POST 00400E : PROTECTION OF MORE COLD SENSITIVE VACCINES

POST 00400E : PROTECTION OF MORE COLD SENSITIVE VACCINES Follow-up to Post00391E (26 November 2001) and Post00386 (23 October 2001) 19 December 2001 ______________________________________________________________________________________ 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. ___________________________________________________________________________________ 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. ______________________________ 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. ____________________________ 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." ___________________________ 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. ______________________________________________________________________________________ -----------------------------------------------------------