Container Closure Integrity Testing
Container closure integrity is a key part in keeping the sterility of products like syringes, vials, and other containers holding drugs or biologics. The stability protocol for sterile products is critical to the validation of container closure system integrity. Whether or not a container can effectively protect its contents, acting as a barrier against potential contaminants, an ingress of microorganisms, or other compromising substances, is largely evaluated by container closure integrity testing.
Container Closure Integrity Testing or CCIT is the validation of the container closure system to keep a sterile barrier to meet the desired amount of protection or containment of the packaging components. The physical attributes of the container closure system are evaluated to quantify the sterility of the contents. This is performed by measuring the biological, chemical, and barrier properties of the container closure system along with the attributes of the product and container closure.
USP 1207 categorizes container closure integrity test methods into two types. These two methodologies are used to evaluate container systems. These are historical methodologies: deterministic and probabilistic. A probabilistic method is premised on an event having a probability of occurring. A deterministic method directly and quantitatively measures a physicochemical property that generates the potential for leakage. Probabilistic testing requires larger sample groups, are more qualitative in nature, and are less quantifiable than the alternative, deterministic methods.
Deterministic methods directly and quantitatively measure a physicochemical property that generates the potential for leakage. Deterministic methods can be used to generate science-based data throughout the product life cycle to develop a package integrity profile that can be used as input for risk management. A “probabilistic method” is based on an event having a probability of occurring, and as such, is less precise. USP 1207 references deterministic methods as preferred but does support probabilistic methods when no deterministic method is available.
Deterministic Tests
Electrical Conductivity and Capacitance Test (HVLD)
High voltage leak detection is based upon the principle of electrical conductivity and resistance. The premise is that the packaging is less conductive than the product held inside. A high voltage and high frequency charge is applied across the packaged product sample. The probe sends the current through the sample. While the sample is rotted on a platform, the detection probe measures voltage received as a function of traveling through the container.
Vacuum Decay Method - ASTM F2338
ASTM F2338 is the Standard Test Method for Nondestructive Detection of Leaks in Packages by Vacuum Decay Method. This method involves drawing a vacuum on a package within a test chamber and monitoring the vacuum level for decay.
- Applicable to test nonporous flexible packages, rigid and semi-rigid packaging
- Leaks down to 1µm can be detected in packs containing water based liquids
- Leaks down to 50 µm can be detected in trays or cups that are non-lidded
- Trays sealed with porous lidded materials can be detected to 125 µm
Headspace Gas Analysis (HGA)
Laser based analysis of a container’s headspace provides a measure of the oxygen, carbon dioxide, water vapor, or internal pressure in rigid or non-rigid package headspace.
- Used primarily with liquid filled paternal drug glass vials or syringes
- Gas ingress testing using CO2 overpressure identifies five micron positive controls
- Quantitative and nondestructive
Helium Leak Testing - ASTM F2391
ASTM F2391 is the Standard Test Method for Measuring Package and Seal Integrity Using Helium as the Tracer Gas. This test method uses a helium leak detector, also known as a Mass Spectrometer Leak Detector (MSLD), equipped with custom designed fixtures for the container or vial that is to be evaluated. The container closure system is calibrated against a NIST-traceable standard to set up parameters.
- Various types of containers such as vials, syringe systems, cartridges, and blister packs can be evaluated
- Quantifiable test method
- Higher sensitivity compared to blue dye ingress test method
Probabilistic Methods
Probabilistic Container Closure Integrity (CCIT) Test Methods: Bubble Emission, Blue Dye Ingress, and Microbial Ingress. While these test methods have been used to confirm package container quality, each is limited in reliability. Probabilistic container closure integrity test methods apply a variable to the test sample to then see a response, while deterministic testing is based on a predictable chain of events.
Leakage is measured using physicochemical techniques that are readily controlled and checked, resulting in quantitative data. Deterministic leak tests are performed on calibrated machines designed to control potential variables, perform uniformly under varying conditions, produce traceable test results, measure smaller leak sizes, and use smaller sample sizes with better reliability.
The importance of paternal packaging and container closure integrity testing is mitigation of the risks of incorrectly confirming these containers. It is highly recommended that deterministic methods are used to qualify and confirm these packaging systems. Probabilistic tests can continue to be used for certain applications. Deterministic testing is needed and recommended for most applications.
In conclusion, container closure integrity (CCI) testing is a vital process that ensures the integrity of the container closure system in pharmaceutical and biopharmaceutical products. The CCI testing process includes evaluating the sealing integrity of each individual container and the closure system as a whole.
The main purpose of CCI testing is to prevent any contamination or leakage of the product during storage, transportation, or administration. This process involves different testing methods, including:
1. Visual inspection: This is a manual inspection where the containers and closures are examined for any visible damages or defects, such as broken seals, cracks, or deformities.
2. Microbial challenge: In this test, a microbial agent is introduced into the container and the closure system is evaluated for any signs of microbial ingress.
3. Leak testing: This test evaluates the leakage of the container closure system through various methods, including vacuum decay, dye ingress, and pressure decay.
4. Headspace analysis: This test involves analyzing any gas leakage through the headspace of a container to ensure its integrity.
Overall, the CCI testing process is essential to ensure the safety, potency, and efficacy of pharmaceutical and biopharmaceutical products.
Why Purple Diamond for Container Closure Integrity Testing?
Purple Diamond can evaluate the product and packaging systems to design, test, and confirm the integrity of your container closure system. Purple Diamond is an all-inclusive testing environment, equipped to ease Container Closure Integrity testing across multiple industries. In addition to product reliability and fragility testing, Purple Diamond offers extensive materials testing and package integrity testing solutions. Our team of expert engineers can evaluate and confirm both the packaging and shipping environment specific to your product.
Evaluating your product’s container closure system in compliance with the standards set forth by ASTM International, Purple Diamond is committed to delivering high-quality results as we develop a comprehensive solution to your specific product testing needs.
Related Testing Standards
- ASTM D642
- ASTM D685
- ASTM D880
- ASTM D951
- ASTM D999
- ASTM D3078
- ASTM D3103
- ASTM D3285
- ASTM D4169
- ASTM D4332
- ASTM D4728
- ASTM D5265
- ASTM D5276
- ASTM D5277
- ASTM D5487
- ASTM D6055
- ASTM D6179
- ASTM D6344
- ASTM D6653
- ASTM D7386
- ASTM F88
- ASTM F1140
- ASTM F1886
- ASTM F1929
- ASTM F1980
- ASTM F2096
- ASTM F2250
- ASTM F3039
- ASTM D1596
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The APASS program was designed by Amazon to help support vendors, sellers, and manufacturers in obtaining certification of their products as Frustration Free Packaging (FFP), Ships in Own Container (SIOC), or Prep-Free Packaging (PFP).
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sterilization, sealing, packaging, leakage, integrity, testing methods, non-destructive testing, leak detection, package closure system, container closure system, microbial ingress, container closure components, packaging materials, closure defects, seal strength, vacuum decay, dye ingress, microbial challenge, seal integrity, capping, fill level assessment
