Presentazione di Marco Fadda di Comecer tenuta al 57° AFI Meeting nella sessione "Diamo voce alle novità tecnologiche". Nella presentazione ha anche descritto il sistema FlexyCult di Comecer. Per dettagli: https://www.comecer.com/flexycult-incubation-system-advanced-therapy-labs/

1. Breaking the limits of cell expansion
management in ATMP applications - Flexycult
57° AFI Meeting – Diamo voce alle novità tecnologiche
Marco Fadda – COMECER Group

2. Trends – The EMA “ATMP” recommendations progress, show a
clear growing interest in the field of Advanced Therapies
0
20
40
60
80
100
120
2012 2013 2014 2015 2016

3. Current Trends

4. Why dealing with ATMP is a different process
• Individual procedures
• Large use of Incubators
• Freezing/Thawing
• Small quantities, small batches
• Large use of manual interventions
• ….

5. Particular applications
• Some diseases are difficult to treat
• Rare diseases – no care known
• Some degenerative processes withlarge social impact
• In some cases it can result in an economic benefit
• …

6. Challenging factors for conscious evaluation of the possible
success, involve manufacturing issues since the beginning
Source: Dodson and Levine BMC Biotechnology (2015) 15:70

7. How the world proceeded till now?
Traditional Cleanroom Technology
• Important layout implications
• Gowning
• Open LAF
• Sanitization
• Environmental monitoring
• High volume of handled air

8. Traditional Cleanroom Technology
Large spaces needed for small manipulation areas (Grade A)

9. Traditional Cleanroom Technology
Process Considerations – influence on working time
The real time worked is highly
influenced
by dressing and pauses:
Up to 20% of the time can be
lost

10. Traditional Cleanroom Technology
Process Considerations – space vs time occupancy
Scheduling patients in a
cleanroom:
• Maintenance and cleaning
days sum to process days
• Lack of patients is a problem
• Continuous use is
recommended
• Restarting time is long
• Full year occupancy is hard
to achieve
busy blocked empty

11. Traditional Cleanroom Technology
Process Considerations – production capacity vs request
• What if your request
exceeds your
production capacity?
• The only option is an
expansion of your
production site
The mechanism is all
but flexible
REQ
PC

12. Can Isolation Technology Help?
Manufacturing Options: Isolator or Clean Room?
Annex 1 to the cGMP:
“21. The utilization of isolator technology to minimize
human interventions in processing areas may result in a
significant decrease in the risk of microbiological
contamination of aseptically manufactured products from
the environment.”

13. Proposed Solution
Challenging Target: Grade A continuity throughout the process

14. “Lab in a box”
Storage
Refrigerator
Microscope
Centrifuge
Transfer Hatch
Env. Monitoring

15. An incubation module in Grade A
Entire volume
(up to 2x400 l)
accessible from
the interior of
the isolator
through 8 small
doors.
Each door
contains two
extractable trays.

16. Solution currently in operation
D Lab

17. Operational costs
0 10000 20000 30000
Gowning
Micro Bio Control
Sanitization
Electricity
Hepa Filters
Gloves
Validation
Isolator Clean Room
0
20000
40000
60000
80000
100000
ISOLATOR Clean Room
Average
Yearly
costs

18. News in incubation process
Learning from experience

19. Incubation Fundamentals
• Cell expansion needs
• Reliable constant environmental conditions, T, RH,
CO2, …
Incubation

20. Incubation dreams – Part 1
• Satisfying the request for additional batches is easy and straightforward
Expandability & Growing Capabilities
• How to keep the same quality level while production capacity is growing?
Scalability
• Is there a way to decrease costs/benefits ratio?
COGS

21. Incubation dreams – Part 2
• Selective and quick Sterilization process
Fast Sterilization on demand
• Ability to recover set point parameter quickly
Fast Reconditioning
• Non stop or minimal out-of-service time
Always Available

22. So… just recap in your brain…
• Every patient treated in a separate incubator…
• One isolator for more incubators…
• Single incubator activated based on request…
• Quickly expand the capacity with additional incubators…
• Expand the manipulation capacity with additional isolators…

24. Merging Isolation and Incubation:

25. How to use it
Undock Transport Connect &
Use

26. How to use it
Close Disconnect Dock

27. Interface with Isolator
A RTP (Rapid Transfer Port) for connecting to isolator

28. Advantages and Benefits
Advanced Cell Therapies

29. Product development
UNDERSTAND SHARE SKETCH DISCUSS
DISCUSS
DETAILED
DESIGN
DISCUSS
FAT INSTALL
SAT –
IQ/OQ
GENERAL
DESIGN
MANUFACTURE
A dedicated approach from customer ideas to final product

30. Product Development
The lessons learned and the basic concepts have general value:
• AIR and Fluid distribution
• Temperature Management
• CO2 Management
• RH Management
• Modularity
• Flexibility
• Environmental classification
• Technical Excellence

31. Air velocity distribution inside the modules
Left
Right
BackFront
Velocity Magnitude scale (m/s)

32. Airflow direction inside the module
Left
Right
BackFront
Airflow direction

33. Pressure Recording
In Line

34. Pressure Recording
Inside the boxes

35. Temperature recording
In supply line In the boxes

36. Decontamination Flexibility
… and more options: flexible sterilization
with top class H2O2 system

37. Incubation Desires
Validated decontamination
Typical Dry Heat
Sterilization Cycle

38. Customizable Modularity
• Growing with needs
• Bespoke solutions on demand

39. Additional benefits
• Flexible management
• Global parameter monitoring and recording
• Automation & Alarm System
• Traceability of the content
(no errors, maximum control)
• Single patient (no cross contamination at all)

40. Conclusions

41. Integration of all critical areas under
isolation technology for ACT
Increased Sterility Assurance Level
Drastic Reduction in the Risk of Cross Contamination
Beneficial to procedure integrity
Adaptable to different processes and sizes
Cost effective
Easy implementation

42. Mobile Incubation Technology
Incubation under Grade A
No Cross contamination at all
Reduced cell transportation
Expandable according to needs
Cost effective w/r to other tech
Easy to be implemented

43. Layout Example 1: Immunotherapy
• 160 Incubator Modules
• 8 Isolator Type1-2
• 1 Isolator Type 3 (fill finishing)
• 1 Isolator Type 3s (fill finishing)

44. Layout Example 2: Tissue
Lab size: 8x6 meters
n.45 Incubation Modules
n.2 Isolator

45. Automation possible, if needed

46. The Future: POC delivery?
Icons by Freepik from www.flaticon.com

47. The Future: POC delivery?
GMP Product for
clinical applications
Patient receives
treatment

48. ‘’ From the heart of safety
the essence of innovation’’
ISOLATION TECHNOLOGY DIVISION FOCUS