Vaccine Cooling – How important is storage in the cold chain to ensure the safe delivery of treatments?

Summary of topics:

How has COVID-19 Affected the Vaccine Storage and Transportation?

The COVID-19 pandemic has dramatically accelerated the timeline for cold chain storage and distribution and shed light on many aspects of the drug and vaccine cold chain, showing that the ultra-low temperature storage is essential to vaccine production and distribution.

How vaccines work and what the mRNA vaccine is

Infections are prevented by vaccines that prepare the body to fight potential external invaders such as bacteria or viruses. Immune action is triggered by introducing a harmless piece of the pathogen into the body. Most vaccines contain a weakened or dead bacteria or virus. However, a new type of vaccine has been developed by scientists: This type of vaccine uses a molecule called messenger RNA or mRNA for short rather than part of an actual bacteria or virus. These vaccines work by introducing a piece of viral protein (mRNA) found on the virus’s outer membrane. The subject is not exposed to the virus nor does it become infected with the virus. mRNA from vaccines doesn’t enter the nucleus and doesn’t alter DNA.

The potential of mRNA vaccines

Scientists have experimented with mRNA for decades, but the pandemic hoisted the platform into the limelight. Researchers are now exploring dozens of new possibilities for the mRNA platform.
The fight against COVID-19 is not the only field in which mRNA has offered promise. Research has been ongoing for several years to create mRNA-based vaccines against certain cancers including melanoma and gastrointestinal cancer. Additionally, there is research under way to develop mRNA-based therapeutics for other medical conditions, such as cystic fibrosis.

The mRNA vaccines for COVID-19

A characteristic of the COVID-19 vaccines is that they require temperature control for transportation and storage. Based on the manufacturer, there are vaccines requiring a stable temperature at -30° and others even between -60° and -80°, so called ultra-low temperatures. This temperature range is a characteristic of the COVID-19 mRNA vaccines. While for most of the standard vaccines the appropriate temperature range for storage and transportation is +2°C to +8°C.

The cold chain problems with mRNA vaccines

Development of mRNA-based vaccines is ongoing and ultra-low temperature vaccine handling, from production to distribution to point of care injection, needs to be developed to quickly close the gaps at all steps of the cold chain evidenced during the COVID-19 pandemic.
Moreover, the ultra-low temperature storage systems consume a great amount of energy, and the storage systems need to be upgraded to reduce energy consumptions. However, transportation systems also need to offer reliable green systems, that don’t waste tons of CO2 and still face the risk of losing precious vials. Thus, efficient, green, reliable, and easy-to-maintain design for ultra-low temperature storage and transportation is a challenge when it comes to the development of the ultra-low temperature part of the medical cold chain.

  • mRNA vaccine
    Figure 1: A vial of an mRNA vaccine, Spencerbdavis, CC BY 4.0, via Wikimedia Commons

Why is the Temperature Control in Vaccine Transportation so Important?

As anticipated in the paragraph before, temperature control is a relevant part of the transport and delivery process because this type of vaccines needs a stable and ultra-low temperature. During the pandemic crisis, the vaccine manufacturers designed some solutions such as reusable packages for transportation and storage. These packages can keep the temperature for 10 days, storing between 1,000 and 5,000 doses. But if we look at the rural or suburban areas where the local labs and hospitals don’t have the proper freezers and infrastructures in general, the challenge remains even if the COVID-19 crisis has been curbed.

Differences between “active” and “passive” cooling in the cold chain

To better understand the improvement of the last years it’s mandatory to compare the technology solution called “active” cooling, with the previous ones so called “passive” cooling boxes.

Passive cooling

Passive cooling (figure 2) is the most common technology, and it simply consists of surrounding the container of the vaccine’s vials with dry ice to keep the temperature at the right level. The positive features of this solution are that they don’t need electricity and for this reason these boxes can reach, with many difficulties, the so-called “last mile” to deliver vials to rural areas of countries without basic infrastructures such as roads: in some countries the vials were delivered thanks to donkeys. But this solution has many limitations and risks:

  • It’s not eco-friendly due to constant evaporation of high mass of frozen dry-ice (CO2) into the atmosphere;
  • The temperature stability is limited due to the low control of it. When the box is opened, the temperature only decreases;
  • The limited opening time frame is another limitation: the time frame is about 1 minute and maximum two times per day;
  • The duration is limited again, maximum ten days;
  • The availability of dry ice is mainly in the industrialized countries;
  • The total cost of ownership is high in the long term due to constant need of re-filling dry-ice, high energy cost for dry-ice production, and limited re-usability of polystyrene/carton dry-ice boxes;

In addition, if we think about the infrastructures and transportation, the countries with good availability of vaccines are very few: 25 countries, around 2.5 billion of people, and thus 30% of the total population on earth.

Active cooling

Active cooling solutions are so defined because they can keep the temperature at the desired level thanks to technological improvements (figure 3): A condensing unit with compressors and a temperature logger device can control the temperature in the box. 
The range of active cooling solutions consists of electrically powered refrigerators and off-grid refrigerators. Mains refrigerators utilize compressors to elevate the pressure of the gas refrigerant. Off-grid refrigerators, however, consist of two primary categories: the absorption refrigerator system and solar-powered refrigerators. The first operates on a heat-activated thermal cycle and exchanges thermal energy with its surroundings. It typically operates at a pressure lower than atmospheric pressure, regulated by the vapor pressure of the working fluid, such as petroleum gas or kerosene. In contrast, solar-powered refrigerators employ electric compressors that can be powered either by batteries, which store the energy generated by solar panels, or directly by the solar panels themselves.

Conclusions

Vaccines must thus be stored in a limited temperature range; from the time they are manufactured until the moment of vaccination. This is because temperatures that are too high or too low can cause the vaccine to lose its potency, in other terms its ability to protect against disease. Once a vaccine loses its potency, it cannot be regained or restored.

  • dry ice vaccine cooling
    Figure 2: Package with loaded dry ice and payload box insider (passive cooling), CC BY 4.0, via Springer Nature Limited
  • portable ULT active cooling box
    Figure 3: Temperature sensor at -80° on an ULT cooling box (active cooling)

Vaccine Storage and Transportation: The Medical Cold Chain

Vaccines travel by plane from the manufacturer as refrigerated cargo to the country where they will be used. Once they land, they are stored in cold rooms before being distributed to regional and sub-regional cold storage facilities by refrigerated vehicles. From storage facilities down to the village level, vaccines are carried in cold boxes and vaccine carriers, traveling by car, motorcycle, bicycle, or even on foot to immunize even in remote villages.

mRNA vaccine cold chain requirements

Storage and transport equipment such as cold rooms, refrigerators, freezers, cold boxes, and vaccine carriers must comply with performance standards defined by the World Health Organization (WHO).
New mRNA vaccines need to be shipped and stored at extremely low temperatures, and this requires freezers capable of handling temperatures of -80°C.

The constraints of mRNA vaccine cold chain

These freezers are not available at every clinical trial site. As a result, supply chains must be developed to overcome logistics challenges, and the cold chain shipping infrastructure must be robust to build a reliable and safe healthcare supply chain. This means end-to-end solutions for storage and transportation at specific temperatures, from the point of manufacture to the healthcare facilities where they will be used. Cold chain storage facilities must be temperature-controlled with a monitoring system to protect shipments before and after transit, including down to -80°C. During shipments, high-performance portable equipment has to guarantee the temperature requirements specified by the manufacturer.

  • medical cold chain
    Figure 4: The cold chain and vaccine storage from the manufacturer to a medical center

The Importance of Temperature Monitoring Systems and Controls

As anticipated above, the temperature during the transportation is the key element to guarantee the success of the goal: the safe delivery of the vials. Yet how is the temperature controlled and guaranteed?
The manufacturers of medical devices used to move the vials install a temperature logger device directly on the unit at the factory. Data loggers are used to monitor the shipment of various types of sensitive products. Depending on the model, they record various parameters such as temperature, humidity, shock, vibrations, or tilt. In general, they have specific features such as real-time monitoring, lid opening, and the GPS position and alarm messages sent via mail or text to ensure a constant control during transportation.

Vaccine Cooling: Stationary and Mobile Devices

Cooling solutions, freezers, and refrigerators can be divided into two main groups: on one hand we have the devices for stational storage such as vertical freezers and refrigerators which are found in laboratories and hospitals, on the other the devices developed for the transportation such as transport boxes. For standard cooling (+2 to +8°C) that can also be connected to solar panels without the use of batteries and regulators.

Ultra-low temperature stationary cooling

In the stationary field there are ultra-low freezers than can store vaccines, tissues, and human cells, for example (figure 5). The temperatures range between -20° C to -80°C. To respond to the request of energy-optimized ULT systems, we exploited years of development and innovation in electronic control for compressors to develop a specific range of compressors with a new generation of control electronics that can achieve optimized energy consumption as well as guarantee a stable and reliable cooling temperature with various additional features suitable to enhance system monitoring. In terms of suitable Secop products, the top models used for ULT freezers are the NLV12.6CN and SLVE18CN compressors.

Ultra-low temperature mobile cooling

Boxes for transportation can be both active or passive. Passive boxes do not actively cool the cabinet, yet the temperature is kept low by some dry-ice boxes and have some other limitations: There is a high risk of vaccine waste caused by the limited transport stability, and dry ice is available mainly in industrialized countries where there is no need for this solution. Moreover, it’s not easy to find dry ice in remote areas where the solution is needed. There are now some active solutions on the market thanks to technology improvements (figure 6). Secop has developed specific ULT cascade condensing units with premium performances in energy consumption and cooling control and with a maximum attention on the reliability of the system.

The Secop solutions for vaccine storage and transportation

As anticipated, the new solutions are available for both storage and transportation: for storage with a cascade of 2 compressor stages with MN13UVULTM or MS18UVULTM medical grade variable-speed AC compressors in the ULT-stage, and for mobile applications with a cascade of MP2UVULTM DC compressor specifically designed for medical mobile applications in the ULT-stage. With the development of the innovative best-in-class mobile condensing unit for vaccine active transportation, we introduced a solution that offers active control of vaccine temperature until the last mile. This solution makes it possible to substitute passive boxes with increased transportation reliability and a reduced carbon footprint even under severe ambient conditions.
These new technologies help our partners design new generations of cabinets to close the gaps in the ultra-low cold chain for vaccine distribution.

  • stationary ULT freezers
    Figure 5: Stationary ULT cooling systems
  • ULT active cascade mobile solution
    Figure 6: Mobile ULT cascade cooling box

Challenges for the Vaccine Cold Chain

Delivering vaccines to all corners of the world is a complex undertaking. It takes a chain of precisely coordinated events in temperature-controlled environments to store, manage, and transport these life-saving products. This is called a cold chain. The Covid pandemic exposed the various gaps in the current distribution network, showing the need to develop more the infrastructure for medical cold chain and remove constraints to build up a network for ultra-low temperature storage and distribution that is able to serve even emerging countries. The lessons learned from COVID-19 vaccine production and distribution must be reapplied to treat other viruses. Logistics service providers are transforming rapidly to keep up the pace with scientific breakthroughs and ensure the safe delivery of promising new treatments that help save lives.

Vaccine delivery: inequalities in the cold chain

At the end of COVID-19 pandemic we witnessed a different reality for vaccines availability between richer countries with a heavily vaccinated population and poorer countries where the access to new vaccines and the target of vaccinating were far below acceptable levels. Vaccine manufactures can produce billion of doses per month, enough to ensure all targets are met but only if an equitable distribution is guaranteed. To guarantee this target, the lack of ultra-low cold chain maturity in lower income regions must be solved, considering the fragility of mRNA vaccines. There is the need to reimagine a pharmaceutical and healthcare supply chain ecosystem for the future end-to-end cold chain. Moving vaccines can be challenging in less developed nations where the transport infrastructure presents some important gaps.

Vaccine delivery: obstacles to ensuring vaccines availability

We can all appreciate that COVID-19 has brought about the biggest vaccination campaign in history. However, vaccine access has been uneven and biased toward more developed nations. Yet one of the biggest barriers remains the conditions and limitations of local and regional cold chains, and in particular, a chronic lack of ultra-low temperature storage. Building up the required infrastructure filling in the gaps in national cold chain calls for access to the very best technologies available. This ensures vaccine availability not only in urban areas but also to rural communities that may be far away from established health centers. The demand for ultra-cold storage solutions has therefore reached an unprecedented high, and as the vaccine delivery program continues, every obstacle must be gradually overcome.

  • last mile vaccine delivery
    Figure 7: Last mile vaccine delivery with mobile cooling solutions (B Medical Systems)
  • vaccination in rural areas
    Figure 8: Vaccination in rural areas

Challenges for ULT Freezers Technology

An ultra-cold freezer stores contents at temperatures down to -86 °C. ULT freezers are vital in the storage of critical material in medical research facilities, labs, hospitals, and anywhere valuable samples need to be stored safely. Also needed throughout the cold chain infrastructure is a temperature-controlled supply chain that uses equipment and logistics to store, transport, and distribute products to prevent the degradation of temperature-sensitive materials and samples. Recently, they’ve become associated with their extensive use during the global health crisis associated with the vaccinations campaign to fight the COVID-19 pandemic (figure 9).

A power outage can cause loss of entire batches of vaccines vials

While a power outage can be annoying when it happens at home, for medical research, it can be an absolute disaster. The reliability of these freezers is fundamental to guarantee safe storage of the precious contents. To close the gaps in medical cold chain storage and distribution for ultra-low temperature, a new generation of equipment is required to increase reliability, reduce energy consumption, introduce green refrigerants, and feature a smaller carbon footprint.

The importance of maintaining low power consumption across the ULT cold chain

The focus on mRNA therapeutics requires ultra-low freezers for various steps in production, including decentralized into small clinics that requires ultra-low freezers that fit into smaller spaces.
The increased demand for cold chain development could drive up power consumption due to refrigeration’s intense energy use. ULT freezers consume an important amount of electrical energy since they must grant a low and stable temperature. In hospitals and labs, ultra-low freezers are identified as one of the larger sources of energy consumption. End-users thus need to carefully consider the energy consumption of ultra-low freezers. Ultra-low freezers aim at meeting the Energy Star and Energy Labelling requirements, and future products will have greater transparency in term sof energy consumption.

Variable speed technology and natural refrigerants can support the vaccines cold chain

To support the demand for lower energy consumption and higher efficiency for medical appliances, manufacturers are adopting new solutions such as variable-speed compressors. On top of reducing energy consumption this technology provides several additional benefits, from reducing noise to improving product longevity because it reduces stress on system components. By consuming less energy, these systems also emit less heat, thereby cutting air conditioning costs for installation areas.
At the same time, the regulatory landscape for cold storage is also evolving with the phasing out of hydrofluorocarbon (HFC) refrigerants linked to global warming. Natural refrigerant hydrocarbons such as ethane and propane have enabled the adoption of sustainable products that perform better.
Of course, sustainability needs to be balanced against product performance. The market must move towards more sustainable refrigerants and target as well improved efficiency to focus on further reducing energy consumption. However, these trends have to be carefully considered so that they do not reduce a product’s performances and ability to recover temperature quickly.

The ULT freezer: product reliability is fundamental

For ULT freezers in the medical cold chain, the key challenge is assessing reliability. When a ULT freezer goes down, the consequences are not limited to repair or replacement only. In many cases the freezer must be revalidated for biomedical use and the product moved to another location. The content inside these freezers is precious and any failure can cause serious setbacks in terms of time, money, and research. The reliability of the product is paramount.
The ULT freezers of today are equipped with monitoring systems that ensure the safety of their contents in the event of an unexpected incident.

  • DHL whitepaper vaccines transportation
    Figure 9: Vaccines transportation remote areas are coloured in orange and red, source: DHL Group, Whitepaper "Delivering Pandemic Resilience", September 2020

Secop's Contribution to ULT Cold Chain Development

The biggest concern for ULT freezers is sample safety. By far the most common safety concern for ultra-low freezers is compressor failure, among the possible sources for freezer failures. That is why an ultra-low temperature condensing unit with its compressors is a critical building block to support the development of the ultra-low temperature cold chain. This guarantee stable performances, low energy consumption, optimization for green refrigerant conversion, and overall maximum reliability.

Secop's experience in serving the cold chain

Secop looks behind the freezer door and makes sure the heart of the freezer, the cooling solution, is designed with innovative technologies to guarantee performances, efficiency, and reliability. To support advancements in the new ULT medical cold chain, we have developed various solutions for the new generation of ultra-low storage units, exploiting decades of experience in medical refrigeration improvements and cooperation with the major worldwide leaders in medical cabinet design.
To support the conversion to green refrigerants of ULT systems, we have used our core knowledge in hydrocarbon green refrigerants and introduced as well as optimized the use of R290 and R170 green refrigerants, by introducing a range of products that can support a fast conversion to low GWP refrigerants in medical systems.

Secop provides innovative cooling solutions for the ULT cold chain

To respond to the request of energy optimized ULT systems we exploited years of development and innovation in electronic control for compressors to develop a specific range of compressors with a new generation of control electronics. This range provides optimized energy consumption, and in addition guarantees a stable and reliable cooling temperature with various additional features suitable to enhanced system monitoring. The top models used for ULT freezers are the NLV12.6CN and SLVE18CN compressors. For mobile active cooling, Secop has developed, as pointed out above, the technology for an ultra-low temperature cooling system. This system has been optimized for the last mile of distribution for the new generations of vaccines and offers mobile operation even under extreme ambient conditions such as in tropical regions. This dedicated condensing unit features a compressor cascade solution with a MP2UVULTM (low stage) and a BD100CN (high stage) compressor and makes use of Secop’s experience in medical applications, vaccine solar freezers, and mobile solutions by combining all these applications. Battery-driven active cooling systems for mRNA-based vaccines provide many advantages compared to existing passive cooling (dry ice) transport boxes.
Active systems offer temperature control, do not need huge quantities of dry ice, are re-usable, do not waste tons of CO2, and prevent vaccine wastage. They are suitable for any distribution point, including in remote areas where the availability of CO2 cannot be guaranteed or ambient conditions are too severe.

Benefits:

  • Safe active fully automated mobile solution based on a 2-stage speed-controlled compressor cascade system with a flexible temperature range from -20°C to -86°C even in tropical ambient conditions (43°C)
  • Ideal solution for mains voltage independent transport and storage of mRNA-based COVID-19 and Ebola vaccines and CGT specimens
  • Low energy consumption and fast pull-down time using low GWP green hydrocarbon refrigerants.
  • Reliable and precise temperature setting and control and reduced risk of wasting temperature sensitive specimens and vaccines
  • Reliable long-lasting system with low TCO life cycle
  • Designed for AC/DC global voltage range and optimized for low-grid regions
  • Easy °CCD® controller customization via Tool4Cool® software

 At the top of this page you can see a video to better understand this cooling solution.

  • Secop ULT condensing unit
    Figure 10: Secop ULT condensing unit (side view)
  • Secop ULT condensing unit
    Figure 11: Secop ULT condensing unit (top view)

Recommendations

WHO (World Health Organization) demonstrates in a training video global vaccine cold chain, how to purchase, install, and manage vaccine cold chain equipment in a proper way. This is for standard vaccines that need to be stored and transported in a temperature range of +2°C to +8°C, appropriate for most standard vaccines.

For temperature-sensitive vaccines, such as new mRNA vaccines, the temperature range for storage and transport is different: below -70°C with standard set-points of about -86° to ensure long-term efficacy of vaccine doses. All other information in the video is fully appropriate also for the medical/vaccine ULT cold chain. In the recent PQS (Performance/Quality/Safety) catalog by the WHO, the first ULT/ultra-low temperature equipment can be found (page 208), with further will follow.

Technical Literature:

  • Compressors for Medical Cold Chain Solutions

    Compressors for Medical Cold Chain Solutions

    | Literature | Quick References

    Download (3.47 MB)
  • ULT Active Mobile Medical Cooling Technology, R170, R290, 12-24 V DC

    ULT Active Mobile Medical Cooling Technology, R170, R290, 12-24 V DC

    | Literature | Leaflets

    Download (2.06 MB)