There have now been over 54 million cases and more than 1 million deaths from COVID-19 worldwide (So and Woo, 2020). Encouragingly, global efforts to produce COVID-19 vaccines have gained momentum, and the first patient in the UK has just received their vaccination in recent weeks. However, it appears that some countries are ahead of others. It is important to examine the difficulties and ease with which countries across the world have in accessing the COVID-19 vaccine, and reasons for this unequal distribution, as well as perhaps most importantly, equitable solutions.
Examining the issue
In a study recently published in the British Medical Journal, So and Woo (2020) analysed the premarket purchase commitments for COVID-19 vaccines from leading manufacturers to recipient countries. This was a cross-sectional analysis, using data from the draft landscape of COVID-19 candidate vaccines from the World Health Organization (WHO), as well as company disclosures to the US Securities and Exchange Commission, company and foundation press releases, government press releases and media reports. The main outcome measures were premarket purchase commitments for COVID-19 vaccine candidates and price per course, vaccine platform, and stage of research and development, as well as procurement agent and the recipient country.
As of 15 November 2020, several countries have made premarket purchase commitments that total 7.48 billion doses, or 3.76 billion courses, of COVID-19 vaccines from 13 vaccine manufacturers. Significantly, just over half (51%) of these doses will go to high-income countries, despite these countries only representing 14% of the world's population (So and Woo, 2020). The United States reserved 800 million doses but does account for a fifth of all COVID-19 cases globally (11.02 million cases), whereas Japan, Australia, and Canada have collectively reserved more than one billion doses but do not account for even 1% of current global COVID-19 cases across the world (0.45 million cases). So and Woo (2020) explained that if these vaccine candidates were all successfully scaled, the total projected manufacturing capacity would be 5.96 billion courses by the end of 2021. This means that up to 40% (or 2.34 billion) of vaccine courses from these manufacturers might potentially remain for low- and middle-income countries, though this may decrease further if high-income countries decide to use scale-up options but increase if they share what they have procured (So and Woo, 2020). The prices of the vaccines were found by this study to vary broadly, costing up to ten times as much per vaccine course. Some were £4.50 per course, while some were as high as £45 per course.
A proposed solution
As a solution to the disparity, So and Woo (2020) discussed the COVAX facility to enable access to the vaccines across the world's poorer nations. The authors stated that with broad-country participation (with the exception of the US and Russia who have so far opted out but are home to a major proportion of the world's COVID-19 vaccine manufacturing), the COVAX Facility, which is the vaccines pillar of WHO's access to COVID-19 tools (ACT) accelerator – has secured at least 500 million doses, or 250 million courses, and has financed for half of the targeted 2 billion doses by the end of 2021 in an effort to support international coordinated access to COVID-19 vaccines.
Effectiveness uncertainty
Forty-eight candidate vaccines have been undergoing clinical testing worldwide, with at least another 164 candidates at preclinical stages (WHO, 2020). Even with such unprecedented levels of public financing and the accelerated pace of bringing these vaccines to market, the global demand will vastly outstrip available supply throughout this ‘scale-up’ period. There has been significant interest in which countries will acquire the vaccine and at what point populations will have access to safe and effective vaccine solutions emerging from research and development.
Pfizer/BioNTech produced the first vaccine to receive regulatory approval, securing emergency use authorisation in the UK in early December 2020. Pfizer/BioNTech and Moderna, with its messenger RNA (mRNA) vaccine, have now gained emergency use authorisation from the US Food and Drug Administration (FDA).
So and Woo (2020) note that the potential sources of inequitable and unjust allocation of COVID-19 vaccines are not hard to find; however, they point out that the solution is much more complex. Several countries prioritised securing vaccine doses to cover their own populations first, despite the need to respond to COVID-19 being possibly greater elsewhere. Facing uncertainty over which vaccines will prove optimally effective, countries with the means to secure future vaccine supplies might ensure against these risks by buying more vaccines than they eventually need or can use, So and Woo (2020) explained.
Equitable access
Financing for COVID-19 vaccines for low- and middle-income countries has lagged significantly behind vaccine deals secured by high-income countries. There have been different paths suggested to achieving a global equitable allocation of vaccines. For example, the WHO's equitable allocation approach is able to organise the distribution of vaccines to ensure a percentage of the world's population is reached, whereas other models such as Fair Priority place emphasis on a more needs-based metric (So and Woo, 2020). Access to vaccines is also important for the economic success in overcoming the pandemic's destruction, with trade and travel being affected, whereby both would be disrupted between countries until access to effective preventive or treatment measures, such as COVID-19 vaccines, become more widely available.
High- and upper-middle-income countries have the means to invest in research and development and are therefore more easily able to procure future vaccines. These countries, therefore, provide important financing to bring about such vaccines to market, but could leave short those who are most in need.
First in line
While the first COVID-19 vaccine candidates have been completing their clinical testing and reached the market in the Western world, policymakers and the public have begun to grapple with who will be vaccinated first when these doses become available. Premarket purchase commitments have been able to offer a snapshot of who will probably control the COVID-19 vaccine doses rolling off production lines. Even if all 13 of these vaccine manufacturers were to succeed in reaching their maximum-production capacity, at least a fifth of the world's population would not have access to vaccines at all, until 2022 (So and Woo, 2020).
‘Even with such unprecedented levels of public financing and the accelerated pace of bringing these vaccines to market, the global demand will vastly outstrip available supply throughout this ‘scale-up’ period’
Oxford vaccine
In addition to reserving more doses proportionally, high-income countries have also secured a wider range of vaccine candidates and platforms. However, over 40% of these premarket vaccine commitments for high-income countries depend on the success of one candidate, the AstraZeneca/Oxford University vaccine (So and Woo, 2020). This candidate is the cheapest, and requires traditional refrigeration for transport and storage, making it easier to distribute. AstraZeneca/Oxford University has made the largest premarket purchase commitment to low- and middle-income countries. By contrast, only high- and upper-middle-income countries have been able to procure mRNA vaccines, such as that from Pfizer/BioNTech and Moderna. These might be among the first to obtain regulatory approval, but they require a cold chain infrastructure which simply is not readily available in resource-limited settings, such as in poorer countries.
Supply and demand
Of the 13 vaccine manufacturers with premarket purchase commitments, most might have potential doses not yet reserved. With regards to supply, 35 of the 48 vaccine manufacturers now in clinical testing also do not have publicly known, premarket purchase commitments, but without such existing commitments, it is also unclear whether they have the financing or facilities to scale. With regards to demand, COVAX may require copayments of $1.60 per dose for upfront, committed purchases by self-financing countries (Berkley, 2020). These copayments may mean some countries have to secure external loans or financing, perhaps from the World Bank's $12 billion envelope for financing COVID-19 vaccines, treatments and tests.
Vaccine nationalism
Therefore, So and Woo (2020) explain, the existing 10-fold variation in vaccine prices could pose serious challenges to affordable access. Vaccine nationalism is one of the reasons So and Woo (2020) carried out their analysis – to further unpack why there are such disparities, according to policy and infrastructure, resources and demand and so on, they note.
So and Woo (2020) also point out that lacking a globally coordinated approach to the distribution of COVID-19 vaccines could lead to stockpiling supplies. Importantly, with financing and logistical challenges in delivery of these vaccines, stockpiles might not be so easily shared. Uncertainty over which vaccines would succeed or fail, the time it has required to pull together participation and financing of COVAX, and the bilateral agreements that had been struck within that timeframe have also contributed to this situation (So and Woo, 2020). COVAX is stepping up such global coordination. The uncertainty over effectiveness, duration of immunity, safety, and dosing regimens of vaccine candidates will continue to diminish as clinical testing is completed (So and Woo, 2020).
Conclusion
The first COVID-19 vaccine to market may not be the most effective, nor the best suited for reaching or immunising all populations. Second-generation vaccines might be more effective but will face additional challenges such as scale-up facilities locked into existing vaccine production; switching costs to transition to more effective vaccines; vaccine hesitancy heightened by any adverse reactions from the first generation of vaccines; and likely barriers to intellectual property rights as patent thickets emerge (So and Woo, 2020). This would lead therefore to a situation critical for scaling-up the global and country-level coordination of head-to-head trials among leading vaccine candidates, the emergence of second-generation vaccines that outperform those first to market, and the ability to switch manufacturing facilities from less effective to more optimal vaccines (So and Woo, 2020).
So and Woo (2020) present an overview of the disproportionate security that high-income countries have in securing future supplies of COVID-19 vaccines when compared with access to the vaccine for the rest of the world, which remains uncertain. The authors stressed the importance of governments and manufacturers in having the power to provide much-needed assurances for the equal distribution of COVID-19 vaccines through greater transparency and accountability over their arrangements.