Feasible actions to expand COVID-19 vaccine supply before the end of 2021
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, and not just because of the lives and livelihoods immediately at stake. Access to vaccines would allow delegates from low- and middle-income economies to meet their counterparts in person safely, to work more effectively on long term issues like climate change, future pandemics, and poverty.
Though the world is now administering about 1 billion vaccine doses per month, access is still highly unequal. Multilateral initiatives including the African Vaccine Acquisition Trust and COVAX, established to procure vaccines for low- and middle-income countries, have contracted with a subset of developers that are facing production delays and export restrictions. Vaccine donations have not filled the gap, with less than one-quarter of pledges for 2021 delivered, and more donations delayed until 2022 as high-income economies prioritize their own populations.
In August, we quantified the impact of six policy and regulatory measures to increase vaccine supply, accounting for these constraints. While many forecasts suggest supply is ramping up, there have been setbacks. Continued lack of transparency in supply and delivery schedules means that it is hard to know for sure. Our measures will expand available supply by year-end.
, and do not require high-income countries to swap delivery dates with low- and middle-income countries. These are:
- Fast-tracking regulatory approval of effective vaccines. Vaccine importers rely on the WHO emergency use listing (EUL) to assure quality. Optimistic supply forecasts often include vaccine candidates that have not yet received WHO EUL, or production capacity for listed candidates that has not been inspected by international authorities. For instance, Brazil, China, Russia, and Thailand have licensed capacity to produce the AstraZeneca vaccine. However, if these facilities do not request WHO inspections, this cannot be exported easily. Only about 10 percent of the 4 billion dose annual production capacity of China’s Sinopharm and Sinovac has been authorized by the WHO. Inspecting these facilities requires expert inspectors to travel (at times with 14 day quarantines) and WHO has relied on consultants that are in short supply. Commitments of human resources from stringent regulatory authorities like the Australian Therapeutic Goods Administration (TGA), the European Medicines Agency (EMA), and the United States Food and Drug Administration (FDA) could help WHO fast-track inspections as emerging markets scale their production capacity.
- Repurposing production capacity to effective vaccines. Not all COVID-19 vaccine development efforts have resulted in highly effective vaccines, but vaccine development has resulted in capacity to produce vaccines. An example is CureVac, a developer that accepted funds from the Coalition for Epidemic Preparedness Innovations (CEPI), the European Investment Bank, and the German and United Kingdom governments to build a network capable of producing 300 million doses in 2021. Unfortunately, the CureVac vaccine is less effective than required for regulatory approval. While the firm plans to hold on to this capacity and develop another candidate, a greater return on public funds could be achieved by reallocating CureVac’s supplies to developers of effective mRNA vaccines through the COVAX marketplace.
- Authorizing half doses without compromising efficacy. The effectiveness of vaccines does not necessarily depend on the size of a dose in a linear fashion. While initial doses chosen in clinical trials can be large given a reasonable desire to demonstrate effectiveness, dosing can be adjusted downward. In the case of yellow fever, the WHO’s Strategic Advisory Group of Experts (SAGE) has recommended dose fractionation down to one-fifth of the standard dose to overcome scarcity in emergencies. Moderna scientists have shown that a 50µg rather than a 100µg dose provides the same immunity response. Regulators could authorize half doses of Moderna, doubling available supply, as well commission more research on the fractionation of this and other vaccines, as Brazil is doing with the Oxford/AstraZeneca vaccine.
We’ve received feedback that these measures might be more politically challenging to undertake than the three above, however the science is clear that they would reduce global mortality. Further, some regulators are not convinced there is benefit from providing first doses or boosters to certain low-risk groups at all.
The measures are:
- Postponing boosters for adults with healthy immune systems. While vaccine manufacturers have a profit motive to market third doses to those willing to pay, an FDA expert advisory panel has said there is insufficient evidence that boosters would provide a health benefit to healthy adults. The health benefit of initial doses however is well known.
- Postponing doses for those with confirmed prior infection. Prior infection confers immunity through the same mechanism that vaccines do. Regulators could adopt the French approach and delay vaccinations for those with prior confirmed COVID-19 infection.
- Postponing doses for adolescents and children. This is perhaps the most politically challenging option, given parents’ strong desire to protect their kids. Nonetheless, the risk of mortality and severe illness for those under age 18 is extremely low compared to health care workers and the elderly in low- and middle-income countries. On this basis, a United Kingdom advisory panel does not recommend immunizing children ages 12-15, judging that the risk of side effects in this age group outweighs the health benefit.
Our analysis does not rule out other scenarios. Economies could reserve supplies to vaccinate only 80 percent rather than 100 percent of their eligible populations. India has announced plans to relax export restrictions constraining COVAX’s supply, though it is unclear by how much. Production could expand more rapidly than anticipated, despite current delays.
But we don’t need to wait and hope for these scenarios to play out. Six actions to expand supply could be implemented immediately and save lives.
We hope that delegates give them, and others, full consideration.
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While most of this is sensible I worry that the Bank's PH policy advice is authored by a pair of economists, and there are some statements that are frankly, troubling.
For example, it is simply not legitimate to assume that dose fractionation in yellow fever can be extrapolated to COVID vaccines.
The statement "some regulators are not convinced there is benefit from providing first doses or boosters to certain low-risk groups at all' is made without reference.
And not vaccinating adolescents and children isnt just politically sensitive, they are sources of infection for older more vulnerable adults particularly in high density multi generational environments. And Delta seems to be a much greater issues in this age group than previous variants.
Advice on repurposing production and fast tracking regulatory approval is fine, but on the other issues it should stay in its lane.
Thank you very much for your interest, Toshi. Our proposals to expand supply are consistent with scientific evidence from health practitioners, not just economists. The example of dose fractionation in the yellow fever case is meant to indicate there is precedent for dose fractionation, though the evidence that it would be effective in the case of Covid-19 comes from Moderna scientists, who have said fractional doses could be delivered without compromising efficacy. A CDC advisory panel has said boosters are not needed for healthy adults (including health care workers) and UK advisors do not recommend vaccines for early adolescents. While vaccines for these groups may nonetheless have some benefit, and we acknowledge that among health professionals there is debate, many health practitioners and economist agree that the same vaccines would have a greater health benefit as first doses for vulnerable groups including the the elderly in developing economies.