Innovations at Interphex 2023 - 18

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 (Song H, Shao L, Prochazkova M, et al
145 Comparison of CAR-T cell manufacturing platforms
reveals distinct phenotypic and transcriptional profiles
Journal for ImmunoTherapy of Cancer 2021). 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, " explains
Yerden. " Automating too early in development is a risk. Only
clinical trials can tell if 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 if a
process change, such as automation, improves or hurts
product
quality. Thus uni-function SUS devices and
multi-function 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, "
adds Yerden.
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
non-obvious
inherent
limitations
compromise the potency? Certain CAR-Ts are effective,
thankfully, but the verdict is still out with other cells, "
explains Yerden.
The X2 modular closed system is not constrained to any particular process
but can accommodate any entire cell production process.
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 example is the Xvivo System model X2
from BioSpherix.
As Yerden explains, " 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, you really have 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, co-chambers, and sub-chambers,
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.
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| Innovations at INTERPHEX 2023
Innovations at Interphex 2023

Table of Contents for the Digital Edition of Innovations at Interphex 2023
