“Overall, securing an end-to-end unbroken cold chain – from vaccine manufacturer to the site of injection, is an extremely hard thing to do. It requires constant monitoring and remedial action.
“Why? The constituent parts of the cold chain are vastly distinct. They are separately operated but uniformly coordinated systems within an overall vaccine supply chain,” said Raja Rao, director, cold chain strategy and markets, B Medical Systems.
Vaccine distribution is complexity at its finest, he said.
“It is almost always the case that the cold chain is relatively strongest between the site of manufacture and arrival at the port of entry, from Belgium to Nairobi, for example. This is because vaccines are air-shipped in modern, cold storage containers, which are either actively powered or passively kept cold by special materials with a lower freezing temperature than water. In both cases, the temperatures are monitored 24/7 through electronic tags.”
The relevant example of this in the US would be the Pfizer ultra-low temperature (ULT) shipping container, which must keep the vaccine at -70-80°C. These are packed in a shipping bag - about the size of a large pizza box - with dry ice able to maintain the temperature at that level for up to 10 days, said Rao.
In terms of storage, very few potential administration sites are equipped today to handle the storage of this and potentially other vaccines, which need to be kept this cold, he told BioPharma-Reporter. "The exception to this would be hospitals, research labs and universities. Yet it can be assumed that these units would not have sufficient spare capacity. A human being, for example, wouldn’t last five minutes wearing arctic cold gear fully exposed to this extreme low temperature. Even fewer sites in the developing world are prepared to handle storage at this level.”
In the US, and presumably in Europe, guidance is being provided by Pfizer to use the shipping bag as a storage device as well, continued the cold chain strategist.
“This presents new challenges, as the freeze duration of these bags will vary depending on the ambient temperature they are being kept. Putting the bag in a standard -20°C freezer would extend this duration, for example. However, health care workers would need to both somehow monitor temperatures of the shipping bag and add dry ice - a commodity in short supply - if they are unable to distribute the vaccines to patients in a timely manner.”
Public health programs and private health care providers are much more prepared to handle storage and transport of vaccines requiring storage temperatures at -20°C, and even more so, at 2-8°C (standard refrigeration temperatures), he added.
Moderna has recently disclosed that its mRNA COVID vaccine candidate could safely be kept at 2-8°C for up to 30 days. “This effectively, potentially, makes this a standard cold storage vaccine, similar to the ones in childhood immunization programs,” said Rao.
The World Health Organization (WHO) says that over half of vaccines are wasted globally because of temperature-control logistics and shipment-related issues.
While Rao agrees vaccine wastage is a significant issue, and challenges both immunization coverage and program costs, he argues the wastage rate would certainly not be as high as over 50%, as claimed by the WHO.
“Typically, wastage happens in two areas, in in-country transport and vaccine administration at health centers. Most portable vaccine carriers and cold boxes in use today simply do not have the ability to keep cold beyond 12 hours, especially when subject to extreme hot temperatures.
“Transportation from a district health depot to immunization sites on motorcycle, boat or bicycle is both time consuming and magnifies the other problem of being able to actively monitor temperatures.
“Even though vaccine vials purchased by UNICEF and financed through the Gavi Alliance (for the world’s lower income and lower middle-income countries) have a vaccine vial monitor, which changes color if the vial is expose to high temperatures, the wastage still occurs.
“All of the studies I’ve seen or sponsored while leading the cold chain program at the Bill and Melinda Gates Foundation, indicate that about 50 to 75% of all vaccine wastage happens during in-country transport (in the developing world). Moreover, some vaccines requiring 2-8°C are exposed to freezing temperatures from improperly using icepacks. Vaccine freezing can render vaccines ineffective and unsafe. Yet, overall, total wastage is about 10-20%.”
Immunization logistics gaps
When asked what gaps in global immunization logistics remain that could, potentially, create hurdles in terms of effective distribution of COVID-19 vaccines, Rao said it depends on the geography in question and other factors but, in general, common challenges globally include significant ULT storage gaps, for -70°C and -20°C, to a lesser degree.
“Just one of B Medicals’ ULT medial freezers, the U701, can store up to 10,000 doses of the Pfizer vaccine, based on a 10ml 2-dose scenario.”
There is also a lack of a centralized Logistics Management Information System (LMIS) to keep real-time track of vaccine storage, demand, and order parameters to help ensure an efficient supply chain and maintain optimal throughput of the system – a critical aspect when talking about the -70°C vaccine, he said.
“Programs cannot afford to let those vaccines pile up, or they risk wastage of those vaccines at worst, or a slowdown in immunization goals, at best.”
Continued reliance on manually entered temperature management systems is another issue, said the expert.
“It is quite sobering to see many private health care providers in the US and Europe still relying on clipboard and pencils to log daily temperatures inside of storage units.
“What’s needed is something called, Remote Temperature Monitoring (RTM). These digital systems are built into the freezers and refrigerators and connected to cellular or WIFI networks giving managers a dashboard type view of the current temperatures of all units, and historical performance. They will signal an alarm if temperatures fall below or above the specified range. B Medical Systems has pioneered the use of RTM technology in all of its units its sells globally.”
B Medical Systems, he said, has been supporting immunization programs since the 1970s, when, as part of its then parent company, Dometic, it was invited by the WHO to be a partner in its ambitious plans to even the playing field of access to childhood immunization between developed and developing countries.
That works continues to this day supported by the Gavi Alliance and UNICEF, he said.
“And we have learned a great deal about medical refrigeration and freezer needs and gaps since then and we are in a constant cycle of innovation to support governments, pharmaceutical companies, laboratories, and hospitals.
“Our U Line of medical-grade ULT freezers, for example, can maintain operating temperatures even when the ambient temperature is +43°C (+109°F). Our full line of Solar Direct Drive (SDD) refrigerators can maintain 2-8°C for more than three days if the solar panels are damaged by weather.
“Maybe the most relevant solution we’ve developed today to help in the fight against COVID-19 is multi-mode temperature technology. The technology inside our -20°C freezers allows health care works to turn the freezer into a refrigerator with the turn of dial, going from -20°C to 2-8°C. It can switch from storing one of the mRNA vaccines to a solution for routine liquid COVID-19 vaccines (e.g., from Oxford/Astra Zeneca) without the added cost and delay to a vaccine program. And our ULT freezers work the same way by going from -80°C to -20°C. This is all within the same unit, and without the need to procure different units for the different vaccine candidates.”
Vaccine delivery timelines
What kind of timeline are we looking at from the approval of COVID-19 vaccines to their eventual delivery to priority population groups in global markets?
“In short, quickly. The COVAX facility has made investments in a portfolio of COVID-19 vaccine candidates, hedging its bet like other national governments and intergovernmental agencies. As soon as those vaccines roll off the production lines, they will be packaged and shipped by air, perhaps even the same day, directly from facilities in Asia and Europe to the national cold storage warehouses and likely even regional hubs across the globe.
“The question, as I’ve just outlined, is whether or not those programs, and, frankly, similar ones in the West, will be able to overcome their cold chain gaps and efficiently execute on the planning of their COVID-19 supply chains, so the world can get back to some sense of normalcy.”
Raja Rao has over 20 years of experience in global health and development. He provided leadership and support to global coalitions of partners such as UNICEF, WHO, and Gavi and supported UNICEF in creating market-based procurement strategies.