White Paper

Container Closure Integrity Testing Of Intravenous Bags

Source: PTI Packaging and Inspection Systems

By Wen Chen Ph.D , and Oliver Stauffer, CEO

Container Closure Integrity (CCI) is defined as whether the container is maintaining a sterile barrier. Intravenous (IV) bags are crucial in delivering fluids or medication quickly. Leaking parenteral packages are considered an extremely high risk as they deliver fluid directly into the bloodstream and have a high potential for microbial growth, requiring the need for sensitive and reliable CCI testing.

VERIPAC VACUUM DECAY TECHNOLOGY

Vacuum Decay technology is one of ASTM Standards “Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method” (F2338-09). This technology is also a physical test method that is recommended by UPS 1207 and is an FDA consensus standard that can be used for CCI testing for high risk package applications with fast, repeatable and reliable test results that provide quantitative and deterministic quality assurance. This technology can be used on a wide variety of package formats, product classes and product combinations.

Packaging can be non-destructively evaluated using the VeriPac inspection method which is based on vacuum decay technology. PTI’s VeriPac vacuum decay technology is capable of detecting package leaks and invisible defects using a differential pressure transducer leak test system. The method is non-invasive, non-subjective and requires no sample preparation.

TESTING OF IV BAGS

Using VeriPac vacuum decay technology IV bags can effectively be evaluated. The VeriPac 455 leak detection system is connected to a manually operated test chamber containing the IV bag. The test method involves drawing vacuum on the IV bag in the test chamber and monitoring for any changes in vacuum level. If the package is defective, air or liquid will leak from the package into the chamber causing a change in pressure. Non leaking packages do not leak any pressure into the chamber holding the chamber vacuum level constant.

VeriPac vacuum decay technology for IV bags is conducted at deep vacuum. When liquid contents are present, a deep vacuum can be achieved vaporizing liquids that may be at the defect site. Positive controlled samples (leaks) are generated to test for leak sensitivity. For testing, a 15 micron barb fitting was inserted into the port of the IV bag to check for liquid leaks. 100 micron defects were generated to test for both liquid and gas leaks inside the package body. Finally, a microcalibrator flowmeter was also used to verify and calibrate results.

Positive controls were introduced to test for leak sensitivity and reliability. The VeriPac 455 is sensitive to the critical leak sizes and can detect them reliably and repeatably. Quantitative results for testing the IV bags show separation between negative control samples and positive control samples. A defect size of 15 microns can be detected with good separation from the mean of the negative samples; resulting in a signal to noise ratio (SNR)1 that is greater than 2.0 for both absolute mbar and differential Pa measurement. This level of SNR provides the highest level of quality control required of high risk applications.

1 Calculation for SNR is PC Result – Avg Neg. Control Result
                                          3x Std. Dev Neg. Control Result

CONCLUSION

Vacuum decay technology is suitable for detecting defects in liquid filled IV bags with a detection capability suitable for the level of risk. The non-destructive nature of this process provides greater understanding of the packages and reduces waste. The VeriPac system provides quantitative test data to ensure leak detection and reduce false positives. Regardless of defect location, the vacuum decay system can pick up both large and small defects. Each defect type was tested multiple times to determine defect detection capability. While specific tooling for the application is required, testing can be performed with ease. The cycle time for the IV bag testing is under 40 seconds and is sensitive and repeatable to 15 microns for both liquid and gas leaks. Depending on fill volume and package size smaller defects can be detected with confidence.

PTI Packaging and Inspection Systems