An Overview of Package and Seal Integrity Testing

1. An Overview of Package and Seal Integrity Testing Darrell R. Morrow, PhD Leak Detection Associates, Inc. Blackwood, New Jersey

2. Package/Seal Integrity TestingVia Helium Leak Detection Methods HELIUM LEAK DETECTION � A Well-Established, �Old� Technology Many Industries, Such As Automotive, Electronic & Aerospace, Have Employed Helium Leak Detection For Many Years. The Primary Focus For These Applications Has Been The Integrity Of Sealed Mechanical Systems; For Example, Brake Line Seals & O-Ring Seals.

3. Package/Seal Integrity TestingVia Helium Leak Detection Methods SEAL INTEGRITY MONITORING OF �CONSUMER� PACKAGING � A Validated, �New� Application. Some Pharmaceutical & Medical Device Companies Have Been Employing Integrated Seal Integrity Monitoring Systems For Up To Seven (7) Years. As An �End-Use Performance Test�, These New Applications Have Been Extended To Include: Design & Development Stability Pack-Out Verification Clinical Trial Pack-Out Verification Tooling Validation Process Validation

4. Gas/Vapor Barrier Requirements Gas and vapor transport can occur via permeation or leakage. The total rate of gas/vapor transport is determined by the total number of holes; regardless of size. Individual gross leaks, due to their size, are readily detectable by most leak test methods. Gross �leaks� due to a multitude of �fine� leaks are not readily detectable by most leak test methods.

5. Sterility/Microbial Barrier Issues Microbial transport can occur only via leakage. The total rate of microbial transport is determined by the total number of holes with dimensions > the minimum. Leaks corresponding to the minimum size needed to block aqueous-borne microbes are not readily detectable by most leak test methods [single �hole� leak rate < ~1E-6 cc-atm/sec.].

6. Leak Detection Test MethodsComparative Sensitivities

7. Pharmaceutical/Device Industry Needs Verify quality of seals and (overall) packaging for stability pack-out samples. Insure integrity of seals and (overall) packages for clinical trials and production run product. Insure medication shelf life.

8. Helium Leak Testing: Vacuum Mode Packages containing helium can be checked for gross, fine and ultra-fine leaks using a vacuum chamber attached to a helium leak detector [�Hard� Vacuum Method]. The range of Helium leak rates detectable spans from low sensitivity (gross leak) values - E-1 - E-4 cc-atm/sec - to medium sensitivity (fine leak) values - E-5 - E-7 cc-atm/sec - to high sensitivity (ultra-fine leak) values - E-8 - E-10 cc-atm/sec.

9. Gas/Vapor/Microbial Sensitive Products Active Ingredient Products (Gas/Vapor) A product�s micro-environment must be protected against gas/vapor loss or gain, as needed. The barrier performance (integrity) of the package combined with external environmental conditions determine a product�s shelf life. Sterile Products The package�s integrity controls microbial ingress of the package and resultant loss of product sterility.

10. LDA Sims 1282+ Unit

11. Helium Leak Testing Packaging Using a SIMS Unit Procedure Helium is flooded at the point of the packaging machine/line process immediately prior to sealing the blister/pouch/card/vial. Helium is, thereby, captured in the head space of the blister/pouch/card/vial.

12. Helium Leak Testing Packaging Using a SIMS Unit Test Method Filled/sealed blisters/pouches/cards/vials are taken from the production line. Each sample is placed inside a VTFM chamber connected to the integrated helium leak detection system (SIMS 1282+). The VTFM chamber encapsulates the entire package ensuring that any He molecules escaping from the package are captured by the sensor.

13. Helium Leak Testing Packaging Using a SIMS Unit Results The leak detector is connected to a computer (integrated into the system). The true leak rate is calculated by the software taking into account the helium concentration inside each package; as measured by the HSAM. The test can be non-destructive, or destructive for the packages and the product, depending on materials & form

14. Advantages of He Leak Rate Methods and Instrumentation Measurement Quality A package-specific vacuum chamber allows the measurement of leak rates of test packages without vacuum-induced failures. The final result takes into account the helium concentration inside the package, thereby providing the actual leak rate (normalized to one atmosphere driving force) for comparison against a pre-set pass/fail (P/F) criterion; dictated by the product.

15. Advantages of Helium Leak Rate Methods and Instrumentation Measurement quality The helium concentration inside each test package is measured (quantified) via a fixture (HSAM) which measures the helium concentration with a calibrated probe. Gross leaks (>E-4 cc-atm/sec) are detected using pre-determined settings which identify spikes of helium during the test.

16. Advantages of He Leak Rate Methods and Instrumentation Measurement Quality/Sensitivity Empty (no Helium) packages are identified by the absence of any signal above background due to a lack of helium in the package. Fine (& Ultra-Fine) leaks (<E-5 to E-9 cc-atm/sec) are readily detectable using the Hard Vacuum Mode. When you require high quality seals and a high quality package, you need Helium leak detection technology & leak testing instrumentation.

17. The End � OF LOW SENSITIVITY PACKAGE INTEGRITY TESTSThe Beginning - OF HIGH SENSITIVITY PACKAGE INTEGRITY TESTS