Quality Control >> Packaging Testing >> Container Closure Integrity Testing

Container Closure Integrity Testing

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As the driving forces behind safety evaluation of materials and container closure systems in the U.S., the United States Pharmacopeia (USP) and Food and Drug Administration (FDA) enforce stringent testing requirements for container closure systems.

A critical step in understanding the biological safety and suitability of a container is the ability to characterize the materials and chemicals that have the potential to migrate through container closure system components and contaminate the drug product. Establishing a safe container closure system is as equally important as the contents of the container itself.

Why Choose Eurofins BioPharma Product Testing?

  • We have more than 15 years of experience developing  and executing methods for various container types.
  • We have completed hundreds of container closure  testing projects.
  • We provide quick turnaround time on method development  for dye ingress testing (in as little as two weeks).
  • We offer generic in-house procedures, as well as customized  approaches for microbial immersion testing.

Key Factors for Dye Ingress Testing

  • The type of product that is in the container will determine  the dye that will be selected.
  • The fill volume of the container will determine the  amount of dye added for controls.
  • If the product is lyophilized, the volume that it  will need to be reconstituted to determine the dye  amount added for controls.
  • The type of container closure being tested to determine  vacuum pressure ranges and total volume  required for submerging of the containers.
  • The type of dye selected for the tests must exhibit a  strong absorbance over a region of wavelengths and  must also be compatible with the sample matrix.  Most dyes are prepared in water, although adjustments  to the dye penetration can be made during the  development process. Brilliant Green and Methylene  Blue are two dyes that we consistently use.

Key Factors for Microbial Immersion Testing

  • The type and size of the container will determine the  immersion approach.
  • The media fill can determine if dye ingress is more  appropriate than microbial immersion.
  • The challenge organism selection can be influenced  by client preference or product formulation.
  • Immersion conditions under vacuum or static are  determined by container type or delivery system.

Key Factors for Microbial Aerosol Challenge Testing

  • The type and size of the container will determine  the size and internal volume of the air-tight testchamber and the Bacillus spores aerosolization  system and design.
  • The media fill can determine a customizer appropriate  worst case scenario approach.
  • The Bacillus spp. Selection, the aerosol density  and the exposure time can be influenced by client  preference
  • Bacillus spores aerosol exposure conditions are  controlled via a thermostated spore delivery  system at 60°C in order to maintain spores dry but  viable.
  • Temperature and RH are monitored in the test  chamber and microbial challenge controls are  performed.
  • An engineering run is always preliminary performed  and the system is fully validated before proceeding  with the main study.

Dye Ingress Methods

In order to develop the best method for your container closure project, we begin by determining whether the approach should be validated or non-validated (or qualified). Qualifications are not performed under protocol unless requested, but must prove the method to be scientifically sound. Typically, information-gathering studies or bulk-product studies do not require validation of the method, and therefore, qualifications are used. This non-validated approach is also used for any drug product prior to Phase II. Once a product reaches Phase II, we recommend the validation approach, which can involve one of two techniques-visual or UV.

Visual vs. UV Dye Ingress Technique


Microbial Immersion Methods

Generic in-house methods are available and may be customized based on individual testing requirements.

Microbial Immersion Techniques


Microbial Aerosol Challenge Methods

Generic in-house methods are available and may be customized based on individual testing requirements.

Microbial Aerosol Challenge Techniques