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

Discovery

Biological Tests

Phase I

Phase II

Phase III NDA

Launch & Commercial production

PRODUCT DEVELOPMENT

-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

-20 0 2 4 6 8 10

YEARS

Commercial Plant Transfer (100 kg- tons)

Pilot Development (1 kg-100 kg)

Optimisation, Capacity Increase

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

-20 0 2 4 6 8 10

YEARS

Commercial Plant Transfer (100 kg- tons)

Pilot Development (1 kg-100 kg)

Plant Operation

Optimisation, Capacity Increase

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

Design, Build, Validate

-20 0 2 4 6 8 10

YEARS

Commercial Plant Transfer (100 kg- tons)

Pilot Development (1 kg-100 kg)

Design, Build, Validate

Subsequent Plant Operation

Optimisation, Capacity Increase

PROCESS DESIGN

The four pivots of process design

Process

Pharmaceutical Process

Science

Mechanical Automation

Validation

Project Life Cycle

Conceptual

Design

PreliminaryDesign

DetailedDesign

Equipment Manufacturing

Construction

Validation

Support

FAT

Start-Up

SAT

Definition of the user requirements• Process

• Production capacity

• Product specification

• Development phase of the product

Conceptual design

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%

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

Conceptual designFle

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y

Process maturity

Laboratory

Pilot plant

First PlantSubsequentplant

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

Conceptual design

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

Process supportCIP, solution prep…

Process Utilitieswater, effluent treatment…

Spacesproduction, mechanical rooms, warehouse…

Building utilitiesHVAC, Steam, chilled water, power…

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

Mechanical components specification

Installation drawing (3D, isometrics)

I/O List

Automation components specifications

Sequences of operation

Alarms Interlocks

Access rights

Control panel drawings loop diagram

wiring diagramProgramming

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 document

(P&ID, specifications)

Data SheetsIsometrics

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 ?