Independent study looking at leak detection & the reality of accuracy using destructive techniques

1. ASSESSING THE INTEGRITY OF
PHARMACEUTICAL PACKAGING USING THE
SEPHA BLISTERSCAN AND CONVENTIONAL
BLUE DYE LEAK TESTING METHODS.
WHITE PAPER
OVERVIEW

2. 01
ASSESSING THE INTEGRITY OF PHARMACEUTICAL
PACKAGING USING THE SEPHA BLISTERSCAN AND
CONVENTIONAL BLUE DYE LEAK TESTING METHODS.
Dr Dorian Dixon, Nanotechnology and Advanced Materials Institute,
University of Ulster. February 2011.
Overview A preliminary study was free, 12µm holes or 20µm holes).
conducted by Dr Dixon to The model defects were laser
A new whitepaper by a leading determine the ability of drilled in the approximate centre
packaging expert from the Blisterscan to identify defects of the foil laminate covering
University of Ulster, Dr Dorian in a wide range of blister pack each pocket and the dimensions
Dixon, into the integrity of designs. A Design of Experiment of the holes were confirmed to
pharmaceutical packaging has approach was used to investigate a tolerance of +/-2µm using an
established that existing methods the effect of pocket dimensions, electron microscope.
for testing the seal integrity of foil thickness, pack material and
blister packs are not as accurate defect size on detection rates
as newer, technology based test by both Blisterscan
equipment. and blue dye testing.
This study found that
In particular Dr Dixon found the Blisterscan test
that the laser based Blisterscan, method detected
manufactured in the UK by 100% of 15µm sized
Sepha, was capable of detecting holes while only 85%
15% more product defects of such defects were
than traditional blue dye test picked up by blue
methods used by the majority of dye testing.
the pharmaceutical market. In
a global market valued at over In his whitepaper
$40 billion per annum, where study Dr Dixon
quality control is of paramount compared the ability
importance, a 15% difference in of Blisterscan and
the ability to detect if a product the blue dye test
is sealed correctly or not is to detect defective
significant. pockets in blister
packs. 30 cavity
Dr Dixon’s whitepaper “Assessing PVC thermoformed
the Integrity of Pharmaceutical packs sealed with a
packaging using Sepha 25µm foil laminate
Blisterscan and Blue Dye Testing” were used, with
comes on the back of internal 12µm or 20µm sized
studies by Sepha highlighting holes laser drilled in
that Blisterscan, a laser based the packs to create
leak detection machine, was defective packs. 90
capable of identifying 50% pockets were tested
more defects in blister packs with for each of the
10 micron holes than blue dye three sample types
test methods. investigated (defect
SEPHA WHITE PAPER

3. 02
“DR DIXON STATES THAT THE APPROACH
IS PREFERABLE TO SYSTEMS THAT RELY
ON CONTACTING THE LID MATERIAL
WITH A PROBE IN ORDER TO MEASURE
PRESSURE OR DISPLACEMENT.”
The current industry standard respond in a different manner
for testing blister pack to a perfectly sealed pocket
integrity is blue dye testing, when a vacuum is applied. Dr
which consists of placing a Dixon states that the approach
selection of packs into blue is preferable to systems that rely
stained water, subjecting the on contacting the lid material
packs to a vacuum of typically with a probe in order to measure
400-600mBar for several pressure or displacement.
minutes and then removing
the vacuum, which allows any Blisterscan testing consists of
defective pockets to take up the initially scanning the surface of
dye. The packs are manually each pocket in order to provide
deblistered and inspected for a datum value for subsequent
dye ingress. This technique deflection measurements.
relies on human subjectivity, A vacuum level of 500mbar
and Dr Dixon states that it is is then applied and held for
unlikely that the accuracy he 10 seconds and the pack re-
achieved in his laboratory tests measured. Deflection refers
could be reproduced during to the difference in average
routine factory quality control height when the vacuum is
procedures. applied compared to the datum
value. The vacuum level is then
Blisterscan is a dry, non- reduced to 400mBar and held
destructive technique which uses for a further 30 seconds before
a laser to measure changes in the pack is scanned again. The
the pack profile which result from variation in average height at
applying a vacuum. The lidding the full and reduced vacuum is
material of defective pockets will referred to as collapse.
SEPHA WHITE PAPER

4. 03
Figure 1a. Figure 1b.
Blisterscan results of a pack containing a 30µm hole and a defect free pack
Figure 1a illustrates the typical was recorded for the defect free after testing. The packs which
difference in deflection behaviour packed compared to only 4µm were submerged in methylene
measured by Blisterscan between for the pack containing the 30µm blue stained water and a vacuum
a defect free pocket (bottom) hole. A large hole i.e. one greater of 500mBar was applied. This
and one containing a 30µm sized than ~20µm allows the pressure vacuum level was maintained
laser drilled defect (top). In Figure inside the pocket to equalise to for a soak time of 1 minute. The
1 the black dotted line is the the applied vacuum inhibiting foil vacuum was then released with
profile of the foil surface before movement. Small holes manifest the packs remaining in the dye
the vacuum is applied. It can be as a greater than normal for a further period of 1 minute
seen that a variation in profile collapse when the vacuum level to allow the dye to penetrate any
exists between packs. The profiles is reduced. This occurs as the air defective pockets. The pockets
after the full and reduced vacuum slowly escapes through a small were then opened and the
is applied are shown by the green defect allowing the pressure contents visually inspected for
and purple lines respectively. inside the pocket to equalise with signs of dye ingress.
the applied vacuum.
The solid blue line denotes the Findings
deflection, which is the difference Once the packs had been
between the profiles before and tested by Blisterscan they were Building on Dr Dixon’s initial
after the vacuum is applied, while then subjected to the blue dye study where 100% of 15 micron
the red line illustrates collapse test. Extensive trials observed holes were detected, Blisterscan
(difference between profiles that repeat testing packs on went on to detect 100% of the
at full and reduced vacuum). BlisterScan had no observable 20 micron holes and 99% of
It can be seen from Figure 1 effect on the deflection the 12 micron holes in the final
that the pack with a 30µm hole behavior of the pack, or on whitepaper study. Conversely
does not deflect significantly the dimensions of any defects. blue dye testing was only capable
from the initial profile when the Multiple BlisterScan testing of detecting 85% of the 15
vacuum is applied. The defect of the same defective pocket micron holes, 90% of the 12
free pocket (Figure 1b) however produced repeatable results. The micron holes and 99% of the 20
displays a large deflection and non-destructive nature of the micron holes.
adopts a domed profile as a BlisterScan technique was also
result of the applied vacuum. In confirmed by electron microscopy
this case a deflection of 410µm analysis of defects before and
Figure 2: The destructive
effect of blue dye on a tablet
SEPHA WHITE PAPER

5. 04
12µm Hole 15 µm Hole 20µm Hole Defect Free
Blisterscan detection accuracy 99% 100% 100% 100%
Blue Dye detection accuracy 90% 85% 99% 100%
Table 1 : Blisterscan test accuracy vs Blue Dye test accuracy
Commenting on the results of
the whitepaper Dr Dixon said,
“Blisterscan testing is a rapid
“BUILDING ON
non-destructive test method
which can detect the presence DR DIXON’S INITIAL
of 12um, 15um and 20um sized
defects in pharmaceutical blister
packaging with a higher degree
STUDY WHERE 100%
of reliability than conventional
blue dye testing.” Dr Dixon went
on to conclude that “The non-
OF 15 MICRON HOLES
subjective nature of Blisterscan
testing removes the possibility
of human error and reliance
WERE DETECTED,
on operator judgement, which
is a key element in the correct BLISTERSCAN WENT
identification of small holes using
traditional blue dye testing.”
ON TO DETECT 100%
As manufacturers seek to
improve their levels of quality
control and drive costs down,
OF THE 20 MICRON
Blisterscan represents a
significant improvement over
traditional blue dye testing.
HOLES AND 99%
Sepha believe that the accurate
and repeatable results proven OF THE 12 MICRON
by this academic whitepaper,
mean that Blisterscan is the
definitive method for testing
HOLES IN THE FINAL
blister packs in the modern global
pharmaceutical market. WHITEPAPER STUDY.”
SEPHA WHITE PAPER

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