critical steps process design by 699qkw

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									Critical Steps in Process Design




        Michel Gigon, Associate, Laporte Consultants
        September 28, 2006
Agenda



   Definitions and General Considerations

   Critical Steps in Process Design
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.
Process Design in the
pharmaceutical industry

  Process Design versus Product Life Cycle
                               PRODUCT DEVELOPMENT


                  Biological             Phase   Phase                  Launch & Commercial
      Discovery                Phase I                       NDA
                  Tests                  II      III                    production




-20        0           2         4          6            8         10
                                         YEARS
                                      PRODUCT DEVELOPMENT


                   Biological                       Phase       Phase                      Launch & Commercial
      Discovery                        Phase I                               NDA
                   Tests                            II          III                        production




                                    PROCESS DEVELOPMENT

                  Process Research (1 gr – 1 kg)

                                      Pilot Development (1 kg-100 kg)

                                                               Commercial Plant Transfer (100 kg- tons)

                                                                                                 Optimisation, Capacity
                                                                                                 Increase




-20           0          2                4            6                 8            10
                                                    YEARS
                                            PRODUCT DEVELOPMENT


                         Biological                        Phase      Phase                        Launch & Commercial
       Discovery                             Phase I                               NDA
                         Tests                             II         III                          production




                                          PROCESS DEVELOPMENT

                        Process Research (1 gr – 1 kg)

                                            Pilot Development (1 kg-100 kg)

                                                                     Commercial Plant Transfer (100 kg- tons)

                                                                                                         Optimisation, Capacity
                                                                                                         Increase
                                           FACILITY AND EQUIPMENT
      Laboratory – Research
                       Laboratory – Development

                                           Pilot Plant Operation


                                                                      First Plant Operation


                                                                                                          Plant Operation




-20             0              2                4            6                8               10
                                                           YEARS
                                            PRODUCT DEVELOPMENT


                         Biological                         Phase       Phase                     Launch & Commercial
       Discovery                             Phase I                                  NDA
                         Tests                              II          III                       production




                                          PROCESS DEVELOPMENT

                        Process Research (1 gr – 1 kg)

                                            Pilot Development (1 kg-100 kg)

                                                                        Commercial Plant Transfer (100 kg- tons)

                                                                                                           Optimisation, Capacity
                                                                                                           Increase
                                           FACILITY AND EQUIPMENT
      Laboratory – Research
                       Laboratory – Development

                          Design, Build, Pilot Plant Operation
                          Validate

                                                       Design, Build,    First Plant Operation
                                                       Validate

                                                                                          Design, Build,   Subsequent Plant
PROCESS DESIGN                                                                            Validate         Operation



-20             0              2                4             6                   8              10
                                                            YEARS
The four pivots of process design
                Mechanical
  Science                            Automation


                   Process


             Validation



            Pharmaceutical Process
  Project Life Cycle
Conceptual
Design
             Preliminary
             Design
                            Detailed
                            Design

                                            Construction
                                                                   Start-Up
                                                                   SAT
                           Equipment Manufacturing         FAT


                                                            Validation


                                                                              Support
Conceptual design

   Definition of the user requirements
    •   Process
    •   Production capacity
    •   Product specification
    •   Development phase of the product
    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
    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 (%)
    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….
    Conceptual design

   Definition of the user requirements
    •   Production capacity
         •   ….
         •   Equipment utilisation (%)
               • Pilot plant :              20-50%
               • First commercial plant :   70% max
               • Mature process :           > 80%
Conceptual design

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

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

                      Laboratory
        Flexibility




                           Pilot plant


                                         First Plant
                                                       Subsequent
                                                       plant

                             Process maturity
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
Preliminary design

   Facility definition and sizing
    •   Preliminary specifications of the process equipment
    •   Sizing of utilities
    •   Sizing of spaces
    •   Preliminary specifications of the automation system
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…)
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,
    Process Utilities                    power…
    water, effluent treatment…
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
Preliminary design

   Facility definition and sizing
   Risks
    •   Inadequate process equipment
    •   Insufficient space and utilities
    •   Inadequate control and automation

    •   => Production capacity cannot be met
    •   => Difficulties of operation
Detailed design
   Detailed specification of all components of the
    installation
       • Mechanical components
           •   Fabrication specification
           •   Installation specification
       • Automation
           •   Hardware
           •   Software
Detailed design
                             P&ID



  Components List             I/O List           Sequences of
                                                   operation


    Mechanical               Automation             Alarms
    components               components            Interlocks
    specification           specifications       Access rights


 Installation drawing   Control panel drawings
   (3D, isometrics)         loop diagram         Programming
                            wiring diagram
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
Construction and
Fabrication
   Construction follow-up
   Documentation follow-up
   Start-up and testing (FAT, SAT)
Construction and
Fabrication
   Construction follow-up
    •   Ergonomy and accessibility
    •   Slopes
    •   Dead legs
    •   Weld quality
    •   Etc…
Construction and
Fabrication
   Documentation follow-up

          Update of design                      Data Sheets
             document                           Isometrics
        (P&ID, specifications)                Test Certificates



                          Turn-Over Package




             Validation                       Maintenance
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
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
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
Questions ?

								
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