GAMP/JETT AGENDAGAMP/JETT AGENDA

Introduction andIntroduction and GAMPGAMP OrganizationOrganization Dale Dale NoteboomNoteboom

GAMP Process Control Supplement GAMP Process Control Supplement Jim JohnJim John Benefits of the GAMP/JETT Benefits of the GAMP/JETT Chris RoerigChris Roerig MethodologyMethodology Working SessionWorking Session JETT TeamJETT Team Questions & AnswersQuestions & Answers JETT TeamJETT Team

GAMP Forum DevelopmentsGAMP Forum Developments ~ 12 Special Interest Groups (SIG's)~ 12 Special Interest Groups (SIG's) GAMP Americas established Sept 2000GAMP Americas established Sept 2000

– 8 New Special Interest Groups established8 New Special Interest Groups established New groups incorporated into GAMP New groups incorporated into GAMP

ForumForum– North American JETT Consortium joined North American JETT Consortium joined

(2000)(2000)– UK Suppliers Forum joining (2001)UK Suppliers Forum joining (2001)

GAMP Americas

Namur Group

APV

ISPE/GAMPJETT

Supplier Forum

GAMP Europe

GAMP Forum Organisation

Executive Summary Executive Summary of of GGood ood AAutomated utomated

MManufacturing anufacturing PPractice (ractice (GAMPGAMP) )

GuideGuide

GAMP Scope: “Automated GAMP Scope: “Automated Systems”Systems” Consist of:Consist of:

– Hardware Hardware - Controlled Functions- Controlled Functions– Software Software - Network Components- Network Components– Associated DocumentationAssociated Documentation

Applies to:Applies to:– Automated Manufacturing EquipmentAutomated Manufacturing Equipment– Control SystemsControl Systems– Automated Laboratory SystemsAutomated Laboratory Systems– Manufacturing Execution SystemsManufacturing Execution Systems– Computers Running Manufacturing or Laboratory DatabasesComputers Running Manufacturing or Laboratory Databases

GAMP PurposeGAMP Purpose ““Help Help supplierssuppliers of automated of automated

systems to the pharmaceutical systems to the pharmaceutical industry industry ensureensure that systems that systems are developed following good are developed following good practice and to provide proper practice and to provide proper documentary evidence documentary evidence that that their systems meet the their systems meet the agreed agreed specificationsspecifications.”.”

A Basic Framework for Specification, Design and Testing

GAMP 4.0 Figure 6.2

Verifies

Verifies

Verifies

USER REQUIREMENTUSER REQUIREMENTSPECIFICATION

FUNCTIONALSPECIFICATION

DESIGN SPECIFICATION

SYSTEMBUILD

PERFORMANCEQUALIFICATION

OPERATIONALQUALIFICATION

INSTALLATIONQUALIFICATION

GAMP Qualification GAMP Qualification PlanPlan

Part 1: User Part 1: User ResponsibilitiesResponsibilities

Validation (Master) Plan & Validation (Master) Plan & System Specific Validation System Specific Validation Plan(s)Plan(s)– Appendix 6Appendix 6

Supplier AuditSupplier Audit– Appendix 7Appendix 7

User Requirements SpecificationUser Requirements Specification– Appendix 5Appendix 5

Supplier EducationSupplier Education

Strategic Framework

Quality Management Procedures

Practical Guidance (Good Practice)

Training/Materials Workshop

New Edition: GAMP 4New Edition: GAMP 4

Software categories developed furtherSoftware categories developed further Validation needs to be scaleable Validation needs to be scaleable Global acceptance Global acceptance Examine the balance of work conducted Examine the balance of work conducted

by pharmaceutical manufacturers and by pharmaceutical manufacturers and their suppliers. their suppliers.

Harmonization of terminology with other Harmonization of terminology with other industry forums.industry forums.

GAMP 4 GoalsGAMP 4 Goals

First WaveFirst Wave– CalibrationCalibration– IT Infrastructure: Networks, IT Infrastructure: Networks,

Desktop,Desktop, – Harmonized TerminologyHarmonized Terminology– Electronic Records and SignaturesElectronic Records and Signatures

Best Practice GuidesBest Practice Guides

Second WaveSecond Wave– Control Systems: including Stand-Control Systems: including Stand-

alone PLC/SCADA/DCS and alone PLC/SCADA/DCS and Packaged Systems”/”Skid Mount Packaged Systems”/”Skid Mount Equipment”Equipment”

– Supplier Management Supplier Management – Analytical Laboratory EquipmentAnalytical Laboratory Equipment– Global Systems: ERP, MRPII, LIMS, Global Systems: ERP, MRPII, LIMS,

EDMSEDMS

Additional Planned GuidesAdditional Planned Guides

Third WaveThird Wave– Legacy SystemsLegacy Systems– Clinical SystemsClinical Systems– Medical DevicesMedical Devices– E-Applications: Web-based softwareE-Applications: Web-based software– Manufacturing Execution SystemsManufacturing Execution Systems

Additional Planned GuidesAdditional Planned Guides

GAMP SummaryGAMP Summary

International guideline.International guideline. Good starter system.Good starter system. Continuing to evolve (GAMP4)Continuing to evolve (GAMP4) Basis for Regulatory Agency Basis for Regulatory Agency

Training and expectationsTraining and expectations Good “common ground” for Good “common ground” for

CSV International AlignmentCSV International Alignment

Joint Equipment Joint Equipment Transition TeamTransition Team

(www.JETTconsortium.c(www.JETTconsortium.com)om)

Mission StatementMission Statement Improve communications Improve communications

between Users and Suppliers between Users and Suppliers to more effectively meet the to more effectively meet the “validation” requirements of “validation” requirements of the pharmaceutical industry.the pharmaceutical industry.

USER RepresentativesUSER Representatives• Abbott Labs – Abbott Labs – Tim Tim

SchuetterSchuetter• Pharmacia - Pharmacia - Dale NoteboomDale Noteboom • Eli Lilly - Eli Lilly - Bret FiskBret Fisk• Aventis Behring – Aventis Behring – John John

DexterDexter• Aventis Pasteur – Aventis Pasteur – Jeff Jeff

O’DonelO’Donel• Perrigo – Perrigo – Paul CouryPaul Coury SUPPLIER SUPPLIER

RepresentativesRepresentatives• Fisher-Rosemount – Fisher-Rosemount – Jon Jon

LustriLustri • Bosch /TL Systems - Bosch /TL Systems - Terry Terry

PetroPetro• Vector Corp - Vector Corp - Don Don

RosendaleRosendale• Rockwell – Rockwell – McCarthy, JiangMcCarthy, Jiang • BOC Edwards – BOC Edwards – Mike StellaMike Stella• Millipore – Millipore – Ramon LeDouxRamon LeDoux• Invensys – Invensys – Russell ReganRussell Regan

JETT MEMBERSJETT MEMBERS CONSULTANT RepsCONSULTANT Reps• VAI Automation - Chris VAI Automation - Chris

Roerig Roerig • Jacobs Engrg – Brokamp, Jacobs Engrg – Brokamp,

BuedeBuede• PV - Filary, Rivera, PV - Filary, Rivera,

LaudermanLauderman• PAC – Bruce LaudermanPAC – Bruce Lauderman• Fluor-Daniel – Mike Fluor-Daniel – Mike

HumphriesHumphries• BE&K Engr – Vince MillerBE&K Engr – Vince Miller• Brock Solutions – John, Brock Solutions – John,

CaseyCasey

~ 14 Active Members~ 14 Active Members+ 45 Assoc. Members & + 45 Assoc. Members &

GrowingGrowing

JETT BASELINE EXAMPLE JETT BASELINE EXAMPLE User Requirement SpecificationUser Requirement Specification Project PlanningProject Planning Functional & Design Functional & Design

SpecificationsSpecifications Acceptance TestsAcceptance Tests

- Hardware- Hardware - System- System- Software - Software - Factory- Factory

Integrate with ValidationDocumentation as appropriate

JETT EQUIPMENT ACQUISITION MODELJETT EQUIPMENT ACQUISITION MODELSUPPLIER

Functional Specification(traceable to URS)

USER/(CONSULTANT if applicable)

Master Validation Plan

RFQ

User Audit

Proposal• Project Plan• Quality & Validation Plan

Equipment Validation Plan• Explanation to Supplier

User RequirementsSpecification

(Living Document)

Proposal Analysis

Proposa

lP.O.

Detailed DesignDocumentation

(traceable to Functional Specification)Review Functional Specification

Review Detailed Design

System Acceptance TestSpecifications (IQ/OQ)

• Hardware • Software

Review SystemAcceptance Test Specifications

System AcceptanceTesting and Results

User Witness Optional

Maintenance & SupportDocumentation

Approval

Approval

Approval

Engineering Feasibility Study and ResultsP.O.

JETT EffortsJETT Efforts Applying GAMP to Automated Applying GAMP to Automated

EquipmentEquipment Communicating GAMP ApproachCommunicating GAMP Approach

– Interphex 1997, 2000, & 2001Interphex 1997, 2000, & 2001– ISPE - Regional & National MeetingsISPE - Regional & National Meetings– Pharmaceutical Online ArticlesPharmaceutical Online Articles– Pharmaceutical Engineering ArticlesPharmaceutical Engineering Articles– Institute of Validation Technology – Institute of Validation Technology –

Conferences and ArticlesConferences and Articles– Published in VPCS Supplement to GAMP 4Published in VPCS Supplement to GAMP 4

JETT EffortsJETT Efforts Providing Input to GAMP ForumProviding Input to GAMP Forum Developing Guidance for Developing Guidance for

Equipment URS’s, Equipment Equipment URS’s, Equipment Validation Plans, Functional and Validation Plans, Functional and Design Specifications and IQ/OQ’sDesign Specifications and IQ/OQ’s

Working directly with Industry Working directly with Industry OEM’sOEM’s

JETT EffortsJETT Efforts Equipment Validation Plan TemplateEquipment Validation Plan Template URS TemplateURS Template Common equipment URS examples Common equipment URS examples

and templatesand templates Baseline example for Pure Steam Baseline example for Pure Steam

GeneratorGenerator– URS, FRS, HDS, SDS, FATURS, FRS, HDS, SDS, FAT

JETT EffortsJETT Efforts Released URS DocumentsReleased URS DocumentsGlassware Washers

Saturated Steam Autoclave

Label Rewinder

Labeler

Multiple-Effect Still

Vial Washer

Barrier Isolator & HVAC System

Chromatography

Pure Steam Generator

JETT EffortsJETT Efforts URS Documents in developmentURS Documents in developmentGranulators

Tablet Press

Variable Data Inspection

BioReactors

Building Management Systems

Centrifuge

CIP Systems

Fluid Bed Dryer

Freeze Dryer

Tablet Coater

Purified Water System

Wide Range Filler

Tangential Flow Filtration System

SCADA System

Cappers

Blender

Depyrogenation Tunnel

GAMP Process Control GAMP Process Control SupplementSupplement

GAMP Process Control GAMP Process Control Supplement - PurposeSupplement - Purpose

“ “This Guide is intended is a supplement to This Guide is intended is a supplement to the GAMP Guide, and provides a the GAMP Guide, and provides a harmonized overview of the key elements harmonized overview of the key elements involved in the lifecycle of process control involved in the lifecycle of process control systems, from inception to retirement. As systems, from inception to retirement. As such, the Guide complements the current such, the Guide complements the current Baseline Guide on Commissioning and Baseline Guide on Commissioning and Qualification from ISPE.”Qualification from ISPE.”

GAMP Process Control GAMP Process Control Supplement - ScopeSupplement - Scope

Systems that control the manufacturing process, Systems that control the manufacturing process, and have direct impact on product quality and have direct impact on product quality attributes at any stage in the life cycle. Product attributes at any stage in the life cycle. Product quality attributes include the identity, efficacy, quality attributes include the identity, efficacy, strength, dosage, quality, disposition, safety, and strength, dosage, quality, disposition, safety, and purity of the productpurity of the product

Systems that process, transfer, or store process Systems that process, transfer, or store process information in electronic formatinformation in electronic format

GAMP Process Control GAMP Process Control Supplement - BenefitsSupplement - Benefits

Application and adaptation of the general principles of GAMP 4 to Application and adaptation of the general principles of GAMP 4 to process control systemsprocess control systems

A comprehensive overview of current best practice techniques for A comprehensive overview of current best practice techniques for process control systemsprocess control systems

Reduction of the cost and time required to achieve compliant Reduction of the cost and time required to achieve compliant process control systemsprocess control systems

Application of good practice to the development and management Application of good practice to the development and management of projects involving process control systems to meet regulatory of projects involving process control systems to meet regulatory expectationsexpectations

Harmonized approaches for embedded as well as standalone Harmonized approaches for embedded as well as standalone systemssystems

Detailed definition of engineering stepsDetailed definition of engineering steps

GAMP Process Control GAMP Process Control Supplement - BenefitsSupplement - Benefits

Detailed guidance on the generation of user requirements Detailed guidance on the generation of user requirements specificationsspecifications

Guidance on functionality and structures of process control systems as Guidance on functionality and structures of process control systems as well as supplier services requiredwell as supplier services required

Guidance on the supplier services required for regulated environmentsGuidance on the supplier services required for regulated environmentsAvoids extensive and time-consuming retrospective validation of Avoids extensive and time-consuming retrospective validation of

legacy process control systems, but provides for the application of a legacy process control systems, but provides for the application of a risk based approach, if requiredrisk based approach, if required

Clarifies the collaboration between user and supplierClarifies the collaboration between user and supplierGuidance on incorporation of supplier documentation into the user Guidance on incorporation of supplier documentation into the user

validation documentation Modified and extended supplier audit to validation documentation Modified and extended supplier audit to ensure compliance of the supplier’s development processes and ensure compliance of the supplier’s development processes and documentationdocumentation

GAMP Process Control GAMP Process Control Supplement - ReleaseSupplement - Release

Global Introduction of the VPCS GuideGlobal Introduction of the VPCS Guide

ISPE Washington Continuing Advancement ISPE Washington Continuing Advancement Conference – June 4 Arlington, VAConference – June 4 Arlington, VA

JETT Benefits AnalysisJETT Benefits Analysis

Chris RoerigChris Roerig

Benefits of JETT Benefits of JETT ApproachApproach

Provides Standards/Guidelines forProvides Standards/Guidelines for Project Lifecycle Project Lifecycle DeliverablesDeliverables DocumentationDocumentation ApprovalsApprovals

Industry ConsistencyIndustry Consistency

Benefits of JETT Benefits of JETT ApproachApproach

"Speed to Market" "Speed to Market" Smoother Procurement ProcessSmoother Procurement Process Smoother Validation Process Smoother Validation Process Shorter Project ScheduleShorter Project ScheduleReduced Project CostsReduced Project Costs Integration Services Integration Services ValidationValidation Re-workRe-work

Savings AnalysisSavings Analysis% of Purchase Price% of Purchase Price

UserUser 5-6 % savings5-6 % savings– Gains:Gains:

Qualification Protocol development & executionQualification Protocol development & execution Life Cycle support (maintenance, upgrades)Life Cycle support (maintenance, upgrades)

– Losses:Losses: Additional AuditingAdditional Auditing Validation Plan Validation Plan URS developmentURS development

Time SavingsTime Savings3 - 14 weeks3 - 14 weeks

Savings AnalysisSavings Analysis% of Purchase Price% of Purchase Price

SupplierSupplier 3 - 6% savings 3 - 6% savings – Gains:Gains:

Functional, Design, & Test spec developmentFunctional, Design, & Test spec development System production costsSystem production costs FAT FAT

– LossesLosses Supplier AuditsSupplier Audits

Time SavingsTime Savings 6 - 8 weeks6 - 8 weeks

Savings AnalysisSavings Analysis% of Purchase Price% of Purchase Price

Consultant Consultant 3 - 4 % savings 3 - 4 % savings – Gains:Gains:

Functional, Design, & Test Spec DevelopmentFunctional, Design, & Test Spec Development FAT FAT

– LossesLosses Integrator Audits Integrator Audits

Time savings Time savings 3-10 weeks3-10 weeks

Real World Real World ExampleExample

Courtesy of:Courtesy of:Dr. David Selby,Dr. David Selby,

David Begg Associates,David Begg Associates,Kirkbymoorside,Kirkbymoorside,

N. Yorks, UKN. Yorks, UKYO6 6AXYO6 6AX

ScenarioScenario• two equivalent sterile filling linestwo equivalent sterile filling lines• 1991 - ampoules (pre GAMP)1991 - ampoules (pre GAMP)• 1994 - vials (post GAMP)1994 - vials (post GAMP)• equivalent equipment trainequivalent equipment train

- tunnel steriliser- tunnel steriliser- filler- filler- automatic crack detection- automatic crack detection- automatic particulate inspection- automatic particulate inspection

• equivalent project cost (~$2m) equivalent project cost (~$2m)

Engineering

Pre-GAMP Project

RequirementsSpecification Minimal

30 days

Design Qualification

Pre-Delivery Inspection

Installation Qualification

Operational Qualification

Software Review

Misc. ControlsValidation

Total Man days(approx.)

Not done

Not done

Not done

0 100

0 7 days

0 5 weeks

Efficiency(Day 1)

Now

Availability(for production)

Wastage

Maintainability

RetrospectiveValidation

Documentation

Significant

Adequate

0 <30% 100

0 70% 100

Poor

0 60% 100

0 8-12% 100

Performance

Post-GAMP Project

RequirementsSpecification

Design Qualification

Pre-Delivery Inspection

Installation Qualification

Operational Qualification

Software Review

Misc. ControlsValidation

Total Man days(approx.)

Efficiency(Day 1)

Now

Availability(for production)

Wastage

Maintainability

RetrospectiveValidation

Documentation

0 75% 100

Good

Good

Unnecessary

0 90%100

0 100

0 1% 100

EngineeringComprehensive - 2 weeks (+ several consultations)

0 100

4 days

2 weeks

Significant0 7 days

5 weeks0

90 days

Performance

SummarySummary

To derive benefit when validating To derive benefit when validating automated systems :-automated systems :-

• adopt “good engineering practices”• adopt the common approach (GAMP)• manage the benefits through• measure them

postpost GAMPGAMP0 75%

0 90%

0 1%

0 100%

How Do I Get Started?How Do I Get Started? JETT Web SiteJETT Web Site

– www.jettconsortium.comwww.jettconsortium.com GAMP Web Site GAMP Web Site ContactContact JETT Members for HelpJETT Members for Help Start with Baseline Piece of Equip.Start with Baseline Piece of Equip. Promote with Users, QA, & SuppliersPromote with Users, QA, & Suppliers Integrate in your Stds and Methods Integrate in your Stds and Methods

Working SessionWorking Session Break into functional groupsBreak into functional groups

– QA/ValidationQA/Validation– Manufacturing/OperationsManufacturing/Operations– Environmental/Safety/Utilities/MaintenanceEnvironmental/Safety/Utilities/Maintenance– EngineeringEngineering

Select a piece of OEM equipment (simple)Select a piece of OEM equipment (simple) Develop portions of a URSDevelop portions of a URS Develop portions of project validation planDevelop portions of project validation plan

URS GuidelinesURS Guidelines Each statement:Each statement:

– Uniquely referencedUniquely referenced– Less than 250 wordsLess than 250 words

Express requirements, not design solutionExpress requirements, not design solution Each requirement should be testableEach requirement should be testable URS should be understandable by user and URS should be understandable by user and

suppliersupplier– No ambiguityNo ambiguity– No contradictionsNo contradictions

Distinguish between mandatory and desirable Distinguish between mandatory and desirable items/requirementsitems/requirements

URS Content ChecklistURS Content Checklist Functions requiredFunctions required

Product requirementProduct requirement Functional requirementFunctional requirement Design requirementDesign requirement

Modes of operationModes of operation Performance and timingPerformance and timing Failure actionsFailure actions

HardwareHardware SoftwareSoftware

URS Content ChecklistURS Content Checklist Safety and securitySafety and security DataData

ArchiveArchiveCapacityCapacitySpeedSpeedDefinition of data and valid rangesDefinition of data and valid ranges

InterfacesInterfaces EnvironmentEnvironment

URS ConstraintsURS Constraints ScheduleSchedule Compatibility with existing networks, Compatibility with existing networks,

hardware, etc.hardware, etc. Reliability requirementsReliability requirements Legal issues, working methods, user skill Legal issues, working methods, user skill

levels, etc.levels, etc. MaintenanceMaintenance

– Ease of maintenanceEase of maintenance– Expansion capabilityExpansion capability– Expected lifetimeExpected lifetime– Long-term supportLong-term support

URS LifecycleURS Lifecycle Development – e.g. project Development – e.g. project

management/QA/mandatory design management/QA/mandatory design methodsmethods

TestingTesting– Special testing under load conditionsSpecial testing under load conditions– Test dataTest data– SimulationsSimulations

DeliveryDelivery– Shipment directionsShipment directions– Documents – what supplier is expected to deliverDocuments – what supplier is expected to deliver

URS LifecycleURS Lifecycle ToolsTools TrainingTraining

– EngineeringEngineering– OperationsOperations– MaintenanceMaintenance

Support from vendor after:Support from vendor after:– FATFAT– Validation completeValidation complete