Flexible Facility for the Future
• Cell production facility cost reductions of 90%
• Respond to any demand just-in-time, eliminating risky long-term bets
AGNOSTIC TO PRODUCTION PROCESS
Quality recognizes that no cell production process should be excluded. Extreme modularity and a large and growing library of general and specialized modules should quickly configure to fit any production process. The Xvivo GMP System® Platform does this now.
PROCESS CHANGE
Quality recognizes that reconfiguring as the process changes should be simple and easy, with 0% variance risk and evidence to prove it. The Platform does this now.
AUTOMATION
Quality recognizes that migration from manual production processes to automated needs to be seamless with every automation option (off-the-shelf, bespoke, man-mimetic robotic arms), and every path to automation needs to be wide open to every different development strategy. All the typical negative side effects of the automated machines need to be neutralized, and all the automation needs to operate aseptically in a cell optimized environment. The Platform does this now.
AUTOMATING WITH OFF-THE-SHELF & BESPOKE ROBOTS
1. MANUAL PRODUCTION PROCESS
2. BUILD NEW ROBOTIC SUBASSEMBLY
3. NEW ROBOTIC SUBASSEMBLY
4. SPLIT WHERE NEW ROBOTICS WILL GO
5. MOVE IN NEW AUTOMATION MODULE SET
6. SPLICE IN NEW AUTOMATION MODULE SET
7. ISOLATED AUTOMATED PRODUCTION
AUTOMATING WITH MAN-MIMETIC INDUSTRIAL ARMS
1. MANUAL PRODUCTION PROCESS
Rate limiting step 1.
2. MAN-MIMETIC SEMI-AUTOMATED PROCESS
No change in process from manual to semi-automated.
3. MAN-MIMETIC SEMI-AUTOMATED PROCESS
Rate limiting step 2.
4. MAN-MIMETIC FULLY AUTOMATED PROCESS
No change in process from manual to automated.
SYNERGIZE ALL MODES OF AUTOMATION
SCALE-UP
Quality recognizes that scale up must be efficient (precisely proportionate, fast, and elastic) with 0% variance risk and evidence to prove it, and just-in- time on demand to eliminate risky long-term projections and commitments. The Platform does this now.
TYPICAL CELL MANUFACTURING
Preparation , expansion, and harvest. Incubation is usually the rate limiting step.
SCALING CYTOCENTRIC INCUBATION
Since incubation is usually rate limiting step, scaling incubation is typical path to scaling up and out. Incubators should be sized small as possible. The smaller the size, the more scaling possible.
CYTOCENTRIC INCUBATORS COME IN 3 SIZES
SCALING SCENARIOS
SCALING INCUBATION IN PROCESS CHAMBERS
Culture vessels and bioreactors that do not need high RH can be incubated in process chambers.
Corning Hyperstacks incubating in process chamber.
Roller bottles incubating in process chamber.
TYPICAL CELL MANUFACTURING
Aseptic transport between steps of the production process segregated in separate isolators achieves unlimited flexibility and efficiency in scaling.
SCALING OUT SEGREGATED INCUBATION
In separate isolators with limited processing for maintenance.
SCALING UP SEGREGATED INCUBATION
In separate isolators with limited processing for maintenance.
SCALING INCUBATION TOO BIG TO CARRY
Bioreactors and large culture vessels incubate in separate isolators that roll to and dock to prep/harvest isolators.
Select among multiple docking options for aseptic transfer of liquid or material from one isolator to the other.
SCALING OUT BIOREACTORS
Segregated incubation in separate isolators that roll to and dock to prep/harvest isolators.
SCALING UP BIOREACTORS
SCALING TERUMO
SCALING CULTURE STEP WITH BIOREACTORS
SCALING BATCH SIZE
SCALING BATCH NUMBER OF SMALL BATCH
SCALING BATCH NUMBER OF LARGE BATCH
SCALING WHEN DOWNSTREAM IS RATE LIMITING
SCALING WHEN UPSTREAM IS RATE LIMITING
SCALING GE FLEXFACTORY
For closed-in-closed cell production line.
The amazing GE FlexFactory consists of several functionally-closed cell processing machines, like the new Sephia shown above in open cleanroom and in closed isolator. In the following drawings the entire FlexFactory production train is represented inside the Xvivo System in a linear production line with prep, expansion, and harvest in sequence left to right for illustration purposes only.
GE FlexFactory Cell Production
Efficient Scaling – Scale each step as it becomes rate limiting.
Efficient GE FlexFactory Scaling
No need to scale upstream and downstream of rate limiting expansion step.
Reconfigure Production Line
Scale Rate Limiting Step Only
3X Scale-up @ 1 bioreactor/batch
Scale Rate Limiting Step Only
10X Scale-up @ 1 bioreactor/batch
Scale Batch Size
1X Scale @ 2 bioreactors/batch
Scale Batch Size
5X Scale-up @ 2 bioreactors/batch
Scale Batch Size
1X Scale @ 6 bioreactors/batch
Scale Batch Size
3X Scale-up @ 6 bioreactor/batch
SCALE-UP: Massively Parallel Large Batch
Quality recognizes that unlimited batches must be producible simultaneously side-by-side (massively parallel) with 0% cross contamination risk and 0% variance risk and evidence to prove it. The Platform does this now.
1X
2X
12X
SCALE-UP: Large Batch
Quality recognizes the need to integrate with external large scale production equipment in order to close and cell optimize the critical upstream inoculums seed train. The Platform does this now.
SCALE-OUT: Different Processes
Quality recognizes that scaling out of different production processes must be efficient (precisely proportionate, fast, and elastic) and not dependent on risky long term predictions (just-in-time on demand) with 0% variance risk and evidence to prove it. The Platform does this now.
4 Different Production Processes
SCALE-OUT: Distributed Manufacturing of Same Process
Quality recognizes that scale out of unlimited numbers of identical batches must be producible widely dispersed globally with 0% variance risk and evidence to prove it. The Platform does this now.
Replication/Reproduction — Cloneable Conditions
Toronto
Replication/Reproduction — Cloneable Conditions
San Diego
Replication/Reproduction — Cloneable Conditions
London
Remote Access: monitor all from one location!
1X Scale
2X National Scale-out
4X National Scale-out
8X International Scale-out
TRACKING QUALITY OF EVERY BATCH GLOBALLY…
with evidence to prove it.
GLOBAL PREVENTIVE MAINTENANCE AND TECH SUPPORT…
with evidence to prove it.
MOBILITY
Quality recognizes that production capacity must be quick and easy to move, to different locations globally, nationally, locally as needed, within weeks, with re- validation guaranteed. The Platform does this now.
Former Location: Biotech incubator/office space for Pre-IND/Phase 1 trials
Current Location: New company headquarters for Phase 2 scale up
ECOFRIENDLY & COST EFFECTIVE
Quality recognizes that cost efficiency and low-carbon footprint are fundamental quality attributes, critical for commercial viability and sustainability. Drastically reducing carbon footprint of facility lifecycle, compared to conventional brick-and-mortar legacy GMP facilities, reduces production facility costs by 90%. Closing processes dramatically alleviates need for expensive, high-carbon footprint cleanroom quantity and quality, and allows smaller facilities that operate more efficiently by an order of magnitude. The Platform does this now.
AT EQUIVALENT PRODUCTION CAPACITY, LEGACY GMP CLEANROOMS COST 10X MORE
TESTIMONIAL
“The move to Cytocentric Isolators reduced costs, processing times and risk to the product as well as provides a safer and more comfortable environment for operators.”
– Victorian Consortium for Cell-based Therapies (VCCT)
CLOSING PROCESSES DECREASES FACILITY COST
Closing decreases classification and square footage requirement for cleanrooms, without affecting production capacity.
