Methodology

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

• Definitions and General Considerations
• Critical Steps in Process Design

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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.

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Process Design in the pharmaceutical industry
Process Design versus Product Life Cycle
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The four pivots of process design
Mechanical
Automation
Science
Process
Validation
Pharmaceutical Process
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Project Life Cycle
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Conceptual design

• Definition of the user requirements
• Process
• Production capacity
• Product specification
• Development phase of the product

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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

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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 ()

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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.

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Conceptual design

• Definition of the user requirements
• Production capacity
• .
• Equipment utilisation ()
• Pilot plant  20-50
• First commercial plant  70 max
• Mature process  gt 80

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Conceptual design

• Definition of the user requirements
• Product specification
• Sterility
• Water quality
• Concentration
• Impurity levels

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Conceptual design

• Definition of the user requirements
• Development phase of the product

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Conceptual design

• 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

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Preliminary design

• Facility definition and sizing
• Preliminary specifications of the process
  equipment
• Sizing of utilities
• Sizing of spaces
• Preliminary specifications of the automation
  system

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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)

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Preliminary design

• Facility definition and sizing
• Sizing of utilities and spaces

Process equipment
Spacesproduction, mechanical rooms, warehouse
Process supportCIP, solution prep
Building utilitiesHVAC, Steam, chilled water,
power
Process Utilitieswater, effluent treatment
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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

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Preliminary design

• Facility definition and sizing
• Risks
• Inadequate process equipment
• Insufficient space and utilities
• Inadequate control and automation
• gt Production capacity cannot be met
• gt Difficulties of operation

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Detailed design

• Detailed specification of all components of the
  installation
• Mechanical components
• Fabrication specification
• Installation specification
• Automation
• Hardware
• Software

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Detailed design
PID
Sequences of operation
I/O List
Components List
Automation components specifications
Alarms InterlocksAccess rights
Mechanical components specification
Control panel drawings loop diagram wiring
diagram
Installation drawing (3D, isometrics)
Programming
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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

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Construction and Fabrication

• Construction follow-up
• Documentation follow-up
• Start-up and testing (FAT, SAT)

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Construction and Fabrication

• Construction follow-up
• Ergonomy and accessibility
• Slopes
• Dead legs
• Weld quality
• Etc

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Construction and Fabrication

• Documentation follow-up

Update of design document (PID, specifications)
Data SheetsIsometricsTest Certificates
Turn-Over Package
Maintenance
Validation
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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

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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

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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

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• Questions ?