Container Closure Integrity Testing (CCIT) is an important component of quality control that measures whether container closure systems can provide an effective barrier toward contaminants which, for example, comprise microorganisms and some volatile reactive materials. This is critical in assuring the quality and safety of pharmaceutical, biological, and vaccine products during their shelf life.

Regulatory Guidelines for Container Closure Integrity

The integrity of the product CCIT is ensured by appropriate regulatory standards defined by:

It states the portion on validated closure techniques. Under this CCIT regulation, and for fusion-sealed vessels, especially ampoules, closure methods, and integrity checking tend to be more stringent and controlled.

  • USP <1207>: Sterile Product Packaging-Integrity Evaluation
  • USP <1207.1>: Package Integrity and Test Method Selection
  • USP <1207.2>: Package Integrity Leak Test Technologies
  • USP <1207.3>: Package Seal Quality Test Methods

21 CFR 211.94. Components of drug product containers and closures shall be non-reactive, non-additive, and non-absorptive on the product, thus preserving its integrity.

States the content of the examining criteria, test methods, and acceptance criteria for packaging materials.

Methods of CCIT

The methods for CCIT can be divided into broad two categories of primary and secondary approaches, with preference given to the accuracy and dependability of deterministic methods over probability ones.

Deterministic Methods (Preferred):

These methods are the preferred choice due to their accuracy and reliability.

Helium Leak Detection

This method uses helium leak detection (HLD) to track leaks in sealed containers using helium as a tracer gas. This test can detect leaks as small as 1 x 10⁻⁷ mbar L/s, making it highly sensitive.

Laser-based Headspace Analysis

This technique inspects the alterations in concentrations of gas within a box’s cavity and is crucial for products that are very sensitive to the amounts of carbon dioxide and oxygen

High-Voltage Leak Detection (HVLD)

This method is utilized for the identification of liquid leakage in non-porous packaging. HVLD is very efficient in discovering tiny cracks and holes in containers.

Ultrasonic Testing

This method is perfect for flexible and rigid containers made of non-porous material, as it employs sound waves to uncover defects in the package without directly interfering with the product.

Vacuum Decay Method

This method is a non-destructive technique that augmentatively uses a gas vacuum chamber. It aids the identification of leaks by measuring changes in pressure within the vacuum chamber and provides quantitative results.

Pressure Decay Testing

This method is the best option for the identification of leaks in flexible packaging while monitoring the changes in the internal pressure of a sealed container and measuring the Permit dimension.

Mass Extraction Testing

This method involves using vacuum devices to assess a sealed container to uncover the amount of gas or air passing out of it. It is very precise and reliable when used for sterile pharmaceutical packages.

Probabilistic Methods (Less Reliable)

This is a non-deterministic method and its purpose is to visually inspect and detect leaks using Ingress dye. Compared to deterministic procedures, this method is much easier to use and, therefore, less reliable.

A technique whereby the container is submerged in water in a vacuum chamber in an attempt to identify if any leaks are present by observing any emitted bubbles.

This method involves how a product or package reacts to microorganisms in a liquid; however, this needs to be done in very specific conditions. This test is used to assess the product’s ability to resist contamination.

Pharmaceutical Packaging Standards and Testing

To avoid a pharmaceutical product’s exposure to moisture, oxygen, heat, or even UV light, the industry implements tough packaging regulations to ensure that contamination and degradation do not occur.

  • USP 661: Describes what is needed for packaging materials.
  • USP 661.1: Deals with constructing plastic materials.
  • USP 661.2: Covers the assessment of the entire packaging system to determine if it is complete and safe.

Testing for Packaging Materials Initial Methods:

Infrared Spectroscopy (IR), Differential Scanning Calorimetry (DSC).

Heavy metals examination and Extraction with solvents, UV absorption, total organic carbon (TOC), and Ignition residue (ROI).

For highest risk uses of USP <87>.

Extractables and leachable assessment (USP 1663, USP 1664).

Measure the moisture permeability level of the container.

Reasons To Opt for Chromak Research

Container closure integrity testing services are best managed by Chromak Research, where clients get:

  • ISO 17025:2017 Certification: Verification of international quality compliance.
  • Registered with FDA & cGMP Services: Satisfying requirements for drug and biologics packaging.
  • Expert team: Numerous years in formulating detailed test scopes for various container systems.
  • Modern Technology: The newest methods of testing container systems for integrity, including deterministic CCIT, are now available.
  • Regulatory Compliance: Services for compliance with USP, CFR, and European Pharmacopeia are provided.

In order to assure the sterility of the contents and the integrity of the pharmaceutical packaging, analysis by CCIT is cooperative. Complying with guidelines, monitoring and implementing sophisticated testing methodologies assures the safety and efficacy of the product. Chromak Research Team includes specialized CCIT service provisions compliant with FDA and GMP requirements. Reach out today for closure integrity testing services or help navigate your specific packaging needs.