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With demand for COVID-19 vaccines outpacing the world’s supplies, a frustrated public and policymakers want to know: How can we get more? A lot more. Right away.

The problem: “It’s not like adding more water to the soup,” said vaccine specialist Maria Elena Bottazzi of Baylor College of Medicine.

Makers of COVID-19 vaccines need everything to go right as they scale up production to hundreds of millions of doses — and any little hiccup could cause a delay. Some of their ingredients have never before been produced at the volume needed.

And seemingly simple suggestions that other factories switch to brewing new kinds of vaccines can’t happen overnight. Just last month, French drugmaker Sanofi took the unusual step of announcing it would help bottle and package some vaccine produced by competitor Pfizer and its German partner BioNTech.

But those doses won’t start arriving until summer. And Sanofi has the space in a factory in Germany only because its own vaccine is delayed — bad news for the world’s supply.

“We think, ‘Well, OK, it’s like men’s shirts, right? I’ll just have another place make it,’” said Dr. Paul Offit of Children’s Hospital of Philadelphia, a vaccine adviser to the U.S. government. “It’s just not that easy.”

Different vaccines, different recipes

The multiple types of COVID-19 vaccines being used in different countries all train the body to recognize the new coronavirus, mostly the spike protein that coats it. But they require different technologies, raw materials, equipment and expertise to do so.

The two vaccines authorized in the U.S so far, from Pfizer and Moderna, are made by putting a piece of genetic code called mRNA — the instructions for that spike protein — inside a little ball of fat.

Making small amounts of mRNA in a research lab is easy, but “prior to this, nobody made a billion doses or 100 million or even a million doses of mRNA,” said Dr. Drew Weissman of the University of Pennsylvania, who helped pioneer mRNA technology.

Scaling up doesn’t just mean multiplying ingredients to fit a bigger vat. Creating mRNA involves a chemical reaction between genetic building blocks and enzymes, and Weissman said the enzymes don’t work as efficiently in larger volumes.

AstraZeneca’s vaccine, already used in Britain and several other countries, and one expected soon from Johnson & Johnson, are made with a cold virus that sneaks the spike protein gene into the body.

It’s a very different form of manufacturing: Living cells in giant bioreactors grow that cold virus, which is extracted and purified.

“If the cells get old or tired or start changing, you might get less,” Weissman said. “There’s a lot more variability and a lot more things you have to check.’’

An old-fashioned variety — “inactivated” vaccines like one made by China’s Sinovac — require even more steps and stiffer biosecurity because they’re made with killed coronavirus.

One thing all vaccines have in common: They must be made under strict rules that require specially inspected facilities and frequent testing of each step — a time-consuming task needed to ensure the quality of each batch.

What about the supply chain?

Production depends on enough raw materials. Moderna CEO Stephane Bancel acknowledges that challenges exist.

With shifts running 24/7, if on any given day “there’s one raw material missing, we cannot start making products, and that capacity will be lost forever because we cannot make it up,” he recently told investors.

Sometimes the batches fall short. AstraZeneca told an outraged European Union that, at least initially, it, too, will deliver fewer doses than originally promised. The reason cited: Lower than expected “yields,” or output, at some European manufacturing sites.

More than in other industries, when brewing with biological ingredients, “there are things that can go wrong and will go wrong,” said Norman Baylor, a former Food and Drug Administration vaccine chief who called yield variability common.

How much is on the way?

That varies by country. Moderna and Pfizer each are on track to deliver 100 million doses to the U.S. by the end of March and another 100 million in the second quarter of the year. Looking even further ahead, President Joe Biden has announced plans to buy still more over the summer, reaching enough to eventually vaccinate 300 million Americans.

Pfizer CEO Albert Bourla told a Bloomberg conference in February that his company will actually wind up providing 120 million doses by the end of March — not by speedier production but because health workers now are allowed to squeeze an extra dose out of every vial.

Moderna recently announced it will be able to supply 600 million doses of vaccine in 2021, up from 500 million, and that it was expanding capacity in hopes of getting to 1 billion.

But possibly the easiest way to get more doses is if other vaccines in the pipeline are proven to work. U.S. emergency authorization of Johnson & Johnson’s one-dose shot is expected soon, and another company, Novavax, also is in final-stage testing.

Penn’s Weissman urged patience, saying that as each vaccine maker gets more experience, “I think every month they’re going to be making more vaccine than the prior month.”                             —AP