accommodate
any entire cell production process. (Credit: BioSpherix, Ltd.)
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Medical Design Briefs, January 2023

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Medical Design Briefs - January 2023

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