6 'k L,Research & Policy Briefs From the World Bank Chile Center and Malaysia Hub WORLD BANK GROUP No. 49 August 23, 2021 Policy Actions to Increase the Supply of COVID-19 Vaccines in the Short Term Mamta Murthi and Tristan Reed Vaccination rates in developing countries log those in developed countries by a huge margin. This Research & Policy Brief identifies and quantifies the impact of six policy and regulatory actions that could increase vaccine supply to developing countries before the end of 2021. The actions focus on measures to accelerate regulatory approvals, optimize production capacity across firms, reconfigure prioritization of low-risk groups, and adjust generous dosage thresholds. Together these actions could help yield enough supply to reach the interim target to vaccinate at least 40 percent of the population of every country by the end of 2021, as a means to vaccinate 60 percent of global population by mid-2022, thereby helping to end the pandemic earlier, reducing uncertainty and raising growth. The Worldwide Shortage of Vaccines Estimating excess COVID-19 vaccine supply through the end of 2021 requires a forecast of (1) global production levels and On May 31, 2021, the heads of the World Bank, International (2) doses that vaccine-producing economies will use for their Monetary Fund (IMF), World Trade Organization (WTO), and own populations. Our approach is as follows. First, we use World Health Organization (WHO) jointly endorsed a $50 billion population data to estimate the number of doses needed for proposal outlining actions to end the COVID-19 pandemic. domestic abundance, by which we mean there are enough Immediately, donors responded by almost entirely fulfilling the vaccine doses to fully vaccinate everyone over the age of 12 and proposal's request for additional vaccine financing, through two provide boosters. Second, we assume the production rate commitments to COVAX, the global vaccine cooperative: an remains constant through the end of 2021, consistent with additional cash grant of almost $4 billion, announced on June 2, persistent shortages of inputs (for examples, see Chatham 2021; and an in-kind grant of at least 800 million vaccine doses House 2021) and the time needed for new capacity to come (valued at $8 billion or more), announced on June 13, 2021. online. Third, excesssupply is calculated as the number of doses Earlier analysis by Agarwal and Reed (2021) shows that these left once the major vaccine-producing economies achieve two commitments would be sufficient to finance vaccines for 60 domestic abundance at the current rate of production. Our percent of the population in 91 low- and lower-middle-income approach is described in further detail in Annex A. economies (a theoretical threshold for herd immunity to the alpha variant, a target of public health authorities, including the Baseline Scenario Africa Centers for Disease Control). Though additional line items included in the $50 billion related to COVID-19 Under our approach, excess supply of COVID-19 vaccines from diagnostics and treatment remain unfunded, donors have the G-10 is expected to be 271 million doses by the end of 2021 committed most of the financial resources requested to (figure 1). China is expected to produce 200 million such doses, procure vaccines for the poorest countries. Nonetheless, the with the G-7 and the EU supplying the remainder. India is pace of vaccination remains unacceptably slow in these unlikely to obtain domestic abundance in 2021. The United countries because of a lack of vaccines. For example, by August States, which has committed to provide 500 million doses of 10, 2021, COVAX was able to supply merely 191 million doses BNT162b2 (the vaccine developed by BioNTech/Pfizer) to against a target of 2 billion doses in 2021. COVAX, of which 200 million doses will be provided in 2021, will also run short unless further policy or regulatory changes are Analytical Approach to Identifying Additional considered. Supplies These baseline results suggest that at current rates of To develop options to increase vaccine supply for low- and production excess supply in the G-10 is insufficient to vaccinate lower-middle income countries, this Brief focuses on potential 40 percent of the population of every country by the end of excess supply in a relevant group of the largest 2021. Accounting for doses already administered and vaccine-producing and purchasing economies: China; the employing all available excess supply of the single-dose vaccine, European Union (EU) members; the G-7 (Canada, France, JNJ-78436735 (the vaccine developed by Jannsen/Johnson & Germany, Italy, Japan, the United Kingdom, the United States); Johnson), 1.625 billion doses are required to fully vaccinate 40 and India, which we call collectively the G-10. These economies percent of the 2.5 billion people in 91 low- and have contractual rights over much of supply through advance lower-middle-income economies eligible for subsidized purchase agreements (Duke Global Health Innovation Center vaccines through the COVAX AMC facility. In these "AMC91" 2021), and according to company-reported production countries, two doses of any vaccine have been administered for estimates, these economies will account for 88 percent of all just 2 percent of the population. In addition, 1.036 billion more COVID-19 vaccine production in 2021 (Casey 2021). doses are required to cover 40 percent the 1.4 billion people Affiliations: Mamta Murthi, Vice President for Human Development, World Bank; Tristan Reed, Economist, Development Research Group, World Bank. Acknowledgements: The authors thank Kathleen Beegle, Richard Hatchett, Alex Tabarrok, and David Wilson for helpful suggestions. Erratum: A previous version of this Brief incorrectly stated the target to vaccinate 40 percent of the population in the AMC91 countries. The correct target is 1.625 billion doses, accounting for doses already administered and employing all available supply of single-dose vaccines. Objective and disclaimer: Research & Policy Briefs synthesize existing research and data to shed light on a useful and interesting question for policy debate. Research & Policy Briefs carry the names of the authors and should be cited accordingly. The findings, interpretations, and conclusions are entirely those of the authors. They do not necessarily represent the views of the World Bank Group, its Executive Directors, or the governments they represent. Figure 1. Making Enough COVID-19 Vaccine Supply Available to Vaccinate 40 percent of the AMC91 economies by the end of 2021 Six policy actions could channel 1.3 billion vaccine doses from vaccine-producing economies to the rest of the world where vaccines are in very short supply. Excess supply of COVID-19 vaccines with WHO EUL from the G-10 economies (China, the European Union, the G-7, and India) Millions of doses available in 2021 Baseline Scenario 55 1,579 * Vaccine production occurs at current delivery 71 rate through end-2021 due to ongoing input 83 shortages and build-time for new capacity 243 * The G-10 economies reserve enough supply of nationally-authorized vaccines to obtain domestic abundance: 275 Interim target for end-2021 - Two doses (one for JNJ-78436735 and 1.625 billion doses needed for 40 percent Ad5-nCoV) for the entire population over age 12 coverage in AMC91 economies - One booster dose for everyone over age 70 - Full vaccine coverage for 40 percent of or immunosuppressed plus one-third of 2.5 billion people, of whom 2 percent have immunocompetent persons ages 17-70 582 recieved two doses * Only excess supply after an economy achieves - 91 low- and lower-middle income economies domestic abundance is available for other plus India are eligible for subsidized vaccines economies through the COVAX AMC facility - Baseline counts only excess supply of vaccines from manufacturing facilities with WHO Emergency Use Listing 71 0 271 200 China excess G-7 and EU excess India excess SUB-TOTAL requring 1. SRAs support 2. EU, Germany and 3. NRAs delay 4. NRAs delay 5. NRAs delay doses 6. NRAs authorize TOTAL requiring production production production no policy change WHO EUL for UK request capacity boosters for second doses for for ages 12-17 half doses of policy change effective vaccines to produce ineffective immunocompetent those with conirmed mRNA-1273 CVnCoV be ages 12-70 prior infection converted to produce BNT162b2 or mRNA-1273 Excess Production Six Scenarios Sources: Authors' calculations based on data from Casey 2021; Duke Global Health Initiative 2021; Harpaz, Dahl, and Dooling 2016; Mathieu et al. 2021; UN 2019; and national health authorities. See Annex A. Note: AMC 91 economies = 91 low- and lower-middle-income economies eligible for subsidized vaccines through the COVAX AMC facility; COVAX = global initiative to develop and distribute COVID-19 vaccines; EU = European Union; EUL = emergency use listing; G-7 = Canada, France, Germany, Italy, Japan, United Kingdom, United States; NRAs = national regulatory authorities; SRAs = stringent regulatory authorities; UK = United Kingdom; WHO = World Health Organization. who live in economies outside the G-10 that are richer than the Union, Switzerland, the United Kingdom, and the United States AMC91. Two doses have been administered for only 3 percent (WHO 2020). The WHO has its own process for providing of this population, though 14 countries in this group have emergency use authorization (called "emergency use listing," or vaccine-manufacturing capabilities. Given the scale of the gap EUL), although in practice it relies on advice from these same between excess supply and requirements, further actions are SRAs to make that decision. SRAs decide to provide emergency needed to meet the interim target for the end of 2021. use authorization if their own analysis of raw clinical trial data submitted by the developer confirms that a vaccine is effective Six Policy Actions to Expand Excess Supply and safe, and an inspection of the manufacturing facility Six policy and regulatory changes are considered to expand provides confidence about the integrity of the production supply. For each policy action, the result from immediate action process. is quantified in terms of additional doses available from the In normal times, this process can increase efficiency since it G-10 economies, using available data and our assumptions means data are reviewed only once by an SRA, rather than about production and use. The responsible party to undertake twice. However, in this pandemic, SRAs may find it difficult to each action is identified: either a government authority or a prioritize approvals for products that are not required urgently national regulatory authority (NRA). for domestic use. Specifically, since economies with SRAs are now expecting to be in domestic abundance with previously 1. Stringent regulatory authorities (SRAs) support WHO authorized vaccines, there is limited incentive to fast-track emergency use listing (EUL) for effective vaccines (+582 approval of additional vaccines that could be deployed in other million doses) economies. COVID-19 vaccine development efforts have resulted in An action to expand supply is for the SRAs to expedite highly effective vaccines that are not yet authorized for use. review of all vaccines that developers have found to be more COVAX, multilateral development banks including the World than 50 percent effective in Phase 3 trials, as required by SRAs Bank, and many NRAs rely on emergency use authorization for authorization. Additional doses would follow satisfactory (EUA) from a group of so-called stringent regulatory authorities EUL inspections of manufacturing facilities in economies with (SRAs), which are the NRAs of Australia, Canada, the European capacity to export. Two candidates for expedited review based 2 L I Research & Policy Brief No.49 on clinical trial evidence are NVX-CoV2373 (the vaccine whether scientific collaboration between Pfizer, Moderna, and developed by Novavax), which has an efficacy of 89.7 percent CureVac would accelerate progress toward a normal cold chain (Heath et al. 2021) and which COVAX supply relies upon; and mRNA vaccine with high efficacy. Gam-COVID-Vac (the vaccine developed by the Gamaleya Research Institute and the Health Ministry of the Russian 3. NRAs delay booster shots for those with healthy immune Federation), which has efficacy of 91.6 percent (Jones and Roy systems (the immunocompetent) aged 12-70 (+243 million 2021). Other vaccines have been authorized for emergency use, doses) but not when they are produced in certain plants. The developers of BBIBP-CorV (the vaccine developed by This policy action entails a global effort to delay booster Sinopharm) and Coronavac (the vaccine developed by Sinovac) shots for low-risk populations. While developers have a private together report 4 billion doses in annual production capacity, profit motive to promote the sale of boosters, evidence though only around 10 percent of this has EUL. Facilities in suggests that delaying boosters for the nonvulnerable will have Argentina, China, Brazil, Russia, and Thailand have licenses to limited consequence for mortality in the G-10 economies. For produce ChAdOx1 nCoV-19 (the vaccine developed by instance, in the presence of more contagious delta variant, a Oxford/AstraZeneca), but have not satisfied site inspections, study in Scotland (Sheikh et al. 2021) found that vaccines remain highly effective after two doses. Rather than using Within the G-10, satisfactory inspections of manufacturing available doses as booster shots now, using them as first and facilities in China would yield the most additional doses. In second shots in economies with scarce supply would China, supporting EUL for 10 percentage points of the annual significantly reduce mortality and morbidity in those capacity of Sinovac and Sinopharm would yield 200 million economies and contain the spread of the pandemic more doses (since the year is half over), for all facilities producing rapidly. The baseline scenario assumed that the G-7 and EU ChAdOx1 nCoV-19, 99 million doses, and all facilities producing economies reserved supply for one-third of the Gam-COVID-Vac, 61 million doses. Canada, the United immunocompetent population ages 12-70, reflecting a status Kingdom, and the United States have advance purchased 222 quo in which individuals can get vaccines for free without million doses of NVX-CoV2373. Additional EUL inspections in documentation. A moratorium until the end of 2021 on India would not yield excess production in 2021, assuming vaccination of this nonvulnerable population-though not the prioritization of domestic needs. In total, satisfactory EUL immunosuppressed and elderly-would free up 243 million inspections at facilities in the G10 economies would deliver a doses. total 582 million doses. 4. NRAs delay second doses for those with confirmed prior 2. The EU, German, and UK governments request that the infection (+83 million doses) capacity to produce ineffective CVnCoV be converted to T i produce BNT162b2 or mRNA-1273 (+275 million doses) There is strong evidence that immunity comparable to two doses of vaccine can be achieved with one dose and confirmed Not all COVID-19 vaccine development efforts have resulted prior infection (Frieman et al. 2021). This policy action involves in highly effective vaccines, but vaccine development efforts by delaying the second dose for those with confirmed infections. firms have resulted in capacity to produce vaccines. This policy The French health authority, for example, has recommended action creates additional production capacity through capacity that immunocompetent people with a dated SARS-CoV-2 conversion-whereby vaccine development efforts that are yet infection (symptomatic or not) proven by polymerase chain to be effective pivot to effective vaccines. One example is reaction (PCR) or antigen test could delay their second dose, CVnCoV (the vaccine developed by CureVac N.V.), which has given post-infection immunity to SARS-CoV-2 (HAS 2021). proven only 48 percent effective against disease across age However, given relatively low case counts as a share of the groups after two doses (CureVac 2021), below the indicative population-for instance, in China (0.01 percent), India (2.3 threshold. This production capacity could be productively precent), and the United States (10.5 percent), this measure repurposed, following precedent. Merck abandoned yields few excess doses. Using these infection rates, a development of its COVID-19 vaccine after unsuccessful trials moratorium until the end of 2021 on the confirmed and, through a partnership brokered by the White House, has convalescent population would yield 83 million doses, though committed two plants to produce the more effective this number will grow over time if infections rise. JNJ-78436735. Similarly, Sanofi Pasteur has bottled and packaged doses of BNT162b2 and JNJ-78436735. 5. NRAs delay doses for the immunocompetent ages 12-17 A new partnership could be executed by the European (+71 million doses) Union and the United Kingdom, which have purchased 225 COVID-19 vaccines are increasingly authorized for younger million and 50 million doses of CVnCoV respectively-a total of populations. This policy action entails delaying vaccination for 275 million doses, while Germany holds an option for additional the youngest low-risk populations. As of August 10th, in the purchases (Duke University Global Health Innovation Center United States 349 people under age 18 have died of COVID-19, 2021). These governments could assess whether CureVac while 606,389 adults have died of the disease (CDC 2021). would be willing to cede reserved production capacity and More deaths of children and adolescents are attributable to whether this capacity is suitable for BNT162b2 and mRNA-1273 cancer, car accidents, heart disease, homicide, or suicide (the vaccine developed by Moderna). They could also assess than to COVID-19 (Woolf, Chapman, and Lee 2021). While susceptibility of children to newer variants bears monitoring, half doses. BNT162b2, which is on the same platform, is G-10 economies prioritized vaccination of the elderly when delivered in 30pEg doses. Melissa Moore, Chief Scientific Officer vaccines were scarce. Today, rather than vaccinating for Moderna, has said that fractional dosing could have the adolescents with extremely small chances of death or serious effect of "reducing side effects without compromising illness, shifting doses to economies with scarce supply to protection." This policy would yield 55 million doses, given significantly reduce mortality and morbidity there would stop mRNA-1273 is just one of many vaccines. Wiqcek et al. (2021) the spread of the pandemic globally. The baseline scenario outline low-cost options to obtain more information about the assumed the G-10 reserved vaccines for all adolescents. A impact of fractional dosing during the implementation of this moratorium until the end of 2021 on vaccinations for the policy, and to explore the feasibility of fractional dosing of other immunocompetent in this age group would yield 71 million vaccines. doses, reflecting the relatively small adolescent population in most G-10 economies. ConClusion Despite financing and production commitments to provide 6. NRAs approvehalfdosesofmRNA-1273(+55milliondoses) sufficient COVID-19 vaccines to reach global herd immunity, at The effectiveness of vaccines does not necessarily depend current production levels and given countries' actions to on the size of a dose in a linear fashion. This policy action is for prioritize their own populations, there is a significant shortage NRAs outside of the G-10 to authorize administration of half of vaccines, especially for low- and lower-middle-income doses, effectively doubling available excess supply while using countries. Without swift action, the pande ic will continue, uig and economic recovery will remain under threat as these the scientific method to ensure efficacy is not compromised. d eoi res remain unabl tvac at a gica While initial doses chosen in clinical trials can be large given a shaelofir ou tis -depi te t fanci a surcescand reasonable desire to demonstrate effectiveness, developers can adjust dosing downward and regulators can authorize fractional pledges from donors. doses, increasing the available supply without a loss in To address this global crisis, this Brief outlines six specific effectiveness (Cowling, Lim, and Cobey 2021). For instance, policy and regulatory actions that would address the vaccine Phase 3 trials of JNJ-78436735 and NVX-CoV2373 proceeded shortages facing these countries. It provides quantitative with the smaller of two dose options tested in early trials, after estimates of the potential impact of each of these actions. those trials found no statistically significant difference in There are several combinations of actions that, if implemented, immune response between the two doses. lay out a path to vaccine availability to achieve interim targets of vaccinating 40 percent of the population of low- and There is precedent for reducing dose sizes in emergencies lower-middle-income countries by the end of 2021. While the (while holding the time between doses constant). In the case of Brief is agnostic about which set of actions should be yellow fever, WHO's Strategic Advisory Group of Experts (SAGE) prioritized, the quantitative estimates provide relative "order of has recommended dose fractionation down to one-fifth of the magnitude" ranking in terms of potential dose availability. standard dose to overcome scarcity during epidemics. 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