Empty vials containing the Pfizer-BioNTech COVID-19 vaccine will be shown this Friday, January 22, 2021 at a vaccination center at the University of Nevada Las Vegas in Las Vegas. COVID-19 vaccine manufacturers must do everything right as they move from early-stage production to hundreds of millions of doses – and any small hiccups can cause delays. (AP Photo / John Locher)

With demand for COVID-19 vaccines surpassing global supply, a frustrated public and policy makers want to know: How can we do 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.

COVID-19 vaccine makers need everything to grow production to hundreds of millions of doses – and any small hiccups can cause delays. Some of their ingredients have never been made in the quantities needed.

And seemingly simple suggestions that other factories are brewing new types of vaccines cannot come overnight. Just this week, the French pharmaceutical company Sanofi took the unusual step of announcing that it will help fill and package a vaccine from competitor Pfizer and its German partner BioNTech. But those doses won’t arrive until the summer – and Sanofi has the place in a factory in Germany only because its own vaccine is delayed, bad news for global supplies.

“We think, well, OK, it’s like men’s shirts, right, I’ll just have another place to do it,” said Dr. Paul Offit of Philadelphia Children’s Hospital, a US government vaccination advisor. “It’s just not that easy.”


The different types of COVID-19 vaccines used in different countries train the body to recognize the new coronavirus, mainly the spike protein that coats it. However, this requires different technologies, raw materials, devices and specialist knowledge.

Pfizer and Moderna’s two US-approved vaccines are made by putting a piece of genetic code called mRNA – the instructions for this spike protein – into a small ball of fat.

Making small amounts of mRNA in a research laboratory is easy, but “nobody has made a billion doses or 100 million or even a million doses of mRNA before,” said Dr. Drew Weissman of the University of Pennsylvania, who pioneered mRNA technology.

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

Already used in the UK and several other countries and expected soon by Johnson & Johnson, AstraZeneca’s vaccine is made with a cold virus that uses the spike protein gene to creep into the body. It is a completely different form of production: living cells in huge bioreactors grow the cold virus, which is extracted and purified.

“As the cells get old or tired or change, they may be less,” Weissman said. “There’s a lot more variability and a lot more things to check.”

Explainer: Why It Is Difficult to Make Vaccines and Improve Care

This October 2020 photo, provided by Pfizer, shows part of a “freezer farm,” a soccer field-sized facility for storing finished COVID-19 vaccines in Puurs, Belgium. COVID-19 vaccine manufacturers must do everything right as they move from early-stage production to hundreds of millions of doses – and any small hiccups can cause delays. (Pfizer via AP)

An old-fashioned variety – “inactivated” vaccines like China’s Sinovac – requires even more steps and stricter biosecurity as it is made with the coronavirus killed.

All vaccines have one thing in common: they must be manufactured according to strict rules that require specially inspected facilities and frequent testing of each step. This is a time consuming necessity in order to be able to trust the quality of each batch.


Production depends on enough raw materials. Pfizer and Moderna insist on having reliable suppliers.

Even so, a US government spokesman said logistics experts are working directly with vaccine manufacturers to anticipate and resolve bottlenecks.

Stephane Bancel, CEO of Moderna, acknowledges that the challenges remain.

When shifts run around the clock and on a given day “a raw material is missing, we can’t start making products and that capacity is lost forever because we can’t make up for it,” he recently told investors.

Pfizer has temporarily slowed deliveries in Europe for several weeks so that the plant in Belgium could be upgraded for more production.

And sometimes the batches fall short. AstraZeneca told an outraged European Union it, too, would immediately deliver fewer doses than originally promised. The reason given: Lower than expected “yields” or production at some European production sites.

More than any other industry, with organic brewing, there are “things that can and will go wrong,” said Norman Baylor, a former Food and Drug Administration vaccines chief who cited yield variability as common.


It differs from country to country. Moderna and Pfizer are each on track to ship 100 million cans in the US by the end of March and an additional 100 million in the second quarter of the year. Looking ahead, President Joe Biden has announced plans to buy even more this summer to eventually vaccinate 300 million Americans.

Explainer: Why It Is Difficult to Make Vaccines and Improve Care

This Sunday, December 20, 2020, boxes of the Moderna COVID-19 vaccine are being prepared for shipment from the McKesson distribution center in Olive Branch, Miss. Prepared. COVID-19 vaccine manufacturers need everything to function properly when scaling up, from early-stage production to hundreds of millions of doses – and any small hiccups can cause delays. (AP Photo / Paul Sancya, Pool)

Albert Bourla, CEO of Pfizer, said at a Bloomberg conference this week that his company will actually deliver 120 million doses by the end of March – not through faster production, but because health workers are now allowed to squeeze an extra dose from each vial.

However, to get six instead of five doses, special syringes must be used and there are questions about global supply. A spokesperson for Health and Human Services said the US is sending kits containing the special syringes with every Pfizer shipment.

Pfizer also said the Belgium plant expansion is painful in the short term for longer-term profits, as the changes will help increase global production to 2 billion cans this year instead of the 1.3 billion originally expected.

Moderna also recently announced that it could deliver 600 million vaccine doses of 500 million in 2021, hoping to expand capacity to 1 billion.

Perhaps the easiest way to get more doses is to show that other vaccines in the pipeline will work. U.S. data on whether Johnson & Johnson’s one-dose shot protects is expected shortly, and another company, Novavax, is also in the final stages of testing.


For months, major vaccine companies set up “contract manufacturers” in the US and Europe to help them increase the doses and then do the final filling steps. Moderna, for example, works with the Swiss Lonza.

Beyond the rich nations, the Serum Institute of India is tasked with making one billion doses of AstraZeneca’s vaccine. It is the world’s largest vaccine manufacturer and is expected to be a major supplier to developing countries.

But some homemade efforts to increase the supply seem limp. Two Brazilian research institutes plan to manufacture millions of doses of the AstraZeneca and Sinovac vaccines, but have been set back due to unexplained delays in shipping key ingredients from China.

And Bottazzi said the world needs to keep producing vaccines against polio, measles, meningitis and other diseases that are still looming even amid the pandemic.

Penn’s Weissman urged patience, saying that every vaccine manufacturer gets more experience: “I think they will be making more vaccines every month than the previous month.”

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