METHODS AND MATERIALS
Figure 3: Helium integrity test (HIT) apparatus.
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The HIT apparatus includes the following main components (see Figure 3):
- Pressurized helium supply (not shown)
- Test chamber
- Spacer unit
- Vacuum pumps for bag evacuation and test chamber evacuation
- Process-control station
- Detector: Varian mass spectrometer.
Leak test method
The HIT apparatus is composed of a test chamber with a closable lid that when closed, forms a tight seal such that no helium
can enter into the test chamber from outside. The test unit is a flexible two-dimensional bag with connecting ports that enable
fluid communication with the helium source and vacuum pump. The test chamber is large enough to house the unit to be tested.
The test chamber is connected to a vacuum pumping group equipped with the tracer-gas detector for chamber evacuation and gas
detection. A second vacuum group is used to evacuate the unit under test before filling it with gas. A tracer-gas filling
device (i.e., helium supply) completes the testing apparatus. The unit to be tested is put into the vacuum chamber and connected
to service hoses, then the vacuum chamber and the unit are evacuated. During chamber evacuation, the test unit is pressurized
with the tracer gas. After a stabilization time, the detector is linked to the vacuum line to detect the tracer gas flow through
a leak and drawn in by the pumping group. This method can be made fully automatic, so it depends little on an operator. Its
sensitivity can reach < 10-10 cc/s flow rates. To prevent long down times, the HIT system employs an in-line pressure-sensing test method as a preliminary
leak test that detects gross leaks before the final automatic leak-test operation using a tracer gas is begun. This approach
prevents large quantities of tracer gas from leaking into the atmosphere. A specialized pumping technique reduces the stress
on the test unit by reducing the internal pressure of the test part along with the external (i.e., chamber) pressure.
To improve test time per test unit, the test chamber was modified to include spacers that allow the simultaneous testing of
four units. The spacers are held upright by connecting rods, and each spacer has enough cavities in it such that when a test
bag inflates against it, it does not block the path of helium molecules flowing through the defect. The spacers constrain
the test bag in the test chamber, further increasing the helium pressure in the bag and resulting in increased sensitivity
of leak detection. The spacers also ensure that test bags experience minimal stress during chamber evacuation by limiting
bag expansion.
Test bags
The test bags were prepared by welding two sheets made from ATMI's proprietary TK8 film. To create defective bags, one of
the two sheets was modified to incorporate a defective patch. A defective patch is a piece of TK8 film (4 in. x 4 in.), with
a 10 μm ± 1 μm hole drilled by a laser. The laser-drilled holes were validated for defect size by measuring flow rate through
the defect area. Hereafter, "defective bags" implies a test bag with a 10 μm defect, and "good bags" implies bags with no
defect.
The size of the test bag depends on the size of the two sheets used in making one. The nominal volumes of test bags in this
study were 1, 5, 10, 20, and 50 L. The helium leak rates through defective bags and good bags measured using HIT technology
are discussed below. The test bags post-HIT tests were further characterized for product performance such as liquid particle
count (USP <788>) to ensure that the HIT process did not affect product performance.
Microbiological challenge test method
In this study, test bags for microbial challenge were prepared by thermally welding TK8 film sheets having defects of specific
sizes (2, 5, 10, 15, 20, and 50 μm). The test bags were aseptically filled with 50 mL microbial growth medium (trypticase
soy broth). The outside of the test bag was sprayed with a 0.9% saline solution containing approximately 106 CFU/mL of Escherichia coli, Staphylococcus aureus and Bacillus spizizenii and approximately 105 CFU/mL of Candida albicans and Aspergillus brasiliensis. The test bags were then transferred to an incubator maintained at 30–35 °C and monitored for 15 d. The growth medium inside
the test bag was periodically checked for microbial growth, which indicates microbial ingress.
Liquid particle count (LPC) test
A test bag was filled with ultrapure water (deionized water filtered using a 0.05 μm filter) and gently shaken to ensure that
all the bag surfaces came into contact with the solution. A sample of the solution from the test bag was then passed through
particle measuring equipment (PMS). The instrument reports the number of particles per mL of solution with particle sizes
greater than 25 and 10 μm.
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