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Leak Detection Basics For Pharmaceutical Applications

Mon, 10/13/2008 - 11:25am

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An examination of the pros and cons of the three main methods available.

By Christoph Zerwas
Product Manager
Pharma Solutions at Paul Lippke Handels-GmbH, division of MOCON Inc.

Pharmaceutical processors concerned about product shelf life and efficacy should make leak detection a mandatory part of their process. Anytime there is any sort of physical breach of the packaging structure, the product integrity is compromised. Using validatable leak detection instrumentation can help insure that your product's efficacy and safety is not negatively impacted.

With three different main types of leak detection methods to choose from, pharma processors frequently have questions on what approach is right for their application. To help put the technology in perspective, here is a general overview of each technology.
Vacuum Leak Method

Typically used for pharmaceutical blister packaging, this simple visual test is the oldest of the three methods. It uses methylene blue dye or another colored liquid to determine whether or not there is a leak. The test is performed by placing the blister pack into a vacuum container which has been filled with methylene blue dye mixed with water. If there is a leak, the liquid will seep into the package, thereby giving visual proof.


The VC 1380 illustrates the automatic vacuum leak method. The photo shows the MOCON Lippke VC 1380 blister tester
Pros:
• It is the least expensive process.
• No major equipment investment is necessary.

Cons:
• No validation.
• Destructive test.
• Manual documentation only.
• Results are operator-subjective.
• Not possible to determine quantifiable leak statistics.
• Not suitable for pouches
Automated Vacuum Leak Method

This approach automates the classic methylene blue dye test and provides comprehensive documentation. It is typically used for blisters, ampoules and vials.

To execute the test, a vacuum chamber is filled with water into which the blue dye is added. The package is placed in the chamber and secured in place to insure submersion. The chamber is closed by a lid.

The operator then enters parameters for vacuum, test and penetration times into a console (or parameters can be pulled from a previously-stored, password-protected database which minimizes human error).

The test begins by creating a vacuum inside the chamber. The packs remain in the methylene blue die under atmospheric pressure, for a predetermined amount of time. After venting the chamber, if there is a leak (pinhole etc.) in the package the dye-filled water will penetrate the specific cell. When the test is concluded, inspection of the blister pack will immediately yield visual results and data can be exported to a PC or printer.

By automating the sequence, users can insure that tests are conducted always under the same parameters, so that they will be reproducible and the procedure validatable. Further, automation enables staff to focus on other work-related tasks while this test is cycling through. Documentation also is simplified via automatic printout of the test report.

Pros:
• Test provides precise leak detection data.
• Automated documentation.
• Repeatable and validatable tests.
• Labor and time savings.
• Well established method.
• Low price.

Cons:
• Destructive test.
• Not suitable for pouches.
Internal Pressure Method

Typically used for larger flexible or semi-rigid packages like bags, bottles, containers, tubes etc. as well as for Tyvek® structures. This method is based on the ASTM F2095 Pressure Loss Test for package leaks. It uses a hermetically-sealed septum or package adaptor, which is adhered onto the package and a probe (needle) which is used to insert air.


The MOCON Lippke 4000 leak detector illustrates the internal pressure method
The pressure builds up in the package until it reaches a pre-selected level. It is then held at a constant level for the required settling time. During the final test phase, the system accurately measures the pressure to detect the slightest amount of loss and displays the corresponding value.

This determines whether or not the package has a leak and, if so, to what degree.

Pros:
• Test provides precise leak detection data.
• Results are not operator-subjective.
• Easy to control pressure levels.
• Repeatable and validatable tests.
• Computer-based data analysis possible.
• Low price.

Cons:
• Destructive test.
• Not suitable for pharmaceutical blister packaging
Trace Gas Detection Method

This non-destructive approach is suitable for a wide variety of package types including blister packs, pouches etc. The test method relies on detecting carbon dioxide or other gas as it escapes through pinholes or cracks in the package. Carbon dioxide is recommended as a tracer gas because it is FDA approved for food and drug applications.
A test sequence begins by placing the package in the test fixture. A vacuum is quickly drawn on the sample. The resultant pressure differential causes carbon dioxide to escape through holes or cracks in the package. At the end of the pre-set dwell time, room air rushes back into the test fixture, sweeping accumulated carbon dioxide into the sensor and notifying the operator if there is a leak.

Pros:
• Non destructive.

Cons:
• Ongoing operating costs due to gas consumption.
• Time consuming test.
• Customized test chambers required for each package type/size.

These test methods detailed represent a wide range of capability and associated costs. Many factors should be considered in order to make the right decision for your operation and package type. Here are a few questions to consider before buying a leak detector:

1. Package type
• Semi- rigid or flexible
• Porous

2. Contents
• Wet or dry
• High or low value product

3. How much head space
• Plenty
• Little or none

4. What do you want to measure or detect
• Leaks
• Gas concentrations
• Head space
• Burst - package integrity
• Seal - strength
• Combination of these items

5. Test purpose
• Research and development
• Quality assurance
• On-line production
• Evaluation of packaging material or process

6. What integration is needed
• Instrument to be used with other systems
• Results need to be fed into other systems

7. Repeatability of tests
• Do I need to be able to validate my tests
• Do I need to verify my suppliers products
• Do I need objective results

8. Compliance with regulations and standards
• What regulations do I have to satisfy
• What standards do I want to meet (ASTM, ISO, AAMI, Pharmacopeia, etc.)

9. Multilingual user ability and ease-of -use
• Do I need my instruments to display languages other than English
• Given my current work force, how simple must the process be

10. Perception of test quality
• How important is it that our tests communicate a high level of quality/accuracy

11. Budget
Conclusion

Although there are a variety of other leak detection methods currently in use (such as the water bubble and the dry vacuum tests), the automated methylene blue dye and the internal pressure tests have become the most established solutions. As a result, they have become quasi-standards.

It is important for today's pharmaceutical companies to be able to guarantee the efficacy of the active ingredients contained in their products. The use of established leak detection methodologies, which are repeatable and validatable, can make a significant impact on product shelf life and quality.
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