Port to patient: Improving country cold chains for COVID-19 vaccines

In many developing countries, limitations of existing cold chains will provide challenges for COVID-19-vaccine distribution. Strategic distribution planning and targeted investment can help.

The global response to the COVID-19 pandemic involves the largest ever single vaccination effort. As of August 22, 2021, there have been approximately 4.9 billion worldwide COVID-19-vaccine doses administered and 34 million are being administered globally every day. Yet there are still many more doses that need to be procured and administered: only 1.4 percent of people in low-income countries have received at least one dose. 1

There has been a global commitment by world leaders to ensure equitable distribution of vaccines through the likes of the African Vaccine Acquisition Trust (AVAT), the COVAX mechanism, and other multilateral deals. However, vaccine inequality is evident around the world, with high- and upper-middle-income countries having secured around 6.0 billion of the 8.6 billion vaccine doses available. 2 In Africa, the African Vaccine Acquisition Task Team of the African Union and the COVAX consortium are hoping to secure 720 million doses of COVID-19 vaccines to achieve 60 percent coverage in Africa by June 2022.

WHO has so far granted an emergency-use listing for six COVID-19-vaccine products (those by China National Pharmaceutical [Sinopharm], the Pfizer and BioNTech collaboration [Pfizer–BioNTech], Janssen Global Services [pharmaceuticals arm of Johnson & Johnson], Moderna, Sinovac Biotech, and the University of Oxford and AstraZeneca collaboration [Oxford–AstraZeneca]), with an additional seven products undergoing dossier review by WHO as of August 19, 2021. 3 Many countries also have local regulatory approval to use other vaccines that are not yet approved by WHO or a stringent regulatory authority (SRA).

Each of the COVID-19 vaccines has a different profile, but they all have one thing in common: the need for cold-chain storage, ranging from around –70°C (–94°F) during specialized shipping to around 2 to 8°C (36 to 46°F) when administered (Exhibit 1). 4 In some cases, manufacturers are working on more thermostable versions of their vaccines, but for now, countries are having to consider how best to plan for distribution to their citizens based on existing thermal-stability profiles and available supply-chain solutions.

Each of the COVID-19 vaccines has a maximum storage duration based on temperature.
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Broadly speaking, developing countries have less mature cold-chain systems than do high-income economies, with various degrees of maturity within them. Thus, they may want to consider how best to ensure that their cold-chain systems can support their COVID-19-vaccination goals, such as vaccinating 20 percent of the total eligible population in 2021. 5

In a previous article, our colleagues discussed the challenges of getting the vaccines from manufacturing plants to countries’ receiving ports. In this article, we seek to provide visibility on four areas:

  • the pathway that vaccines will likely follow from port to patient, and the specific cold-chain requirements, within developing countries
  • the specific challenges related to the cold chain and cold-chain equipment (CCE) within developing countries
  • the steps that countries may wish to consider to improve their cold-chain systems and their distribution planning, with a resulting improvement in the effectiveness of their COVID-19-vaccination programs
  • how investments in cold chains for COVID-19 vaccines could be made through the lens of longer-term sustainability of the immunization system

Visibility into what happens from port to patient and cold-chain requirements

The vaccine supply chain in most developing countries is complex and fragmented, with many different configurations, levels of supply-chain maturity and performance, and degrees of private-sector involvement. Exhibit 2 shows three typical supply-chain models that vary based on whether the procurer is the government, a nongovernmental organization, or the private sector. Regardless of the procurer model, in most countries, the government plays a major role in the planning, operations, and monitoring of the COVID-19-vaccine supply chain.

In-country supply-chain models for getting vaccines to patients vary based on different procurers.
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Most vaccines will travel the following logistics step in the supply-chain pathway (Exhibit 3):

  1. Vaccines arrive at the port of entry by air, land, or sea in specialized cooling containers as packaged by manufacturers.
  2. Vaccines are processed and then cleared by port authorities, as well as health and quality regulatory bodies. This can take one to 14 days, depending on the local approval process.
  3. Trucks transport the vaccines in their original packaging to a central medical warehouse, which is usually near the port of entry:
    • Ideally, the trucks are refrigerator or freezer trucks with their own temperature-control capability. But in many countries, such specialized vehicles are not available, and standard large-haulage trucks are used instead.
    • This can take one to three days, depending on the bulk and number of available trucks.
  4. At the central medical warehouse, the regulators perform additional quality checks, and the logisticians “break bulk,” or split the packaging into units that can be transported to specific regions of the country:
    • A best practice is for the splits to be done by trained warehouse staff wearing special cold-storage clothing and within specialized freezers or cold rooms that maintain the required temperature and preserve the cold chain.
    • The methodology for the split of the vaccine packages is typically based on a preprepared allocation plan indicating how many vaccine doses should go to specific areas of the country.
    • The process can take one to five days, depending on the amount of vaccine doses and the availability of trained personnel and equipment.
    • Usually, the vaccine units may be kept in the manufacturers’ subpackaging, thus preserving the cold chain. However, if the manufacturer’s packaging is broken and vaccine vials are exposed outside of the packaging, the appropriate cold-chain temperature (in some cases as low as –70°C) still needs to be preserved. 6
  5. Trucks move the products to the cold rooms at district, state, or regional warehouses:
    • Ideally, specialized refrigerated trucks are used, but in developing countries, regular-haulage trucks transporting vaccines in specialized storage containers are usually used.
    • The trucks may also carry the syringes required to administer vaccine doses, or those can be transported separately.
    • Transport usually takes one to five days for a one-way trip, depending on the distance to be covered.
    • Different trucks are usually needed, subject to the volumes to be transported and terrain. The trucks required for this segment of the journey are typically smaller than the trucks required for transportation from the port to the central warehouse.
  6. At the subdistrict, district, state, or regional warehouse (depending on the complexity of the supply-chain architecture in the country), another break-bulk step usually occurs to split the doses into the volumes required by individual healthcare facilities, healthcare posts, or vaccination centers (a hospital, healthcare facility, or specially arranged venue):
    • Generally, the process is not well defined, and some rationing may take place per the prerogative of the immunization officer in the region.
    • The overall process can take one to 14 days.
    • In the warehouse at this level, some developing countries have specialized freezers, but most do not. This is the step when the manufacturer’s packaging is most likely to be broken, with dose vials exposed outside of the packaging and stored at 2 to 8°C in vaccine refrigerators. It is at that moment that the “clock begins to tick,” as many vaccines have a limited time period when they can be stored at the standard refrigerated temperature (Moderna for 30 days, Pfizer–BioNTech for 31 days, Johnson & Johnson for three months, and Oxford–AstraZeneca for six months). 7
  7. Transportation to the vaccination center is the final step, usually referred to as the “last mile,” and is when the most common challenges in the cold chain are encountered:
    • The vaccines are transported to vaccination centers in cold boxes with ice packs or other cooling agents. The boxes can keep the vaccine temperature below 10°C for around two to seven days if using ice packs. 8
    • Once at a vaccination center, the vaccines can be refrigerated. If the site does not have a refrigerator, the administration of the vaccines to patients must occur rapidly to avoid heat exposure. 9
    • Once vials are taken out of cold storage, opened, and made ready for immunizing patients, they cannot be placed back in storage. At the end of each day (or after six hours), any unused doses remaining in open vials are no longer viable and should be discarded. Such wasted doses can be planned for in advance when considering dose demand.
  8. In some circumstances, a healthcare facility may perform immunization-outreach visits to remote villages by motorbike or car using a small quantity of vaccines in a vaccine carrier with ice packs or other cooling agents.
Most vaccines travel a typical in-country supply-chain pathway.
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Challenges of CCE and the cold-chain system

There could be a myriad of challenges related to supply-chain logistics in developing countries, typically in the areas of operational efficiency, planning, talent availability, transportation, and warehousing infrastructure, as well as data systems and governance models. This article will focus on the CCE-related challenges, as our colleagues have previously written about the broader challenges.

The CCE challenges are highly limited capacity in ultra-cold-chain (UCC) and freezer storage, limited capacity in cold-chain storage, outdated storage technology, and limited transportation capacity.

Highly limited capacity in UCC and traditional freezer storage

Existing cold-chain capacity within developing countries is largely geared for the 2 to 8°C temperatures required for most routine immunization vaccines. However, UCC freezer capacity at –70°C and traditional freezer capacity at –20°C may be required for specific vaccines. For example, the Pfizer–BioNTech vaccine requires UCC capacity for storage longer than about six weeks, 10 and the Moderna vaccine requires traditional freezer capacity for storage longer than about one month. 11

Minor storage volumes may be available at –20°C at national and state stores, typically in those countries still using an oral polio vaccine. However, UCC storage at –70°C is typically extremely limited and exists only for specialist applications, such as storage of Ebola vaccines and diagnostic laboratories’ biological samples. Adding fixed UCC and traditional freezer capacity may be problematic for several reasons: it can require significant funding; the ability for multiple countries to procure sufficient freezers simultaneously may be limited by global manufacturer capacity and lead times; it would require significant expertise to install correctly and conduct capability building in operations staff to ensure proper and safe handling; and the equipment (UCC freezers, in particular) may have limited application after the COVID-19 pandemic unless mRNA vaccines become more common in the future.

An alternative approach to adding fixed capacity could be to use dry ice. Some infrastructure for dry ice (for example, at carbonated beverage bottlers) typically already exists in each country, but it would need to be expanded for healthcare-system use and may have many of the same challenges as adding fixed-freezer capacity would. Specialized training would also be required for dry-ice handling.

Limited capacity in cold-chain storage

At central or national and subnational storage warehouses across most countries, there may be inadequate amounts of cold rooms and specialized protective and handling equipment. In most developing countries, there are only a small number of specialized cold rooms, and they are usually stocked with other vaccines that are part of other national immunization programs.

The sufficiency of cold-chain capacity to handle both routine- and COVID-19-vaccine volumes may depend on COVID-19-vaccine coverage targets and the number of shipments that the vaccine supply is spread across. UNICEF Supply Division estimates that for a typical country with vaccines received in two to four deliveries, an additional 4,200 liters of storage (roughly one cold room or one freezer room), on average, would be required at the national level if the COVID-19-immunization target is 3 percent of the population. The additional storage need rises to an average of 15,000–35,000 liters (roughly three to seven cold rooms or freezer rooms 12 ) if the immunization target is 20 percent of the population. 13

Exhibit 4 illustrates the summary of such analysis at a national level for a country in sub-Saharan Africa. The lack of storage infrastructure at this level is the most basic challenge. Apart from limiting the quantity of vaccines that can be stored, it can make it more difficult to break bulk packages into the allocation packets needed for states, districts, or regions efficiently, since that is an operation that should take place within a cold room or freezer room. Overall capacity and speed of operations are also influenced by a country’s digitalization levels (for example, electronic logistics-management systems) and communication technologies that allow for tracing and tracking.

Analysis of one sub-Saharan African country illustrates the national cold-chain capacity for that country.
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At the last mile, the challenges may be starker. Limited CCE at a healthcare facility is a major challenge in many countries. Historically, up to 20 percent of vaccination centers and healthcare facilities have not had a refrigerator to store routine vaccines, 14 and many that do, do not have enough storage space to add COVID-19 vaccines. Temperature excursions occur most commonly at the local levels of the supply chain, especially at district stores, at healthcare facilities, and during outreach sessions. 15 Poor maintenance also has a limiting effect on installed capacity. Historically, roughly 15–20 percent of the currently installed cold-chain devices at the last mile have been nonfunctional, 16 although this number may be dropping as ministries of health deploy new equipment with long-term warranty agreements.

Outdated storage technology

Over the past 15 years, vaccine-refrigerator technology has improved in both reliability and temperature control. In particular, for healthcare facilities that have inconsistent power-grid access or are completely off grid, advances in solar-powered refrigerators have significantly improved storage reliability. The latest-generation technology is the solar-direct-drive (SDD) refrigerator, which significantly improves reliability compared with prior-generation solar-battery refrigerators and older gas or kerosene fridges. However, challenges remain, as the currently installed SDD capacity is less than 20 to 30 percent of requirements.

Apart from the refrigerators, cold boxes are also used to transport vaccines in the last mile, but they are less efficient. There has been some use of solar-powered carrier boxes, but they have not been scaled up enough to be beneficial on a large scale for the COVID-19-pandemic response.

Limited transportation capacity

Lack of specialized refrigerated vehicles that can preserve the temperature integrity between central or regional stores and vaccination centers (and other levels in between), as well as the long duration of trips, could mean that COVID-19 vaccines are at risk of temperature excursions during each break point and each level of the journey. That can be especially true for hard-to-reach communities (for example, riverine communities typically accessed by boat).

Perspective on steps that countries can take to improve their cold-chain systems

There are a number of actions that could be considered by decisions makers to help strengthen a country’s ability to overcome the cold-chain challenges and help ensure successful COVID-19-vaccination campaigns. They include new distribution approaches, more efficient shipment size and frequency, and a targeted increase in cold-chain-storage capacity.

Design distribution approaches that reduce freezer requirements

Each COVID-19 vaccine has a certain amount of time it can be stored at 2 to 8°C before patient administration must occur. When a vaccine vial’s time in the distribution channel is reliably less than that amount, it can be moved into 2 to 8°C storage (the most common cold storage available—and often the only existing storage available at subnational levels). This means that reducing the end-to-end distribution time can reduce the need for UCC or –20°C freezer capacity, especially at subnational levels. Countries can plan around this and could consider the following approaches:

  • Campaign-based immunization approaches (for example, mass-immunization events and mobile immunization clinics) can greatly reduce the time taken for vaccines to be administered once they arrive at local districts. For this, countries can leverage planning expertise used in prior campaigns (for example, those for meningitis and yellow fever immunization) or emergency-operations centers, but it may need to be adapted, given the national scope and large target-population cohorts.
  • Innovative distribution techniques can shorten distribution time from national stores to local districts. For example, Ghana is making drone-based deliveries to rural clinics, allowing for same-day delivery from a few national hubs.
  • Packaging optimization is another potential approach. Countries could explore the potential of having vaccines packed in smaller UCC-packaging units. While this may be less cost efficient for shipping, it may enable distribution from national to state stores without break bulking at the national level, hence better preserving the UCC without additional equipment. This could also help reduce waste or breakage.

Optimize shipment size and frequency to limit requirements for new cold-chain capacity

The amount of new capacity needed at any node in the supply chain is determined by the largest volume of vaccine vials that must be stored at that node at any specific point in time. When taking delivery of COVID-19 vaccines from manufacturers, countries might explore the potential for large shipments to be broken into a few smaller shipments spread out over a period of a few days. Provided that each small shipment can be moved down the supply chain before the next shipment arrives (and efficiently administered once it reaches the local level), this approach would allow the amount of any new cold-chain capacity required to be significantly reduced. Subnational shipments within a country can be staggered in this fashion to alleviate capacity needs at subnational levels.

Increase cold-chain-storage capacity in a targeted way, leveraging private-sector support, especially for freezer capacity.

Even with careful planning, countries may still require additional cold-chain capacity. There could be three reasons for this: to meet any UCC or traditional freezer requirements that the existing cold chain was not designed for; to ensure the routine 2 to 8°C cold chain can handle the planned incremental volume associated with COVID-19 vaccines, including sufficient local capacity to support mass immunization events; and to provide buffer capacity in case of any unexpected delays in distribution and backup of COVID-19 vaccines at national and subnational stores.

Additional capacity could take different forms. At national and state levels, it could include the following:

  • permanent UCC, freezer, or cold-room capacity
  • temporary warehouse capacity rented from the private sector, such as pharmaceutical- or food-warehouse cold storage at the required temperature band

At district and clinic levels and for mass-immunization events, additional capacity could include the following:

  • additional portable freezer, refrigerator, or cold-box storage and the associated capacity to produce ice packs
  • mobile cold storage (freezer or reefer trucks)

Before procuring new CCE, countries may want to determine how much of the required capacity could be met by repairing existing broken CCE, since repairs are typically more cost effective and quicker than adding all new capacity. A best practice is for CCE capacity to be backed up with emergency generators (if reliant on electrical power) and for it to be supported with proper maintenance plans to ensure that its useful life is maximized.

As countries plan their cold-chain equipment resources, they could base their investment decisions around opportunities that not only meet immediate COVID-19-vaccine distribution needs but also provide long-term benefit to their healthcare systems once the pandemic is over.

Designing the cold-chain-distribution plan with long-term benefit in mind

Ideally, any investment made in expanding cold-chain capacity for COVID-19 vaccines would be made in such a way that it also provided benefit to the healthcare system in the long term. For instance, any additional cold-chain storage at national and state levels could be temperature adjustable to serve the future needs of the routine immunization cold chain (for example, a new freezer room at –20°C that is easily convertible to a 2 to 8°C cold room once COVID-19-vaccine distribution is complete). Acquiring new CCE investments for district stores that use the latest-generation technology would enable outdated or poorly functioning equipment to be retired at a suitable moment. Investments in data systems to support the campaigns could be made with future pandemics or campaigns in mind and have a clear long-term owner within the national healthcare agency (for example, an emergency operations center).


The design choices that countries make for COVID-19-vaccine distribution have the potential to greatly mitigate many of the associated CCE challenges. Careful advance preparation and investment can help countries to address the remainder of the challenges. As countries plan their CCE resources, they could seek to base their investment decisions around opportunities that not only meet immediate requirements for COVID-19-vaccine distribution but also provide long-term benefit to their healthcare systems once the pandemic is over. Given the long lead times for activities such as procuring new CCE and contracting with the private sector, countries that wish to maximize their level of success may want to start such planning immediately if they have not already done so.

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