Phased distribution

Many countries have implemented phased distribution plans that prioritize those at highest risk of complications such as the elderly and those at high risk of exposure and transmission such as healthcare workers.^[13]

In the United States, the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) voted in December 2020, that the first doses of the vaccine should be prioritized for healthcare workers and residents and staff of nursing homes.^[14] ACIP recommended that the second phase of distribution (Phase 1b) include persons aged ≥75 years and non-healthcare frontline essential workers such as those employed in grocery stores, restaurants, military, law enforcement, fire departments, retail, sanitation, schools, public transportation, self-storage, hotels, warehousing, and news media.^[15] However, states control the final plans for prioritization, distribution, and logistics of vaccinating everyone as supply becomes available.^[16]

The European Union began phased vaccine rollout on 27 December 2020. Each member state is managing distribution with a common focus on prioritizing healthcare workers, people at high risk of exposure, the elderly, and those with serious health conditions.^[17][18]

The COVID‑19 vaccination programme in the United Kingdom prioritized elder care facility residents and carers, followed by healthcare workers and those over 80 years of age. Subsequent phases are based largely on age, declining from 75 years in 5-year increments.^[19]

Some countries used accelerated dose 1 plans with extended dose 2 intervals after the first dose in order to extend vaccination to as many people as possible until vaccine availability improved.^{[20][21][22][23]} Data suggests that people who have recovered from COVID-19 may only require a single dose of an mRNA vaccine to reach full two dose immunity.^[24]

Mixed series

The use of the different vaccines in a two-shot regimen is not widespread; there is no data on the efficacy of mixed series for COVID-19 vaccines but such series are not expected to be unsafe or ineffective.^[25] The US Centers for Disease Control and Prevention (CDC) recommends the use of a mixed series only in exceptional circumstances, such as where a second dose of the same vaccine cannot be delivered in a reasonable timeframe.^[26] In Canada, authorities were investigating the effectiveness of a mixed series and ultimately recommended the use of a first shot consisting of the Oxford-AstraZeneca COVID-19 vaccine, followed by one of the mRNA vaccines.^[27][28][29] In June 2021, German authorities recommended using mRNA vaccines as a second shot after an AstraZeneca shot in younger people as a precaution to avoid a rare blood clotting side effect associated with the AstraZeneca vaccine.^[30] Thailand began mixing-and-matching doses of the AstraZeneca and Sinovac vaccines in July 2021 amid concerns about the Sinovac vaccine's long-term protection.^[31]

Equitable access

Health officials distribute the Moderna COVID-19 vaccine to frontline health workers and first responders in Baltimore County, Maryland, United States.

During 2020, as the COVID‑19 pandemic escalated globally and vaccine development intensified, the World Health Organization (WHO) COVAX facility adopted the motto "No one is safe unless everyone is safe" to emphasize the need for equitable vaccination.^[32] The facility set a goal of supplying COVID‑19 vaccines to nearly 100 low-to-middle income countries that could not afford them. COVAX sought to fundraise US$6.8 billion to purchase and deliver vaccines to participating countries in proportion to their populations.^[32] On 18 December 2020, the facility announced agreements with vaccine manufacturers to supply 1.3 billion doses for 92 low-middle income countries in the first half of 2021.^[33]

Yet, by mid-December, some 16 countries representing only 14% of the world's population had preordered more than 10 billion vaccine doses or about 51% of the available world supply.^[34][35] Specifically, Canada, Australia, and Japan – having only 1% of the world's COVID‑19 cases – had collectively reserved some 1 billion vaccine doses,^[35] while the COVAX facility had reserved only a few hundred million doses.^[32] At the Group of Seven summit in June 2021, the United States promised to distribute 500 million vaccine doses internationally; this distribution began on 17 August.^[36]

Preorders from rich countries were made during 2020 with 13 different vaccine manufacturers, whereas those for low-to-middle income countries were made primarily for the Oxford–AstraZeneca COVID-19 vaccine, which is lowest in cost and has no special refrigeration needs.^[34][35]

World Health Organization communication describing factors involved in National Plans for Vaccines

The CEPI, the WHO, and charitable vaccine organizations, such as the Gates Foundation and GAVI, raised over US$20 billion during the first half of 2020, to fund vaccine development and preparedness for vaccinations, particularly for children in under-developed countries.^[6][37][38] CEPI, which was created to monitor fair distribution of infectious disease vaccines to low- and middle-income countries,^[39][40] has recommended considering manufacturing capacity, financing and purchasing, and releasing vaccine developers from liability.^[41] Despite opposition from some vaccine manufacturers,^[40][42] CEPI revised its February 2020 equitable access policy to apply specifically to its COVID‑19 vaccine funding:

1. "prices for vaccines will be set as low as possible for territories that are or may be affected by an outbreak of a disease for which CEPI funding was used to develop a vaccine;
2. "information, know-how and materials related to vaccine development must be shared with (or transferred to) CEPI" so that it can assume responsibility for vaccine development if a company discontinues expenditures for a promising vaccine candidate;
3. CEPI would have access to, and possible management of, intellectual property rights (i.e., patents) for promising vaccines;
4. "CEPI would receive a share of financial benefits that might accrue from CEPI-sponsored vaccine development, to re-invest in support of its mission to provide global public health benefit"; and
5. data transparency among development partners should maintain the WHO Statement on Public Disclosure of Clinical Trial Results, and require results to be published in open-access publications.^[40]

International groups, such as the Centre for Artistic Activism and Universities Allied for Essential Medicines, advocate for equitable access.^[43][44] Scientists have encouraged collaboration between the WHO, CEPI, corporations, and governments to ensure that vaccines are distributed in an evidence-based manner based on infection risk^[39][40] and to prioritize healthcare workers, vulnerable populations, and children.^[5][6][42]

By mid-March 2021, 67 countries, mostly in Africa and the Middle East, had not yet reported any vaccinations.^[45] Countries that had begun vaccinations were generally prioritizing populations such as health workers or the elderly. It has also been suggested that elective surgery recipients should be prioritized since a patient recovering from surgery would be more vulnerable than average.^[46] Some expressed concern over the short shelf-life of the Moderna and Pfizer-BioNTech vaccines, which expire within hours after being removed from the freezer; they argued that, once the vaccine is unfrozen, it is better to apply these doses to anyone who can be found rather than discard the doses.^[47]

As of March 2021, the United States had ordered twice the necessary doses to cover its own population, but it remained unclear when it might share surplus doses with other countries.^[48][49] In April 2021, Vanity Fair reported that it would be difficult to share surplus doses with other countries because the U.S. government had expressly agreed in its contracts with vaccine manufacturers to use doses only in the United States and its territories.^[50] The manufacturers requested this clause because most other countries do not have liability protections for vaccines as expansive as the Public Readiness and Emergency Preparedness Act.^[50]

In late November 2021 the World Health Organization published, "it is vitally important that inequities in access to COVID-19 vaccines are urgently addressed to ensure that vulnerable groups everywhere, including health workers and older persons, receive their first and second doses, alongside equitable access to treatment and diagnostics." Inequalities in vaccine distribution facilitate the emergence of new variants like SARS-CoV-2 Omicron variant.^[51]

Intellectual property

The first polio vaccine was never patented; some have argued that similar treatment of an effective COVID‑19 vaccine could enable fair distribution.^[57]

Initially, negotiations at the World Trade Organization (WTO) on the issue of waiving patent rights were blocked for months by resistance by the US, Switzerland, Norway, and the EU.^[58] Initially one observer considered the US position unlikely to change,^[59] but as of April 2021 the US administration was discussing the issue^[60] and then reversed course and announced its support for a patent waiver for COVID-19 vaccines on 5 May 2021.^[61] 400 non-profit organizations and 115 members of the European Commission have signed a letter urging the United States and Europe to side with the WTO members in the global south.^[62]

Sovereignty

Favored distribution of vaccines within one or a few select countries, called "vaccine sovereignty", is a criticism of some of the vaccine development partnerships,^[39][42] such as for the AstraZeneca-University of Oxford vaccine candidate, concerning whether there may be prioritized distribution first within the UK and to the "highest bidder" – the United States, which made an advance payment of US$1.2 billion to secure 300 million vaccine doses for Americans, even before the AstraZeneca-Oxford vaccine or a Sanofi vaccine was proved safe or effective.^[92][93][94] Concerns exist about whether some countries producing vaccines may impose protectionist controls by export restrictions that would stockpile a COVID‑19 vaccine for their own population.^[39]

The Chinese government pledged in May 2020, that a successful Chinese vaccine would become a "global, public good", implying enough doses would be manufactured for both national and global distribution.^[95] Unlike mRNA vaccines, which have to be stored at subzero temperatures, inactivated vaccines from Sinovac and Sinopharm require ordinary refrigeration^[96] and may have more appeal in developing countries.^[97] In November 2021, the Chinese government pledged to donate in 2022 a further 600 million vaccine doses to Africa, and supply another 400 million through other routes including production by Chinese companies in Africa.^[98][99]

In June 2020, the Serum Institute of India (SII) – a major manufacturer of global vaccines – reached a licensing agreement with AstraZeneca to make 1 billion doses of vaccine for low-and-middle income countries,^[100] of which half of the doses would go to India.^[101] Similar preferential homeland distribution may exist if a vaccine is manufactured in Australia.^[102]

Illegal distribution

In the United States, the vaccine distribution line, while varying by state, has placed healthcare workers and senior citizens high on the list for COVID-19 vaccination, while less essential workers are secondary recipients.^[103][104] Due to the long process of distribution,^[105] some individuals tried to secure a more favorable position on the vaccination list, such as by bribery or making donations to hospitals.^[106][107] In response, state governments imposed large fines and other penalties for violation of federal vaccine distribution guidelines.^[108] A COVID-19 vaccine black market enabled some individuals to buy illegal early access to a vaccine.^[109]

By mid-February 2021, China had arrested 80 people involved in vaccine contraband, and the Colombian government intercepted a freezer with 70 doses of a Chinese-manufactured vaccine that a traveler brought with her into the airport without any accompanying paperwork.^[110]

Vaccine tourism

In the later half of February 2021, it was reported that wealthy and influential people from Canada^[111] and European countries flew to the United Arab Emirates to secure early access to the vaccine.^[112] The UAE has been promoting Dubai as a vaccine holiday hub for the wealthy, who can pay a hefty amount to get inoculated before they become eligible.^[113] Some Canadians who maintained second homes in the United States were able to get vaccines earlier.^[114]

As restrictions on vaccine eligibility were lowered in the United States, wealthier individuals from other countries with slower vaccination rates were reportedly travelling to the United States to be vaccinated.^{[115][116][117]} The U.S. state of Alaska announced in April 2021 that it would intentionally offer free vaccinations to tourists at major Alaskan airports starting 1 June 2021.^[118] In an effort to guard against vaccine tourism, Greece restricted its eligibility to those with a social security number. However, this had the effect of excluding part of the elderly or immigrant population as well as some Greek citizens who worked abroad before the pandemic.^[119]

In the European Union, several travel agencies are offering "vaccine vacations".^[120] The Maldives are also offering vaccines as part of holiday travel packages.^[121][122]

Logistics

Logistics vaccination services assure necessary equipment, staff, and supply of licensed vaccines across international borders.^[148] Central logistics include vaccine handling and monitoring, cold chain management, and safety of distribution within the vaccination network.^[149] The purpose of the COVAX facility is to centralize and equitably administer logistics resources among participating countries, merging manufacturing, transport, and overall supply chain infrastructure.^[139][140] Included are logistics tools for vaccine forecasting and needs estimation, in-country vaccine management, potential for wastage, and stock management.^[149]

Other logistics factors conducted internationally during distribution of a COVID‑19 vaccine may include:^{[133][150][151]}

• visibility and traceability by barcodes for each vaccine vial
• sharing of supplier audits
• sharing of chain of custody for a vaccine vial from manufacturer to the individual being vaccinated
• use of vaccine temperature monitoring tools
• temperature stability testing and assurance
• new packaging and delivery technologies
• stockpiling
• coordination of supplies within each country (personal protective equipment, diluent, syringes, needles, rubber stoppers, refrigeration fuel or power sources, waste-handling, among others)
• communications technology
• environmental impacts in each country

A logistics shortage in any one step may derail the whole supply chain, according to one vaccine developer.^[152] If the vaccine supply chain fails, the economic and human costs of the pandemic may be extended for years.^[135]

Manufacturing capacity

By August 2020, when only a few vaccine candidates were in Phase III trials and were many months away from establishing safety and efficacy, numerous governments pre-ordered more than 2 billion doses at a cost of more than US$5 billion.^{[101][152][157]} Pre-orders from the British government for 2021 were for five vaccine doses per person, a number dispiriting to organizations like the WHO and GAVI which are promoting fair and equitable access worldwide, especially for developing countries.^[101] In September, CEPI was financially supporting basic and clinical research for nine vaccine candidates, with nine more in evaluation, under financing commitments to manufacture 2 billion doses of three licensed vaccines by the end of 2021.^[142] Before 2022, 7–10 billion COVID‑19 vaccine doses may be manufactured worldwide, but the sizable pre-orders by affluent countries – called "vaccine nationalism" – threaten vaccine availability for poorer nations.^{[152][101][158]}

The RNA vaccines from Moderna and Pfizer-BioNTech are unusually difficult to produce because they rely upon encapsulation of mRNA in lipid nanoparticles, a novel technology which has never been scaled up before for mass production. As of February 2021, this was thought to be the primary bottleneck in the manufacturing of such vaccines.^[159] In November 2021, Moderna CEO Stéphane Bancel claimed that the company had a backlog of tens of millions of doses of its vaccine destined for Africa because COVAX or individual governments could not take delivery. He cited delays with dose administration, a shortage of refrigerator space, and delays getting customs documents.^[160]

Vaccines must be handled and transported according to international regulations, be maintained at controlled temperatures that vary across vaccine technologies, and be used for immunization before deterioration in storage.^[101][152] The scale of the COVID‑19 vaccine supply chain is expected to be vast to ensure delivery worldwide to vulnerable populations.^[134] Priorities for preparing facilities for such distribution include temperature-controlled facilities and equipment, optimizing infrastructure, training immunization staff, and rigorous monitoring.^{[134][137][143]} RFID technologies are being implemented to track and authenticate a vaccine dose from the manufacturer along the entire supply chain to the vaccination.^[161]

In September 2020, Grand River Aseptic Manufacturing agreed with Johnson & Johnson to support the manufacture of its vaccine candidate, including technology transfer and fill and finish manufacturing.^[162] In October 2020, it was announced that the Moderna vaccine candidate will be manufactured in Visp, Switzerland by its partner Lonza Group, which plans to produce the first doses in December 2020.^[163] The newly built 2,000-square-metre facility will ramp up production to 300 million doses annually. The ingredient will be shipped frozen at −70 °C to Spain's Laboratorios Farmacéuticos Rovi SA for the final stage of manufacturing.^[163] Lonza's site in Portsmouth, New Hampshire, aimed to start making vaccine ingredients exclusively for the U.S. by November 2020.^[163] Compounding the concerns over massive pre-orders by wealthy countries, manufacturing capacity is also limited by the fact that most vaccines are patented by companies in those countries. India and South Africa proposed a waiver to the TRIPS Agreement which would remove exclusivity agreements as a barrier to setting up new facilities but the measure is being blocked by the G7.^[164]

Cold chain

COVID‑19 vaccine shipment protected by thermal wrapping while in transit. (Delta, 16 December 2020)

Different vaccines have different shipping and handling requirements. For example, the Pfizer-BioNTech COVID‑19 vaccine must be shipped and stored between −80 and −60 °C (−112 and −76 °F),^[165] must be used within five days of thawing,^[165] and has a minimum order of 975 doses, making it unlikely to be rolled out in settings other than large, well-equipped hospitals.^[166] The Moderna vaccine vials require storage above −40 °C (−40 °F) and between −25 and −15 °C (−13 and 5 °F).^[167] Once refrigerated, the Moderna vaccine can be kept between 2 and 8 °C (36 and 46 °F) for up to 30 days.^[167]

Vaccines (and adjuvants) are inherently unstable during temperature changes, requiring cold chain management throughout the entire supply chain, typically at temperatures of 2–8 °C (36–46 °F).^[151][168] Because COVID‑19 vaccine technologies are varied among several novel technologies, there are new challenges for cold chain management, with some vaccines that are stable while frozen but liable to heat, while others should not be frozen at all, and some are stable across temperatures.^[168] Failure to maintain cold chain temperature stability results in damage that can reduce or even eliminate vaccine efficacy.^[169][170] Sinopharm and Sinovac's vaccines are examples of inactivated vaccines which can be transported using existing cold chain systems at 2–8 °C (36–46 °F).^[171][172]

modRNA vaccine technologies in development may be more difficult to manufacture at scale and control degradation, requiring ultracold storage and transport.^[135] As examples, Moderna's RNA vaccine candidate requires cold chain management just above freezing temperatures between 2 and 8 °C (36 and 46 °F) with limited storage duration (30 days),^[173] but the Pfizer-BioNTech RNA candidate requires storage between −80 and −60 °C (−112 and −76 °F),^[165] or colder throughout deployment until vaccination.^[174][175] In February 2021, Pfizer and BioNTech asked the U.S. Food and Drug Administration (FDA) to update the emergency use authorization (EUA) to permit the vaccine to be stored at between −25 and −15 °C (−13 and 5 °F) for up to two weeks before use.^[176] As of May 2021, Walvax is conducting Phase III trials for its mRNA vaccine which could be stored at room temperature for six months.^[177]

After a vaccine vial is punctured to administer a dose, it is viable for only six hours, then must be discarded, requiring attention to local management of cold storage and vaccination processes.^[178] Because the COVID‑19 vaccine will likely be in short supply for many locations during early deployment, vaccination staff will have to avoid spoilage and waste, which typically are as much as 30% of the supply.^[133][178] The cold chain is further challenged by the type of local transportation for the vaccines in rural communities, such as by motorcycle or delivery drone, need for booster doses, use of diluents, and access to vulnerable populations, such as healthcare staff, children and the elderly.^[143][179]

Air and land transport

Boxes of AstraZeneca's COVID-19 vaccine from India are delivered in Brazil (January 2021).

Coordination of international air cargo is an essential component of time- and temperature-sensitive distribution of COVID‑19 vaccines, but, as of September 2020, the air freight network is not prepared for multinational deployment.^{[134][138][180]} "Safely delivering COVID‑19 vaccines will be the mission of the century for the global air cargo industry. But it won't happen without careful advance planning. And the time for that is now. We urge governments to take the lead in facilitating cooperation across the logistics chain so that the facilities, security arrangements and border processes are ready for the mammoth and complex task ahead," said IATA's Director General and CEO, Alexandre de Juniac, in September 2020.^[180]

For the severe reduction in passenger air traffic during 2020, airlines downsized personnel, trimmed destination networks, and put aircraft into long-term storage.^[134][180] As the lead agencies for procurement and supply of the COVID‑19 vaccine within the WHO COVAX facility, GAVI and UNICEF are preparing for the largest and fastest vaccine deployment ever, necessitating international air freight collaboration, customs and border control, and possibly as many as 8,000 cargo planes to deliver just one vaccine dose to multiple countries.^[143][180]

Two of the first approved vaccines, Pfizer and BioNTech's Pfizer-BioNTech COVID‑19 vaccine and Moderna's mRNA-1273, must be kept cold during transport. Keeping the temperatures sufficiently low is accomplished with specially-designed containers^{[lower-alpha 1]} and dry ice, but dry ice is only allowed in limited quantities on airplanes as the gases released via sublimation may be toxic. In the United States, the Federal Aviation Administration (FAA) limits the amount of dry ice on a Boeing 777-224 to 3,000 lb (1,400 kg), but it temporarily allowed United Airlines to transport up to 15,000 lb (6,800 kg)—nearly 1 million doses—between Brussels and Chicago. The Centers for Disease Control and Prevention (CDC) has tasked McKesson with vaccine distribution in the US; the company will handle all major vaccines except Pfizer's. American Airlines, Boeing, and Delta Air Lines are also working to increase dry ice transportation capacity, and American, Delta, and United each operate their own cold storage networks in the US. FedEx and UPS have installed ultra-cold freezers at air cargo hubs in Europe and North America, and UPS can manufacture 1,200 lb (540 kg) of dry ice per hour.^[183]

Security and corruption

Federal police escort COVID-19 vaccine shipment in Brazil (January 2021).

Medicines are the world's largest fraud market, worth some $200 billion per year, making the widespread demand for a COVID‑19 vaccine vulnerable to counterfeit, theft, scams, and cyberattacks throughout the supply chain.^[140][184] The vaccine has been referred to as "the most valuable asset on earth"; Interpol called it "liquid gold" and warned of an "onslaught of all types of criminal activity".^[185] Anticorruption, transparency, and accountability safeguards are being established to reduce and eliminate corruption of COVID‑19 vaccine supplies.^[184][186] Absence of harmonized regulatory frameworks among countries, including low technical capacity, constrained access, and ineffective capability to identify and track genuine vs. counterfeit vaccines, may be life-threatening for vaccine recipients, and would potentially perpetuate the COVID‑19 pandemic.^[184] Tracking system technologies for packaging are being used by manufacturers to trace vaccine vials across the supply chain,^[140] and to use digital and biometric tools to assure security for vaccination teams.^[161][187] In December 2020, Interpol warned that organized crime could infiltrate the vaccine supply chain, steal product through physical means, and data theft, or even offer counterfeit vaccine kits.^[188] Further, vaccines which require constant freezing temperatures are also susceptible to sabotage.^[185]

GPS devices will be used in the United States to track the vaccines. In Colorado, the vaccine shipments will be escorted by Colorado State Patrol officers from Denver International Airport to the state's eight distribution points; the exact plans are confidential and law enforcement will "maintain a low-key profile".^[182]

Peripheral businesses may also be affected. An IBM security analyst told The New York Times that petrochemical companies are being targeted by hackers due to their central role in producing dry ice.^[185]

On 21 May 2020, the FDA made public the cease-and-desist notice it had sent to North Coast Biologics, a Seattle-based company that had been selling a purported "nCoV19 spike protein vaccine".^[189] On 21 January 2021, its founder, Johnny Stine, was arrested on a federal warrant charging him with introducing misbranded drugs into interstate commerce, a misdemeanor.^[190] Stine pleaded guilty in August 2021. On 8 March 2022, he was sentenced to five years' probation and ordered to pay $246,986 in restitution.^[191]

National infrastructure

The WHO has implemented an "Effective Vaccine Management" system,^[192] which includes constructing priorities to prepare national and subnational personnel and facilities for vaccine distribution, including:

• Trained staff to handle time- and temperature-sensitive vaccines
• Robust monitoring capabilities to ensure optimal vaccine storage and transport
• Temperature-controlled facilities and equipment
• Traceability
• Security

Border processes for efficient handling and customs clearance within individual countries may include:^[148][192]

• Facilitating flight and landing permits
• Exempting flight crews from quarantine requirements
• Facilitating flexible operations for efficient national deployment
• Granting arrival priority to maintain vaccine temperature requirements