Given that the demand for COVID-19 vaccines exceeds the world’s supply, a frustrated public and policy makers want to know: How can we get more? A lot more. Immediate.
The problem: “It’s not like adding more water to the soup,” said Maria Elena Bottazzi, a vaccine specialist at Baylor College of Medicine.
Manufacturers of COVID-19 vaccines need everything to go right, as they increase production to hundreds of millions of doses – and any small hiccups could cause a delay. Some of their ingredients have not been produced to the required volume so far.
And the seemingly simple suggestions that other factories are switching to new types of vaccines cannot happen overnight. Earlier this week, French doctor Sanofi took the unusual step of announcing that it would help bottle and package vaccines produced by competitor Pfizer and its German partner BioNTech. But these doses will not start until the summer – and Sanofi has space in a factory in Germany only because its own vaccine is delayed, bad news for the global supply of the world.
“We’re thinking, ‘Well, OK, it’s like men’s shirts, isn’t it? I’ll just have another place to do it, “said Dr. Paul Offit of Philadelphia Children’s Hospital, a U.S. government vaccine advisor. “It’s not that easy.”
DIFFERENT VACCINES, DIFFERENT RECIPES
Many types of COVID-19 vaccines used in different countries train the body to recognize the new coronavirus, especially the protein that covers it. But it requires different technologies, raw materials, equipment and expertise to do this.
The two vaccines authorized in the US so far, from Pfizer and Moderna, are made by inserting a piece of genetic code called mRNA – the instructions for that protein – into a small ball of fat.
Carrying out small amounts of mRNA in a research lab is easy, but “before that, no one made a billion doses or 100 million or even a million doses of mRNA,” said Dr. Drew Weissman of University of Pennsylvania, which helped initiate mRNA technology. .
Expansion doesn’t just mean multiplying the ingredients to fit a larger tub. Creating mRNA involves a chemical reaction between genetic blocks and enzymes, and Weissman said the enzymes do not work as efficiently in larger volumes.
The AstraZeneca vaccine, already used in the UK and several other countries, and soon expected from Johnson & Johnson, is made with a cold virus that infiltrates the spike protein gene into the body. It is a very different form of manufacture: living cells in giant bioreactors grow the cold virus, which is extracted and purified.
“If the cells age or get tired or start to change, you might get less,” Weissman said. “There’s a lot more variability and more things you need to check.”
An old-fashioned variety – “inactivated” vaccines, such as the one made by China’s Sinovac, require even more steps and stricter biosecurity, as they are made with killed coronavirus.
One thing all vaccines have in common: they must be made in accordance with strict rules that require specially inspected facilities and frequent testing of each stage, which requires a long time to be confident in the quality of each batch.
WHAT ABOUT THE SUPPLY CHAIN?
Production depends on sufficient raw materials. Pfizer and Moderna insist they have reliable suppliers.
Even so, a U.S. government spokesman said logistics experts are working directly with vaccine manufacturers to anticipate and resolve any bottlenecks that arise.
Moderna CEO Stephane Bancel acknowledges that challenges remain.
With shifts running 24/7, if one day “a raw material is missing, we can’t start producing products and this capacity will be lost forever because we can’t compose it,” he recently told investors.
Pfizer has temporarily slowed deliveries in Europe for a few weeks, so it could upgrade its Belgian plant to handle more production.
And sometimes the batches are short. AstraZeneca told an outraged European Union that it would also deliver fewer doses than initially promised immediately. Reason cited: “yields” or lower results than expected in some European factories.
More than in other industries, when made with organic ingredients, “there are things that can go wrong and will go wrong,” said Norman Baylor, former head of the Food and Drug Administration who called common yield variability.
HOW MUCH IS THAT?
That varies by country. Moderna and Pfizer are set 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, President Joe Biden announced plans to buy even more over the summer, reaching enough to eventually vaccinate 300 million Americans.
Pfizer CEO Albert Bourla told a Bloomberg conference this week that his company would actually end up delivering 120 million doses by the end of March – not through faster production, but because workers in the field of health they are now allowed to take an extra dose out of each vial.
But getting six doses instead of five requires the use of specialized syringes and there are questions about the overall supply. A spokesman for health and human services said the US sends kits that include special syringes to each Pfizer shipment.
Pfizer also said modernizing its plant in Belgium is a short-term pain for long-term gains, as the changes will help increase world production to 2 billion doses this year instead of the initially anticipated 1.3 billion.
Moderna also recently announced that it will be able to supply 600 million doses of vaccine in 2021, up from 500 million, and that it is expanding its capacity in the hope of reaching 1 billion.
But probably the easiest way to get more doses is if other ongoing vaccines are proven to work. US data on Johnson & Johnson’s single-dose protection is expected soon, and another company, Novavax, is also testing the final stage.
OTHER OPTIONS
For months, major vaccination companies have lined up “contract manufacturers” in the US and Europe to help them take out doses and then move on to the final stages of bottling. Moderna, for example, works with the Swiss Lonza.
Beyond the rich nations, the Serum Institute of India has a contract to manufacture a billion doses of AstraZeneca vaccine. It is the largest producer of vaccines in the world and is expected to be a key supplier to developing countries.
But some own efforts to increase supply seem to be reduced. Two Brazilian research institutes intend to produce millions of doses of AstraZeneca and Sinovac vaccines, but have been removed by unexplained delays in shipments of key ingredients from China.
Bottazzi also said that the world must simultaneously maintain the production of vaccines against polio, measles, meningitis and other diseases that still threaten even in the midst of the pandemic.
Penn’s Weissman called for patience, saying that as each vaccine maker gains more experience, “I think they’ll make more vaccines each month than the previous month.”
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The Associated Press Department of Health and Science receives support from the Howard Hughes Medical Institute’s Department of Science Education. AP is solely responsible for all content.