1. Julie Kerby, Head of Manufacturing Development Mar 2017
Challenges in developing a flexible, multi-user manufacturing space to accelerate to the clinic
Julie Kerby, Head of Manufacturing Development
Mar 2017

2. Why are flexible facilities interesting?
672+ companies worldwide
185 Europe & Israel
112
Asia
349 North America 1
Africa 10
South America 15
Australia & New Zealand
Data from Alliance for Regenerative medicine and Informa Sciences SOTI 2015

3. Why are flexible facilities interesting?
Data from Alliance for Regenerative medicine and Informa Sciences SOTI 2015

4. Why are flexible facilities interesting?
Data from Alliance for Regenerative medicine and Informa Sciences SOTI 2015

5. 51 clinical trials in the UK in 2015
The UK landscape
51 clinical trials in the UK in 2015
41 in 2014

6. UK Cell and gene therapy manufacturing sector 2016
22 facilities
>11000m2
total facility footprint
102 cleanrooms
>4000m2 total cleanroom footprint
386 full time employees
16 cell therapy manufacturers
6 gene therapy manufacturers
391 full time employees
4 multi-functional (cell and gene)
A network of 22 GMP facilities, supplying over 4000m2 of licensed total cleanroom space and a 391  strong workforce with a diverse track record for a range of projects  

7. Manufacturing facility choice
CMO
Tech transfer
Know-how
Scheduling
Comparability
Owner operated
Capitol investment
Technical expertise
Capacity

8. Large-scale cell and gene therapy manufacturing centre

9. Considerations in design
Quality
Scale
Location
Flexibility

10. Quality Risk Management
Fundamental to any GMP facility
Up to you to demonstrate appropriate control and risk management
Codified approach and toolkits
Eudralex Volume 4 (framework) etc
Complexity elevated in some regards with multi products
Question: Controls between batches for single products within the same facility have to demonstrate prevention of cross-contamination. Is it different to preventing cross-contamination with a different batch of autologous product?
Risk has to be understood and controlled

12. Risk Review R i s k C o m u n c a t
Risk Assessment
Risk Evaluation
unacceptable
Risk Control
Risk Analysis
Risk Reduction
Risk Identification
Review Events
Risk Acceptance
Initiate
Quality Risk Management Process
Output / Result of the M g e T l
"Quality Risk Management is a systematic process for the assessment, control, communication and review of risks to the quality of the medicinal product across the product lifecycle."
ICH Q9
Summarised nicely in ICH guidlines

13. QRM in reality for CGT multi product centre
Future proofed
Multi-user
Multi-product including Viral vectors
QMS & QA interface
Client confidentiality
EU/US GMP requirements
Client expectations
Risk Based Approach

14. QRM in reality Risk based approach Pragmatic Lean Solutions
Future proofed
Multi-user
Multi-product including Viral vectors
QMS & QA interface
Client confidentiality
EU/US GMP requirements
Client expectations
Risk based approach
Lean Solutions
Proportionate
Physical vs Operational
Active Process

15. Refresh of business model
Flexibility for multiple ATMP processes and products
Containment for simultaneous ATMP and viral vector manufacture
Collaborators will occupy one or more modules
Collaborators use their own production staff
Collaborators use their own Process and Control documentation
EU GMP compliance

16. External (production) Grade A/B processing environment
Risk elements
External (production)
environment
Support areas
Cleanroom modules
Grade A/B processing environment
Personnel QC
samples
Human starting materials, raw materials and supplies
Waste
Product

17. Resulting operational control strategies
Complete physical segregation of Grade B / C modules
Containment for simultaneous ATMP and viral vector manufacture
Simultaneous multiple collaborator occupancy and product manufacture
Product segregation
QC (IPC) segregation
Logistics – incoming and dispatch
Know-how and I.P. protection
Data segregation
Serviced QC space plus segregated space
Core QMS with well defined interfaces with collaborator QMS

18. Design, build and inspection process
Use it to better control risk

19. Stages of build Specification (URS) Build Commission Qualification
Building/facilities
Equipment
Process validation

20. MHRA inspection stages
To discuss strategy, design and operation
Planning meetings
Planning complete
Full set of drawings
Pre-building inspection
To review progress
Discuss changes/deviations
During build site visits
First formal inspection
Facility commissioned
Phased inspections
Facility and equipment qualification
Approval inspection
Completion

21. Outputs of our risk based approach

22. Flexible module layout
500L STR
Allogenic
Viral vectors
Static systems
USP and DSP
Min. 6 Autologous processes
Tissue products

23. Flexible module layout
500L STR
Allogenic
Viral vectors
Static systems
USP and DSP
Min. 6 Autologous processes
Tissue products

24. Flexible module layout
500L STR
Allogenic
Viral vectors
Static systems
USP and DSP
Min. 6 Autologous processes
Tissue products

25. QA

26. Controlled quality Manufacturing centre overarching quality systems
Inspection and testing
QP / QMS
Raw materials testing and release
Cyro and warehousing
Logistics controls
Facility License
Client quality and manufacturing systems
GMP trained operators
Manufacturing records
Batch release
Quality technical agreement

27. Quality / technical agreement
Details technical aspects of the contract between two parties
Defines the responsibilities in place between both parties
Inspectable by MHRA
Will cover
QMS Elements (Deviations, complaints, OOS/OOT, product recall, complaints etc.)
Material sourcing
Roles and Responsibilities
Manufacturing modules
Shared areas
QP agreements

28. Conclusion

29. Conclude Quality Risk Management has to be applied to all facilities
Assess, understand, manage risk
Ongoing-process
Reduces chance of failing to manage risk
Use physical and operational solutions
Physical often better but be pragmatic
Regular and open communication with MHRA

30. Cell and Gene Therapy Catapult
12th Floor Tower Wing Guy’s Hospital Great Maze Pond London SE1 9RT
+44 (0) ct.catapult.org.uk
Introduction