Container Closure Integrity Testing
Drug product comes in a variety of forms, from liquid to frozen and lyophilized. It is filled and stored in a number of container closure systems, including the common glass or plastic vial with rubber stopper and aluminum seal or plastic or glass syringe with needle assembly. In all cases, and for all drug product forms, the container closure system must provide an integral barrier that protects stability and sterility of the dosage form for the duration of the product shelf-life. The United States Pharmacopeia (USP) and Food and Drug Administration (FDA) enforce stringent testing requirements for container closure systems.
Eurofins Sinensis provides the most up-to-date methods for testing the closure systems for final drug product packaging and has invested in state-of-the-art instrumentations to meet the regulatory guidelines and verify the safety of your container closure system.
Additionally, we can help you determine which method is best for your project needs.
Why Choose Eurofins Sinensis?
- We have more than 15 years of experience developing and executing methods for various container types
- We provide quick turnaround times
- We offer generic in-house procedures, as well as customized approaches
- Single point of contact within our organization
Techniques for Container Closure Integrity Testing (CCIT)
Dye Ingress and Microbial Challenge Testing Microbial (both probabilistic tests) were the two leading methods for Container Closure Integrity Testing. These tests are destructive to the test articles, and typically require a significant number of units for method development and validation. While we do offer the traditional Dye Ingress and Microbial Challenge Testing for container closure systems, these methodologies are not considered quantitative.
In addition to the traditional Dye Ingress and Microbial Immersion methods, we also offer more sophisticated, quantitative methods such as:
Helium Leak Detection
Instrumentation: Helium Mass Spectrometer - Tracer Gas Detection, Vacuum Mode
Description: Quantifies the flow rate of helium from leaks in packaging after having been flooded with helium as a tracer gas. If a defect is present, the helium is then drawn out of the packaging through the defect by vacuum and detected using a mass spectrometer. This method is the most sensitive option, allowing for the detection of defects as small as 0.2 microns.
Best Application: This technology is suitable for package development to verify the package type is appropriate for the type of drug, as well as routine testing and stability for a wide variety of package types.
Instrumentation: VeriPac 455-M5 Vacuum Decay
Description: Measures leaks by vacuum decay based upon ASTM F2338. Performs leak testing with sensitivity to detect leaks down to approximately 5-10 microns. This option reduces the amount of valuable finished drug product required for stability testing as the testing is non-destructive to the sample, and therefore, the same sample can be used for other laboratory tests typically required during stability studies once the vacuum decay test has been performed.
Best Application: This technology is suitable for leak testing on container/closure systems such as syringes, vials, and pouches. Because this method is nondestructive to the sample under test, it is a great option for leak testing both before and during stability studies.
Instrumentation: TM Electronics BT Integra Burst, Creep and Leak Tester
Description: Measures leaks by pressure decay based upon ASTM F2095.
Best Application: This technology accommodates both seal strength and package integrity testing for flexible packaging, such as bags and pouches.
High Voltage Leak Detection
Instrumentation: E-Scan 655 MicroCurrent High Voltage Leak Detector (HVLD)
Description: Detects package defects using an electrical current.
Best Application: This technology is suitable for use with liquid-filled parenteral drug product containers and syringes, where the packaging is far less conductive than the liquid inside.
Instrumentation: FMS-760 Oxygen Headspace Analyzer
Description: Uses Frequency Modulation Spectroscopy (FMS) to detect oxygen in the headspace of transparent rigid containers and measures rise or fall in the oxygen levels in the container’s headspace to identify a potential leak. It can also be used to determine the rate of oxygen permeation into a sealed container over time.
Best Application: Because this method is nondestructive to the sample under test, it is a great option for leak testing 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 Sinensis can help you determine which method is best for your project needs.
Feel free to contact us.