The United Kingdom’s emergency approval of a COVID-19 vaccine is an historic milestone in the global fight against the pandemic. But vaccine experts warn that the move may trigger a domino effect as other countries jockey for approvals—one that could reduce access for poorer nations for months or even years.
To better ensure equitable distribution, the World Health Organization and one of its major partners—the European Medicines Agency (EMA)—are now moving into their final stages of evaluation for the Pfizer-BioNTech vaccine, which the U.K. approved on December 2. A day earlier, the EMA accepted Pfizer’s application for authorization and is expected to conclude its assessment no later than December 29. An identical review was also launched for Moderna’s vaccine candidate. Its completion is expected on January 12.
“We are co-reviewing with them, so we're on a similar time table to what the EMA timetable is,” Katherine O’Brien, the WHO director of immunization, vaccines and biologicals, told National Geographic on Friday. “We can't guarantee what the outcome of those reviews will be, but they are ongoing.”
The decision shows just how much the vaccine race has accelerated in the wake of Britain’s emergency authorization. But that endorsement also adds uncertainty about when richer countries—such as the United States—will receive their doses once they approve the vaccine.
“As the manufacturing capacity ramps up month by month, it is not entirely clear which countries have dibs, so to speak,” says Krishna Udayakumar, founding director of Duke University’s Global Health Innovation Center.
The COVAX conundrum
In recent months, wealthier nations have pre-purchased huge amounts of the vaccines promised by frontrunner producers, such as Pfizer, Moderna, and AstraZeneca. Of the billions of doses that vaccine-makers have committed to make, three of every four already have been bought. By beating the rest of the world to approval, the U.K. has put immense pressure on other well-off nations and the WHO to authorize COVID-19 vaccines so they don’t have to wait for the limited early supply. Pfizer expects to manufacture about 50 million doses in 2020 and 1.3 billion next year.
The United States and the European Union are scheduled to review vaccine candidates from Pfizer-BioNTech and Moderna in the coming weeks, and those major economies may begin rollouts well before the new year arrives. CNN reported this week that the Trump Administration’s Operation Warp Speed plans to deliver the first doses of Pfizer’s vaccine to states by December 15, while shipments of Moderna’s vaccine will arrive by December 22.
For some middle- and low-resource countries, the World Health Organization’s selection process will dictate their vaccine choices through its COVAX initiative. While the WHO isn’t a regulator for sovereign nations, many follow its stamp of approval, especially for early-stage vaccine rollouts.
The COVAX plan aims to secure 20 percent of any signatory nation’s vaccine needs in the long term, with a goal of two billion doses being delivered globally by the end of 2021. The project is co-led by the international vaccine alliance known as GAVI, and the Coalition for Epidemic Preparedness Innovations (CEPI). More than 180 countries have signed up, including well-resourced countries such as Canada and the U.K. The United States declined to participate under President Donald Trump, but the head of GAVI expects to hold talks soon with president-elect Joe Biden.
“Most low- and middle-income countries will go through COVAX,” says Maria Elena Bottazzi, co-director of the Texas Children’s Hospital Center for Vaccine Development in Houston, noting that those countries cannot afford to negotiate direct agreements with the pharmaceutical firms.
Pfizer says it is committed to equitable and affordable access for COVID-19 vaccines for all people around the world. “Given the urgency and the global nature of the pandemic, we fully support the COVAX Facility and have put forward an expression of interest and are in active conversations for possible supply of our COVID-19 vaccine candidate,” Jerica Pitts, Pfizer’s director of global media relations, wrote in an email to National Geographic.
But COVAX’s bargaining power is at risk. Its funding depends on donations from its signatories, which have been slow to arrive. Meanwhile, some 9.8 billion doses of COVID-19 vaccines are already reserved as of November 30, and more than half are dedicated to well-off countries through pre-purchase agreements, according to data compiled by Udayakumar’s center at Duke. Assuming the vaccines prove effective, the United States has already secured enough doses to vaccinate its population twice over. For the U.K., it’s thrice. And if it fulfills its orders, Canada could offer five doses to all of its 38 million citizens with some left over.
“If we look at the overall purchases of vaccines today, we've counted about seven billion doses that have already been purchased, of which only 10 percent—or 700 million doses—are purchased through the COVAX facility,” Udayakumar says.
He estimates that due to this skewed distribution the globe won’t achieve herd immunity—and fully control the COVID-19 pandemic—for another three to four years at the earliest.
Still, hope isn’t lost yet for low- and middle-income nations, says Benjamin Schreiber, deputy chief for UNICEF’s global immunization program. Their experience fighting other epidemics, such as Ebola and Zika, has better prepared many of these places to distribute vaccines whenever they’re ultimately acquired.
The early-bird medal
If securing a COVID-19 vaccine is like a race, the most suitable comparison may be an Olympic marathon. When a nation successfully brokers a deal with a vaccine company, its team has won a medal. The number of doses it gets signifies whether the medal is gold, silver, or bronze.
The U.S., the European Union, and India are among the gold medal winners. They’ve secured the most hypothetical doses from the potential supplies on offer. Britain would land on the silver podium, but its expedited approval means that its medal will arrive before everyone else’s.
The United Kingdom obtained this advantage by conducting a “rolling review” of the Pfizer-BioNTech vaccine, which allowed it to complete the assessment in the shortest time possible, June Raine, chief executive of the U.K.’s Medicines and Healthcare products Regulatory Agency (MHRA), said during Tuesday’s approval announcement.
Starting in the summer, British health regulators charted a plan to vet a vaccine company’s production lines while those firms were still wrapping up their clinical trials. This oversight included an independent commission of virologists, epidemiologists, drug experts, toxicologists, and other academics tasked with reviewing data from the clinical trials.
“If you're climbing a mountain, you prepare and prepare,” Raine said. “We started that in June, so by the time the interim results became available on the 10th of November, we were at base camp. And then when we got the final analysis, we were ready for that last sprint that takes us to today.”
Despite the pace, outside experts doubt that the U.K. has cut any corners in terms of safety.
“This is not typical and was done because of the exceptional environment of a pandemic,” Aliasger K. Salem, chair of pharmaceutical sciences at the University of Iowa, said in an email. However, he adds that reviewers still needed to see data on safety and efficacy before the drug could be approved. O’Brien from the WHO agrees.
“Stringent oversight and stringent regulatory review of data is essential for making an assessment for authorization for use,” O’Brien says. “The U.K. is a regulator that we certainly recognize as having that performance standard.”
As part of the rolling review, the U.K. evaluated partial data as it was released by Pfizer and BioNTech, instead of waiting for the clinical research to be fully completed. That meant relying on the companies’ assessments. The WHO and the EMA have also conducted rolling reviews of four vaccine frontrunners from Pfizer, Moderna, AstraZeneca-Oxford, and Johnson & Johnson, though with raw data. The U.S. Food and Drug Administration also plans to conduct more thorough reviews based on independent findings.
In the meantime, publicly available data shows that 95 percent of Pfizer’s already committed supply has been purchased by high-income nations. Similar discrepancies apply to nearly all the other vaccine options in late-stage clinical trials, aside from those made in Russia and China, which so far will stay mostly within their borders, with some exceptions. AstraZeneca has cut a deal with India’s Serum Institute to allow the low-income nation to produce billions of doses and keep half for its own citizens.
These arrangements mean disadvantaged countries will need to procure the remaining vaccines pretty much the same way that they always have: by doing more with less.
Getting ready for rollouts
Moderna developed and started clinical trials for its vaccine about two months after the SARS-CoV-2 virus emerged, a breakneck pace. It was soon joined in the race by potential rivals. Once it became clear that several vaccines might be available by 2021, humanitarian agencies launched preparations for what could be the largest mass rollout of immunizations in history.
“We've been working on this basically since April, putting the pieces together, all the global goods,” says Schreiber of UNICEF. “It will be one of many vaccines that we've been rolling out the last 10 years.”
This experience makes Schreiber confident that resource-limited nations—and rural areas in developed countries—will be able to catch up whenever vaccine supplies become available to them. As one example, he says that they are uniquely prepared to deal with the mRNA vaccines from Pfizer and Moderna, which require ultra-cold freezing or refrigeration to keep the drugs stable, a challenge in the so-called Global South that harbors most of the world’s populations.
“We’ve been looking at these scenarios for the last few weeks…You can work with dry ice. You can work with quicker distribution,” Schreiber says. But he adds that ultra-cold infrastructure is more complex and would require additional training and investments. In 2017, the WHO estimated that supplying five vaccination teams with freezers, portable coolers, and other cold-chain necessities would cost more than $1 million.
Yet Schreiber notes that Ebola ushered in the rapid development of a vaccine that also required cold storage. In the Democratic Republic of the Congo and elsewhere in Africa, this led to changes in the supply chain. The countries not only bought refrigeration equipment, but also “service bundle” arrangements with suppliers to ensure installation in rural and urban clinics. It has been a tremendous game changer. This year, the DRC beat back its Ebola outbreak.
“We've invested a lot of money into fridges—a quarter of a billion dollars over the last five years to procure 40,000 fridges,” he says. Many, he adds, were “solar fridges because they have to be set up in remote, not electrified settings.”
At this stage, O’Brien couldn’t provide a hard number of how many fridge units might be required, but some estimates suggest that three billion people live in regions that lack access to fridges and freezers, and addressing those needs will be extremely difficult. That’s why the WHO, UNICEF, and others are developing templates for country-scale deployments. They’re also devising checklists that nations can follow to guide their approval practices for the individual vaccines.
“It's really country by country,” O’Brien says, adding that many countries may use a strategy of having ultra-cold freezers in a capital city and then finding ways to quickly move the vaccines to remote areas, like the hub and spokes of a wheel. But she added that every country is probably going to use a combination of vaccines, which should aid flexibility.
Meanwhile, some high-income countries that have secured vaccine doses are reconsidering the global consequences. Canada has reportedly floated the idea of donating excess doses to the COVAX program, which the WHO will accept as long as the donors agree to the overall plan. “It's not a question of accepting the leftovers,” O’Brien adds.
So while a country’s initial purchase and those made by other nations may have driven up the price of the vaccines overall, these donations may ultimately help the COVAX supply catch up. Rising prices can also explain why the Global South has pre-purchased larger batches of lower cost options, such as the AstraZeneca vaccine. Moreover, having to wait for these candidates may actually be advantageous if the drugs don’t require such specialized handling.
Globally speaking, “we will not have the supply for everybody who needs vaccines right away,” O’Brien says. “There are people who need to go first, and that should be based on public health decisions. And it should be based on science.”