Autotest – Calibrated Leak

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)

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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

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”

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

Thank you! Questions & Comments?