Cell based therapy is the most promising innovation in medical. The biggest challenge? It’s a complex, extensive and manual production which results in a small scale and expensive treatment. We’ll dive in the technical challenges to automate and scale cell production and how cell transfection can be stimulated by the technology transfer of optics.

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CONFIDENTIAL Innovation Day 2018CONFIDENTIAL
SCALING PRODUCTION OF CELL
BASED THERAPIES
Jan Calliauw
Business Development Medical
Jan.Calliauw@Verhaert.com
TRACK 5 - SPACE TECHNOLOGY FOR A BETTER WORLD
Thomas De Greef
Physics System Engineer
Thomas.degreef@Verhaert.com

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CONTENT
Cell based therapies?
State of Things
Challenges
How space can help

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CELL BASED THERAPIES:
CREATING A BETTER WORLD
Click to insert subtitle

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Goal: locate, recognize and attack
invaders
Problems:
• Malignant cells hide from
immune system (eg. cancer)
• Side effects of current
treatments
IMMUNE SYSTEM

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IMMUNO THERAPY
= reprogramming a patient’s
immune system to better
confront malignant cells

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• 40% will be diagnosed with cancer
• Better treatment
• Less side effects
• Vaccinating within reach
• Stronger infectious diseases are emerging (swine flu, ebola, … )
• Personalized medicine
HOW IT WILL CHANGE & IMPROVE THE WORLD
Vaccinate
Against
cancer ?

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STATE OF THINGS

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Some mature cell based therapies
• Stem cell transplantation
• Blood transfusion
Some just entered the market
• Provenge (came & went)
• Novartis’ Kymriah®
• Kite Pharma’s Yescata®
Majority in early development stage (clinical phase I or II)
• Still an emerging field of science => Iterative learning
• Eg. T-cells show efficacy after 20 years
STATE OF THINGS

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• Lots of new developments
• 500 products in phase 2 trials
DEVELOPMENTS: SOME THERAPIES

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• Mostly labour-intensive lab
processes
• Automation of discrete
process steps
• Cell expansion in wave-type
bioreactors
• Cell selection/washing in closed
filtration systems
DEVELOPMENTS: MANUFACTURING

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DEVELOPMENTS: AUTOMATION

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Some Blue chip pharma invests
MARKET HEAT

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REGULATORY
• Stringent requirements on environment & QC
• Biohazard related to viral vector use
• Process = product
• Biological product is difficult to fully characterize
• regulators put emphasis on process
• automate has to replicate the manual process

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AUTOLOGOUS CAR-T CELL THERAPY WORKFLOW

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CHALLENGES

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MAIN CHALLENGE
Lower COGs to reach reimbursement point
• Manual production in GMP compliant lab (50% of COGs)
• Under investment in automation
• Unjustifiable before proven clinical effect
• Goal is to be acquired by big pharma
• Results in high cost per treatment
Be aware of cost drivers from the beginning

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COST BASED APPROACH

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CHALLENGES
1
Cell culture
5
Logistics for
live cells
3
Contami-
nation
4
Automation
2
Cell imaging

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CHALLENGE 1: YIELD & CELL CULTURE
Improve yield to treat more patients
• Reduce batch failures
• Produce more cells per batch
• Produce stronger cells
• Reduce in process cell loss
• Quality control: IPC
• Changing cells
• Transducing
• Transfection
• Electrophoresis

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CHALLENGE 2: CONTAMINATION
Cost of disposable vs cost to clean, sterilize & validate.
• Integrated cartridge – tube sets - pipetting
• Potential to be fully closed
• control of temp, humidity, CO2, ...
• lower chance on contamination
• lower grade lab (up to 50% of COGS)
• Contactless
• Prove fluid-path polymers have no adverse effect
on the cells/therapy

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CHALLENGE 3: CELL IMAGING
Cost effective design of custom microscopes.
• Optical alignment
• Optimized imaging technology
• Continuous view on cell growth
• Non destructive quality control
• IPC
• Distributed QC (Intermediate & product stability)

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CHALLENGE 4: AUTOMATION
Automation of complex &
lengthy lab processes
• Integrated vs modular
• Decrease operator variability
• Increase operational efficiency
• Improve product consistency
• Reduce loss
• Non destructive IPC on small
samples

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CHALLENGE 5: LOGISTICS FOR LIVE CELLS
Short cell shelve life (raw material & therapy)
Decentralized production or logistics
• Cost
• Supply of raw materials
• Distribution of final product
• Moving patient is risky

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CREATING A BETTER WORLD
HOW SPACE HELPS

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WHY SPACE?
Similar challenges
• Effects in health of long term spaceflight
• Contamination
• Automation: (un)manned space
BIOLAB Fluid Science LabISS

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CHALLENGES
SIMILAR CHALLENGES TACKLED
1
Yield & Cell
culture
5
Logistics for
live cells
3
Contaminati
on
4
Automation
2
Cell imaging
Availability &
shelve life of cells
SOME PROJECTS
EPU
Experiment
Preparation
Unit
EPU
Disposable
unit
Safety
requirements
Cell imaging
Spectrometry
On site
monitoring
Unmanned
flight
Fluidpac Thermal Control
Units
European
Transport Carrier
Protection of
biological
material
(launch/landing)

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EXPERIMENT PREPARATION UNIT EPU
Cryogenic defreezing
• -180°C to +10°C
• Minimized cell loss
Avoid contamination
• Disposable with septum & shielded
needles
• Sterilization
• Disposables with gamma rays
• System 100ppm Ozone sterilization

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Space observation => cell imaging
• HYPE: retrofit hyperspectral module
• Flumias: 4D cell monitoring for fast live-cell imaging in microgravity
• Digital Holographic Microscope to monitor protein crystal growth
CELL IMAGING

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FLUIDPAC: UNMANNED FLUID SCIENCE LABORATORY
• Automation
• Closed system

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BUBBLE-FREE FILLING
• Performance of bubble free filling
• Demonstrate absence of dead/trapped volumes

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Goal: Open cell membrane to delivering exogenous material (i.e.
transfecting cells) and change cell characteristics.
Applications: cell biology research, cell-based therapies, crop
modification, etc.
Space tech: Architecture of confocal laser scanning microscope
for 3D fluorescence imaging of biological samples.
CELL PREPARATION-PHOTOPORATION

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• Compatible with common cell culture substrates
• Macromolecules too large to go through cell membrane
• Minimal cytotoxicity
Electrophoresis (alternative tech) causes 60-90% cell loss
• High accuracy into cells
Only technology that can focus on individual cells
PHOTOPORATION

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SPACE SOLUTIONS
Spacesolutions.be

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1. Immunotherapy has great potential to cope cancer
2. State of the art is on its way
3. Cost is major bottleneck for wide roll-out
4. Space technologies can provide solutions
CONCLUSION

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WANT TO SUPPORT IMMUNOTHERAPY RESEARCH?
uza.be/schenking

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One group, five brands
Our services are marketed through 5 brands each
addressing specific missions in product development.
INTEGRATED PRODUCT DEVELOPMENT
ON-SITE
PRODUCT
DEVELOPMENT
DIGITAL
PRODUCTS
DEVELOPMENT
OPTICAL
PRODUCTS
DEVELOPMENT
VENTURING