The document describes CO.DON AG's plans to establish a new production site in Leipzig, Germany for the industrial-scale production of autologous human cell therapeutics. The facility will utilize a new flexible and computerized production system based on modular incubator units to increase efficiency and capacity over the company's current integrated isolator technology. The goals are to enable greater flexibility, automation, traceability, quality control and sustainability in the industrial manufacturing of autologous cell therapies. The investment of approximately 10 million euros is expected to allow production of 4,500 units per year once operational.

1. A GMP facility of the future
implemented in the present
Phacilitate Leaders Europe
11th September 2018, London

2. Firmenpräsentation 20182
Dr. Andreas Eberle
Vice President
Head of Global Manufacturing
September 2018

3. A Leading Cartilage Repair Company – Facts and Figures
•CO.DON AG
3
Headquarter in Teltow and Berlin, GER
Subsidiaries in CH, UK, NL
New production site Leipzig (2019)
Headcount of ~ 100 (FTE‘s)
Supervisory Board
Prof. Hans B. Bauerfeind, Chairman
Thommy Stählin, Vice Chairman
Dr. Bernd Wegener
Prof. Dr. Barbara Sickmüller
Thomas Krause
Beatrix Bauerfeind-Johnson
Board/Management
Ralf M. Jakobs, Executive Board
A. Wolschner, C. Kaps
M. Mulder, A. Gottschalk, A. Eberle
Company
with good liquidity
Market leader in cartilage repair
Minimal invasive technology
Only strictly autologous
cartilage repair product worldwide
Highest level of personalized medicine
Approved in Germany for all joints
Approved in EU for knee

4. •Natural Cours for Cartilage Repair
Only available EMA licensed cell-based pharmaceutical product for the
regenerative treatment option of knee cartilage defects
4
Spherox is the only 100% personalised
knee therapy restoring patients
lasting mobility by delivering the
highest quality cartilage
Indication:
“Repair of symptomatic articular cartilage defects of the femoral condyle and the patella of the knee
(International Cartilage Repair Society [ICRS] grade III or IV) with defect sizes up to 10 cm² in adults.”

5. •Natural Course
1. Harvesting of healthy cartilage biopsy from non- /
less-weight bearing area (used for chondrocyte
preparation, expansion and spheroid formation).
2. Debridement of defective cartilage and application
(arthroscopic, mini-open, open) of Spherox product
using the co.fix applicator.
3. Spheroids adhere within 10 - 20 minutes on dry
subchondral bone. No need for additional defect
cover.
4. Spheroids synthesize extracellular hyaline-like
cartilage matrix filling the cartilage defect.
Procedure
5
1
2
3
4
Production Process
(cell cultivation,
spheroid/
transplant-
manufacturing,
applicator)

6. Integrated Isolator Technology (IIT)
•CO.DON AG – Current Technology
6
• In 1999 the design of the integrated Isolator
technology was developed
• The intend was to have the cells continuously
under class A (ISO 5) conditions
• One Isolator contains 3 modules:
Module 1 and 3 contain the incubators and
are the main working modules
Module 2 is for storage (fridge and freezer),
VHP-material-lock and contains the
microscope
IIT

7. Integrated Isolator Technology (IIT)
•CO.DON AG – Current Technology
7
+ Advantages
• Complete integration of all required materials and
equipment into the isolator (no transfer of cells)
• Complete manufacturing process is conducted within the
isolator – from beginning to end of process
• No transfer process for semi-finished product
• Most of the maintenance work could be done from the
back of the isolator/incubator system

8. Disadvantages
• Fully loaded incubators isolator blocked
• No problem with low utilization, but inflexible
• For capacity increase, more isolator systems are needed
(costs for equipment and space)
• In case of technical defects on isolator or incubators the
cells cannot be transferred to another system
• No computerized system, cannot be upgraded
• Process mainly paper based without interface to an
ERP system
Solution: decentralized and computerized system
Integrated Isolator Technology (IIT)
•CO.DON AG – Current Technology
8
-

9. 9
Production Expansion and Redesign Leipzig

10. Investment volume
approx. 10 million EUR - capacity
approx. 4,500 units / year
Establishing of new production site at
Leipzig / Germany
Production site will be the world’s
first, largest and most modern plant for
the industrial-scale production of
autologous human cell therapeutics
Setting the next stage –
industrial manufacturing of human
autologous cells
10
Facts
Project

11. Schedule
11
2018 2019
Kick-off
PQ
equipment
03/18 10/18
Concurrent validation
04/19
Delivery of
Equipment
09/18
Readiness of
PMS/PCS
MecDox
(ongoing)
FAT
Equipment
Concepts for
Validation
and Method
transfer
ready
04/18
liason
Start of
Construction
Project

12. 12
Project

13. What does industrialization mean
for autologous ATMP ?
FLEXIBILITY QA & QC TRACEABILITY
AUTOMATION SUSTAINABILITY

14. What does industrialization mean
for autologous ATMP ?
FLEXIBILITY QA & QC TRACEABILITY
AUTOMATION SUSTAINABILITY

15. TO BEAS IS
Flexibility – in process management
Processing unit should wait
for the end of incubation
Incubation time is independent,
since the isolator can work in
parallel on another process

16. Flexibility – in process management
As incubation time is usually much longer than
processing time, multiple processes should be
alternated in the same Processing Unit, saving
classified processing space.

17. Flexibility – making incubation modular
Click to watch FlexyCult video on YouTube

18. Flexibility - in patient/lot changeover
Cleaning/Decontamination
Flexibility

19. What does industrialization mean
for autologous ATMP ?
FLEXIBILITY QA & QC TRACEABILITY
AUTOMATION SUSTAINABILITY

20. QA QC – cGMP Grade A continuity
Every environment in which the cells are processed is classified and continuously
monitored as Grade A:
Incubation Continuous Monitoring:
Temperature Pressure CO2

21. What does industrialization mean
for autologous ATMP ?
FLEXIBILITY QA & QC TRACEABILITY
AUTOMATION SUSTAINABILITY

22. RFID
Bar
code
SCADA
to ERP
SOP on
HMI
Traceability – Track&Trace Architecture
Extended control interface

23. What does industrialization mean
for autologous ATMP ?
FLEXIBILITY QA & QC TRACEABILITY
AUTOMATION SUSTAINABILITY

24. Automation
• AGV for incubator modules moving from processing to docking station
and vice versa
• Local GPS positioning
• Automatic docking and undocking
Logistic Automation

25. What does industrialization mean
for autologous ATMP ?
FLEXIBILITY QA & QC TRACEABILITY
AUTOMATION SUSTAINABILITY

26. Sustainability
• Massive energy savings compared to
traditional cleanroom technology
• Reduction in power consumption:
50% less than old IIT (Isolator
Integrated Technology)
85% less than traditional
cleanroom technology processing
• Drastically reduced OPEX

27. What it is going to look like
Click to view this video on YouTube

28. FAQ
• How many operators are imagined to be involved ? Were they involved in
the selection of the technology? Was it more a management driven choice
rather than coming from end users?
• Do you think process automation could be implemented? To what extent ?
Would it be better to use fully closed technology?
• Is this really suitable for any kind of autologous
therapy?
• What has been the reaction of the authorities to such
level of innovation ?
• Which are the limitations in the use of isolators for
ATMP?

29. Thank you
Andreas Eberle
Vice President
Head of Global Manufacturing
a.eberle@codon.de
Massimiliano Cesarini
Global Sales Manager
mcesarini@comecer.com