The Path to Package Integrity

Transcription

1 The Path to Package Integrity

2 Outline Package integrity logic and thought process. Establishing quality standards. Evaluation of common methodologies. Alternative methodologies. Driving forward with package integrity solutions.

3 Package Integrity Package Integrity maintaining a sterile barrier. Package integrity is a subcategory of quality and is exclusive of: Peel Strength Burst Testing Visual Inspection Package Integrity Package Quality

4 Implications of Integrity Deviations Transfer of environmental contaminants. Release of critical ingredients/flavors. Synergistic effects of contaminants (O 2, H 2 O, Bacteria). Defects that will progress to leakage.

5 How to discuss integrity? What is important to your customer? What is important to the product? What is Important to the package? Integrity can be defined. Level of assurance is open to discussion.

6 Six Sigma Framework DMAIC Define Measure Analyze Improve Control

7 Foundation of Quality 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.

8 Determining Critical to Quality Baseline Package validation via ISO Package validation should include CTQ defect studies respective of the product. Desiccant weight gain Flavor evaluation Product performance What level of defect will deteriorate my product?

9 Microbes & Target Leak Sizes Wolf, et al, PDA J Pharma Sci & Technol 2009, 63, Kirsch, et al, PDA J Pharm Sci & Technol 1997, 51, 5, p. 200

10 Characterizing Defects Pinholes Flex Cracks Channel Defects <3mm Incomplete Seal >3mm Wolf, et al, PDA J Pharma Sci & Technol 2009, 63, Torturous path of channel defects. Pinhole is not equal to a channel defect

11 Flow Rate is the Critical Parameter Leak Size (microns) Flow Rate (ccm) Wolf, et al, PDA J Pharma Sci & Technol 2009, 63,

12 Pinhole vs. Channel Defect µ Pinhole ~44 sccm Differential Pressure, Pa micron 100 micron Expon. (75 micron) Expon. (100 micron) 75µ 20mm Channel ~6.4 sccm 75µ 40mm Channel ~3.2 sccm Capillary Length, mm

13 Common Approaches to Defining Package Integrity Looks good Capability (Best Available Technology) Equal to/better than Third Party White Papers Grandfathered Industry Standards Critical, Major, Minor

14 Industry Codification Visually O.K. Visually Defective No Physical Leak/ No Contamination Major Minor Physical Leak/ Contamination Critical Critical

15 The Ideal Test Method Informative Accurate Simple Cost Effective Reduces Waste Increases Productivity

16 Navigating Regulation FDA recognizes methodology. Manufacturers must prove validated methodology consistent with product requirements for label claims. Methods listed by organizations (ASTM, ISO, USP) are only guidance's. Listed methodologies: Capabilities are irrespective of package/product requirements. Capabilities vary based on package a product characteristics.

17 Direct Measures of Quality ISO Annex B Vacuum Decay (ASTM F2338) Seal Strength (ASTM F88) Airborne Ultrasound Seal Inspection* Visual Inspection (ASTM F1886) Dye Migration (F1929) High Voltage Leak Detection* Burst Strength (ASTM F2054) Bubble Immersion (ASTM F2096, D3078) * Not listed in ISO or ASTM

18 Test Method Cost ASTM F Water Bath Flexible Barrier Systems Moisture/Flavor critical defect size 15 microns Green Coffee Wholesale Prices Water bath sensitive to microns Typically test 20 pouches/line/hour cents/lb Current market price of coffee > $2.00/lb 0 Jan 09 Apr 09 Jul 09 Oct 09 Jan 10 Apr 10 Jul 10 Oct 10 Jan 11 Apr 11 Jul 11 Bags Tested 1lb Bags $/lb Hours, Days, Weeks Up Time 20 x 1 x $2 x 24 x 7 x 52 x 0.5 = $174,720

19 Cost of Deploying Destructive Methods Product Dry Fill Soup Mix Effervescent Tablets Coffee Singles Pod Luer Lok Syringe Pharma Blister Pack Cost of Raw Materials Quantity Tested Frequency $ Every 30 min. $ Every 30 min. Cost/8 Hour Shift $29.44 $14,720 $51.20 $25,600 $ Every Hour $96 $48,000 $ Every 30 min. $ Every 30 min. $160 $80,000 $ $89,600 Cost/Year (2 Shifts, 250 Days)

20 Test Method Effectivity ASTM F1886 Channel leaks down to 75 μm [0.003 in.] with a % probability 1. 80% 80% 80% 80% Assumptions 1,000 Packs/Day 1% Defect Rate 10 Defects/Day ~2,500 Defects Per Year 80% POD (Above Average) Probability of Detection Time on Task, min Drury & Watson, % Inspection = 500 Defects/Year 200% Inspection = 100 Defects/Year 400% Inspection (4 Operators) 4 Undetected Defects/Year 0.16% probability that a defect will go undetected. 1

21 Cost of Slow Information 0 2 Head Space Analysis. 6 day dwell. 3% pass/fail limit. 50 micron defect 700 gr. dry fill pouch. O 2 shifted from ~1% to ~2.5%. ppm Up Time Minutes, Hours, Days Units 60 x.5 x 60 x 24 x 6 = 259,200 ASTM F sc.edu $4.41/kg kg/unit Cost/kg 259,200 x.7 x $4.41 = $800,150

22 Consider Alternative Methods Non Destructive vs. Destructive Quantitative vs. Attribute Non Subjective vs. Operator Dependent Calibration Capability Validation Effectiveness Simple Methodology (no sample prep)

23 Direct Measures of Quality ISO Annex B Vacuum Decay (ASTM F2338) Seal Strength (ASTM F88) Airborne Ultrasound Seal Inspection* Visual Inspection (ASTM F1886) Dye Migration (F1929) High Voltage Leak Detection* Burst Strength (ASTM F2054) Bubble Immersion (ASTM F2096, D3078) * Not listed in ISO or ASTM

24 Non Subjective, Quantitative Vacuum Decay (ASTM F2338) Seal Strength (ASTM F88) Airborne Ultrasound Seal Inspection High Voltage Leak Detection Burst Strength (ASTM F2054)

25 Non Destructive Vacuum Decay (ASTM F2338) Airborne Ultrasound Seal Inspection High Voltage Leak Detection

26 Vacuum Decay Leak Testing

27 Vacuum Decay Test Method ASTM F Vacuum Level Below Atmospheric Pressure, mb Differential Pressure, Pa/sec (Secondary Transducer) Test Cycle Test Cycle Pass Test Cycle Fail dp Pass dp Fail

28 Vacuum Decay for Flexible Packaging ASTM F TEST PARAMETERS TStroke 1.50 TEqual Vac TTest 5.00 Vacuum, mb dp/dt, Pa/s TFill, s 600 Ref Test # Vacuum, mb 400dP/dt, Pa/s Pass/Fail 15 Comments P Good Product P Good Product P Good Product P Good Product P Good Product F 25 micron Test Cycle F 25 micron F 15 micron F 15 micron F 10 micron F 10 micron Vacuum Level Below Atmospheric Pressure, mb Differential Pressure, Pa/sec (Secondary Transducer) Test Cycle Pass Test Cycle Fail dp Pass dp Fail

29 Micro Leak Detection Diff dp, Pa Avg dp Upper 99% Limit Lower 99% Limit (3.4 μm) 0.5 (7.5 μm) Leak Rate cc/min

30 Vacuum Decay Application Flexible/Rigid Barrier Air/Liquid Contents No Sample Preparation Quantitative and Repeatable Test Data Non Subjective Zero Waste

31 Airborne Ultrasound Through Transmission

32 Ultrasonic Signal Propagate through single or multiple layers of well bonded materials. Reflection/absorption of sound waves by multiple layers.

33 Analysis of Ultrasonic Sealing Power Setting (Joules) Side Seal (Heat Seal) Side Seal (Heat Seal) C scan Image Average Signal

34 Controlled Seal Quality Avg, % Power (Joules)

35 Seal Scan Online Pouch Seal Inspection

36 Integrated Solution

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

38 High Voltage Leak Detection (HVLD)

39 HVLD Defect Detection for Pouches Micro leaks down to 5 microns Pinholes Cracks Crystallized leaks Channel defects

40 HVLD Technology High voltage applied to container Ideally non conductive materials Liquid triggers conductivity spike

41 HVLD Detection

42 HVLD Application Quantitative High Speed Inspection Non porous, Non conductive Materials Package Contents: liquid products protein based liquids suspensions or emulsions Flexible or Rigid Barrier

43 When to Develop Methodology Should begin at the point of package development. Phase III Pharma Development. New production line engineering. When the method in place has failed. Packaging that is immune to test methodology plagues the industry.

44 Pitfalls Mixing methods and test requirements. Taking test method standards as law and not guidance. Taking white papers as applied fact to specific applications. Process improvements are vulnerable to validation hurdles. Patching the problem, not developing a solution.

45 What s ahead? PDA s TR27 Moving to quantitative test methodology. Track & Trace Connecting non destructive test results with specific units. Green Initiatives Eliminating line waste with nondestructive methods. CTQ defect stability package validation. Automated SPC testing.

46 Package Integrity Package Integrity maintaining a sterile barrier. Package integrity is a subcategory of quality and is exclusive of: Peel Strength Burst Testing Visual Inspection Package Integrity Package Quality

47 Foundation of Quality 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.

48 Thank You! Oliver Stauffer

49 Simple Cases in Testing Some products are moisture sensitive, but contents are marginally affected by leaks. Detection to the moisture level may be over kill. Some product have desiccants to keep them dry, but real concern may be mold or bacteria. Common methods may not cut it. Some production processes have high incidence of random catastrophic defects. Statistical Process Control (SPC) will not meet quality needs.

50 Quantitative Measures Provide Greater Access to Statistical Tools Ultrasonic Attenuation Thickness Peel Strength Permeation Leak Rate Attribute data fails to produce predictive measures of quality.