1. Critical Steps in Process Design
Michel Gigon, Associate, Laporte Consultants September 28, 2006

2. Agenda Definitions and General Considerations
Critical Steps in Process Design

3. Definitions Product Development : Creation of a new product
Process Development : Development of a production method (recipe)
Process Design : Design of the equipment required for the production of a product, according to a pre-determined process.

4. Process Design in the pharmaceutical industry
Process Design versus Product Life Cycle

5. YEARS Discovery Biological Tests Phase I Phase II Phase III NDA
Launch & Commercial production
PRODUCT DEVELOPMENT
YEARS

6. -20 0 2 4 6 8 10 YEARS Discovery Biological Tests Phase I Phase II
Phase III
NDA
Launch & Commercial production
Process Research (1 gr – 1 kg)
PRODUCT DEVELOPMENT
PROCESS DEVELOPMENT
YEARS
Commercial Plant Transfer (100 kg- tons)
Pilot Development (1 kg-100 kg)
Optimisation, Capacity Increase

7. FACILITY AND EQUIPMENT
Discovery
Biological Tests
Phase I
Phase II
Phase III
NDA
Launch & Commercial production
Process Research (1 gr – 1 kg)
Pilot Plant Operation
First Plant Operation
Laboratory – Research
Laboratory – Development
PRODUCT DEVELOPMENT
PROCESS DEVELOPMENT
FACILITY AND EQUIPMENT
YEARS
Commercial Plant Transfer (100 kg- tons)
Pilot Development (1 kg-100 kg)
Plant Operation
Optimisation, Capacity Increase

8. FACILITY AND EQUIPMENT
Discovery
Biological Tests
Phase I
Phase II
Phase III
NDA
Launch & Commercial production
Process Research (1 gr – 1 kg)
Pilot Plant Operation
First Plant Operation
Laboratory – Research
Laboratory – Development
PRODUCT DEVELOPMENT
PROCESS DEVELOPMENT
FACILITY AND EQUIPMENT
Design, Build, Validate
YEARS
Commercial Plant Transfer (100 kg- tons)
Pilot Development (1 kg-100 kg)
Subsequent Plant Operation
Optimisation, Capacity Increase
PROCESS DESIGN

9. The four pivots of process design
Mechanical
Science
Automation
Process
Validation
Pharmaceutical Process

10. Project Life Cycle Conceptual Design Preliminary Detailed
Equipment Manufacturing
Construction
Validation
Support
FAT
Start-Up
SAT

11. Conceptual design Definition of the user requirements Process
Production capacity
Product specification
Development phase of the product

12. Conceptual design Definition of the user requirements Process
Pilot plant : unit operations, lab procedure example
First commercial plant : lab method, preliminary results from pilot plant
Subsequent facility : existing process

13. Conceptual design Definition of the user requirements
Production capacity
Requirements (kg/year, units/year)
Batch size (kg/batch, units/lot)
Titre (kg/L)
Production time (days/lot)
Production schedule (24/7, 8/5)
Operation (by campaign, by lots)
Production opening (weeks/year)
Losses (%)
Equipment utilisation (%)

14. Conceptual design Definition of the user requirements
Production capacity
Requirements (kg/year, units/year)
Batch size (kg/batch, units/lot)
Titre (kg/L)
Production time (days/lot)
Set-up, production process, cleaning, sterilisation, testing, product change-over….

15. Conceptual design Definition of the user requirements
Production capacity ….
Equipment utilisation (%)
Pilot plant : %
First commercial plant : 70% max
Mature process : > 80%

16. Conceptual design Definition of the user requirements
Product specification
Sterility
Water quality
Concentration
Impurity levels

17. Conceptual design Definition of the user requirements
Development phase of the product
Flexibility
Process maturity
Laboratory
Pilot plant
First Plant
Subsequentplant

18. Conceptual design Risks Definition of the user requirements Process
Production capacity
Product specification
Development phase of the product
Risks
Inability to manufacture the product
Inadequate plant capacity
Lower quality product
Inappropriate flexibility

19. Preliminary design Facility definition and sizing
Preliminary specifications of the process equipment
Sizing of utilities
Sizing of spaces
Preliminary specifications of the automation system

20. Preliminary design Facility definition and sizing
Preliminary specification of the process equipment
Volume, capacity
Material
Functionality
Process paramaters
Design and operation range (pressure, temperature, etc…)

21. Preliminary design Facility definition and sizing
Sizing of utilities and spaces
Process equipment
Spaces production, mechanical rooms, warehouse…
Process support CIP, solution prep…
Building utilities HVAC, Steam, chilled water, power…
Process Utilities water, effluent treatment…

22. Preliminary design Facility definition and sizing
Preliminary specification of the automation system
Manual vs automated operation
Transfer panel vs manifold…
Level of automation
Local controller, unit operation control, batching, archiving
General architecture

23. Preliminary design Risks Facility definition and sizing
Inadequate process equipment
Insufficient space and utilities
Inadequate control and automation
=> Production capacity cannot be met
=> Difficulties of operation

24. Detailed design
Detailed specification of all components of the installation
Mechanical components
Fabrication specification
Installation specification
Automation
Hardware
Software

25. Detailed design P&ID Components List I/O List Sequences of operation
Mechanical components specification
Automation components specifications
Alarms Interlocks Access rights
Installation drawing (3D, isometrics)
Control panel drawings loop diagram wiring diagram
Programming

26. Detailed design
Detailed specification of all components of the installation
Risks
Inappropriate installation
Cleaning and sterilisation issues
Corrosion issues
Operational difficulties
Maintenance difficulties
Accessibility issues

27. Construction and Fabrication
Construction follow-up
Documentation follow-up
Start-up and testing (FAT, SAT)

28. Construction and Fabrication
Construction follow-up
Ergonomy and accessibility
Slopes
Dead legs
Weld quality
Etc…

29. Construction and Fabrication
Documentation follow-up
Update of design document (P&ID, specifications)
Data Sheets Isometrics Test Certificates
Turn-Over Package
Validation
Maintenance

30. Construction and Fabrication
Start-up and testing
Verification of the quality of fabrication
Verification of all design hypothesis
Control of process parameters
Process sequences are achievable
Equipment drainable, cleanable and sterilisable

31. Construction and Fabrication
Construction follow-up
Documentation follow-up
Start-up and testing (FAT, SAT)
Risks
Inadequate installation
Cleaning and contamination issues
Ergonomic and operational issues
Inadequate documentation
Validation issues
Maintenance issues

32. Validation
Adequate documentation facilitates protocol preparation and execution
Review of validation criterion can avoid unnecessary deviation
Participation in protocol execution facilitates and accelerates protocol execution

33. Questions ?