Integrity Testing of Flexible Containers - Defects as small as 10 μm can be detected without compromising product cleanliness using helium integrity testing. - BioPharm International


Integrity Testing of Flexible Containers
Defects as small as 10 μm can be detected without compromising product cleanliness using helium integrity testing.

BioPharm International
Volume 24, Issue 11, pp. 42-49


Figure 1: Leak detection sensitivity chart. (ALL FIGURES ARE COURTESY OF THE AUTHORS)
A defect can be defined as an unintended crack, hole, or porosity in an enveloping wall or joint, which must contain or exclude different fluids and gases allowing the escape of closed medium. The shapes of defects (e.g., cracks, fissures, porosity, damages, etc.) are very different, unknown, and nonuniform. Therefore, it is impossible to measure their sizes with any precision except in the case of an ideal or artificial leak as used for calibration. There are many methods for detecting defects, a list of which along with their sensitivities can be found in the literature (6–11). Figure 1 summarizes the sensitivity limits of each of them.

Figure 2: Pressure-decay curve.
The most practiced method in the industry involves observation of gas or fluid flow through a test bag under defined conditions of temperature and pressure. Consequently, defect sizes are measured by the pressure decay method or by the tracer gas leak testing method. The pressure decay method is discussed below to illustrate some of the limitations observed in ensuring integrity of test bags, and varying adaptations of the tracer gas leak testing method are discussed along with their limitations.

Pressure-decay test

The pressure-decay test consists of pressurizing the system with a high pressure gas, usually dry air or nitrogen. The test part is isolated from the gas supply and, after a stabilizing period, its internal pressure is monitored over time. The pressure drop (Δp) is measured over the interval (Δt) (see Figure 2). If the pressure in the system drops quickly, there is a large leak present in that component or section of the system. If the system's pressure drops slowly, there is a small leak present. If the pressure remains the same, that component is leak-free. The leak rate, Q, can easily be computed considering the volume V of the component by using the following equation:

Leak-detection sensitivity is related to the test time, the pressure transducer resolution, and the test bag volume. Several external factors, such as temperature variations and mechanical deformations, affect this test. The internal pressure depends on temperature, and therefore thermal fluctuations may cause changes in pressure, altering the results. Longer test times allow for a more sensitive check, but make the test very time-consuming because smaller defects may require holding periods of several hours. The higher the pressure, the faster leak determination can be made. However, operator safety concerns along with the risk of damaging the test product limit the maximum admissible pressure value.

The difficulties increase when using this technique for checking the defects in flexible bags. Calibrating the system when the test product being measured is extremely pliant is challenging. Therefore, reliable test sensitivity is reduced for flexible bags. This issue can be addressed by the use of constraining plates to constrain bag stretching or internal volume (11, 12). For products with a more complex shape it may be necessary to make a tool that conforms closely to the product outline. However, it is not always possible to fit the final product into the test assembly, leading to products being tested without final assembly elements such as tubing connections or filters, because tubing port connections and manifolds are sensitive to over stretching or bending caused by constraining plates. In the case of large test bags, such as 1000-L or 2000-L, it may require hours to fill the test bag with pressurized gas and to empty the bag. Even after such long test times, one can only detect defects as small as 500 μm while smaller defects go unchecked. Thus, the inability to test fully assembled product risks assuring integrity of a finished product. It is therefore necessary to have a method that is easy to implement (e.g., not bulky or cumbersome), reliable, and that does not contaminate the interior compartment of the container undergoing testing.

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