Deployment of COVID-19 vaccines

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.[16]

In the United States, the CDC's Advisory Committee on Immunization Practices (ACIP) voted on 1 December that the first doses of the vaccine should be prioritized for healthcare workers and residents and staff of nursing homes.[17] ACIP recommended that the second phase of distribution (Phase 1b) include persons aged ≥75 years and non-healthcare frontline essential workers.[18] However, states control the final plans for prioritization, distribution, and logistics of vaccinating everyone as supply becomes available.[19]

The European Union began phased vaccine rollout on 27 December. 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.[20][21]

The COVID‑19 vaccination program 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.[22]

During 2020, as the COVID‑19 pandemic escalated globally and vaccine development intensified, the WHO COVAX Facility adopted the phrase, "No one is safe unless everyone is safe", to emphasize the need for equitable distribution of COVID‑19 vaccines authorized for marketing.[23] 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.[24][25]Specifically, Canada, Australia, and Japan – having only 1% of the world's COVID‑19 cases – had collectively reserved some one billion vaccine doses,[25] while the COVAX Facility, with a goal to supply vaccines to nearly 100 low-to-middle income countries that cannot fully afford to pay for COVID‑19 vaccines, had reserved only a few hundred million doses.[23] 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 AstraZeneca-Oxford vaccine, which is lowest in cost and has no special refrigeration needs.[24][25]

Due to the high demand for preorders in 2020–21 by wealthy countries, people in developing countries may be excluded from vaccinations until 2023–24 from the first vaccines to be authorized.[25] On 18 December, the COVAX Facility announced it had established agreements with vaccine manufacturers to supply 1.3  billion doses for 92 low-middle income countries in the first half of 2021.[26] To execute its equitable distribution plan in 2021, COVAX remains in an urgent fundraising campaign to raise US$6.8 billion for vaccine purchases and delivery to participating countries in proportion to their populations.[23]

As many of the efforts on vaccine candidates have open-ended outcomes, including a high potential for failure during human testing, CEPI, 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.[5][27][28] CEPI had stated that governments should ensure implementation of a globally-fair allocation system for eventual vaccines, using a coordinated system of manufacturing capacity, financing and purchasing, and indemnification from liability to offset risks taken by vaccine developers.[10] Having been created to monitor fair distribution of infectious disease vaccines to low- and middle-income countries,[29][30] CEPI revised its equitable access policy that was published in February to apply 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.[30] Some vaccine manufacturers opposed parts of these proposals.[30][31]

International groups, such as the Centre for Artistic Activism and Universities Allied for Essential Medicines, advocate for equitable access to licensed COVID‑19 vaccines.[32][33] Scientists have encouraged that the WHO, CEPI, corporations, and governments collaborate to assure evidence-based allocation of eventual COVID‑19 vaccines determined on infection risk,[29][30] particularly urgent vaccinations provided first for healthcare workers, vulnerable populations, and children.[4][5][31] Similar to the development of the first polio vaccine that was never patented, an effective COVID‑19 vaccine would be available for production and approval by a number of countries and pharmaceutical manufacturing centers worldwide, therefore allowing for a more even and cost-effective distribution on a global scale.[34]

In the initial period of availability, states have prioritized certain groups such as health workers or the elderly to be vaccinated. However, since the Moderna and Pfizer-BioNTech vaccines have a validity of hours after being prepared for administration, ready doses may remain after the day's scheduled persons have been vaccinated (due to last-moment rejection or illness). Due to the scarcity of the vaccine, these doses should be applied rather than discarded. This case may lead to improvisation with ensuing criticism on the choices made.[35]

Favored distribution of vaccines within one or a few select countries, called "vaccine sovereignty", is a criticism of some of the vaccine development partnerships,[29][31] 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.[36][37][38] 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.[29]

The Chinese government pledged in May that a successful Chinese vaccine would become a "global, public good", implying enough doses would be manufactured for both national and global distribution.[39] Unlike mRNA vaccines, which have to be stored at subzero temperatures, inactivated vaccines from Sinovac and Sinopharm require ordinary refrigeration[40] and may have more appeal in developing countries.[41]

In June, 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,[42] of which half of the doses would go to India.[43] Similar preferential homeland distribution may exist if a vaccine is manufactured in Australia.[44]

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.[45][46] Due to the long process of distribution,[47] some individuals tried to secure a more favorable position on the vaccination list, such as by bribery or making donations to hospitals.[48][49] In response, state governments imposed large fines and other penalties for violation of federal vaccine distribution guidelines.[50] Because of strict guidelines, a COVID-19 vaccine black market enabled some individuals to buy illegal early access to a vaccine.[51]

Logistics vaccination services assure necessary equipment, staff, and supply of licensed vaccines across international borders.[70] Central logistics include vaccine handling and monitoring, cold chain management, and safety of distribution within the vaccination network.[71] 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.[12][65] Included are logistics tools for vaccine forecasting and needs estimation, in-country vaccine management, potential for wastage, and stock management.[71]

Other logistics factors conducted internationally during distribution of a COVID‑19 vaccine may include:[59][72][73]

• 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.[74] If the vaccine supply chain fails, the economic and human costs of the pandemic may be extended for years.[61]

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 two billion doses at a cost of more than US$5 billion.[43][74][75] 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.[43] In September, CEPI was financially supporting basic and clinical research for nine vaccine candidates, with nine more in evaluation, under financing commitments to manufacture two billion doses of three licensed vaccines by the end of 2021.[67] 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.[3][74][43]

After joining COVAX in October, China initially shared that it would produce 600 million vaccine doses before the end of 2020 and another one billion doses in 2021, although it was unsure how many would be for the country's own population of 1.4 billion.[76] Sinopharm said it may have the capacity to produce more than 1 billion doses in 2021,[77] while its Dubai partner G42 Healthcare aimed to produce up to 100 million doses in 2021 focused on the middle east.[78] Sinovac aimed to complete a second production line by February 2021 to increase production of CoronaVac to 1 billion doses from 500 million,[79] while its Brazilian partner Instituto Butantan planned to produce 100 million doses[80] and its Indonesian partner Bio Farma planned to produce up to 250 million doses of CoronaVac a year.[81]

The Serum Institute of India plans to produce at least one billion vaccine doses, although the institute has stated that half the doses will be used in India.[43]

AstraZeneca CEO, Pascal Soriot, stated: "The challenge is not making the vaccine itself, it's filling vials. There just aren't enough vials in the world."[82] Preparing for high demand in manufacturing vials, an American glass producer invested $163 million in July for a vial factory.[83] Glass availability for vial manufacturing and contaminant control are issues of concern,[84] indicating higher production costs with lower profit potential for developers amid demands for vaccines to be affordable.[12][43][61]

Vaccines must be handled and transported using international regulations, be maintained at controlled temperatures that vary across vaccine technologies, and be used for immunization before deterioration in storage.[43][74] The scale of the COVID‑19 vaccine supply chain is expected to be vast to ensure delivery worldwide to vulnerable populations.[3][60] Priorities for preparing facilities for such distribution include temperature-controlled facilities and equipment, optimizing infrastructure, training immunization staff, and rigorous monitoring.[60][63][68] RFID technologies are being implemented to track and authenticate a vaccine dose from the manufacturer along the entire supply chain to the vaccination.[85]

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.[86] 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.[87] 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.[87] Lonza's site in Portsmouth, New Hampshire, aims to start making vaccine ingredients exclusively for the U.S. as early as November.[87]

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),[88] must be used within five days of thawing,[88] and has a minimum order of 975 doses, making it unlikely to be rolled out in settings other than large, well-equipped hospitals.[89] The Moderna vaccine vials require storage above −40 °C (−40 °F) and between −25 and −15 °C (−13 and 5 °F).[90] Once refrigerated, the Moderna vaccine can be kept between 2 and 8 °C (36 and 46 °F) for up to 30 days.[90]

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).[73][91] 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 labile to heat, while others should not be frozen at all, and some are stable across temperatures.[91] Freezing damage and inadequate training of personnel in the local vaccination process are major concerns.[92] If more than one COVID‑19 vaccine is approved, the vaccine cold chain may have to accommodate all these temperature sensitivities across different countries with variable climate conditions and local resources for temperature maintenance.[91] Sinopharm and Sinovac's vaccines are examples of inactivated vaccines in Phase III testing which can be transported using existing cold chain systems at 2–8 °C (36–46 °F).[93][94]

modRNA vaccine technologies in development may be more difficult to manufacture at scale and control degradation, requiring ultracold storage and transport.[61] 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),[95] but the Pfizer-BioNTech RNA candidate requires storage between −80 and −60 °C (−112 and −76 °F),[88] or colder throughout deployment until vaccination.[96][97]

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.[3][98] 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.[59][98] 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.[3][68][99]

Boxes of AstraZeneca's COVID-19 vaccine from India are delivered in Brazil (Jan 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.[60][64][100] "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.[100]

For the severe reduction in passenger air traffic during 2020, airlines downsized personnel, trimmed destination networks, and put aircraft into long-term storage.[60][100] 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.[68][100]

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 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 Airlines 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.[103]

Federal police escort COVID-19 vaccine shipment in Brazil (Jan 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.[65][104] 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".[105] Anticorruption, transparency, and accountability safeguards are being established to reduce and eliminate corruption of COVID‑19 vaccine supplies.[104][106] 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.[104] Tracking system technologies for packaging are being used by manufacturers to trace vaccine vials across the supply chain,[65] and to use digital and biometric tools to assure security for vaccination teams.[85][107] 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.[108] Further, vaccines which require constant freezing temperatures are also susceptible to sabotage.[105]

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".[102]

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.[105]

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".[109] On 21 January 2021, its founder, Johnny Stine, was arrested on a federal warrant charging him with introducing misbranded drugs into interstate commerce.[110]

The WHO has implemented an "Effective Vaccine Management" system,[111] 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:[70][111]

• 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