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Why is it hard to manufacture vaccines and raise supplies?

A disappointed public and politicians want to know: How do we get more? With demand for COVID-19 vaccines outpacing the world’s stocks. Just a lot more. Only right away. The problem: “It’s not like adding more water to the soup,” Baylor College of Medicine vaccine specialist Maria Elena Bottazzi sai

A disappointed public and politicians want to know: How do we get more? With demand for COVID-19 vaccines outpacing the world’s stocks. Just a lot more. Only right away.

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

As they scale up production to hundreds of millions of doses, manufacturers of COVID-19 vaccines need everything to go right, and any little hiccup could cause a delay. Some of their ingredients have never been manufactured at the necessary sheer volume before.

And seemingly simple recommendations can’t happen immediately that other factories turn to brewing new kinds of vaccines. Just this week, the French drugmaker Sanofi took an unprecedented move to announce that it would assist in bottling and packaging a vaccine developed by rival Pfizer and its German partner BioNTech. But these doses will not begin to arrive until summer, and Sanofi only has room in a plant in Germany because its own vaccine is overdue, bad news for the overall supply of the world.

“We think, well, OK, it’s like men’s shirts, right, I’m just going to have another place to make it,” said Dr. Paul Offit of Philadelphia Children’s Hospital, a U.S. government vaccine advisor. “It just isn’t so easy.”


The numerous forms of COVID-19 vaccines used in various countries all train the body, mainly the spike protein that coats it, to identify the new coronavirus. But in order to do so, they need various technology, raw materials, equipment and expertise.

The two vaccines approved so far in the U.S., from Pfizer and Moderna, are created inside a small ball of fat by placing a piece of genetic code called mRNA, the instructions for that spike protein.

It is easy to create small quantities of mRNA in a research laboratory, but “before that, no one produced a billion doses or 100 million or even a million mRNA doses,” said Dr. Drew Weissman of the University of Pennsylvania, who helped pioneer mRNA technology.

Scaling up doesn’t just mean the ingredients multiply to suit a larger vat. A chemical reaction between genetic building blocks and enzymes is involved in producing mRNA, and Weissman said the enzymes do not function in larger quantities as effectively.

The AstraZeneca vaccine, already used in Britain and many other nations, and one predicted soon by Johnson & Johnson, is made from a cold virus that sneaks the gene of the spike protein into the body. It’s a very different method of production: in giant bioreactors, living cells develop the cold virus, which is extracted and purified.

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

An old-fashioned variety needs even more measures and more stiffer biosecurity since they are made with killed coronavirus, “inactivated” vaccines such as one made by China’s Sinovac.

All vaccines have one thing in common: they must be manufactured under strict rules requiring specially inspected equipment and regular testing of each phase, a time-consuming requirement to be secure in the consistency of each batch.

What about the chain of supply?

Production depends on raw materials that are necessary. Pfizer and Moderna say they have suppliers that are reliable.

Even so, a spokesperson for the U.S. government said logistics experts work closely with vaccine manufacturers to predict and overcome any bottlenecks that occur.

Stephane Bancel, CEO of Moderna, recognises the problems exist.

With shifts running 24/7, if one raw material is lacking on any given day, we will not start manufacturing goods and that potential will be lost forever because we will not make it up,” he told investors recently.”

For several weeks, Pfizer has been temporarily slowing deliveries in Europe, so it could upgrade its Belgian factory to handle more demand.

And the batches fall short occasionally. AstraZeneca told the outraged European Union that it, too, would instantly deliver fewer doses than initially promised. The explanation cited: in some European manufacturing sites, lower than planned “yields,” or production.

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

How much of it is on the way?

That varies according to country. By the end of March, Moderna and Pfizer are each on target to deliver 100 million doses to the U.S. and a further 100 million in the second quarter of the year. Looking even farther forward, President Joe Biden has revealed plans to purchase more over the summer, enough to vaccinate 300 million Americans eventually.

This week, Pfizer CEO Albert Bourla told a Bloomberg conference that his business will likely end up delivering 120 million doses by the end of March, not by quicker development, but because health workers are now allowed to squeeze an extra dose from each vial.

But getting six doses instead of five involves the use of specialised syringes, and global supply issues arise. The U.S. is sending kits that include the special syringes for each Pfizer shipment, a Health and Human Services spokesperson said.

Pfizer has said that the upgrade of its factory in Belgium is short-term pain for longer-term benefit, as the improvements would help boost global production this year to 2 billion doses instead of the originally planned 1.3 billion.

Likewise, Moderna recently announced that it will be able to produce 600 million doses of vaccine in 2021, up from 500 million in 2021, and that capacity will be extended in hopes of reaching 1 billion.

But maybe the best way to get more doses is if it is confirmed that other vaccines in the pipeline are working. U.S. data on whether the one-dose shot protects Johnson & Johnson is anticipated shortly, and there is also another firm, Novavax, in final-stage research.

Any Choices

In the U.S. and Europe, the chief vaccine firms lined up “contract manufacturers” for months to help them churn out doses and then endure the final steps of bottling. For instance, Moderna is working with Lonza of Switzerland.

In addition to rich nations, India’s Serum Institute has a deal to produce a billion doses of the AstraZeneca vaccine. It is the biggest producer of vaccines in the world and is expected to be a primary supplier to developing countries.

But some homegrown attempts to expand supplies seem hobbled. Two Brazilian research institutes intend to manufacture millions of doses of vaccines for AstraZeneca and Sinovac, but unexplained delays in shipments of key ingredients from China have set them back.

And Bottazzi said that at the same time, the world would continue to manufacture vaccines against polio, measles, meningitis and other diseases, which are still at risk even in the midst of a pandemic.

Penn’s Weissman urged patience, saying that “I think every month they will make more vaccines than the previous month,” as each vaccine maker gets more experience.