An underrated way to boost global vaccine supply

We need western regulators to cooperate with Chinese producers

Two issues very much on the minds of the college-educated urban parents I mostly socialize with these days are Covid booster shots and vaccines for kids. I would say only a distinct minority of those people are living like the extreme Covid neurotics that you see on Twitter, but it’s not nobody, and a lot of our new social norms tend to reflect the concerns and preferences of the most cautious. So both the people who are directly desperate for these shots and those of us hoping for a general sense of increased normalcy are eager for these things to happen.

And in both cases, the issue — formally speaking — is that the FDA has not approved them yet.

But I strongly suspect that a major factor slowing down the FDA is a sense, somewhat outside their mandate, that it’s bad to authorize these uses of precious mRNA vaccines when there are much higher-value uses of them abroad. However urgent I may feel it is to get my kid vaccinated, objectively, the risks to him are very low, and the expected value of lives saved is much higher if those doses go to a middle-aged person in a poor country.

That said, regulatory foot-dragging is only going to get us so far. What we actually need are ways to boost the global vaccine supply. I really wanted the answer here to be that we should spend a bunch more money. The problem is there’s something like a one-year lag (see this Tristan Reed paper) between when purchase commitments are made and when that money can be put to use scaling up output. If the world had been more aggressive about funding this back in 2020, we’d be in a better place today. We’d be better off if rich countries had put up more funds for global vaccination, but the honest truth is we’d also be better off if rich countries (especially laggards Japan, Australia, New Zealand, Taiwan, and South Korea) had bought more vaccines for themselves since even that would have expanded supply.

What we’re seeing now is that by next spring we’ll have plenty of doses, but more money now probably can’t speed up that timeline much.

By contrast, something that could speed up vaccine availability a lot is the full utilization of China’s vaccine production capacity. The two Chinese vaccines, from Sinopharm and Sinovac, are old-fashioned vaccines that do not require as much in the way of fancy new facilities as some of the others.

But when you bring a pharmaceutical product to market, regulators can’t just approve your medicine; they also need to inspect and approve the specific facility that you’re using. So while Sinopharm and Sinovac say they can make about four billion doses a year across their various facilities, only around 10% of that actually has regulatory approval. And the way the global governance of this works, the regulators who need to do the work are basically the western regulatory agencies — agencies that have a lot on their plate and have not prioritized this.

A zero-sum scramble for vaccines

Tyler Cowen, complaining about regulatory foot-dragging from the FDA on booster shots, writes, “I’ll say it again simply: they refuse to apply scientific reasoning under the heading of expected value theory. I should note, however, that if they recommend it all be sent to Brazil I will agree, but even that decision they should be able to reach within the end of business day.”

I really wanted to write a post endorsing this viewpoint, but after talking to some folks, I’ve come to think that it is wrong.

The FDA does not have the authority to rule that we need to ship mRNA doses to Brazil rather than using them as boosters at home. But given the current mechanics of global vaccine shipments, it actually is the case that stalling on the regulatory approval here leads to more doses shipped abroad. Or, rather, as soon as broad boosters (or shots for kids) are authorized, vaccine supply that is currently going to fulfill purchase agreements in foreign countries will be diverted to fulfill U.S. domestic orders. So stalling really does have a positive expected value in the global sense. And we see things like The Lancet editorializing against boosters on global equity grounds and doctors co-writing Atlantic articles about how it’s wrong to vaccinate kids ahead of foreign adults.

The people who work for the U.S. regulatory agencies are aware of these debates. Again, it would be overstepping for the regulators to refuse to approve on this basis. But they can “work to rule” and slow things down, generating complaints from people who think the FDA is too slow in general but earning praise from development folks.

Now don’t get me wrong, I really want vaccines for kids authorized.

In part that’s because I want my kid to get one, even though I judge the health risks he’s facing to be relatively minor. The other part is that living as I do in an urban liberal bubble, there’s just a lot of stuff around kids that’s still being handled gingerly out of deference to the most cautious. I’ve been looking into joining a new progressive synagogue, and they’re doing outdoor services until kids can get vaccines. We have parent friends who aren’t comfortable with indoor playdates. I try to talk everyone into being a bit less nervous, but vaccinating the kids is the psychological endpoint for a lot of people, and I want it to happen.

Objectively, though, the Gentrifying Children of Logan Circle need the shots less than people in poor countries. But a regulatory strategy of delay is only going to go so far. If boosters are helpful, and it seems like they are, then people are going to want them. And holding them back to help foreigners isn’t going to fly.

What we need are more vaccines.

Meet the stringent regulatory authorities

In America, we have the FDA. Europe has the European Medicines Agency (EMA). But lots of countries don’t bother to replicate this work. Instead, the national regulatory authority tends to piggyback on the work of what are known as Stringent Regulatory Authorities — basically the medical regulators of some rich and well-regarded countries. And Covax, the big global vaccine purchase and distribution agency for poor countries, is specifically counting on the FDA, the EMA, Australia’s TGA, Swissmedic, Health Canada, and the UK’s MHRA as their go-to SRAs on this.

This brings us back to the Chinese factories.

To get more production online, we would need to verify that these extra facilities that could allegedly produce millions more doses are actually up to snuff. Maybe some aren’t, but at least some of them probably are!

The issue is that actually inspecting facilities and doing the work takes nontrivial amounts of time and effort, and these SRAs have a lot going on at the moment. And the real problem, in this case, is that the U.S. and EU (the big players who count here) don’t particularly want the Chinese vaccines. Normally the idea is we would do the inspections because we want to use the product. But in this case, we have plenty of doses. The people who’d gain from this are not American or European, so it’s not shocking that neither the U.S. nor the EU government has prioritized doing the work.

Indeed, from a certain perspective, getting more Chinese factories certified is probably worse than useless for the United States — we’re talking about spending time and money on delivering a propaganda win for Xi Jinping.

But it’s still a good idea.

The Chinese vaccines work

Before I started looking into this, I had a vague sense that Chinese vaccine production is irrelevant because the Chinese vaccines don’t actually work.

This isn’t true. What is true is that their vaccines do not seem to be as good as the mRNA vaccines developed by Pfizer and Moderna. If you’re Australia, a country that is small, rich, and has kept Covid pretty much contained, then I think it arguably does make sense to just keep things locked down until you can get an mRNA shot to everyone who wants one.

But developing countries generally can’t afford to pursue this strategy, and giving people a vaccine as soon as possible is a lot better than waiting (possibly a long time) for the best possible vaccine. The fact that boosters are looking more likely only strengthens that case. Whenever your country can get mRNA, those can be your boosters rather than your first shots.

Confusion on this point stems from three sources:

  • Healthy western pride in our mRNA scientific achievements can turn into nationalist bluster that misleadingly downplays the utility of the Chinese vaccines.

  • This misinformation makes it even less likely that our regulators would go out of their way to approve the use of an inferior vaccine when we already have vaccine plenty.

  • Before Delta, I think we were hoping that adequate levels of mRNA vaccination would produce “herd immunity,” which is probably not possible with Sinovac or Sinopharm.

This last point is important because Delta undermines the efficacy of all vaccines in a way that is unfortunate and naturally generates the sentiment that only the best will do. But on a societal level, it’s the opposite. The mRNA vaccines were so effective against the older variants that we could hope that if 70-80% of the population got vaccinated, the virus would just be unable to spread. Breakthrough cases of measles are very possible, biologically speaking. If only 5% of the U.S. population were vaccinated against measles, members of the 5% would need to worry a bit about breakthroughs. But we have measles vaccination rates up to a high enough level that in most years, there are no measles outbreaks anywhere, so nobody has to worry about breakthroughs.

That was the dream, and the greater efficacy of the mRNA vaccines over Sinovac and Sinopharm was very relevant to the herd immunity math.

But Delta is so contagious that this now looks unrealistic. We are instead in the Covid-1889 scenario where this virus is going to keep bouncing around essentially forever. The hope is that a combination of vaccinations and acquired immunity will eventually wrestle it into a situation where it’s comparable to a normal cold or flu rather than a major crisis. Moderna is developing a combination flu/Covid shot that would further reduce the distinction if it comes to market — it’ll just be something that conscientious people do every year.

Saving lives is a good idea

So what could we actually expect from expanded Sinovac and Sinopharm production?

Well, the WHO studied the use of the Sinovac vaccine in non-elderly adults and found it reduced the incidence of symptomatic disease by 51% and hospitalization by 100% in the studied population. Naturally, you would expect less dramatic results in the elderly or perhaps people with serious co-morbidities, but there are also a lot of non-elderly people, especially in the developing world where the age structure of the population tends to be younger. A New England Journal of Medicine Sinovac study found a better result with regard to mild illness (66%) but a worse one with regard to hospitalization and death (both around 86-87%).

An unfortunate reality about the government of the People’s Republic of China is that they are not as forthcoming and cooperative as one would like. They have not conducted a large-scale trial that includes plenty of elderly people and would let us get a really strong assessment. But experts who’ve reviewed the range of small-scale studies out there are confident that these vaccines substantially cut the risk of hospitalization or death.

Their weak results against mild disease mean that they wouldn’t have been good enough to generate herd immunity, which was a rational basis for discounting them last spring. But now that Delta is upon us and herd immunity seems out of reach, it would be a mistake to downplay the value of these vaccines to the huge number of unvaccinated people in poorer countries.

Throughout the entire continent of Africa, for example, only 3.2% of the population is fully vaccinated. Not only does the cost and scarcity of mRNA doses make it unlikely that the bulk of the African population will have access to those shots anytime soon, but the difficulty of arranging cold storage for mRNA vaccines means the logistics of delivery would be very difficult. The good news is that compared to the U.S. or Europe, Africa is extremely young — only 3% of the population is over the age of 65 — so the odds of developing serious illness are much lower.

That said, we’re talking about poor countries with weak healthcare systems. A volume of serious cases that the United States can easily treat could easily overwhelm developing country health systems, leading to spiking case fatality rates. The lower-prestige vaccines, including the AstraZeneca shot and the Chinese vaccines, are extremely helpful in this context, and boosting their availability could save tons of lives. It seems like the antibodies from these vaccines do fade over time, making boosters desirable, but that’s exactly where we are with the mRNA shots. The point is that we need all the supply we can get, and having American and European regulators cooperate with Chinese manufacturers is a good way to increase production.

We should actually do the research

Given the varying efficacy of the different vaccines and the apparent desirability of some form of booster in almost all cases, I’ve been wondering about the viability of mixing and matching.

I’m sitting here, 40 years old in a rich country, and feeling both like I would like to get a Covid booster shot at some point and also that, morally speaking, I don’t love the idea of snatching a vaccine away from someone who needs it more. Maybe people like me should get Chinese booster shots, and mRNA doses can be given to senior citizens or healthcare workers in poorer countries. Who knows?

Right now the WHO says you shouldn’t do that because it hasn’t really been studied, but a bunch of countries are considering it anyway. There are also pretty strong indications that half-doses of mRNA vaccines are much more than half as effective as full doses, and that would allow us to expand supply. The WHO is skeptical about this, again because it hasn’t been studied in a totally rigorous way. But at the same time, the WHO is very negative about boosters because they reduce supply. All these cautions are reasonable, but it also smacks of status quo bias. What we actually need to do is do the research.

I don’t want to rehash the whole human challenge trials debate, but it continues to be the case that there are lots and lots of vaccine-related scientific questions that it would be nice to have the answer to, and recruiting heroic volunteers to get fast answers could be very useful. It seems like we are going to be vaccinating and boosting against Covid-19 for a while, and figuring out how to optimize dosing and mix-and-match strategies while getting as many factories online as possible is critical to that. I know the regulators feel they’re already swamped, and that these are not happy times for U.S.-China cooperation, but the stakes are genuinely enormous, and we should all try to rise to the occasion.