A fundamental part of ensuring product integrity is the crucial phase of leak testing.

For the assessment of product efficacy and shelf-life, and meeting good manufacturing practices for finished pharmaceuticals, leak testing plays a critical role.

It is essential that you have an objective, robust and repeatable procedure for leak testing in place. This is the key to reducing the risk of product recalls or contamination – and also proving product stability. Furthermore, it helps in preventing a reduction in drug efficacy. 

 

What are the factors that lead to product integrity being compromised?

Typically process-related – any sort of physical breach in the packaging structure, like:

  • Weak seals
  • Capillaries
  • Pin holes
  • Micro cracks
  • Pocket damage and
  • Cutter misalignment
 
In order to assess the integrity of their blister packs, a vast majority of pharmaceutical companies have almost exclusively used the dye ingress test. The type of packaging, environment, cost, sensitivity and level of testing are important factors that will help you narrow down the best testing method for your applications.
 
In addition, companies should take into consideration these key points – which every effective leak testing solution should focus on: 

  • Objectivity
  • Repeatability 
  • Validation requirements 
  • Accuracy 
  • Non-destructive 
  • Sensitivity 
  • Environment 
  • User involvement 
  • Implementation 
  • Flexibility 
  • Cost
 
What are the common leak detection methods?


Destructive and non-destructive are the two basic categories.


The right method required by you should be based on: 

  • Tradition
  • Product cost
  • Perceived ease of use 
  • Quality assurance and
  • Cost of implementation

Let us take a look at the 5 destructive leak detection tests


Dye Ingress Test:


For integrity testing of blister packs the ‘blue dye test’ has been the most employed and accepted destructive method. It has been adopted by almost all pharmaceutical companies as it is simple to use with low costs. Especially for blisters, this method of testing has been used for many years.


The test is simple to carry out and the equipment required is of very low cost. However, it is difficult to validate as this method is only as good as the settings being used and the operator carrying out the test.

 

Currently, many pharmaceutical companies are re-evaluating its use because of the time taken to carry out the test, its destructive nature, the general mess and the inability to generate batch data associated with it.

 

Companies are looking out for an objective, non-destructive and modern alternative to this method. 


Gas Analysers Test:


They are often referred and also known as ‘trace gas tests’. Helium is commonly used to find holes in the blister packs. Very tiny holes are found because of the small size of the helium molecules. The ‘sniffer test’ and ‘bomb test’ are the two most commonly used methods.


Presently, helium gas testing is the most sensitive leak testing method. It is the apparent method where users require holes as small as five microns to be found.


On the other hand, many blister leak testing applications do not have a requirement to locate holes of this size. In most instances, this method is impractical because of its inability to find large holes, operating difficulties, complexity, its time-consuming nature and associated costs.


Vacuum Decay Test: 


A blister pack present inside a vacuum chamber will be tested. The vacuum decay method measures the change in pressure with the blister pack being subjected to a vacuum. It is monitored for any kind of changes.

 

Within the chamber a pack with no hole present will cause little change in pressure. However, a pack having a small hole will cause the pressure level in the chamber to change. This is because the air within the pack escapes into the chamber.


Vacuum decay leak testing is specially used for containers such as bottles and vials. It works best for products with a consistent free volume of air.


The tooling has to closely match the test product in order to locate the small holes. A secondary method of detection is required to find large holes. Especially when testing blisters – the tooling can become very involved and expensive.

 

The difference in the size of pockets and blister formats can also limit the flexibility of this kind of leak testing method.


Force Decay Test:


Flexible packaging that includes blisters employ the force decay method. Under a vacuum due to the difference in pressure inside and outside the packaging, this method measures the force generated by the test product.


This kind of methodology makes up of three phases. They are evacuation, stabilisation and test. 

 

A force is generated during the evacuation phase, when the packaging is defect-free. It differs according to the magnitude of the vacuum in the chamber. Later, both force and vacuum are held constant during the remaining duration of the test.


Relative to its free volume the packaging with a large hole will generate little force under vacuum. Subsequently, it will soon dissipate. The pack with a small hole will generate force under vacuum – however this force will then subside during the test period. 

 

To find leaks in packaging the force decay method of leak testing is highly effective. Depending on the type of packaging it is simple in principle and can be set up to find small holes down to 10 microns. It is ideal for finding leaks in flexible packaging and provides a quick non-destructive test.


Laser / Vision Test:


Primarily used for blister packs is the method of laser / vision leak detection test. A datum measurement is taken when the blister packs are placed in a vacuum chamber.


Pockets without defects begin to inflate when a vacuum is applied. Whether there have been any changes in the form of the blister pockets, a second measurement is taken. Between the two measurements, large holes in pockets can be identified as they will not show significant changes.


Encouraging movement by reducing the vacuum within the chamber, small holes can be identified by taking a further measurement after a period of time. 


Naturally suited to testing blisters is the laser / vision method. In a single test cycle it allows the user to test multiple packs. Without requiring expensive tooling it provides leakage information about every blister cavity. To identify good pockets it relies on the movement of lidding material. Therefore it is not ideal for blisters which do not show pocket movement with changes in pressure.

 

Laser / Vision test is suitable for packages with small volumes like blisters.

 

In the pharmaceutical industry, destructive leak testing methods for blisters have been used for decades.

 

However, a reconsideration of their effectiveness, understanding the actual leak test requirements for blister products, and taking advantage of the benefits offered by non-destructive methods have to be given more attention.

 

For modern pharmaceutical blister packaging lines – the non-destructive technologies play an ideal and significant role. They will help improve the quality assurance processes, increase accuracy and notably reduce the long-term production costs.