With demand for COVID-19 vaccines outstripping global supplies, a frustrated public and policymakers want to know, How can we get more? Much 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.
Producers of COVID-19 vaccines need everything they can to thrive when they scale production to hundreds of millions of doses – and every little hiccup can cause a delay. Some of their ingredients have never been produced with the required volume before.
And seemingly simple suggestions that other factories will switch to brewing new types of vaccines cannot happen overnight. This week, French drug company Sanofi took the unusual step of announcing it would help bottling and packaging a vaccine produced by competitor Pfizer and its German partner BioNTech. But those doses aren’t starting to arrive until the summer – and Sanofi only has the space in a factory in Germany because its own vaccine has been delayed, bad news for overall world supply.
“We think, ‘Well, okay, it’s like men’s shirts, right? I’ll just have another place to save it,'” said Dr. Paul Offit of Children’s Hospital in Philadelphia, a vaccine adviser for the US government. “It’s just not that easy.”
DIFFERENT VACCINES, DIFFERENT RECIPES
The multiple types of COVID-19 vaccines used in different countries all train the body to recognize the new coronavirus, usually the spike protein that envelops it. But for that they need different technologies, raw materials, equipment and expertise.
The two vaccines approved so far in the US, from Pfizer and Moderna, are made by putting a piece of genetic code called mRNA – the instructions for that spike protein – into a ball of fat.
Making small amounts of mRNA in a research lab is easy, but “no one has made a billion doses or 100 million or even a million doses of mRNA for that,” says Dr. Drew Weissman of the University of Pennsylvania, who pioneered mRNA technology. .
Scaling up doesn’t just mean multiplying ingredients to fit in a bigger barrel. 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.
The AstraZeneca vaccine, which is already in use in Britain and several other countries, and is expected soon from Johnson & Johnson, is made with a cold virus that enters the spike protein gene. It’s a very different form of production: living cells in giant bioreactors grow that cold virus, which is extracted and purified.
“When the cells get old or tired or start to change, you might get less,” Weissman said. “There is a lot more variability and you have to check a lot more things.”
An old-fashioned variant – “inactivated” vaccines such as those from China’s Sinovac – requires even more steps and stricter biosecurity because they are made with killed coronavirus.
All vaccines have one thing in common: they must be made under strict rules requiring specially inspected facilities and regular testing of every step, a time-consuming need to be confident in the quality of each batch.
WHAT ABOUT THE SUPPLY CHAIN?
Production depends on sufficient raw materials. Pfizer and Moderna insist that they have reliable suppliers.
Still, a US government spokesperson said logistics experts are working directly with vaccine manufacturers to anticipate and resolve any bottlenecks.
Moderna CEO Stephane Bancel recognizes that challenges remain.
With services running 24 hours a day, 7 days a week, and if on a given day “one raw material is missing, we can’t start making products and that capacity will be lost forever because we can’t catch up” , he recently told investors.
Pfizer has temporarily delayed deliveries in Europe for several weeks so it could upgrade its factory in Belgium to handle more production.
And sometimes the batches fall short. AstraZeneca told an outraged European Union that it too will immediately deliver fewer doses than originally promised. The reason given: lower than expected “revenues” or output at some European production sites.
More than in other industries, when brewing with organic ingredients, “there are things that can and will go wrong,” said Norman Baylor, a former Food and Drug Administration chief vaccine who often mentioned variability in yield.
HOW MUCH IS ON THE ROAD?
That differs per country. Moderna and Pfizer are each on track to deliver 100 million doses to the US by the end of March and an additional 100 million in the second quarter of the year. Looking even further ahead, President Joe Biden has announced plans to buy even more in the summer, enough to eventually vaccinate 300 million Americans.
Pfizer CEO Albert Bourla told a Bloomberg conference this week that his company will actually deliver 120 million doses by the end of March – not because of faster production, but because health workers are now allowed to squeeze an extra dose from each vial.
But getting six doses instead of five requires special syringes, and there are questions about the global supply. A Health and Human Services spokesperson said the US will send kits containing the special syringes with every shipment from Pfizer.
Pfizer also said the upgrade of the factory in Belgium is hurting for longer-term profit in the short term, as the changes will help increase global production this year to 2 billion doses instead of the 1.3 billion originally expected.
Moderna also recently announced that it will be able to deliver 600 million doses of vaccine by 2021, up from 500 million, and expand its capacity in hopes of reaching 1 billion.
But possibly the easiest way to get more doses is if other vaccines in the pipeline have been proven to work. US data on whether Johnson & Johnson’s one-time injection protects is expected soon, and another company, Novavax, is also in the final stages of testing.
OTHER OPTIONS
For months, the major vaccine companies lined up with “contract manufacturers” in the US and Europe to help them ramp up the doses and then go through the final bottling steps. Moderna, for example, works together with the Swiss Lonza.
Outside of rich countries, the Serum Institute of India has a contract to produce one billion doses of AstraZeneca’s vaccine. It is the world’s largest vaccine producer and is expected to be a major supplier to developing countries.
But some homegrown efforts to boost stocks seem to have been hindered. Two Brazilian research institutes plan to make millions of doses of the AstraZeneca and Sinovac vaccines, but are delayed by unexplained delays in shipping key ingredients from China.
And Bottazzi said the world must simultaneously continue to produce vaccines against polio, measles, meningitis and other diseases that continue to threaten even in the midst of the pandemic.
Penn’s Weissman insisted on patience, saying that as each vaccine manufacturer gains experience, “I think they will be making more vaccines every month than the previous month.”
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The Associated Press’s Health and Science Department is supported by the Howard Hughes Medical Institute’s Science Education Department. The AP is solely responsible for all content.