Doug Hostetler

Principal SME, Medimop/SA

February 20, 2012

Testing for Container Closure Integrity Using Helium Leak Testing

Container closure integrity is defined as the ability and quality of a container closure system to provide protection and maintain efficacy and sterility during the shelf life of a sterile drug product. The ability of rubber components to prevent microbial ingress of parenteral containers can be measured by seal integrity.

In practice, there are numerous types of container closure integrity methods that are available with varying sensitivities. West Analytical Services offers as part of our standard capabilities a validated Helium Leak Test Method that is state of the art in addition to other traditional methods that have been used by the industry for many years.

Helium Leak Testing

The most sensitive seal integrity testing technique is the use of helium leak detection. This technique offers advantages over other conventional seal integrity test methods. West uses a Seal Integrity Monitoring System (SIMS™) for helium leak detection. The system is based on a helium mass spectrometer leak detector equipped with custom fixtures for the particular vial or parenteral container to be tested. The instrument is calibrated against a NIST-traceable standard leak and measures the rate of helium leak from the vial/container as well as the actual percent of helium that is filled within the vial/container. Various types of containers including vials, syringe systems, cartridges and blister packs can be evaluated.

By using the tracer helium gas technique, the leakages could be determined quantitatively. Published research [see Kirsch, et. al., PDA J. Pharm. Sci. & Tech., Vol. 51, pp. 195-207 (1997)] has demonstrated that a helium leak rate greater than 10-6 cc/sec can be considered a failure for closure integrity. Helium leak rates lower than 10-6 cc/sec have been associated with acceptable microbial challenge results. For sensitivity comparison, conventional seal integrity methods (i.e. dye leakage) have leak rates of 10-3 cc/sec.

Recommended Applications:

  •    General container closure integrity testing
  •    Seal integrity monitoring during stability studies
  •    Closure formulation/configuration selection
  •    Sealing machinery optimization/validation
  •    Prediction of shelf life seal integrity through use of proprietary software
  •    Identifying the source of leaks using the “sniffer mode”

Traditional Methods

West Analytical Services provide other traditional seal integrity test methods that are widely accepted by the industry and are routinely used by clients for research and development studies, problem solving and to generate baseline data. Options available for client testing include:

  •     Vacuum Decay by PTI Micro Leak Detection
  •     Determination of the amount of vacuum within a sealed vial – Lighthouse Capability
  •     Determination of sealability of rubber closures – Methylene Blue Dye
  •     Residual Seal Force