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Container Closure Integrity Test Using Frequency Modulation Spectroscopy Headspace Analysis with Carbon Dioxide as a

Allison Alix Caudill1, Ken Victor2, Michael Timmins2

  • 1Lighthouse Instruments, LLC., Charlottesville, VA 22902, USA acaudill@lighthouseinstruments.com.

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|October 17, 2020
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Summary
This summary is machine-generated.

A new, non-destructive method using carbon dioxide gas reliably detects small defects in pharmaceutical container closure integrity (CCI). This fast, sensitive test ensures product sterility and stability throughout the lifecycle.

Keywords:
Blue dye ingress testContainer closure integrityFrequency modulation spectroscopyHeadspace gas analysisLaser-drilled defectsMicrobial ingress testMicrowiresUSP <1207>

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Area of Science:

  • Pharmaceutical Science
  • Analytical Chemistry
  • Materials Science

Background:

  • Maintaining pharmaceutical container closure integrity (CCI) is critical for product sterility and stability, as mandated by USP <1207>.
  • Existing CCI testing methods are often time-consuming, destructive, and lack sufficient sensitivity for detecting minute defects.
  • There is a need for advanced, non-destructive CCI testing technologies that are both rapid and highly sensitive.

Purpose of the Study:

  • To present a novel, rapid, and non-destructive method for assessing container closure integrity (CCI).
  • To evaluate the sensitivity of a carbon dioxide headspace analysis method for detecting various defect types and sizes in pharmaceutical vials.
  • To demonstrate the applicability of this method across different vial types and headspace compositions.

Main Methods:

  • A new CCI testing approach utilizing carbon dioxide as a tracer gas under effusive pressure conditions was developed.
  • Vials underwent pressure cycling (vacuum followed by carbon dioxide overpressure) within a sealed chamber.
  • Defect detection was performed using a tunable diode laser absorption spectroscopy (TDLAS) based FMS-Carbon Dioxide Headspace Analyzer, detecting leaks via increased headspace CO2 concentration (≥1 torr).

Main Results:

  • The method successfully detected laser-drilled defects as small as 2 µm in glass vial bodies.
  • It also identified tungsten wire defects (effective size ~2 µm) at the stopper-seal interface in empty vials.
  • In filled vials, defects of 5 µm (below liquid) and 6.1 µm (above liquid) were accurately detected, demonstrating effectiveness with product present.

Conclusions:

  • The developed carbon dioxide headspace analysis method offers a fast, non-destructive, and highly sensitive approach for pharmaceutical CCI testing.
  • This technique reliably detects critical defects, ensuring the integrity of pharmaceutical packaging.
  • The method's versatility makes it suitable for a wide range of pharmaceutical vials and headspace conditions.