In response to the Ebola outbreak, researchers are launching clinical trials in Sierra Leone and Guinea to determine the efficacy of Ebola vaccine candidates. An important requirement in keeping the Ebola vaccine safe and effective throughout a trial is keeping the vaccines at extremely low temperatures until being thawed for injection.
Due to the urgency of the Ebola outbreak unusually low temperatures are required to store and transport the vaccine candidates. (Typically, separate studies that look at the efficacy of vaccines at different storage temperatures are completed before a trial commences.) A storage device was needed to keep the vaccine candidates between -60° and -80° Celsius while being transported and distributed among healthcare workers.
The World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) identified conditions for a storage device to safely transport vaccines in Sierra Leone and Guinea, including:
- Stay cold (-60° and -80° C) for a minimum of three days without external power, in extreme heat
- Very low probability of device failure (i.e. the temperatures will be maintained)
- Store enough vaccinations for 200 doses at a time, and treat a community of up to 9,000 people
- Be intuitive and easy-to-use for health workers
- Be transportable portable enough for long-distance travel on rough roads
- Require minimum maintenance
- Keep a robust log of vaccine temperatures
- Track performance and location
If you have been following IV Lab and our partners at Global Good, you likely know about our passive vaccine storage device, the Arktek™. This invention employs super insulation techniques similar to those used to store cryogenic fluids and protect spacecraft from extreme temperatures. Once stocked with water ice, Arktek can keep life-saving vaccines at appropriate temperatures for a month or more, without any source for external power.
The Arktek was initially designed for vaccines that required storage temperatures between 0° and 8°C under a wide range of ambient temperatures, including environmental temperatures of 43°C. The temperature difference for the Ebola vaccine trials are three times that of the initial Arktek use case, -60 to -80°C storage temperatures in up to 43°C environmental temperatures. Fortunately, the original Arktek design allowed IV Lab and commercial partner AUCMA to make significant modifications to the device to meet the very specific standards and constraints outlined by the WHO and CDC for Ebola vaccine trials, chief among the requirements are the temperature requirements for the vaccines: -60° to -80° C.
To determine if a modified Arktek could meet the requirements of the Ebola vaccine trials, a team of engineers at IV Lab undertook substantial research and testing. First, the team needed to identify a material to replace the water ice used for thermal storage inside the Arktek to keep the vaccines at such low temperatures.
In the developed world, dry ice is the material of choice for storage temperatures between -60° and -80°C because of its high energy storage by weight, however it is unavailable in the Ebola affected areas. The team identified a phase change material (PCM) designed for -78°C as a potential alternative, however very little information on the material was available. The team quickly started a variety of material studies to determine if it could fulfill the requirements, as well as to understand its performance and use (i.e. become experts very quickly). Thankfully, the -78°C PCM worked, and was able to keep vaccines cold inside the Arktek for over six days, one of the requirements outlined by the WHO and CDC.
Another technical challenge the team evaluated was whether the Arktek could structurally withstand the extreme cold. At -60° to -80° C materials can become very brittle and shrink; different materials will shrink at different rates as the temperature changes. When you have parts made of different materials joined together and expose them to extreme temperature change it adds stress to the parts. If the stress if high enough, the parts can break. So our team designed a series of tests to confirm the Arktek would withstand the cold. The device itself withstood the vibration and drop tests, however the original plastic ice-blocks within the device became too brittle and shattered when dropped. New ice-blocks were created using a different plastic, as well as aluminum ice-blocks, due to concern that the special PCM might not be compatible with the plastic, and could corrode or seep through.
To verify that these Arktek modifications met the required temperature and hold time specifications, IV Lab’s team conducted the following verification:
- Durability (vibration and drop testing of the Arktek and individual components at low temperatures)
- Measuring the heat leak of the device with an ambient temperature of 43° C and an internal temperature of -78° C
- Hold time in a 43° C environment with multiple daily vaccine access (up to 8 times a day)
- Hold time in a 32° C environment with multiple daily vaccine access
- Hold time with dry ice (instead of PCM) at 43°C ambient conditions
- Thermal cycling of the PCM to see if it degraded over time
- Thermal cycling of the DF Arktek to see if it degraded over time
- Measurement of the internal temperature distribution within the device.
Vaccines trials require carefully maintained data on the vaccine candidates, this way the research can focus on the efficiency of the vaccine without other variables. The original monitoring system was not designed for the low temperature requirements, so IV Lab’s team designed a new system to monitor them to the specifics required by the trials.
As part of the monitoring system requirements, a notification system was requested to send a SMS warning message if the vaccines were nearing the safe temperature range. Because of the thermal characteristics of the device and the phase change material, the team was able to design an alert system that provides a warning one-day before the vaccines exceed the safe range. This gives the trial team enough time to retrieve and recharge the Deep Freeze Arktek.
In addition, a multitude of tests were also performed in order to determine the optimal way to use the device. The results of these tests were then transformed into use protocols and a user’s guide. This material was very useful in transferring the information to the end users (the CDC and WHO in Sierra Leone and MSF and WHO in Guinea).