With demand for COVID-19 vaccines surpassing global stocks, a frustrated public and legislators want to know: how can we get more? A lot more. Immediately.
The problem: “It’s not like adding more water to the soup,” said vaccine expert Maria Elena Bottazzi, of Baylor College of Medicine.
COVID-19 vaccine manufacturers need everything to work, as they increase production to hundreds of millions of doses – and any small hiccup can cause a delay. Some of its ingredients were never produced with the necessary volume.
And seemingly simple suggestions that other factories switch to preparing new types of vaccines cannot happen overnight. Just this week, French drugmaker Sanofi took an unusual step by announcing that it would help to bottle and package some vaccines produced by competitor Pfizer and its German partner BioNTech. But those doses won’t start arriving until the summer – and Sanofi has space at a factory in Germany just because its own vaccine is late, bad news for global supplies.
“We think, well, okay, it’s like men’s shirts, okay, I’ll just have another place to do it,” said Dr. Paul Offit of Children’s Hospital of Philadelphia, a vaccine consultant for the United States government. “It’s not that easy.”
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DIFFERENT VACCINES, DIFFERENT RECIPES
The various types of COVID-19 vaccines used in different countries train the body to recognize the new coronavirus, especially the spike protein that surrounds it. But they require different technologies, raw materials, equipment and knowledge for this.
The two vaccines authorized in the United States so far, by Pfizer and Moderna, are made by placing a piece of genetic code called mRNA – the instructions for that spike protein – inside a fat ball.
Making small amounts of mRNA in a research lab is easy, but “before that, 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 the pioneer in mRNA technology.
Scaling up doesn’t just mean multiplying the ingredients to fit in a larger tank. Creating mRNA involves a chemical reaction between genetic building blocks and enzymes, and Weissman said that enzymes don’t work as efficiently in larger volumes.
AstraZeneca vaccines, already used in Britain and several other countries, and one expected soon from Johnson & Johnson, are made with a cold virus that penetrates the spike protein gene into the body. It is a very different form of manufacture: living cells in giant bioreactors grow that cold virus, which is extracted and purified.
“If the cells age, become tired or start to change, you could be less,” said Weissman. “There is a lot more variability and a lot more things that you need to check.”
An outdated variety – “inactivated” vaccines like one made by Sinovac of China – requires even more steps and more stringent biosafety because they are made with dead coronavirus.
One thing that 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 need to have confidence in the quality of each batch.
WHAT HAPPENS TO THE SUPPLY CHAIN?
Production depends on sufficient raw materials. Pfizer and Moderna insist that they have reliable suppliers.
Still, a U.S. government spokesman said logistics experts are working directly with vaccine manufacturers to anticipate and resolve any bottlenecks that may arise.
Moderna CEO Stephane Bancel recognizes that the challenges remain.
With shifts operating 24 hours a day, 7 days a week, if on any given day “a raw material is missing, we cannot start making products and that capacity will be lost forever because we cannot compensate for it,” he said recently. investors.
Pfizer temporarily cut deliveries to Europe for several weeks, so it could upgrade its factory in Belgium to handle more production.
And sometimes the lots fall short. AstraZeneca told the indignant European Union that it will also deliver fewer doses than originally promised. The reason given: “yields” or production below expectations in some European manufacturing locations.
More than in other industries, when brewing beer with organic ingredients, “there are things that can go wrong and will go wrong,” said Norman Baylor, a former head of vaccines at the Food and Drug Administration who considered production variability common.
HOW MUCH IS THE WAY?
This varies by country. Moderna and Pfizer are on track to deliver 100 million doses to the United States by the end of March and another 100 million in the second quarter of the year. Looking further ahead, President Joe Biden announced plans to buy even more over the summer, reaching enough to vaccinate 300 million Americans.
Pfizer CEO Albert Bourla said at a Bloomberg conference this week that his company will end up supplying 120 million doses by the end of March – not for faster production, but because healthcare professionals are now allowed to squeeze a dose extra from each bottle.
But taking six doses instead of five requires the use of specialized syringes, and there are doubts about the global supply. A Health and Human Services spokesman said the United States is shipping kits that include special syringes with each shipment from Pfizer.
Pfizer also said that upgrading its plant in Belgium is a short-term problem for long-term gains, as the changes will help increase world production to 2 billion doses this year, instead of the 1.3 billion originally expected.
Similarly, Moderna recently announced that it will be able to supply 600 million doses of vaccine in 2021, against 500 million, and that it is expanding capacity in the hope of reaching 1 billion.
But possibly the easiest way to get more doses is to check that other developing vaccines work. US data on whether Johnson & Johnson’s single dose protects are expected soon, and another company, Novavax, is also in the final testing phase.
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OTHER OPTIONS
For months, leading vaccine companies lined up “contract manufacturers” in the United States and Europe to help them distribute doses and then go through the final stages of bottling. Moderna, for example, is working with the Swiss Lonza.
In addition to the wealthy nations, the Serum Institute of India has a contract to manufacture one billion doses of the AstraZeneca vaccine. It is the world’s largest manufacturer of vaccines and is expected to be an important supplier to developing countries.
But some local efforts to increase supplies seem to have failed. Two Brazilian research institutes plan to produce millions of doses of the AstraZeneca and Sinovac vaccines, but have been hampered by unexplained delays in shipments of important ingredients from China.
And Bottazzi said the world must simultaneously keep producing vaccines against polio, measles, meningitis and other diseases that still threaten even in the midst of the pandemic.
Penn’s Weissman asked for patience, saying that as each vaccine manufacturer gains more experience, “I think that each month they will make more vaccines than the previous month.”