Monday, 12 March 2018

Liquid Immersion Microbial Challenge Tests


The container closure system for pharmaceutical products intended to be sterile is critical and this criticality relates to the physical properties of the container closure system in that a poorly designed or manufactured system will result in microbiological penetration. Factors to take into account with, for example, rubber-stoppered glass vials include having the correct dimensional specifications for the internal diameter of the neck opening and its depth, the internal and external diameters of the flange. Other factors are the concentricity of the flange, the neck and the body of the vial. Any angularity of the flange versus the vertical center line of the vial must be specified; so must the physical finish of the surface of the flange and internal neck bore to ensure satisfactory mating with the closure. Closures must be specified in terms of diameters, depth, thickness and elasticity.
This is the basis of a new article by Tim Sandle.


Tests to verify the container-closure can be grouped as microbial tests or non-microbial (physical) tests. Physical tests include the dye test; vacuum testing (typically leak testing with sensitivity to detect leaks down to approximately 5-10 microns); gas leakage determined using a bubble test; liquid leakage detected by atomic absorption of a copper ion tracer solution; laser-based gas headspace analysis using a frequency modulation spectroscopy; high voltage leak detection (which detects package defects using an electrical current); or a helium leak rate test (which quantitates the flow rate of helium from leaks in packaging after having been flooded with helium as a tracer gas).

Where microbial tests are required, there are various factors to consider. These form the basis of the paper.

Then reference is:

Sandle, T. (2017) Liquid Immersion Microbial Challenge Tests: Microbial Testing for Container Closure Integrity, Journal of Validation Technology, 23 (6): 1-10 (see: http://www.ivtnetwork.com/article/liquid-immersion-microbial-challenge-tests-microbial-testing-container-closure-integrity)

Posted by Dr. Tim Sandle

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