Isolation Technology | White Paper

GLOVE INTEGRITY TESTING PRESSURE DECAY METHOD: PERFORMANCE QUALIFICATION

In recent years, Glove Integrity Testing has been profoundly
discussed and numerous articles have been written on this
topic. However, many doubts still remain within the industry
due to the lack of norms and clear guidance available. In 2008
Annex 1 to EU Guidelines to Good Manufacturing Practice
reiterated the importance of having glove integrity testing:
25. Monitoring should be carried out routinely and should
include frequent leak testing of the isolator and glove/sleeve
system.
Over the course of the past few years different industry
specific associations have conducted statistical studies about
the frequency in which this type of testing is performed in
the pharma industry and the results indicated that the test
is executed normally prior to each batch of a production run.
However as far as performance requirements the question is
still open: which hole diameter should I be able to detect?
The theoretical answer would probably be 1m (bacteria
spores diameter), but the practical answer is much larger due
to technological limitations at this time. The methodologies
of testing available today are many, but few of them may be
automated and many times they are not suitable for the routine.
Moreover today it is difficult to find equipment to test the
integrity of gloves that comes with performance qualification
(PQ) and this is mainly due to the lack of test repeatability.
Although there are many different methods available in the
industry, the method used by the greatest portion of the users
to test the integrity of the gloves is the Positive Pressure Decay
method which follows the international standard ISO 14644-7
Annex E.5.
The ISO 14644 Part 7 doesnt detail specific methodologies for
the Positive Pressure Decay. In terms of acceptance criteria
many different interpretations can be reached. The box below
shows what the ISO norm states about the test procedure and
the results.

E.5.3.2 Test procedure

When the sealing cap is placed over the glove-port ring, a space is formed between the cap and the inside surface of the glove. This space is then pressurised to 1
000 Pa and allowed to stabilise. A drop in this pressure will indicate a leak through the glove fabric or securing arrangement. The following steps should be followed.
a) Prior to commencement of test it is important to visually inspect the glove/gauntlets for any obvious damage.
b) Make sure all fingers on the glove extend into the separative device.
c) Connect the air line to the separative device.
d) Switch on the manometer.
e) Adjust manometer to zero by pressing the zeroing button while holding the glove-leak tester in free space. Small variations of 3 Pa to 4 Pa from zero
will not adversely affect the result or the sensitivity of the tests.
f) Fit the sealing cap of the glove-leak tester over the outer port ring of the glove to be tested.
g) Inflate the glove by operating the valve. The gauge of the manometer will display the pressure within the glove in pascals. The glove should be inflated
to a minimum of 500 Pa and a maximum of 1 000 Pa; this may take a number of injections of air to reach the required pressure as the system stabilizes.
h) Observe the reading on the manometer. A stable reading will indicate a sound glove.

With experience, operators will be able to identify potential problems in a 10 s test period. Suspect gloves/gauntlets should be re-tested, and a longer test period
may be required to confirm results.

E.5.3.3 Results
E.5.3.3.1 Pass
If the glove/gauntlet is sound, then the reading shown on the manometer will remain static within 2 Pa to 10 Pa, subject to the small variations noted in E.5.3.2.
E.5.3.3.2 Fail
If the glove/gauntlet is damaged, then the reading shown on the manometer will fall (i.e. 500 Pa, 495 Pa, 490 Pa). This trend will be distinct and progressive. The rate
of change will be proportional to the level of damage to the integrity of the glove.
Any test showing probable damage should be repeated.
Any tests that record a distinct change in pressure should be closely investigated and the fault (e.g. incorrectly positioned cuff ring, damaged glove) either re-tested
or the suspect glove/gauntlet changed and a successful test conducted.
COMECER SPA | All rights reserved | 22/01/14

Many questions can arise from such a simple test procedure
and such a wide interpretation of the results.
What is the performance of this method? Which hole diameters
will I be able to detect?
The first step is to create a mathematical model which can
describe an inflated glove with an orifice, as this will provide you
with a formula relating to the hole diameter for the expected
pressure drop. Unfortunately the calculation is very complex
due to different elastic properties of the glove material (different
elastomers, thickness, and sizes) so different strategies need to
be followed.
The glove materials available in the industry vary (Hypalon,
Butadyl, Neoprene, EPDM). In particular, Hypalon is a mixture
of polymers such as plastic and rubber, with a very different
reaction to stress and elasticity. These gloves, very common in
aseptic applications, result in more of a challenge to integrity
testing than other types of materials. Thickness and size,
together with the flange mounting, greatly contribute to the
determination of a customized testing procedure for each kind
of glove material. Therefore an experimental approach needs to
be strictly followed.
Isolation Technology | White Paper

For the positive pressure decay method, performance tests (< 1000 Pa) for the hole whose performance we are trying to
may be carried out in different ways, such as calibrated hole prove and collect a statistical set of data from these tests4.
on the flange, needle inserted through the glove or pinholes on Definition of test parameters and acceptance criteria:
the glove1. Based on our experience, the calibrated hole method
From the two sets of curves the following test parameters are
is the most appropriate and precise method of the three listed
then defined:
above, so this configuration,
Inflate Pressure (between 500 and 1000Pa)
together with the Automatic
Stabilization Time
Glove Tester2, was used
Testing Time
for this study. After testing
Acceptance Criteria (P limit)
gloves of different sizes and
COMPRESSED AIR
materials currently available
The objective is to locate the value of these paremeters so that
in the market, we were
they will correspond to a significant difference between the
able to collect a significant
Pressure Drop of the Open System (Pos) and the Pressure
amount of data to support
Drop of the Closed System (Pcs), i.e. Pcs - Pos . The
the methodology described
statistical deviation of the collected data needs to be as small
below that is based on the
as possible and the accuracy of the pressure transmitters
comparison between these COMPRESSED AIR
must be considered in order to reach an effective and valuable
two systems:
acceptance criteria. Basically what we look for is a large
Closed System - brand new
difference between the slopes of the two curves based on the
glove correctly mounted on
collected data of the two systems during testing: a smaller
the flange.
difference between the two curves may result in a longer overall
Open System - brand new
test procedure time until a significant difference is observed.
glove correctly mounted
COMPRESSED AIR As such, the equipment and the test can be easily validated
with a calibrated hole device
while the specific glove and fixing mechanism (flange and
connected.
counterflange, o-ring, etc.) is characterized in terms of normal
The expected behavior of the two systems should be like the
leakage (Closed System curve). Before running the test, it is
one shown in the graph below.
important that the integrity of the machine running the test is
also verified and assured.

CLOSED SYSTEM With the method described above a variety of hole diameters
can be detected developing the correct test parameters.
However the detection limits are primarily influenced by the
precision of the adopted transmitters, statistics involved and
time constraints.

Using this method with a calibrated hole of 100 m a high

OPEN SYSTEM
To achieve a Qualified Performance the following activities have
to be performed:
Characterization of the Closed System:
Study the pressure decay curve at several inflatable pressures
(< 1000 Pa)3 and collect a statistica set of data from these tests.
Characterization of the Open System:
Study the pressure decay curve at several inflatable pressures
(1) Different studies have demonstrated that the position of the pinhole on the
glove can also affect its detectability
(2) AGT Automatic Glove Tester made by Comecer SpA
(3) The referenced ISO norm clearly states that the inflatable pressure has to
be lower than 1000 Pa, and so this value has been taken as the limit to not
enlarge an existing hole or even damage the elastic polymer
level of reproducibility and a very, very low frequency of false
positives has been observed. This means that an automatic
glove tester machine may be easily validated. Lower detection
limits may be achieved by the use of smaller calibrated hole
sizes, but this practice will impact the reproducibility and the
probability of false positives. Data collected and PQ protocols
in this study are available upon request with an e-mail to
comecer@comecer.com.
(4) Dedicated software able to run consequent tests and to record data is used for
data collection both on the Closed and Open systems.
ABOUT COMECER
Comecer (Costruzioni Meccaniche Certificate) is a
world leader in protection technologies in nuclear medicine,
in isolation technology and nuclear power plant equipment.
Comecer produces screening systems and equipment for
special applications, designed for large industrial groups and
research organizations. We work for hospitals, universities and
pharmaceutical companies on tailored projects for the production
of isolators for the treatment of toxic and hazardous substances.
For nuclear power plants we make equipment for the processing,
decommissioning and disposal of radioactive substances.

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Phone +39 0546656375 Fax +39 0546656353 E-mail: comecer@comecer.com http://www.comecer.com