POST 00400E : PROTECTION OF MORE COLD SENSITIVE VACCINES
Follow-up to Post00391E (26 November 2001) and Post00386 (23 October 2001)
19 December 2001
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1. CAN CURRENT VVMs BE USED TO PREVENT FREEZING? Post00391E, point 3
In Post 00391E, James Cheynes from PATH had suggested
that WHO calls for inventors of a new "freeze indicator". Carib Nelson
had reported that PATH continues to comb technologies
and talk with potential manufacturers to develop such a product but no
suitable technology has yet emerged.
Ted Prusik from LifeLines Technology sent a
comment concerning that point. He doesn't seem to share the enthusiasm of
James Cheyne or Bob Davis about
possibilities for the discovery of a new technology. Here are Ted's comments :
"Several years ago, LifeLines attempted to develop a freeze indicator.
Performing this research allowed us to understand that the technical
problems involved in the development of a freeze indicator are more complex
than that of the heat-sensitive VVM. Unhappily as of today, we have not
identified a technology which could be developed for a freeze indicator.
We are ready to continue to think about the application, but we anticipate
a long and costly discovery and development process".
It should be stressed again that VVMs are a currently available tool that
could play a major role in reducing vaccine freezing, as Carib Nelson
had commented. VVMs will allow out of the cold chain
storage, transport and delivery (of vaccines), he added.
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2. FREEZING IN THE COLD BOXES : WELL-DOCUMENTED PROBLEM, BUT HOW PRACTICES
WOULD CHANGE? Post 00391E, point 6
Conditioning icepacks is the procedure to bring their temperature from
freezer level (more or less -25?C) to 0?C. It is so far considered the key
to prevent freezing due to too cold icepacks. The standard advice has been
that an icepack is adequately "conditioned" as soon as beads of water cover
its surface. Experiments have shown that this is not always the case and
that cold-sensitive vaccines can still freeze inside the cold box even when
icepacks have apparently been conditioned correctly.
Andrew Garnett had suggested in his
"Guideline for establishing or improving primary and intermediate vaccine
stores", a procedure for conditioning icepacks. As was reported in Post
00391E, the procedure which attempts to take account of Anthony's findings
is the following :
1. Lay out icepacks, preferably in single rows but never in more than two rows.
2. Leave a 5cm space all round each icepack.
3. Wait until there is a small amount of liquid water inside the icepacks.
This will take up to one hour at +20?C and rather less at higher
temperatures. Shake one of the icepacks every few minutes. The ice is
conditioned as soon as it begins to move about slightly inside its container.
Andrew wants to explain further. "The logic of the proposed procedure, he
says, is that the presence of some liquid water in the icepack indicates
that the ice is at, or near to, the 'phase transition' stage. However,
based on Anthony's evidence, this is still not going to prevent the
temperature in the cold box eventually dropping slightly below 0? C.
The reason for laying the packs spaced out in single or double rows is to
reduce the 'microclimate' effect which arises when icepacks are laid close
together in a large block - the ones in the centre of the block lie in a
pool of cold air and Anthony's evidence indicates that these 'condition'
significantly more slowly than the ones at the edge - the inverse of the
'Emperor Penguin' effect.
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Ian Wylie contributed these interesting comments based
on his experience in Northern Sudan. On conditioning icepacks to ensure
that their temperature is 0?C before they are introduced to the space to be
refrigerated, Ian has two points to make, the first of which is a human
issue and the second a technical one.
During extensive field research among governmental, I & NGO workers in N
Sudan who were engaged in delivering PHC at field level, I did not record a
single incident of cold packs being "conditioned" Further during detailed
interviews concerning practice I did not record any technician or
co-ordinator being aware that this was a recommended action. I appreciate
that N Sudan is a difficult area, but believe that this may highlight a
number of issues:
Firstly, there may be a training issue relating to the dissemination of
information to some of the more difficult areas of EPI operations.
Secondly, from the field perspective much carefully considered guidance
based on thermodynamic considerations, like that of conditioning icepacks,
appears entirely arbitrary because the thermodynamic understanding required
for it to appear logical is lacking. The lack of understanding was found in:
Expatriate and National Doctors
Expatriate and National Logisticians
National Medical assistants and Cold Chain
Technicians.
as evidenced by a question asked by an international doctor: "why if we
freeze the icepacks to -10?C is it not 10 times more effective than if we
freeze them to 0-1?C ?"
The physics of stored cold refrigeration and holdover is non trivial to lay
people, involving as it does, non steady state heat transfer and latent
heat, and my personal view is that the engineers may need to slow down to
ensure that what is distributed is intelligible to colleagues from other
areas of professional expertise.
The second main point is more fundamental. Conditioning the icepack may
prevent the temperature in the stored cold system dipping to -4?C to -6?C
when new icepacks are introduced, but it does not alter the fact that the
cooled environment is going to trend towards an equilibrium temperature of
0?C effectively until the phase change in the water is complete.
Therefore while the conditioning process may make the freezing less visible
to monitoring for a variety of reasons, probably including reading
inaccuracies by technicians, it does not mean that vaccine damage will be
avoided.
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A small group initiated a discussion based on Ian's comments. It inspired
WHO to make a series of new field and laboratory tests that may lead to a
policy change. Highlights from that discussion are reported here:
Anthony Battersby says that nothing will actually
prevent the internal temperature of a large well insulated cold box from
stabilising at a temperature below zero. The advice, he says, to wrap the
freeze sensitive vaccine in newspaper is quite useless for vaccine in a
large cold box.
He reports that Allan Bass also has experience of freezing in cold boxes
from Uzbekistan. Our problem, highlighted recently by John Lloyd is that
the new freeze sensitive vaccines freeze at a much higher temperature than
DPT. Hep B freezes at -.5?C so do the pneumococcal vaccines. I for one do
not feel comfortable with a margin of only 0.3?C. John suggested that we
should take Hep B out of the cold chain at the lower levels, but what about
services to people in cold climates? Well over a billion people live is
such climates. What about the confusion that will arise in people's minds
when some vaccines are to be kept cold and some are not? If after 20 years
the message about conditioning ice packs has not been absorbed how can we
ensure that new messages will be?
If we take Hep B out of the cold chain then what is the storage temperature
to be? How long may we keep the vaccine at that temperature? How will we
know the conditions it has been stored in before we take it out of the cold
chain? I do not know the answers but we need to have them, now that GAVI
funded initiatives are making Hep B almost universally available."
Anthony is very grateful to Ian for having raised a knotty problem that has
been sculling around for a long time.
Hans Everts, Technical Officer /EPI at WHO Geneva agrees
with Ian Wyllie's conclusions. During the years that he gave cold chain
trainings in the countries, he always taught the conditioning method, but
has not seen many health workers follow it up. A question that needs to be
addressed as soon as possible is the causal relationship between freezing -
quality of the vaccine - sero conversion.
Lots of studies have shown that some antigens lose potency due to freezing,
but the impact on sero-conversion, which after all is what it is all about,
is much less clear. Far from wanting to minimize the freezing problem we
must have a much better grasp on the problem. Some countries have
eradicated polio with a vaccine that far from complies with the WHO
requirements and given the quality of the average cold chain it is
surprising immunization programmes had the impact on disease incidence they
seem to have had.
Based on the ongoing discussions, Umit Kartoglu, Technical Officer/ATT at
WHO Geneva , had preliminary contacts with a group of
EPI managers who were participating in the 9th Task Force on Immunization
and 8th ARICC meeting that were held in Addis Ababa, Ethiopia, 4-7 December
2001. All EPI managers said that conditioning icepacks are not well
practiced and they did not think that a new method of "waiting longer
hours" would work. More creative solutions are needed. As agreed in the
side meeting, he started to write up a summary of available technologies
and practices to protect more freeze sensitive vaccines. When reviewing the
international packaging and shipping guidelines, he started asking himself
the following questions:
* For international shipment of (freeze sensitive) vaccines, we do not ask
manufacturers to use frozen icepacks. Why then are we making the life more
complicated for field staff with frozen icepacks?
* Isn't it a bit awkward that we tell people first to freeze the icepacks
and then thaw them afterwards? Why they cannot just use cold packs?
* Cold Chain Monitor (CCM) card indicates that even if all ABC windows are
turned BLUE, all freeze sensitive vaccines can be used. For all ABC windows
to turn blue it takes 11 to 14 days at +12?C to +21?C. And as the
transportation of vaccines from say a central store to an intermediate or
service level would never take more than a day, why we are pushing the
limits with frozen icepacks? If the issue is to prevent them being exposed
to heat, we have quite a large tolerance here. So, cannot we just use cold
packs?
Umit continues: "I started to discuss these questions with a group of
colleagues in WHO and in other partner organizations. As a reality check,
first I talked to Mr. Paul Tollet from GSK to learn all details of DTP-HepB
vaccine shipments. As expected, DTP-HepB (which freezes at minus 0.5?C) is
transported with COOLED PACKS (at +2?C to +8?C). International packaging
and shipping guidelines requires that the warmest storage temperature of
the vaccine does not rise above +30?C in continuous outside ambient
temperatures of +43?C for a period of at least 48 hours; and for vaccines
sensitive to freezing only, the coolest storage temperature of the vaccine
must not fall below +2?C in continuous external temperatures of minus 5?C
for a period of at least 48 hours.
Now, the challenge is to show that these conditions can be met with
different models of cold boxes using only +2?C to +8?C cooled packs. Field
tests monitoring actual vaccine transportation and test at laboratory
conditions will be initiated in December. We are hoping to get results
pretty soon that may lead us to a policy change in transportation of
vaccines. VVMs would definitely ease everybody's life, but it may take some
time for all vaccines to have VVMs on, and something has to be done to
advise smart solutions to the field. Of course, as a start point we should
be thinking of separating OPV transportation from all other vaccines since
we do not have such technology that provides enough cold for OPV and at the
same time protect freeze sensitive vaccines from freezing. Using cold packs
will also be the first concrete step towards taking vaccines out of cold
chain."
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Carl Erikson also contributed these comments on point
6 of POST 00391E.
In regard to John Lloyd's response to his contribution to
TechNet 0391E, Carl wants to clarify that the vaccine "refrigerator" is
like a vaccine carrier or vaccine cold box. There is no refrigeration
system in it. It would have to be replenished with ice. Vaccines would be
safe from freezing unless the ice cooled way below zero. It would be used
in conjunction with a separate icemaker, such as an ISAAC Solar Icemaker.
It is designed for permanent installation at a health clinic.
One characteristic of the ISAAC, Carl says, is that the ice is not
sub-cooled ("conditioned"), when it is operated properly. This is because
the amount of water put into the ISAAC is just the amount that would freeze
according to the amount of refrigerant available.
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