Challenges in developing a flexible,
multi-user manufacturing space to
accelerate to the clinic
Julie Kerby, Head of Manufacturing Development
Mar 2017
Why are flexible facilities interesting?
672+ companies worldwide
185
Europe
& Israel
112
Asia
349
North
America
10
South
America
1
Africa
Data from Alliance for Regenerative medicine and Informa Sciences SOTI 2015
15
Australia
& New
Zealand
Why are flexible facilities interesting?
Data from Alliance for Regenerative medicine and Informa Sciences SOTI 2015
Why are flexible facilities interesting?
Data from Alliance for Regenerative medicine and Informa Sciences SOTI 2015
The UK landscape
51 clinical trials in the UK in 2015
41 in 2014
UK Cell and gene therapy manufacturing
sector 2016
>4000m2
total
cleanroom
footprint
6 gene therapy
manufacturers
102
cleanrooms
16 cell therapy
manufacturers
391 full time
employees
22
facilities
>11000m2
total facility
footprint
4 multi-
386
full time
functional
(cell
employees
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
Manufacturing facility choice
•
•
•
•
CMO
Tech transfer
Know-how
Scheduling
Comparability
Owner operated
• Capitol investment
• Technical expertise
• Capacity
Large-scale cell and gene therapy
manufacturing centre
Considerations in design
Quality
Scale
Location
Flexibility
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
11
Initiate
Quality Risk Management Process
Risk Assessment
Risk Identification
Risk Analysis
Risk Evaluation
Risk Communication
Risk Control
Risk Reduction
Risk Acceptance
Output / Result of the
Quality Risk Management Process
Risk Review
Review Events
Risk Management Tools
unacceptable
"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
QRM in reality for CGT multi product centre
Future proofed
Client
expectations
EU/US GMP
requirements
Multi-user
Risk
Based
Approach
Client
confidentiality
QMS & QA
interface
Multi-product
including Viral
vectors
QRM in reality
Future proofed
Pragmatic
Lean
Solutions
Client
expectations
Proportionate
Physical
vs
Operational
Active
Process
EU/US GMP
requirements
Multi-user
Risk
based
approach
Client
confidentiality
QMS & QA
interface
Multi-product
including Viral
vectors
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
Risk elements
Personnel
External
(production)
environment
Support
areas
Human starting
materials, raw
materials and
supplies
QC
samples
Cleanroom
modules
Grade A/B
processing
environment
Waste
Product
16
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
Design, build and inspection process
Use it to better control risk
Stages of build
Specification (URS)
Build
Commission
Qualification
• Building/facilities
• Equipment
Process validation
MHRA inspection stages
Planning meetings
Pre-building inspection
Planning meetings
• To discuss strategy, design and operation
• Planning complete
• Full set of drawings
• To discuss strategy, design and operation
During build site visits
• To review progress
• Discuss changes/deviations
Facility commissioned
• Phased inspections
Facility and equipment
qualification
• First formal inspection
Completion
• Approval inspection
Outputs of our risk based approach
Flexible module layout
• 500L STR
• Allogenic
• Viral vectors
• Static systems
• USP and DSP
• Min. 6 Autologous
processes
• Tissue products
Flexible module layout
• 500L STR
• Allogenic
• Viral vectors
• Static systems
• USP and DSP
• Min. 6 Autologous
processes
• Tissue products
Flexible module layout
• 500L STR
• Allogenic
• Viral vectors
• Static systems
• USP and DSP
• Min. 6 Autologous
processes
• Tissue products
QA
Controlled quality
Manufacturing centre overarching quality systems
Inspection and
testing
QP / QMS
Client quality and manufacturing
systems
Raw materials
testing and release
Cyro and
warehousing
Logistics controls
Facility License
GMP trained
operators
Manufacturing
records
Batch release
Quality technical
agreement
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
Conclusion
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
Cell and Gene
Therapy Catapult
12th Floor Tower Wing
Guy’s Hospital
Great Maze Pond
London SE1 9RT
+44 (0)20 3728 9500
[email protected]
ct.catapult.org.uk
Twitter: @CTCatapult
Introduction
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