12/11/2013

Project
Engineering
Under
ASTME2500

AndrewFaden,PMP,
CPIP

PresentationObjective

Thepurposeofmypresentationistolook
atindustryexpectationsforGMPprojects
inlightoftheASTME2500guidance.Iwill
alsolookattheroleoftheProjectEngineer
infulfillingtheseexpectations.

1
 12/11/2013

PresentationOutline
Background
Currentstateofpractice
EngineeringDiscipline
ReviewofASTME2500andotherrelevant
guides
ProjectManagementProcess
PracticalintegrationofASTME2500with
ProjectManagement

PrevailingGuidancein2007
ICHQ82005(R1) PharmaceuticalDevelopment
Approveddesignspace
Provenacceptablerange
Controlstrategy
CPP,CQA,QTPP

ICHQ92005 QualityRiskManagement
Evaluationofrisktoqualityshouldbebasedonscientific
knowledgeandlinktoprotectionofpatient
LevelofeffortoftheQRMprocessshouldbe
commensuratewithlevelofrisk.

2
 12/11/2013

PrevailingGuidancein2007
PharmaceuticalcGMPs forthe21stCentury aRiskBased
Approach (FDA),Guidingprinciplesinclude:
Riskbasedorientation
Sciencebasedpoliciesandprocedures
Strongpublichealthprotection

TheISPEBaselineGuideVolume5,Commissioningand
Validation
Design,construction,commissioning,andqualificationoffacilities
SystemLevelImpactAssessments
ApplyGEPandcommissioningtoIndirectandNoImpactSystems
AdditionallyapplyQualificationPractices(IQ,OQ,PQ)toDirectImpact
Systems

PrevailingPracticeToday
Practitionercomments:

Thetraditionalvalidationactivitieshavebecomecentered
arounddocumentation,insteadofensuringqualityTraditional
validationactivitiesstifleinnovation,causecompliancerisk
andcompromisealifesciencefirmsabilitytobringproductsto
themarketontime. 2013,Valgenesis Webpage

TheQualityUnitessentiallybehavedasaQualityControlunit
checking,reviewingandapprovingalmosteveryvalidation
document.Thiscreatedatenseandbottlenecksituation. 2012,
JoseOchoa

3
 12/11/2013

PrevailingPracticeToday
Legacyguidancehasnotbeenfollowedasintended:
ISPEBaselineGuideVolume5providesDirectImpact
CriteriabutstatesthatThesecriteriashouldbe
usedtoinformajudgmentbasedonthe
comprehensiveunderstandingoftheproduct,
process,andnatureofthesystem.Theyshouldnot
beusedtoreplacetheexerciseofinformed
judgmentbyappropriatelyqualifiedpersonnel.
AccordingtoFSE(2011),Thestatementregarding
informedjudgmentoftenhasnotbeenapplied.

ASTME2500Intent
Riskbased andsciencebasedapproach tothe
specification,design,andverificationofmanufacturing
systemsandequipment thathavethepotentialtoaffect
productqualityandpatientsafety.

Providemanufacturingcapabilitytosupportdefinedand
controlledprocessesthatcanconsistentlyproduce
productmeetingdefinedqualityrequirements.

SubjectMatterExperts(SMEs)withatechnical
understandingofthecriticalaspectsofmanufacturing
systemstodrivethespecification,design,andverification
offacilitiesandequipment.

4
 12/11/2013

EngineersaretheSMEsforFacilities,
Systems,andEquipment
Theindustryhasbeenslowtorecognize
thattheSMEswithatechnical
understandingoffacilities,systems,and
equipmentareengineers.
Inmanycases,theindustrydoesnot
recognizetheengineeringdiscipline.
ThetermProjectEngineerisrarelyfound
intheindustryvernacular itisnoteven
mentionedintheISPEGPGforProject
Management!

WhatisaProjectEngineer?
Breakingitdown:

A PROJECT isatemporary endeavorundertakento

createaunique product,serviceorresult.
PMBOKGuide

AnENGINEER isconcernedwithapplyingscientific
knowledgetodevelopsolutionsfortechnicalproblems.
Engineersdesignsystemswhileconsideringthe
limitationsimposedbypracticality,regulation,safety,
andcost.
Wikipedia
10

5
 12/11/2013

EngineersareWiredDifferently

PressPlayhere

11

ProjectEngineering

ProjectEngineeringbridgestheboundaries
betweenengineeringandproject
managementInsomecases,theproject
engineeristhesameasaprojectmanagerbut
inmostcasesthesetwoprofessionalshave
jointresponsibilityforleadingaproject.
Wikipedia

12

6
 12/11/2013

CurrentGuidanceshaping
theGMPProjectEngineerrole
ASTME250007StandardGuideforSpecification,
Design,andVerificationofPharmaceuticaland
BiopharmaceuticalManufacturingSystemsAnd
Equipment
ISPEGPG:ScienceandRiskbasedApproachfor
theDeliveryofFacilities,Systems,andEquipment,
(FSEGuide)2011
ISPEGPG:ProjectManagementforthe
PharmaceuticalIndustry,2011
PMIPMBOK ProjectManagementBodyof
Knowledge

13

SignificanceofASTME2500

Applicationoftheapproachisintendedto
satisfyinternationalregulatoryexpectations
inensuringthatmanufacturingsystemsand
equipmentarefitforintendeduse,and
satisfyrequirementsfordesign,installation,
operation,andperformanceASTME2500
5.1

14

7
 12/11/2013

KeyconceptsofASTME2500
Riskbasedapproach
Theevaluationofrisktoqualityshouldbe
basedonscientificknowledge andultimately
linktotheprotectionofthepatientASTM
E25006.2.2.1

15

KeyconceptsofASTMEE2500
Sciencebasedapproach
Sciencebasedapproach Productandprocess
information,asitrelatestoproductqualityand
patientsafety,shouldbeusedasthebasisfor
makingscience andriskbaseddecisionsthat
ensurethatthemanufacturingsystemsare
designedandverifiedtobefitfortheirintended
use.ASTME25006.3.1

16

8
 12/11/2013

KeyconceptsofASTMEE2500
Sciencebasedapproach
Examplesofproductandprocessinformation
toconsiderinclude:CQAs,CPPs,processcontrol
strategyinformation,andpriorproduction
experience.ASTME25006.3.2

17

KeyconceptsofASTMEE2500
Criticalsystemaspects
Criticalaspectsofmanufacturingsystemsare
typicallyfunctions,features,abilities,and
performance orcharacteristicsnecessaryforthe
manufacturingprocessandsystemstoensure
consistentproductqualityandpatientsafety.
ASTME25006.4.1

18

9
 12/11/2013

KeyconceptsofASTMEE2500
QualitybyDesign
Qualitybydesignconceptsshouldbeapplied
toensurethatcriticalaspectsaredesignedinto
systemsduringthespecificationanddesign
process.ASTME25006.5.1

19

KeyconceptsofASTMEE2500
GoodEngineeringPractice
GoodEngineeringPractice(GEP)should
underpinandsupportthespecification,design,
andverificationactivities.ASTME25006.6.1

20

10
 12/11/2013

KeyconceptsofASTMEE2500
Specification,Design,Verification

21

KeyconceptsofASTMEE2500
SubjectMatterExperts
SubjectMatterExpertsaredefinedasthoseindividuals
withspecificexpertiseandresponsibilityinaparticular
areaorfield(forexample,qualityunit,engineering,
automation, development,operations).ASTME2500
6.7.1.

SubjectMatterExpertsshouldtaketheleadroleinthe
verificationofmanufacturingsystemsasappropriatewithin
theirareaofexpertiseandresponsibility.ASTME2500
6.7.2.

22

11
 12/11/2013

KeyconceptsofASTMEE2500
VendorDocumentation
Thedecisionandjustificationtousevendor
documentation,tosupporttheverificationof
criticalaspectsofthemanufacturing
elementshouldbedocumentedandapproved
bySMEs...
ASTME25006.8.3.

23

ASTME2500isonlyfivepages
long,yetitreferstoSMEs21
times!

24

12
 12/11/2013

ISPEFSEGuide

TheGPGScienceandRiskbasedApproachfor
theDeliveryofFacilities,Systems,and
Equipment (FSEGuide,2011)
Providesdirectiontoindustryonthe
implementationofascienceandriskbased
approach
CompatiblewithQ8,Q9,Q10andE2500

25

ObjectiveofFSE

tofacilitatethetranslationofthescientific
knowledge abouttheproductandprocess
intodocumentedspecification,design,and
verificationofequipment,systemsand
facilitieswhicharefitforintendeduse,and
minimizerisktoproductqualityandpatient
safety.FSE1.2

26

13
 12/11/2013

FSEonSMERole

SMEsshouldtaketheleadroleinthe
verificationofmanufacturingelements.FSE
2.8.1
Beforeacceptanceandrelease,change
managementshouldbeapplied.Thisprocess
shouldbemanagedbyandchangesapproved
bySMEs.10.4

27

FSE TypicalAreasofSME

HighlightsfromTable21
ProcessScientists determineCQAsandCPPs
Engineering/Technical specification,verification
AutomationSME develop,verify,andoptimize
automationandprocesscontrolelements
Quality developandapproveverificationplans
withotherSMEs;compliancewithsiteQMS
Manufacturingpersonnel operability,SOPs

28

14
 12/11/2013

FSE Tools

FSEAppendicesdemonstratetoolsfor:
RiskAssessments
FMEA&FMECA
FTA
HACCP
HAZOP
Fishbone,etc.
ImpactAssessments
Commissioning

29

FSE QualificationApproach

FSEAppendix14: QualificationApproaches
GuidanceonhowPMscanapply[the
guides]principlestoeliminatenonvalueadded
Qualificationpractices...FSE14
TechnicalSMEscandetermineseparatelyhowto
inspectortestagivenengineeringaspect,andthe
fieldworkcanbecarriedoutanddocumented
underGEPFSE14.2

30

15
 12/11/2013

ISPEAppliedRiskManagementGuide

Theguidedescribeshoworganizationscan
movefromestablishedbaselinepractice
(Volume5)toamoreefficientscience andrisk
basedframework(FSE).

31

PMBOK

Describestheprojectmanagementlifecycle
Recognizes47processesinfivebasicprocess
groupsandtenknowledgeareas

32

16
 12/11/2013

PMBOK

Insertprocessgroupmatrixhere

33

ISPEGPG:ProjectManagementforthe
PharmaceuticalIndustry
Itisconsideredgoodprojectmanagement
practicetointegrateGxP withrelevantproject
managementactivitiestoensurethat
complianceriskismanagedeffectivelyand
proactively.PMPI1.1

34

17
 12/11/2013

PurposeoftheISPEPMPIGuide

toprovideareferencesourceofgood
practicesforprojectmanagementforawide
varietyofprojecttypeswithinthe
pharmaceuticalindustry.PMPI1.2

35

PMPIAlignmentwithASTME2500
SMEs

ProjectManagersmayneedtocoordinatea
widerangeofknowledgeinpharmaceutical
industryprojectsandmaynotbeaSMEforthe
projecttype.PMPI2.2.1

36

18
 12/11/2013

PMPIAlignmentwithASTME2500
ProductQuality
Projectrequirementsthatrelatetoproduct
qualityaredefinedinASTME250007as:
Productknowledge
Processknowledge
Regulatoryrequirements
Companyqualityrequirements

37

PMPIAlignmentwithASTME2500
AQuestionofBalance

TeammembersneedtounderstandtheirSME
roleandalsotheneedtobalancedeliverables
andexpectationswithcostandschedule,asthe
PMdoes.FSE2.4

38

19
 12/11/2013

ProjectManagementFlowchart(PMPI)
SuggestedPEinvolvementinblue(mine)

39

ProposedTool CSARegistry

TheCSARegistryisatracematrixthat
linksCQAs,CPPs,andcriticalsystem
aspectswithpatientsafetytohelpmeet
theintentofASTME2500

40

20
 12/11/2013

CQA,CPP,PriorProductionExperience,and
CriticalAspectsofaManufacturingSystem

Syringe

Component
Rubber Washer
Plunger

CartridgeandNeedle

41

CSARegistry Process
Performanimpactassessmentonproposedchanges,
perFSEAppendix2,toidentifycriticalaspects
Collectproductandprocessknowledge(CQAs,CPPs,etc.)
DeterminetheimpacttoallCQAsandCPPsforeachcritical
systemaspect
Determinetheimpacttopatientsafetyforeach
impactedCQA
Developtestprotocolstoverifyeachcriticalsystem
aspectandincludethecorrespondingtestreferencesin
theCSAregistry
CreateatracematrixorregistrylinkingCQAs,CPPs,
criticalsystemaspects,andverificationresultsto
patientsafety 42

21
 12/11/2013

ProposedTool CriticalSystemAspect
Registry

Critical Impacted CQAs Impacted CPPs Verification

Critical system Acceptable Acceptable Test
system aspect CQAs range CPPs range Reference Risk to patient safety
4.5 to 6.0 Film thickness of 12 High plunger force can cause
Silicone Plunger force newtons silicone on plunger microns VT 1.1.1 cartridge to break during use
Component
dosing of Low epi concentration can
washer
plungers Epinephrine Amount of silicone cause anesthetic to wear off
concentration 5 7 % in solution < 1 PPM VT 1.1.2 before procedure is complete

43

Summary
TheintentofASTME2500istoprovideaRiskbased andsciencebased
approach tothespecification,design,andverificationofmanufacturing
systemsandequipment thathavethepotentialtoaffectproductquality
andpatientsafety.TheguiderequiresthatSMEsleadthiseffort.

TheSMEsformanufacturingsystemsandequipmentareengineers.

PartneringaProjectEngineerwithaProjectManagercanleadtomore
efficientandeffectiveprojectdelivery.ItdeliversontheASTME2500
requirementtoincorporatesciencebasedandriskbasedunderstanding
ofmanufacturingsystemsthatcanimpactpatientsafety.ThePMcan
focusonthebusinessandadministrativetaskswhilethePEcanfocuson
thetechnicalaspects.

ACriticalSystemAspectRegistryisproposedasanewtoolandprocess
forhelpingtomanagethelifecycleofcriticalsystemsunderE2500.

44

22
 12/11/2013

Work
Breakdown
Structure

AndrewFaden,PMP,
CPIP

PMBOKProcessMap

46

23
 12/11/2013

WhyisWBSImportant?

47

WhyisWBSImportant?

48

24
 12/11/2013

WBSProcess Inputs
TheinputstotheWBSprocessare:
Projectscopestatement narrativedescriptionof
scopewithmajordeliverables
Requirementsdocumentation conditionsand
capabilitiesthatmustbemettosatisfyformally
imposeddocuments
Thewants,needs,andexpectationsofsponsors,
customers,andotherstakeholders
OrganizationalProcessAssets formalandinformal
policiesandprocedures

PMIPMBOKGuideFourthEdition

49

Definitions
WorkBreakdownStructure Adeliverableoriented
hierarchicaldecompositionoftheworktobeexecuted

WorkBreakdownStructureComponent Anentryinthe
WBSthatcanbeatanylevel

WorkBreakdownStructureDictionary Adocumentthat
describeseachcomponentintheWBS

WorkPackage Adeliverableorprojectworkcomponentat
thelowestlevelofeachbranchoftheWBS

PMIPMBOKGuideFourthEdition

50

25
 12/11/2013

WBSProcess

Breakthetotalprojectworkintoworkpackages:
Identifyandanalyzethedeliverablesandrelated
workrequiredbytheinputs.
StructureandorganizetheWBS
DecomposetheupperWBSlevelsintolower
leveldetailedcomponents.
Developandassignidentificationcodestothe
WBScomponents
Verifythatthedegreeofdecompositionis
necessaryandsufficient.

51

WBSProcess Structure

Thestructurecanbecreatedinanumberofforms:
Firstlevelcanbeprojectphasesormajor
deliverables
Firstlevelcomponentsshouldmatch,wordfor
word,thenouns usedtodescribetheoutcomes
oftheprojectintheScopeStatement.
Whereasubprojectisperformedbyanexternal
vendorthevendorcansupplyaseparateWBS
forthiswork.

52

26
 12/11/2013

WBSProcess Decomposition

Subdividetheworkforeachofthedeliverablesor
subprojectsintoitsfundamentalcomponents
TheWBScomponentsrepresentverifiableproducts,
services,orresults
Verifyingcorrectnessofdecompositionrequires
determiningthatthelowerlevelWBScomponents
arethosethatarenecessaryandsufficientfor
completionofthehigherlevelcomponent.
Differentdeliverablescanhavedifferentlevelsof
decomposition.
Asworkisdecomposedtogreaterdetail,theability
toplan,manage,andcontroltheworkisenhanced.
Excessivedecompositioncandecreaseefficiency.

53

WBSProcess 100%Rule

TheWBSmustinclude100%oftheworkdefined
bytheprojectscope.Thisincludesalldeliverables
intermsofworktobecompleted,includingproject
management.Theruleappliesatalllevelswithin
thehierarchy:thesumoftheworkatthechild
levelmustequal100%oftheworkrepresentedby
theparent.TheWBSshouldnotincludeanywork
thatfallsoutsidetheactualscopeoftheproject.

54

27
 12/11/2013

WBSProcess CodeofAccount

Useahierarchicalcodingschemetoidentifyeach
WorkComponent

55

ContactInfo
AndrewD.Faden,CPIP,PMP
fadenad1@gmail.com
5088466700

56

28