1. Autotest – Calibrated Leak

2. Leakages Detection Validation
The required Leak Rate Specification is set…
…the Leak Testing Machine must comply with it
Challenge Test set-up:
Conforming Packages
Non Conforming Packages with potential defects:
External leak: Calibrated tubular capillaries
Calibrated wires between sealed parts
Laser drilled holes
Calibrated Leak (Autotest)

3. Autotest: Key Objectives & Benefits
“Autotest” function is:
Reliable
Repeatable
Not Operator Subjective
Quick in delivering results
Fully Automated
Automatically controlled by System for proper functioning
Compliant with Regulatory Agencies standards & requirements

4. Autotest: Function with BFS/FFS
All Test Chambers are provided with Calibrated Leaks
Simulation of a preset leak rate
Autotest generates a controlled Vacuum Decay in Test Chamber

5. Calibrated Leaks & Tubular Capillaries
Calibrated Leaks are implemented according to an approved QMS procedure
Objectives:
Verify Machine detection sensitivity
Recipes setting
Validation

6. Preparation by using Capillaries (1)
Sizing: use the Bonfiglioli Software tool “Flow-Rate & Hole-Diameter Calculator” (2 available Methods)
Flow Rate
Determine the leak value (in std cc/min) with reference to the required test pressure value
Hole Size
Determine the theoretical hole diameter (in micrometers) with reference to the required test pressure value

7. Preparation by using Capillaries (2)
Selection from Calibrated Tubular Capillaries Kit Set having known internal diameter
Look for the Capillary mechanical features (diameter and length) reporting the Design of Experiment data inherent to already manufactured leakers (look for the pressure and leak values equivalent to the reference ones)

8. Preparation by using Capillaries (3)
Capillary calibrated cut off
Installation of the Capillary Tube within the threaded fitting
Flow Rate Verification with Calibrated Flow-Meter
Calibrated Leak ready to be installed 3 4 5 6

9. Flow-Meter Calibration Certificate
Calibration Certificate is:
Taken as a reference for Flow-Meter relevance
Attached to Validation Package for qualification traceability
The following main data are reported:
Designation, Model, Series, Type
Serial Number
Test Pressure and Flow Rate Range
Calibration Method, Procedure, Condition
Calibration record and data
Date of Issue and Validity of calibration status

10. Calibrated Leaks Calibration Certificate
Calibration Certificate is issued and attached to Validation Package for qualification traceability
The following main data are reported:
Progressive identification code
Theoretical Flow Rate value
Measured Flow Rate value
Test Pressure value
Temperature
Theoretical Hole size referred to Flow Rate
Installation on Machine data

11. Calibrated Leak Periodic Verification
GMP Manuals:
How to maintain Calibration status
Routine verification
Control System expected outcomes

12. Validation Package Planned FAT / SAT Tests
Check consistency of Machine Recipe Parameters
Check the Machine capability to detect simulated Non Conforming outcomes by means of Calibrated Leaks activation

13. Validation Package Planned IQ Tests (1)
Installation Verification
Objective:
Check that each of the available Calibrated Leaks was correctly installed onto Machine
Verify installation status for each Test Chamber
Verify that calibration certificate is available and complete with all required data

14. Validation Package Planned IQ Tests (2)
Hardware Verification
Objective:
Check that each of the installed Calibrated Leaks is still in proper calibration status
Qualify that required Flow Rate is compliant with relevant specifications
Ensure that they can be used for routine verification of Machine Measurement System detection capability

15. Validation Package Planned OQ Tests (1)
Functional Verification
Objective:
Check that pneumatic actuators that are managing Calibrated Leaks activation are fully operational
Verify Control System behaviour in case that a functioning failure is detected with Autodiagnostics tool enabled

16. Validation Package Planned OQ Tests (2)
Functional Verification
Objective:
Check that installed Calibrated Leaks are fully operational
Verify Control System behaviour in case that a functioning failure is detected during Machine run-time

17. Validation Package Planned OQ Tests (3)
Characterization
Calibrated Leaks are used to determine Recipe Configuration
HMI System records raw data and provides proper Recipe Settings
All Data are stored in compliance with FDA 21 CFR Part 11

18. Focus: How to Set Threshold (1)
Perform N Tests on Conforming Packs and calculate statistics for Delta “Δ”:
with disabled Autotest (“Good”)
with enabled Autotest (“Leak”)
Consider number of samples N adequate to confidence level
Apply the “Three Sigma Rule”
Hp: Gaussian distribution
Th: 99.7% of values lie within 3 standard deviations “σ” of the mean “µ”

19. Focus: How to Set Threshold (2)
Elaboration:
“Good”: µ + 3σ
“Leak”: µ - 3σ
Set the Threshold THR in the middle
“Leak”
THR
“Good”

20. Thank you!
Questions & Comments?