Container Closure Integrity Test

What is container closure integrity?

Container closure integrity is the ability of a package to prevent product loss, to block microorganism ingress, and to limit entry of detrimental gases or other substances, thus ensuring that the product meets all necessary safety and quality standards. Synonymous with Package integrity.

What is container closure integrity test?

A container closure integrity test is any package leak test (either physicochemical or microbiological) that detects the presence of a package breach or gap. Some tests may also be able to identify the leak magnitude and/or location. The term container closure integrity test is synonymous with package leak test or package integrity test.

CCI testing should generally performed during three phases: 

(1) During initial development of the product packaging system

(2) Routine manufacturing

(3) Shelf life stability assessments

Development of CCI and relevance guidelines:

Container closure integrity testing methods:

➡️ It can be performed in many different ways. Broadly, container closure integrity test methods can be categorized into following two types:

1. Deterministic leak test method:

➡️ A deterministic leak test method is one in which the leakage event being detected or measured is based on phenomena that follow a predictable chain of events. In addition, the measure of leak detection is based on physicochemical technologies that are readily controlled and monitored, yielding objective quantitative data.

2. Probabilistic leak test method:

➡️ A probabilistic tests relies on a series of sequential and/or simultaneous events that are associated with large uncertainties that require large sample sizes and rigorous test condition controls.

➡️ Deterministic leak test methods are more reliable, easier to develop, validate and implement.

Differences between deterministic leak test and probabilistic leak test method:

CCIT methods:

➡️ Each test method having its different procedures, advantages and disadvantages. We have understand each and every test based on functions. 

1. Electrical conductivity test method (High voltage leak detection):

Mode: Filled container are exposed to electric current. Sparking when breach detect. 

Advantages:

• Rapid test
• Non destructive 
• No sample preparation required
• Can be used on line

Disadvantage:

• Need conductive solution
• Method development/validation needed for each package 
• Package must be non porous

2. Laser-based gas headspace analysis test method:

Mode:  A near infrared diode laser light passes through the gas headspace region. The light is absorbed as a function of gas concentration and pressure. This absorption information is processed using phase-sensitive detection techniques. A microprocessor analyzes the data and yields the test results. 

Advantages:

• Can be used for lyophilized products or oxygen-sensitive liquid products
• Nondestructive and provides quantitative results
• Can be used on line

Disadvantage:

• Required a gas headspace 
• Package must be non porous 

3. Pressure decay:

Mode: Introduces increased pressure in to the package and monitors the change (decay) in headspace pressure. 

Advantages:

• Rigid or flexible containers

Disadvantage:

• Only for non porous packages

4. Tracer gas detection test method:

Mode: Tracer gas e.g. Helium introduced in to the test package and spectrophotometric detection of any leaked helium. 

Advantages:

• Rigid or flexible containers 
• Can be used on line 

Disadvantage:

• Liquid or solid in the leak path results in false negatives 
• Potential to be destructive 
• Can be slow (seconds to minutes) 
• Package must be non-porous

5. Vacuum decay test:

Mode: Package is placed in a vacuum and the change (decay) in vacuum monitored over time. 
Advantages:

• Rigid or flexible containers 
• Transparent or opaque 
• Non-destructive 
• Porous packaging can be tested 

Disadvantage:

• Gas headspace required at atmospheric pressure 

6. Mass extraction:

Mode: Container placed in chamber which connected to mass extraction leak test system. measurements of absolute pressure, pressure decay rate, and/or gas mass flow rate are captured. 

Advantages:

• Rigid or flexible containers
• Packages with a porous component can be tested with the mass extraction assay by masking the porous package component

Disadvantage:

• Can be slow
• Assembly time required 

7. Microbial challenge, immersion exposure test method:

Mode: Package content is replaced with microbial growth medium. The package is immersed in a suspension (air or fluid) of microorganisms. Microorganisms enter the container via any leak. Visually observed microbial growth indicates a leak.

Advantages:

• Rigid or flexible containers 

Disadvantage:

• Destructive 
• Qualitative 
• Must be non-porous & transparent containers 
• Slow (several days or weeks) 
• Microorganisms must be present at the leak site and access the leak freely

8. Liquid tracer test method (includes dye ingress method):

Mode:  Test package is immersed in a tracer liquid, diffusive flow of the tracer in to the container through leaks occur. The contents of the package are tested for the tracer. 

Advantages:

• Rigid or flexible containers

Disadvantage:

• Destructive 
• Qualitative 
• Must be non-porous containers 
• Slow (minutes to hours)

9. Bubble  test method

Mode: Test package is immersed under water or coated with surfactant, maintained under pressure and bubbles visually observed. 

Advantages:

• Rigid or flexible containers 
• Porous packaging can be tested

Disadvantage:

• Gas headspace required 
• Destructive 
• Qualitative 
• Can be slow (seconds to hours) 
• Trapping of bubbles can result in false negatives

10. Tracer gas (sniffer mode):

Mode: Test samples are flooded completely or partially with the tracer gas. “Soaking” a closed test sample by pressurizing with tracer gas. 

Advantages:

• Rigid or flexible containers
• Chosen when the leak location must be identified  

Disadvantage:

• Destructive
• Qualitative 

Reference: USP <1207>

About the Author:

Dhansukh Viradiya is a highly accomplished expert in the pharmaceutical and biopharmaceutical industries. With over 10 years of experience in the field, he has gained comprehensive knowledge and expertise in various areas, including Process Validation, Cleaning Validation, Quality Management System, In-process quality assurance, Qualification etc.

Mr. Dhansukh holds a Master's degree in Pharmacy from a renowned University, where he specialized in Quality Assurance. 

As a thought leader, Mr. Dhansukh has published numerous articles and white papers on various topics related to pharmaceutical and biopharmaceutical industries. His research work focuses on emerging trends, current regulatory expectations, advancements in technology, personalized medicine, and the intersection of healthcare and technology.

With his passion for improving patient care and dedication to advancing the field, Dhansukh Viradiya continues to make significant contributions to the pharmaceutical and biopharmaceutical industries. His insights and expertise make him a valuable resource in understanding the dynamic landscape of these sectors and their impact on global healthcare.

Disclaimer:

The author's biography is provided for informational purposes only and does not imply any endorsement or affiliation with the article or its content.