Caution needed in using oral polio vaccine beyond the cold chain: Vaccine vial monitors may be unreliable at high temperatures
Indian J Med Res 135, April 2012, pp 36-38
Background & objectives: Stabilized live attenuated oral polio vaccine (OPV) is used to immunize
children up to the age of five years to prevent poliomyelitis. It is strongly advised that the cold-chain
should be maintained until the vaccine is administered. It is assumed, that vaccine vial monitors (VVMs)
are reliable at all temperatures. VVMs are tested at 37°C and it is assumed that the labels reach discard
point before vaccine potency drops to >0.6 log10. This study was undertaken to see if VVMs were reliable
when exposed to high temperatures as can occur in field conditions in India.
Methods: Vaccine vials with VVMs were incubated (10 vials for each temperature) in an incubator at
different temperatures at 37, 41, 45 and 49.5°C. Time-lapse photographs of the VVMs on vials were
taken hourly to look for their discard-point.
Results: At 37 and 41°C the VVMs worked well. At 45°C, vaccine potency is known to drop to the discard
level within 14 h whereas the VVM discard point was reached at 16 h. At 49.5°C the VVMs reached
discard point at 9 h when these should have reached it at 3 h.
Conclusion: Absolute reliance cannot be placed on VVM in situation where environmental temperatures
are high. Caution is needed when using ‘outside the cold chain’ (OCC) protocols.
Key words Cold chain - oral polio vaccine - vaccine potency- vaccine vial monitors
Poliomyelitis is a disease caused by poliovirus.
Stabilized live attenuated oral polio vaccine (OPV)
is used to immunize children up to the age of five
years. The vaccine being highly thermo-labile needs a
stringently monitored cold-chain. All the vials of OPV
have a temperature sensitive label, the vaccine vial
monitor (VVM), attached at the time of manufacture,
to prominently display the cumulative exposure to heat.
It is a standard practice to discard vials when VVM
colour changes to grey from white suggesting that the
potency of the vaccine has dropped to >0.6 log101.
It is strongly advised that the cold-chain should
be maintained until the vaccine is administered. In a
recent study2 reliance on VVMs was recommended to
achieve less wastage. There was greater user-preference
for carrying vaccines without cold packs on national
immunization days (NIDs).
It is assumed, that VVMs are completely reliable
at all temperatures. Routinely, VVMs are tested in
an accelerated degradation test at 37°C3,4. The heat
sensitive polymers in the label change colour and it
represents the cumulative exposure to heat. When vaccine potency has dropped to >0.6 log10 (vaccine
unlikely to provide protection), the VVM inner square
becomes darker than the outer reference ring (vial
discard-point)4. It has been proven repeatedly that
the monitors work well at 37°C and the labels reach
discard point well before vaccine potency drops to
>0.6 log101.
However, it is not necessarily true that because
vaccine virus degeneration matches colour changes
on the VVM at 37°C, this will hold true at other
temperatures. At higher temperatures virus may
degenerate faster than the heat sensitive polymer. We
carried out this study based on the known degradation
rate of vaccine virus; to see if VVMs were reliable
when exposed to higher temperatures as can occur
in field conditions in India. In India, in the northern
States of Uttar Pradesh, Bihar and Rajasthan, summer
temperatures rise to 45°C routinely and sometimes go
as high as 50°C5,6. The half life of polio vaccine virus
is 48 to 72 h at 37°C, 24 h at 41°C, 14 h at 45°C and
3 h at 50°C7.
Material & Methods
The study was conducted in National Institute of
Immunology, New Delhi in January 2010. For this
study the VVMs on OPV bottles used for routine
immunization in India were used. The bottles were kept
in the deep freezer at -20°C. The vials were incubated
in a lighted dry-incubator (Galaxy 48S made by New
Brunswick, UK) at different temperatures. The tests
were performed at 37, 41, 45 and 49.5°C. Ten vials were
used for each test-run for convenience in calculations,
in terms of percentages. Time-lapse photographs of the
VVMs were taken hourly, using a Nikon D70s camera
(Nikon D70s, Thailand) controlled by a PC through the
Camera Control Pro 2 software (version 2.5.0, Japan).
The digital images were examined to look for the
time at which VVMs reached their discard-point. Two
investigators (AS and NG) independently examined the
digital images for the discard point and the difference
of opinion (<5% cases) was resolved with the help of
another investigator (JP).
Results & Discussion
At 37°C all 10 vials reached discard point within
43 h (well before 48 h when the vaccine potency
deteriorates to a level that the vaccine is useless). At
41°C the vials reached discard point within 24 h. Here
again the VVMs worked well. However at 45°C, only
three vials reached discard point at 14 h. At 49.5°C no
bottle reached discard point at 3 h which was the half life point of vaccine. Only 40 per cent vials reached
discard point at 6 h, all 10 vials reached discard point
only after 9 h (Table). The Fig. shows the disparity
between virus viability and the discard point of the
VVMs.
Conventionally, VVMs were used within the cold
chain where the vaccine is stored at temperatures below
8°C. Field workers are trained to place reliance on
VVMs8. Experiments using the VVMs outside the cold
chain were done by Halm and colleagues2. They used
20 dose vials, and at the end of the day, unopened vials
were returned to cold storage for use on the following
day, and so on, till the VVM reached discard point.
They found that no vials reached discard point and
needed to be thrown away unused, when this protocol
was utilized. On the other hand, in the control group,
three vials carried in ice-lined vaccine-carriers had to
be disposed of, because the labels got wet and detached
from their bottles. The ambient temperatures went up
to 40°C during the study. Over 90 per cent supervisors
and vaccinators preferred NIDs without ice packs and
this will soon become the standard practice2. There is
support for this form of innovation9.
This study was done in the context of the
temperatures in the states of Uttar Pradesh and Bihar
in India where polio has been difficult to control and
where summer temperatures rise to 45°C routinely and
sometimes go as high as 50°C5. Our findings suggest
that the VVMs are not reliable when exposed to high
environmental temperatures. Previous studies have
shown deterioration in virus levels resulting from thawfreeze
cycles which are not indicated by the VVMs1.
This makes the practice of returning vials exposed to
ambient temperatures, to the freezer for storage at night
and reuse later, particularly risky.
The main shortcoming of our study was that we
did not test for vaccine potency but depended on
literature for determining the half life of the virus strain
at different temperatures. It was not considered crucial
because VVMs are not specific to any one strain of
polio virus but generic to all polio viruses. Studies
recommend looking at total virus load although specific
virus, with differing heat labiality, may have different
rates of degradation4. Under such circumstances,
immunization against one strain may be ineffective
although the total number of virus would be higher than
the number required for passing the test of potency.
The WHO recommends VVMs to be sealed in a
plastic cover and tested in a water bath at 37°C8. In
the present study incubator was used as this was more
likely to mimic conditions in the field. In conclusion, absolute reliance cannot be placed
on VVM in situation where environmental temperatures
are high. Caution is recommended when using ‘outside
the cold chain’ (OCC) protocols.
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