Medical Devices >> Packaging and Seal integrity Testing >> Container Closure Integrity Testing

Container Closure Integrity Testing

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Pharmaceutical products are formulated in various forms: from liquid to solid and frozen forms and also lyophilized. Formulated drugs are filled and stored in a variety of container closure systems, made from glass, plastic and metal, and including blisters, bottles, vials, ampules, syringes and cartridges.

The United States Pharmacopeia (USP) and Food and Drug Administration (FDA) are the main driving forces to assess and to regulate the safety of materials and container closure systems1. The container closure systems should provide an integral barrier that protects stability and sterility of the drug product during the shelf-life against microorganisms, reactive gases and moisture2. Container Closure Integrity Testing (CCIT) is a test which evaluates the appropriateness of the container closure systems for product safety.

Eurofins PROXY Laboratories provides a state of the art method for CCIT, verifying the safety of your container closure system to meet the regulatory guidelines. Since we are part of an international network of laboratories and testing units with global reach, we can assist you to determine the best CCIT method in order to meet the needs of your project.

Why Choose Eurofins BioPharma Product Testing Netherlands

  • We have more than 15 years of experience developing and executing methods for various container types
  • We provide short turnaround times
  • We offer generic in-house procedures, as well as customized approaches
  • We offer a single point of contact within our organization

Techniques for Container Closure Integrity Testing (CCIT)

Based on the drug formulation (e.g. liquid or lyophilized) and the type of the container (e.g. bottle, vial, ampule and syringe etc.) various methods can be employed to perform the container closure integrity testing. In general methods can be divided in two groups: Probabilistic – Destructive and Deterministic – Non-destructive methods.

Non-destructive and deterministic tests:

  • Headspace (both Qualitative and Quantitative)
  • Vacuum/Pressure Decay (Qualitative, Quantitative feasible)
  • Mass Extraction (Quantitative)
  • High Voltage Leak Detection (HVLD) (Qualitative, Quantitative feasible) offered by Eurofins PROXY Laboratories
  • Helium Leak Detection (both Qualitative and Quantitative)
  • Optical Emission Spectroscopy (Quantitative)

Destructive and probabilistic tests:

  • Dye ingress (Qualitative only) offered by Eurofins PROXY Laboratories & Eurofins MicroSafe Laboratories
  • Microbial Ingress (Qualitative only) offered by Eurofins Bactimm

High Voltage Leak Detection (using E-Scan 655 MicroCurrent High Voltage Leak Detector) is currently available at Eurofins PROXY Laboratories. In  this technology leakage due to the package defects are detected employing high electrical voltage to the intact test article. Therefore, the HVLD technology is applicable to perform CCI testing on liquid-filled parenteral drug product containers, prefilled syringes, vials and ampules where the packaging is less conductive than the liquid inside. The advantages of this system are as follows:

  • Listed in USP Chapter <1207> for parenteral liquid package testing
  • Non-destructive, non-invasive and deterministic method
  • High level of repeatability and accuracy
  • 2-5 mm size leak detection
  • Applicable to high-concentration proteinaceous products
  • Also effective for low conductive liquid containing samples (e.g. WFI)
  • Low voltage exposure to the product and environment (with negligible ozone formation)
  • Fast and simple for 100% visual inspection and validation process?

In addition to the HVLD technology we also offer Dye Immersion and Microbial Challenge by Immersion (both Probabilistic tests) which have been used as leading methods for CCIT until recently. These tests are destructive to the samples under test, and typically require a significant number of units for method development and validation. The overview of other Deterministic, non-destructive technologies are presented in below table. These technologies are available within EBPT (Eurofins Lancaster).

Technology

Instrumentation

Description

Best Applications

Helium Leak Detection

 

Helium Mass Spectrometer - Tracer Gas Detection, Vacuum Mode

- The flow rate of helium from leaks in packaging is quantitatively determined after having been flooded with helium as a tracer gas.

- In the presence of defect, the helium is drawn out of the packaging through the defect by vacuum and detected using a mass spectrometer.

- This method is the most sensitive offering to detect 0.2 mm defects

This technology is suitable for package development to verify whether the package type is convenient for the type of drug, as well as routine testing and stability of various package types.

Vacuum Decay

 

VeriPac 455-M5 Vacuum Decay

- Leaks are measured via vacuum decay based upon ASTM F2338.

- Very sensitive to determine the leaks down to approximately 5-10 microns.

- It is non-destructive thus the stability testing can be performed on the same sample.

This technology is non-destructive and suitable for leak testing on syringes, vials, and pouches both before and during stability studies.

Pressure Decay

 

TM Electronics BT Integra Burst, Creep and Leak Tester

Measures leaks by pressure decay based upon ASTM F2095.

This technology offers both seal strength and package integrity testing for flexible packaging (e.g. bags and pouches)

Oxygen Headspace

 

FMS-760 Oxygen Headspace Analyzer

- Frequency Modulation Spectroscopy (FMS) is employed to detect oxygen in the headspace of transparent rigid containers.

- The decrease or increase in the oxygen levels in the container’s headspace is measured to detect a potential leak.

- The rate of oxygen permeation into a sealed container can also be determined.

This methodis non-destructive to the sample under test and convenient to perform leak testing of parenteral containers both before and during stability studies.

 

Container Closure Integrity Testing (CCIT) Standards

  • Food and Drug Administration (FDA)
  • United States Pharmacopeia (USP)
  • ICH Q2 (R1): Validation of Analytical procedures

Eurofins PROXY Laboratories can help you determine which method is best for your project needs. Feel free to contact us.

References

  1. USP<1207> Sterile Product Packaging – Integrity Evaluation
  2. Ewan, S. et al. 2015. “White Paper: Container Closure Integrity Control versus Integrity Testing during Routine Manufacturing”. PDA Journal of Pharmaceutical Science and Technology.