ThePathto

PackageIntegrity

Outline

Packageintegritylogicandthoughtprocess.
Establishingqualitystandards.
Evaluationofcommonmethodologies.
Alternativemethodologies.
Drivingforwardwithpackageintegritysolutions.

PackageIntegrity
PackageIntegrity
maintainingasterilebarrier.
Packageintegrityisasub
categoryofqualityandis
exclusiveof:
PeelStrength
BurstTesting
VisualInspection

Package
Integrity

Package
Quality

ImplicationsofIntegrityDeviations
Transferofenvironmentalcontaminants.
Releaseofcriticalingredients/flavors.
Synergisticeffectsofcontaminants(O2,
H2O,Bacteria).
Defectsthatwillprogresstoleakage.

Howtodiscussintegrity?
Whatisimportanttoyourcustomer?
Whatisimportanttotheproduct?
WhatisImportanttothepackage?

Integritycanbedefined.
Levelofassuranceisopentodiscussion.

SixSigmaFramework DMAIC
Define
Measure
Analyze
Improve
Control

FoundationofQualityControl
Define
Qualitycannotbecontrolledwithoutdiscrete
andmeasurablecharacterizationsofquality.

Measure
Qualitycannotbecontrolledwithoutaccurate
anddefinitivemeasuresofquality.

DeterminingCriticaltoQualityBaseline
PackagevalidationviaISO11607.
PackagevalidationshouldincludeCTQdefectstudies
respectiveoftheproduct.
Desiccantweightgain
Flavorevaluation
Productperformance

Whatlevelofdefectwilldeterioratemyproduct?

Microbes&TargetLeakSizes

Wolf,etal,PDAJPharma Sci &Technol 2009, 63,5 489498

Kirsch,etal,PDAJPharmSci &Technol 1997,51,5,p.200

CharacterizingDefects
Pinholes
FlexCracks
ChannelDefects<3mm
IncompleteSeal>3mm Wolf,etal,PDAJPharma Sci &Technol 2009, 63,5 489498
Torturouspathofchanneldefects.
Pinholeisnotequaltoachanneldefect

FlowRateistheCriticalParameter
300

LeakSize(microns)

250
200
150
Wolf,etal,PDAJPharma Sci &Technol 2009, 63,5 489498

100
50
0
0

200

400
FlowRate(ccm)

600

800

Pinholevs.ChannelDefect
800

75Pinhole ~44sccm

700

7520mmChannel
~6.4sccm

DifferentialPressure,Pa

600

500

75micron

400

100micron
Expon.(75micron)
Expon.(100micron)

300

200

100

0
0

10

20

30

40

50

CapillaryLength,mm

60

70

80

7540mmChannel
~3.2sccm

CommonApproaches
toDefiningPackageIntegrity

Looksgood
Capability(BestAvailableTechnology)
Equalto/Betterthan
ThirdPartyWhitePapers
GrandfatheredIndustryStandards
Critical,Major,Minor

IndustryCodification
VisuallyO.K.

VisuallyDefective

Major

NoPhysicalLeak/
NoContamination

Minor

PhysicalLeak/
Contamination

Critical

Critical

TheIdealTestMethod
Informative
Accurate
Simple
CostEffective
ReducesWaste
IncreasesProductivity

NavigatingRegulation
FDArecognizesmethodology.
Manufacturersmustprovevalidatedmethodology
consistentwithproductrequirementsforlabelclaims.
Methodslistedbyorganizations(ASTM,ISO,USP)are
onlyguidance's.
Listedmethodologies:
Capabilitiesareirrespectiveofpackage/product
requirements.
Capabilitiesvarybasedonpackageaproductcharacteristics.

DirectMeasuresofQuality
ISO11607 AnnexB

VacuumDecay(ASTMF2338)
SealStrength(ASTMF88)
AirborneUltrasoundSealInspection*
VisualInspection(ASTMF1886)
DyeMigration(F1929)
HighVoltageLeakDetection*
BurstStrength(ASTMF2054)
BubbleImmersion(ASTMF2096,D3078)
*NotlistedinISO11607orASTM

TestMethodCost

GreenCoffeeWholesalePrices
250
200
150
100
50

Jul11

Apr11

Jan11

Oct10

Jul10

Apr10

Jan10

Oct09

Jul09

Apr09

0
Jan09

WaterBath FlexibleBarrierSystems
Moisture/Flavorcriticaldefectsize 15
microns
Waterbathsensitiveto2550microns
Typicallytest20pouches/line/hour
Currentmarketpriceofcoffee>$2.00/lb

cents/lb

ASTMF209604

www.ico.org

BagsTested 1lbBags $/lb

Hours, Days,Weeks UpTime

20x1x$2x24x7x52x0.5=$174,720

CostofDeployingDestructiveMethods
Product

Costof
Raw
Materials

Quantity Frequency
Tested

Cost/8
Cost/Year
HourShift (2Shifts,250Days)

Dry FillSoup $0.23

Mix

Every30
min.

$29.44

$14,720

Effervescent $0.04
Tablets

80

Every 30
min.

$51.20

$25,600

Coffee
Singles Pod

$0.06

200

EveryHour

$96

$48,000

LuerLok
Syringe

$0.20

50

Every30
min.

$160

$80,000

Pharma
BlisterPack

$1.12

10

Every30
min.

$179.20

$89,600

TestMethodEffectivity

ASTMF1886

Channelleaksdownto75 m [0.003in.]
witha60100%probability1.
80%

Assumptions
1,000Packs/Day 1%DefectRate
10Defects/Day
~2,500DefectsPerYear
80%POD(AboveAverage)

80%
80%
80%

100%Inspection=500Defects/Year
200%Inspection=100Defects/Year

ProbabilityofDetection

100
90
80
70
60

400%Inspection(4Operators)
4UndetectedDefects/Year

50
40
30
20

0.16%probabilitythatadefectwillgoundetected.

10
0
10

20

30

40

50

60

TimeonTask,min

70

80

90

Drury&Watson,
2002

1http://www.astm.org/Standards/F1886.htm

ASTMF271408

CostofSlowInformation

02 HeadSpaceAnalysis.
6daydwell.
3%pass/faillimit.
50microndefect700gr.dryfillpouch.
O2 shiftedfrom~1%to~2.5%.
ppm

UpTime

Minutes,Hours,Days

Units

60x.5x60x24x6=259,200
kg/unit

http://future.aae.wi
sc.edu

$4.41/kg

Cost/kg

259,200x.7x$4.41=$800,150

ConsiderAlternativeMethods

NonDestructivevs.Destructive
Quantitativevs.Attribute
NonSubjectivevs.OperatorDependent
CalibrationCapability
ValidationEffectiveness
SimpleMethodology(nosampleprep)

DirectMeasuresofQuality
ISO11607 AnnexB

VacuumDecay(ASTMF2338)
SealStrength(ASTMF88)
AirborneUltrasoundSealInspection*
VisualInspection(ASTMF1886)
DyeMigration(F1929)
HighVoltageLeakDetection*
BurstStrength(ASTMF2054)
BubbleImmersion(ASTMF2096,D3078)
*NotlistedinISO11607orASTM

NonSubjective,Quantitative
VacuumDecay(ASTMF2338)
SealStrength(ASTMF88)
AirborneUltrasoundSealInspection

HighVoltageLeakDetection
BurstStrength(ASTMF2054)

NonDestructive
VacuumDecay(ASTMF2338)
AirborneUltrasoundSealInspection

HighVoltageLeakDetection

VacuumDecayLeakTesting

ASTMF233809

VacuumDecayTestMethod

VacuumLevelBelow
AtmosphericPressure,mb

18
500

16
14

400

12
10

300

8
200

6
4

100

2
0

0
0

5
TestCycle

10

DifferentialPressure,Pa/sec
(SecondaryTransducer)

20

600

TestCyclePass
TestCycleFail
dPPass
dPFail

ASTMF233809

TESTPARAMETERS

Ref
Test#
1
2
3
4
5
6
7
8
9
10
11

700.2
Vacuum,mb
450.2

VacuumLevelBelow
AtmosphericPressure,mb

Vac.

Vacuum,mb
644.8
639.3
635.7
638.0
633.7
586.6
576.8
638.0
634.7
636.0
641.6

TStroke
TEqual
TTest
dP/dt,Pa/s
600
35.2

1.50
20.00
5.00
TFill,s
15.00

20

500
400dP/dt,Pa/s
300
200
100
0

Pass/Fail
27.3
P
27.3
P
26.7
P
25.7
P
26.7
P
0 1 2 3 4 5 6 7 8
95.4
F
TestCycle
90.5
F
56.6
F
52.4
F
40.4
F
39.4
F

15

DifferentialPressure,Pa/sec
(SecondaryTransducer)

VacuumDecayforFlexiblePackaging

Comments

GoodProduct
10
GoodProduct
5
GoodProduct
GoodProduct
0
GoodProduct
9 10
25micron
25micron
15micron
15micron
10micron
10micron

TestCyclePass
TestCycleFail
dPPass
dPFail

MicroLeakDetection

90
80
70

DiffdP,Pa

60
50
40
30

Avgdp

20

Upper99%Limit
Lower99%Limit

10
0
0

0.1 (3.4m)
LeakRatecc/min

0.5 (7.5m)

VacuumDecayApplication

Flexible/RigidBarrier
Air/LiquidContents
NoSamplePreparation
Quantitativeand
RepeatableTestData
NonSubjective
ZeroWaste

AirborneUltrasoundThroughTransmission

UltrasonicSignal
Propagatethroughsingleor
multiplelayersofwellbonded
materials.
Reflection/absorption ofsound
wavesbymultiple layers.

AnalysisofUltrasonicSealing
PowerSetting CscanImage
(Joules)
105

Average
Signal
0.7

90

2.2

75

5.6

60

10.1

45

20.6

SideSeal
(HeatSeal)
SideSeal
(HeatSeal)

17.6
16.9

ControlledSealQuality
0
0

20

40

60

5
10
Avg,%
15
20
25
Power(Joules)

80

100

120

SealScan OnlinePouchSealInspection

IntegratedSolution

AirborneUltrasoundApplication

NonDestructiveSealInspection
QuantitativeMaterialsAnalysis
FlexibleandSemiRigidPackaging
SealProcessOptimization
OnlineDefectDetection

HighVoltageLeakDetection
(HVLD)

HVLDDefectDetectionforPouches

Microleaksdownto5microns
Pinholes
Cracks
Crystallizedleaks
Channeldefects

HVLDTechnology
Highvoltageappliedtocontainer
Ideallynonconductivematerials
Liquidtriggersconductivityspike

HVLDDetection

HVLDApplication
QuantitativeHighSpeedInspection
Nonporous,NonconductiveMaterials
PackageContents:
liquidproducts
proteinbasedliquids
suspensionsoremulsions
FlexibleorRigidBarrier

WhentoDevelopMethodology

Shouldbeginatthepointofpackagedevelopment.
PhaseIIIPharma Development.
Newproductionlineengineering.
Whenthemethodinplacehasfailed.
Packagingthatisimmunetotestmethodology
plaguestheindustry.

Pitfalls
Mixingmethodsandtestrequirements.
Takingtestmethodstandardsaslawandnot
guidance.
Takingwhitepapersasappliedfacttospecific
applications.
Processimprovementsarevulnerabletovalidation
hurdles.
Patchingtheproblem,notdevelopingasolution.

Whatsahead?
PDAsTR27 Movingtoquantitativetest
methodology.
Track&Trace Connectingnondestructivetest
resultswithspecificunits.
GreenInitiatives Eliminatinglinewastewithnon
destructivemethods.
CTQdefectstabilitypackagevalidation.
AutomatedSPCtesting.

PackageIntegrity
PackageIntegrity
maintainingasterilebarrier.
Packageintegrityisasub
categoryofqualityandis
exclusiveof:
PeelStrength
BurstTesting
VisualInspection

Package
Integrity

Package
Quality

FoundationofQualityControl
Define
Qualitycannotbecontrolledwithoutdiscrete
andmeasurablecharacterizationsofquality.

Measure
Qualitycannotbecontrolledwithoutaccurate
anddefinitivemeasuresofquality.

ThankYou!
OliverStauffer
o.stauffer@ptiusa.com
914.337.2005
www.ptiusa.com

SimpleCasesinTesting
Someproductsaremoisturesensitive,butcontents
aremarginallyaffectedbyleaks.Detectiontothe
moisturelevelmaybeoverkill.
Someproducthavedesiccantstokeepthemdry,but
realconcernmaybemoldorbacteria.Common
methodsmaynotcutit.
Someproductionprocesseshavehighincidenceof
randomcatastrophicdefects.StatisticalProcess
Control(SPC)willnotmeetqualityneeds.

QuantitativeMeasuresProvide
GreaterAccesstoStatisticalTools

UltrasonicAttenuation
Thickness
PeelStrength
Permeation
LeakRate

Attributedatafailstoproduce
predictivemeasuresofquality.