BIOTECHNOLOGY
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.
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, centralised 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 car, you really have to look under the bonnet to find out if it is old gas or new electric. Unlike any other isolator, the Xvivo system is infinitely configurable with impressive plug & 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. Cell production often consists of many widely diverse steps. Technicians or industrial robotic arms use the gloves from the outside for manual or man-mimetic robotic steps, or for tending to the equipment or automation inside. However, in the context of
producing high-quality cells by avoiding contamination and toxic chemicals, it is more comparable to SUSs. “It is not a SUS of any kind, but like a SUS it makes aseptic cell production easy,”
34
www.scientistlive.com
says Yerden. “Instead of ease with pre- sterilised disposables, it self-sanitises the entire internal production environment automatically without risky biocides. No biocides may sound like heresy according to GMP dogma, but it works, and the data trumps the dogma. In this regard it could also be called a next generation isolator, or Cytocentric isolator.” Instead of air inside, it is filled with a mix of pure N2 tanks. CO2
at optimal levels for cells throughout the system, just like an incubator or bioreactor. Temperature can also be controlled, just like an incubator or bioreactor. “By eliminating the fluctuations and transient exposures to suboptimal temperature, CO2
and O2
by all the typical exposures to air in cleanrooms or traditional isolators, you always get cells with better consistency and quality. Sometimes radically better,” emphasises Yerden. Notably most stem cells and primary
, and O2
cultures fresh from the patient do best at low O2
levels, which simulate normal
physiologic levels. In fact, it is the only cell manufacturing platform that can optimise this critical parameter at every step of production, simultaneously with physiologic CO2
, O2 , and CO2 gases from can be controlled The Xvivo system is infinitely configurable usually caused
nitrogen, or chill down to refrigerator temperatures. Compared to cleanrooms, it reduces facility costs by 90% when you look at total cost of ownership at equivalent production capacity over the facility lifecycle. Extremely low operating cost is the gamechanger, although many forget to factor that into future facility cost estimates. “When you do, it brings cGMP cell
and temperature.
However, where necessary, you can simulate air without air, inert with 100%
production within reach of even the smallest companies. Combine that with the speed and flexibility of deployment, multi-modal capability due to closure, easy path to regulatory approval due to closure, reduction in virtually all the risks, and high quality of the live cell products, it is next generation regardless of what you call it,” concludes Yerden.
Eliminating the fluctuations caused by exposure to air means the user always get cells with better consistency and quality
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60
