Porous Packaging Inspection Solutions Non-Destructive Package Testing

Package Integrity Syringes Blister Packs Transfer of environmental contaminants. Synergistic effects of contaminants (O 2, H 2 O, Bacteria). Maximum Allowable Leakage Limit (MALL) Vials / Ampoules Transdermal Patches Auto Injector

Three Applications Porous Header Bag Porous Lidded Tray Hermetically Sealed Pouch/Tray

The Challenge 106 107 107 Kirsch, et al, PDA J Pharm Sci & Technol 51, 5, 1997 p. 200

100% inspection using definitive measurable methods provides much needed answers. Supplier Process Pinholes Seals Cracks Delaminations Design Personnel Pinholes Seals Cracks Tears/Abrasions Configuration Other Pinholes Seals Tears/Abrasions Other 100% Seals

Manual Visual Inspection Channel leaks down to 75 μm [0.003 in.] with a 60 100 % probability 1. 80% 80% 80% 80% Assumptions 1,000 Packs/Day 1% Defect Rate 10 Defects/Day ~2,500 Defects Per Year 100% Inspection = 500 Defects/Year 400% Inspection = 4 Defects/Year Probability of Detection 100 90 80 70 60 50 40 30 20 10 0 10 20 30 40 50 60 70 80 90 Time on Task, min Drury & Watson, 2002 Visual Physical 1 http://www.astm.org/standards/f1886.htm

Speed-Capability Detection Capability Speed Measurement access and detail Reliability of measure Non-subjective, manageable and traceable

DMAIC Control Define Quality cannot be controlled without discrete and measurable characterizations of quality. Measure Quality cannot be controlled without accurate and definitive measures of quality.

Deterministic Methods Non-Destructive vs. Destructive Quantitative vs. Attribute Non-Subjective vs. Operator Dependent Calibration Capability Validation Effectiveness Simple Methodology (no sample prep) DETERMINISTIC vs. PROBABILISTIC Without a reliable test method you have no test method.

ASTM F2338-05 Vacuum Decay Medical Device

P, mbar dp, Pa ASTM F2338-09 Vacuum Decay 1000 900 800 700 600 120 100 80 500 400 300 200 100 60 40 20 0 0 1 2 3 4 5 6 7 8 9 10 Time, sec 0

dp, Pa Vacuum Decay for Non-Porous Packaging ASTM F2338-09 80 70 60 50 40 30 20 10 0 0.00cc/min 0.85cc/min 0.50cc/min Simulated Leak Rate

ASTM F2338-05 for Tyvek Package Leak Testing

Tyvek Tray Test Results Vacuum Level, mb 127 cc/min 536.2 87 cc/min 49 cc/min 22 cc/min 527.9 519.8 515.5 (1.5)* 100 Micron Wire 75 Micron Wire Good 509.7 (3.3)* 531.3 539.7 (3.8)* 490.0 500.0 510.0 520.0 530.0 540.0 550.0 Differential Pressure, mb 127 cc/min 29.1 87 cc/min 22.2 49 cc/min 22 cc/min 11.6 15.5 (1.0)* 100 Micron Wire 75 Micron Wire Good 7.1 (2.2)* 25.2 (1.8)* 32.1 0.0 5.0 10.0 15.0 20.0 25.0 30.0 35.0 * 3 x Standard Deviation (99% Confidence Range)

Differential Pressure, Pa Pinhole vs. Channel Defect 800 700 75µ Pinhole ~44 sccm 600 75µ 20mm Channel ~6.4 sccm 500 400 75 micron 100 micron 300 200 Expon. (75 micron) Expon. (100 micron) 75µ 40mm Channel ~3.2 sccm 100 0 0 10 20 30 40 50 60 70 80 Capillary Length, mm

Micro Capillary

Large Format Tyvek Applications 80cm x 20cm

Large Tray Sensitivity 1000 950 Vacuum, mbar 900 850 800 750 700 650 Good Bad -5 5 15 25 35 Sample ID round1 round2 round3 1~30 - Normal good 31-100 um wire 32-150 um wire 33-200 um wire 34 - channel 35 - seal open on the corner

Differential Pressure, mb Pressure, mb Distinct Process Characterization 700 650 600 550 500 160 140 120 100 80 60 40 20 0 Absolute Vacuum 1 2 3 4 5 6 7 8 9 Sample Set Groups Differential Pressure 1 2 3 4 5 6 7 8 9 Sample Set Groups Round 1 Round 2 Round 1 Round 2 Incomplete seals Dot pattern Seal Inclusions Channel leaks Wrinkles Pinholes/Cracks in Tray

Porous Header Bag

Airborne Ultrasound Through Transmission ASTM F3004-13

Seal-Scan Technology

Airborne Ultrasound Seal Analysis Offline Seal Imaging Online Seal Inspection

C-Scan C-Scan Seal width profile Seal width profile L-Scan L-Scan Avg Min Max StD 33.1 27.7 41.2 1.9 Avg Min Max StD 1.7-80.5 10.0 8.0

Optimizing the Sealing Process Maximum and Minimum Signal Values at Different Temperature 100.0 80.0 60.0 40.0 20.0 Signal Value 0.0 100 110 120 130 140 150 160 170 180 190-20.0 Max Min -40.0-60.0-80.0 As the the temperature at which the seal is created increases, the maximum signal values are not affected. However, the minimum values experienced increase with higher temperatures, producing optimum seals at 160 and 180. -100.0 Temperature at Which Pouch is Sealed

Typical Seal Defects Good Seal Incomplete Seal Critical Incomplete Seal Critical Wrinkle/Inclusion Major Inclusion Minor

Sealer Integration

Positive Controls 100.0 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0.0.0 50.0 100.0 150.0 200.0 250.0

Positive Controls

Airborne Ultrasound Non-Destructive Seal Inspection Quantitative Materials Analysis Flexible and Semi-Rigid Packaging Seal Process Optimization On-line Defect Detection

5 Technologies VACUUM DECAY AIRBORNE ULTRASOUND DETERMINISTIC QUALITY FORCE DECAY HIGH VOLTAGE VOLUMETRIC IMAGING

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