FlexAct BT (Bag Tester) Validation November, 2015

Transcription

1 FlexAct BT (Bag Tester) Validation November, 2015

2 Agenda 1 Validation Approach and Method 2 Development Case Study 3 Materials

3 Scope of the Validation Point-of-use leak test for Flexboy 2D bags from 50mL to 50L Pressure decay leak test method with Sartocheck 4 plus Bag tester Constrained plate test method and porous spacers with FlexAct BT Safe, Fast & Easy, Reliable and Easy-to-Validate leak test system at customer production facility to enhance assurance of Single-use Container Closure Integrity

4 Objective of the Validation A reliable test method using samples from multiple production lots and 700 tests. A reproducible and accurate test method using restraining plates, which allows small inflation volume and high test pressure. A sensitive test method using 30µm hole calibrated film samples and applying a 6 sigma confidence interval for the differentiation between defective and non-defective samples An easy-to-validate test method with single set of test parameters and test specifications across Flexboy 2D bags from 50mL to 50L.

5 Validation Approach A two-phase validation approach using the pressure decay test method - Method development: Test parameter study - Method validation: Statistically based validation study Phase 1: Determination of the optimum test parameters Phase 2: Validation of the test parameters and specifications using a large number of test samples

6 Pressure Decay Test Method Derived from ASTM F : Standard Leak Test for Pressure Decay Leak Test for Nonporous Flexible Packages with and without Restraining Plates Compatible with a 100% leak test at customer production facility Test procedure: - Pressurization of the bag at the set test pressure - Stabilization of the test pressure to compensate for thermal effect - Measurement of the pressure decay over the test time - Comparison of the pressure decay to a maximum allowable pressure decay specification

7 Agenda 1 Validation Approach and Method 2 Development Case Study 3 Materials

8 Definition of Target Hole Size Confirmation of Defect Test Parameter Study Validation Target hole size for point of use leak test based on : Good understanding of the leak failure modes with 20 years and >20 million bags produced Risk assessment on potential defect size occurring during transport, handling and storage (complaint history) Preliminary study Smallest acupuncture needle is 100 µm 30 µm selected as target hole size : - Across Flexboy 2D range from 50mL to 50L - Below visual detection limit 8

9 Definition of Target Hole Size Confirmation of Defects Test Parameter Study Validation Confirmation of defects: Circular sheet of film sample Laser drilled calibrated hole 30µm hole in 300µm thick film Confirmation of hole size via flow measurement Each defect confirmed before, during and after use 9

10 Definition of Target Hole Size Confirmation of Defect Test Parameter Study Validation Phase 1 of validation approach Target hole size fixed at 30µm Test pressure fixed at 300 mbar maximum pressure for constrained bags Target of the parameter study: Determine optimum stabilization time Determine optimum test time 10

11 Definition of Target Hole Size Confirmation of Defect Test Parameter Study Validation Each test run tested at four stabilization times: 60, 120, 180 and 240 seconds Pressure drops continuously measured (every second) across the entire test time period (240 seconds) 10 Flexboy 2D bag volume tested with 3 defective and 3 non-defective film samples: 60 tests x 240 measurements = 14,400 data points 11

12 Definition of Target Hole Size Confirmation of Defect Test Parameter Study Validation Test Parameter Study: Clear split-up between defective and non-defective test samples with a 6 sigma confidence interval Additional safety margin with longer stabilization and test times: - Decrease data scatter - Improve reliability - Increase gap between defective and non-defective Selected test parameters at - Avoid false positive or false negative results under real 240 seconds stabilization and 180 seconds test times testing conditions 12

13 Definition of Target Hole Size Confirmation of Defect Test Parameter Study Validation Phase 2 of validation approach Target hole size detection fixed at 30µm Test pressure fixed at 300 mbar Target of the parameter study: Verification of selected test parameters using a statistically significant number of samples Determine maximum allowable pressure drop 13

14 Definition of Target Hole Size Confirmation of Defect Test Parameter Study Validation Stabilization time fixed at 240 seconds Test time fixed at 180 seconds Pressure drops continuously measured (every second) across the entire test time period (180 seconds) 10 Flexboy 2D bag volume tested with 32 defective and 32 non-defective film samples 640 tests x 180 measurements = 115,200 data points 14

15 Definition of Target Hole Size Confirmation of Defect Test Parameter Study Validation +3 Sigma Pressure decay validated at 3,1 mbar at the optimum test parameters and specifications +3 Sigma -3 Sigma mean value A 6 sigma confidence interval on the maximum pressure drop value for the non-defective test samples and the minimum pressure drop value for the 50L defective test sample Pressure Decay validated at 3.1 mbar

16 Definition of Target Hole Size Confirmation of Defect Test Parameter Study Validation Validation Results: 30µm detection limit 300 mbar test pressure 240 seconds stabilization time 180 seconds test time 7 minute total test time 3.1mbar maximum allowable pressure drop 6 Sigma confidence interval Flexboy 2D bag range from 50mL to 50L 16

17 Agenda 1 Validation Approach and Method 2 Development Case Study 3 Materials

18 FlexAct BT Bag Tester (1/2) Test methodology is pressure decay within restraining plates and porous spacers Porous spacers avoid masking effect of potential leaks Restraining plates reduce stress on bag, provide a small inflation volume and allow high test pressure: 300 mbar The combination of the small volume, high test pressure and spacers provides a reproducible, accurate and sensitive test in 7 min total test time FlexAct BT Sartocheck 4 Plus Bag tester

19 Restraining Plate Flexboy Restraining Plate FlexAct BT Bag Tester (2/2) FlexAct BT with Sartocheck 4 plus Bag tester & MultiUnit Inside Filter holder Restraining plates Weight: 375kg (826 lbs) Porous spacer

20 Sartocheck 4 plus Bag tester Bags require low test pressure with high accuracy: 600 mbar pressure sensor Faster pressure increase for STR: bigger inner diameter valves Temp. sensitive measurement: Ext. T sensor checking stable conditions

21 Flexboy 2D Bag Design: Scope of the validation The validation is performed on a given design rule for bags from 50mL to 50L Finished custom or standard bags are not part of the validation (can be ordered as a Service) A B C D C IN A: Sampling line B: Draining line C: Filling line D: Filter test line with Midisart BV sterilizing vent filter Final connection Final connection scope of the validation for the 30µm leak detection

22 Flexboy 2D Bag Design : Filter Test Line Clear C-FLEX 1/4 x 3/8-300mm Tri Clamp SSB 1/4 Midisart BV Sterilizing vent filter Tube Si Tuflux 1/4 x 7/16-100mm

23 Conclusion The development and validation method approach allowed to establish reliable and robust test parameters and specifications with a statistically significant number of tests (700 tests) and the application of a 6 sigma confidence interval for critical parameters The 30µm detection limit is a science and risk based approach combining 20- year experience of 2D bag leak testing and understanding of failures modes both at supplier and at end-user. This strong validation method allows to validate other test parameters by varying the volume and / or the test time. It can reasonably be concluded that a smaller leak size, down to 15µm, could be detected with FlexAct BT.

24 Thank you for your attention Any questions?