Indutrialization of Stem Cell Processes – how to identify

Indutrialization of Stem Cell
Processes – how to identify
the right strategy ?
ISCT, April 26, Paris
Jose Castillo
Cell Culture Technologies Director
Pall Life Sciences
Agenda
Pall Life Sciences and the cell therapy industry
Process industrialization challenges
Integrating available technologies in process development
and manufacturing
Pall approach
Pall Life Sciences
Where we come from?
PALL LIFE SCIENCES
 Pall supports leading companies in
the field of vaccines, MAbs and
protein production for 10 years
 Pall offers process intensification
integrated technologies for cell
culture based processes
 Pall leverages process development
competencies to develop
intensification innovative technologies
and efficient processes
Pall Life Sciences
“Customer Problem Solving” approach
Application & Development Centers
 Pall approach combines both Product
development , Process development &
optimization
 PALL/ATMI has two Applications &
Development centers:
Equipped cell culture clean rooms.
45 experienced team including
Engineers & Bioengineers
PD for New Bioreactor development
PD Services / Support of our technologies
Tech transfer to your facility or to your CMO
Brussels
Minneapolis
500m²
100m²
Class 10,000 (ISO 7)
Non-classified
BSL-2
BSL-2
PALL Life Sciences
The offer for the cell therapy industry
Complete solutions for cell based
product manufacturing
Offer the complete solution for cell
grow and harvest based on the best
technologies available, Pall and
others
Leverage our expertize in stem cells
process development to streamline
industrialization of cell therapy products
Optimize process and enable high
volume manufacturing of cell based
therapies
Develop second generation solutions
Process industrialization challenges
The process is the product
Manuf.
Process
QA system
Validation
Supply
Capacity
Availability
Product
CAPEX
Facility
Costs
Costs of Goods
Affordablity
Upstream technologies
Available & next generation systems
Surface area
cm²/unit
> 1M
122,400
25,000
18,000
Hollow fiber
Bioreactors
Multilayer
Stacks
• Terumo
• Biovest
• Fibercell
• Corning
• Thermo
Fisher
Multilplate
Bioreactors
Microcarrier
stirred tank
• PALL
•
•
•
•
•
PALLSoloHill
TFS
Millipore
Sartorius
GEHC
Others
(Microfibers,
hydrogel, ...)
Scale-up in multilayer systems
Technical and manufacturing considerations
Multilayer Systems
Limited process development
needs
Manufacturing strategy = Scaleout
Large facility & labor intensive
Automation has to be considered
Scale-up in multilayer systems
Technical and manufacturing considerations
Multilayer Bioreactors
Process development is required:
Optimize process parameters
Harvest protocol
Keep same micro-environement as
multilayer, so reduce process
development time and regulatory risk
Linear scalability from 10 to 200 plates
(122,400 cm²)
Enable scaling up while minimizing
footprint and reducing manual
operations
Scale-up with microcarriers
Technical and manufacturing considerations
Microcarriers
Process development challenges: time & expertise
Microcarrier:
Density, cm²/g, g/L achievable, surface coating
Impacts on : mixing requirements, cells/ml and
product quality
Bioreactor:
Seed train (bead to bead transfer) and scale up
Low shear while maintaining mixing efficiency
Scalable harvest protocol
Product quality / similarity vs 2D layers
Requires Process development:
Clinical development timelines need to be considered
May need clinical bridging data
Very high volume manufacturing
Downstream process scale-up
Considerations
Intermediate storage not allowed
Streamline the unit operations of the complete manufacturing process
Main challenges for downstream at large scale :
Cells detachment from 2D multilayers / multilayer bioreactors / microcarriers
Microcarrier / cells separation
Cells concentration & washing
Formulation
In-line filling
Downstream process scale-up
Available technologies
Criteria for technology selection:
Harvest volumes to process
Cells integrity / resistance to mechanical constrains
Time constraints
Concentration factor and final targeted volume
Technology scale and associated R&D efforts
Ana S. Simaria, Sally Hassan, Hemanthram Varadaraju, Jon Rowley, Kim Warren, Philip Vanek, Suzanne S. Farid,
Allogeneic cell therapy bioprocess economics and optimization: Single-use cell expansion technologies, Biotechnology &
Bioengineering, released online on August 16th, 2013
Pall approach
Dose range / Patients per year
Pall approach
Product lifecycle
Product Development
Pall approach
Conclusion
Pall Approach
Industrializing process from R&D to
GMP manufacturing:
Consider process as a whole
Implement “fundamental”
changes step by step
Support product devt while
minimizing process/product
changes – market approval
strategy
Align technology roadmap and
product roadmap
PRODUCT
ROADMAP
Product quality
Clinical plan
MARKET DEMAND
Available
Affordable
Process
Design
Decisions
Thank you for
your attention
Thank you for your attention