The regulatory focus of facilities that manufacture therapeutic products for humans is centered on a product-process-facility attribute driven methodology where risk identification and mitigation are critical quality attributes. Under this methodology, the manufacturing process and the product requirements, not the building, become not only the main drivers for CD efforts, but must also provide a clear approach and understanding of how the building elements must be defined and operated in order to ensure patient safety in the manufacture of the product. This requires an enterprise approach to facility design focusing on: Process-driven understanding around operational analysis Regulatory philosophy Business drivers Management needs Integrated hand-off to detailed design activities

1. Strategic
Conceptual
Design
The Backbone of
Project Success
Jeff Odum
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2. Strategic Manufacturing in the 21st Century
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3. Where to Start…Conceptual Design – The key
Project definition
• The CD framework should focus on the product attributes and the process
• unit operations required for manufacturing the product and the risks
• introduced by implementing the right technology
PROCESS
FACILITY INFRASTRUCTURE
PROCESS
• Product produced
– Logical operating
units (LOUs)
• Equipment
– Steel and Single-use
• Input materials
INFRASTRUCTURE
• Control system
– Procedures/SOP’
– Computer systems
– Operating and
maintenance systems
– Documentation
• People
– Personal discipline
– Qualification/training
FACILITY
• Layout - flow
• Environment
• Utility systems

4. End goal…Design to Operate
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• Product-driven process solutions
• Risk-mitigated solutions
• Integrated Engineering solutions
• Business-focused solutions
Design with the end in mind

5. Drivers for using a risk-based GMP approach
in the Front-end/CD phase
• Patient needs and reliability in launch of new pharma products
• Regulatory requirements and expectations
• Customer feedback and expressed ambitions
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6. Elements in a risk-based GMP Design Strategy
initiated in Front-End/CD’s:
• A systematic and structured approach
• Common framework focusing on GMP and risk in Front-End/CD’s
• A solid basis for customer decisions
• Basis for concepts & design
• Process understanding linking directly to the control strategy
1 2 3 Decision
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7. GMP Design Strategy & a risk-based approach
• GMP, control and risk are tied together
• GMP requirements and challenges are used
actively to inform concept development
• Provision of a qualified, fact and risk-based
control strategy for decision and design
• Use GMP risk assessment as tool to highlight
GMP constraints
• Our approach does not apply unnecessary levels
of GMP
• You now have product/process understanding and
control strategy and operational philosophy
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8. We know the 80 – 20 Rule…
80%of total project cost is committed in
initial project phase (Front-end/CD 20%)
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9. Success leads to success
REGULATORY DECISION MAKING
COMMITTED IN FRONT-END/CD
The more product and process understanding...
...the higher rate of committed Regulatory
...the more robust GMP design and solutions
...the fewer re-design/re-work
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10. Strategic Manufacturing Concept Group
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The regulatory focus of facilities that manufacture
therapeutic products for humans is centered on a
product-process-facility attribute driven methodology
where risk identification and mitigation are critical
quality attributes. Under this type of methodology, the
manufacturing process and the product requirements,
not the building, has to become not only the main
driver for CD efforts, but it must also provide a clear
approach and understanding of how the building
elements must be defined and operated in order to
ensure patient safety in the manufacture of the
product.

11. Transparent risk-based GMP approach
- the stepping stone to the next project phases
• Transparent risk-based GMP approach as stepping stone to next project phases
• Focused transition from front-end/CD to subsequent phases
• Streamlined hand-off to next phases and higher probability of success
• Risk-based GMP approach linked to behavior
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12. Our Front-End/CD Roadmap (OurModel)
1 2 3
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13. 13
CONTROL STRATEGY
Risk Mitigation
Solutions Quality Control
Process Mapping :
Steps, Sub-Steps
In Process Factors
: Factors: PP, DA, MA
(influencing each step)
In Process Factors
Failure Modes
In Process Factors
Failures
Consequences
In Process Factors
Failures Impact on
CQAs
In Process Factors
Failures Impact on
KPAs
CPFs: CPPs, CDAs,
CMAs
KPFs : Business
Impacting Factors
Quality Critical
Design Solutions
Quality
Operationnal
Design Solutions
Key Performance
Design Solutions
Key Performance
Operational
Design Solutions
Product Quality
related URS &
Technical
Specification:
Parameters Settings,
Design Requirements...
PAT, In-Line/On-
Line IPCs
SOPs, Instructions,
At-Line/Off-Line IPCs
: Raw Matrial QCs,
Intermediate Product
QCs, Requalification,
Product Annual
Review...
Complimentary
URS & Technical
Specification: Yield,
Duration
Requirement...
PAT, In-Line/On-
Line IPCs
SOPs, Instructions,
At-Line/Off-Line
IPCs
Control through
Design
Continuous
Process
Verification (EU)
Ongoing Process
Verification (EU)
Performance
Control
SEVERITY
SEVERITY
C&Q
Q
C&Q
C&Q
Q
Control through
Design
Continuous
Process
Verification (EU)
Ongoing Process
Verification (EU)
C
C
C
R&D
Production
Patient
Engineering
Product CQAs
Schematic Diagrams
(PMD, PFD,…)
KPA List
Intermediate
Products
CQAs
DOE,
Parameters Limits
Legend:
PP: Process parameter (Temperature, Pressure…)
DA: Design Attribute (SS316L, Roughness…)
MA: Material Attribute (WFI, Powder Purity…)
CQA: Critical Quality Attribute
KPA: Key Performance Attribute
CPF: Critical In-Process Factor
CPP: Critical Process Parameter
CDA: Critical Design Attribute
CMA: Critical Material Attribute
KPF: Key Performance In-Process Factor
PAT: Process Analytical Technology
IPC: In Process Control
URS: User Requirement Specification
PMD: Process Module Diagram
PFD: Process Flow Diagram
QCs: Quality Controls
C&Q: Commissioning & Qualification
C: Commissioning
Q: Qualification
Legend:
PP: Process parameter (Temperature, Pressure…)
DA: Design Attribute (SS316L, Roughness…)
MA: Material Attribute (WFI, Powder Purity…)
CQA: Critical Quality Attribute
KPA: Key Performance Attribute
CPF: Critical In-Process Factor
CPP: Critical Process Parameter
CDA: Critical Design Attribute
CMA: Critical Material Attribute
KPF: Key Performance In-Process Factor
PAT: Process Analytical Technology
IPC: In Process Control
URS: User Requirement Specification
PMD: Process Module Diagram
PFD: Process Flow Diagram
QCs: Quality Controls
C&Q: Commissioning & Qualification
C: Commissioning
Q: Qualification
RISK MANAGEMENT SYSTEM
RMS By HSBE
Subject Matter
Experts (SMEs)

14. What are our Agile Design Tools?
• Integrated Design Approach
• Lean & Automated facility logistics
• Decreased human interaction
• Modular Design around Standardized Logical Operating Units
• Process Centric
• Process Intensification
• Autonomous
• Re-configurable
• Model around 3D operational simulation
• Technology-Focus
• Single-use optimization/modelling
• Standard Design Modules
• 3D visualization
• 3D printing

15. Example: Real Time Simulation

16. 3D real time
simulation
of processes and
procedures as part of
Front-End concept
development
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17. ON THE WAY TO SUCCESS
THERE ARE NO SHORTCUTS
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18. Thank you
For further information please contact
Jeff Odum
Global Technology Partner
Managing Partner, Global Concept Group
ouj@nne.com
919-673-4745