The pandemic surge at home is threatening an Indian vaccinemaker’s bid to protect the world

Serum Institute of India

By Jon CohenMay. 14, 2021 , 5:40 PM

Reporting for this story was supported by the Pulitzer Center.

PUNE, INDIA—In a world of have and have-nots, Adar Poonawalla is most decidedly a have, with both abundant personal wealth and a corner on what promises to be a massive supply of one of the world’s most desperately sought commodities: COVID-19 vaccines. Affable but feisty and a fan of bespoke suits, the 40-year-old heads the Serum Institute of India, the world’s largest maker of vaccines. Before the pandemic, the company’s factories in India annually churned out 1.5 billion doses of vaccines—50% more than the next largest producer—to protect against 13 different diseases.

Poonawalla’s list of personal haves is long: an office fashioned from a retired Airbus 320 jetliner set on Serum’s 40-hectare campus. Ferraris, a Rolls Royce, and a Batmobile. A helicopter and a fleet of private jets. He splits his time between a luxurious ranch house on the family’s stud farm abutting the company, a 9-hectare home across town in the upscale Salisbury Park neighborhood, a former maharaja’s mansion in Mumbai, and a $69,000-a-week rental in London.

But when Poonawalla met with Science in early April, he shied away from the airplane office. “I’ve had a lot of flak on my lifestyle and opulence, and I don’t want that to take away from the serious work we’re doing here,” said Poonawalla, sitting in a new office that sports a bust on his desk of Apollo, the Olympian god of healing and epidemics. Part of that work was to supply the world this year with hundreds of millions of doses of an inexpensive, effective COVID-19 vaccine dubbed Covishield that was the brainchild of the University of Oxford and shepherded through clinical trials by AstraZeneca.

It hasn’t worked out as planned. A catastrophic fire and temporary U.S. restrictions on the export of key raw materials slowed production early this spring. The Oxford-AstraZeneca vaccine ran into difficulties, with confusing efficacy results and, more recently, challenges to its safety as some recipients experienced serious or even fatal blood clotting. And, most devastating to Serum’s aim to become the world’s premier COVID-19 vaccine supplier, India has in recent weeks faced an enormous surge of infections and a dire need for an ample vaccine supply of its own. Under government pressure, the company reduced Covishield exports in March and stopped them altogether in mid April. “I don’t like to use the word ‘forced,’” Poonawalla says. “We are, after all, an Indian company that supplies vaccines globally. Right now, our nation needs us.”

Raja Sengupta

Serum’s woes—and India’s—have exacerbated a global COVID-19 vaccine inequity between haves and have-nots. By 12 May, 122 countries and territories had only received a total of 59 million doses of any COVID-19 vaccine, while a single country—China—had 343 million. The COVID-19 Vaccines Global Access (COVAX) Facility, which coordinates distribution of vaccine doses to the world’s poor, had tried to forestall the inequity by investing heavily in Covishield, which it bought for just $3 per dose—far less than competitors charge for other vaccines—and is easy to store and transport. But Serum’s export halt prevented 90 million ordered doses from reaching low-income countries in March and April, and COVAX will fall far short of its target of 247 million delivered vaccine doses by the end of May. “Right now, it’s quite depressing,” says the World Health Organization’s (WHO’s) chief scientist and liaison to COVAX, Soumya Swaminathan, who is from India.

The wild COVID-19 vaccine ride exasperates Poonawalla. He has faced challenges from a leading Indian vaccine competitor, a slight from Prime Minister Narendra Modi, and a media trouncing for threatening to sue a Covishield recipient who alleged injury. “I’ve chosen to just grow a thick skin and ignore everything,” Poonawalla says.

But no one can ignore that the vaccine bet placed by COVAX, on behalf of the world, hasn’t paid off yet. Serum still does not know when it can fulfill its promise of producing enough doses to help stymie the pandemic, at home or abroad. “Everything that we do—good, bad, ugly—is going to be examined with a microscope, and we’ll have to deal with it,” Poonawalla says.

Right now, our nation needs us.

Cyrus Poonawalla, Adar’s father, told his own father 55 years ago he wanted to break from the family’s lucrative racehorses. The stud farm back then donated retired horses to a Bombay scientific institute that made treatments for venoms and tetanus toxins by injecting the animals with the substances and collecting their antibody-filled serum. Now, Cyrus wanted to go into the serum business himself. With his brother Zavaray Poonawalla as a partner, Cyrus raised $12,000 selling horses, which their father matched. They set up the new company on 5 hectares the farm used as a horse graveyard. Within 2 years, it had an anti-tetanus product on the market.

From the outset, Serum wanted to undersell the competition. “When we launched the tetanus antitoxin, I could have sold it at five times the price,” Cyrus says. “From day one, we had the philosophy of being philanthropic or reasonable.”

Serum has always been a for-profit company, not a charity, but both Cyrus and Adar repeatedly refer to their work as philanthropic. “All the products right from then until today, I could have doubled my price [every so often], but I’ve refrained from doing so and that’s still not stopped me, with the grace of God, from becoming a billionaire,” Cyrus says.

The company has profited from sheer volume, building one modestly sized plant after another to steadily increase output. It began to supply India’s expanded program on immunization for children in 1978 and selling vaccines to U.N. agencies in 1993. When Gavi, the Vaccine Alliance launched in 2000 with $750 million from the Bill & Melinda Gates Foundation, Serum’s vaccines helped the organization further bolster childhood immunization in developing countries. By now 65% of the world’s children receive at least one product made by the company. “It’s phenomenal,” says Anthony Fauci, head of the U.S. National Institute of Allergy and Infectious Diseases. “They have the capability of making enough vaccine for six planets.”

Raja Sengupta

Today, the company has 5000 employees and annual revenue of $850 million. “Cyrus has built an incredible franchise, and he was able to grow the capacity and modernize it and be a high-quality producer of vaccines in enormous volumes,” says epidemiologist Seth Berkley, CEO of Gavi, which in 2018 gave Cyrus a “vaccine hero” award. “And he did it without being greedy.” 

So Serum was a natural partner for a team at Oxford developing what it hoped would become a “global vaccine,” which meant affordable to low- and middle-income countries. Sarah Gilbert at Oxford’s Jenner Institute had created a candidate COVID-19 vaccine from a putatively harmless chimpanzee adenovirus, engineering it to carry the gene for the spike protein on the surface of SARS-CoV-2. Adrian Hill, who runs the Jenner Institute, had been making a candidate malaria vaccine for 3 years with Serum, and already had strong relationships with its head of R&D.

Gavi and the Coalition for Epidemic Preparedness Innovations (CEPI)—another COVAX partner—encouraged the marriage, too. Representatives from the Gates foundation, a major funder of CEPI, also joined the matchmaking. CEPI urged the Oxford team to bring in a third partner, as well: a large pharmaceutical company that had experience staging clinical trials and navigating regulatory approval processes. “It didn’t seem ridiculous that we could have it both ways: Serum doing most of the world, and a Big Pharma partner for high-income countries,” Hill says. Ultimately, an agreement was sealed with AstraZeneca.

The Poonawallas were, at first, chagrined that Oxford enlisted AstraZeneca. “We were the ones aligned to them in terms of being philanthropic,” says Adar, who began working at Serum straight of out college in 2001 and became CEO 10 years later. “In hindsight, I don’t think that was the wrong decision because of AstraZeneca’s capabilities to conduct these global trials. That would have been something that we would have struggled with.”

In the end, a patchwork of clinical trials in three countries funded by Oxford, AstraZeneca, governments, and foundations showed in December 2020 that the adenovirus-based vaccine effectively protects people from COVID-19, although not as well as the messenger RNA (mRNA) vaccines from other companies. Serum got the rights to sell the vaccine to 92 low- and middle-income countries that have joined COVAX, whereas AstraZeneca can supply the rest of the world. For the time being, AstraZeneca has agreed to sell the vaccine at no profit, inking country-specific deals ranging from $5 per dose to below Serum’s $3-per-dose contract with COVAX. (Serum with the government’s permission recently began to sell Covishield to private hospitals in India for $8 per dose, and it charged Bangladesh a similar amount in one of its many bilateral deals.)

As this year began, Serum’s role in supplying the neediest countries with vaccine seemed assured. The Gates foundation gave $300 million to Gavi, which directed it to Serum to both accelerate manufacturing of Covishield and another low-cost vaccine, developed by Novavax, and contribute to COVAX’s initial purchase of 100 million doses of each product. COVAX has an option for another 900 million doses of the two vaccines. Serum devoted unused production lines set aside for other vaccines to Covishield, investing $300 million of its own money, and WHO granted Covishield an emergency use listing (EUL)—a COVAX prerequisite—on 15 February. Serum shipped out 18 million doses to COVAX 10 days later. “They were unbelievable,” Berkley says.

But Serum, like the maker of almost every COVID-19 vaccine, has had unforeseen delays. In January, a fire killed five construction workers building a new plant to fill and finish vaccines. Then, the U.S. government, which until recently was worried about its own COVID-19 vaccine supply, restricted exports of vaccine raw materials such as liners for bioreactors and filters. Adar predicted last year that Serum would produce 100 million doses of Covishield per month by February, but production has never topped 70 million.

Shots for the world

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Serum’s distribution

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Delivered COVID-19 vaccine doses

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In late April, with daily COVID-19 cases in India spiking to nearly 350,000, the U.S. government relented and said it would make the materials available “immediately.” But by then India’s burgeoning need for vaccines had largely negated Serum’s ability to supply doses to COVAX, and the world. To date, it has delivered about 220 million doses of Covishield. More than 155 million of those doses have stayed home, supplying 90% of the shots delivered in India. COVAX has received just 28 million.

Indian politics have added to Serum’s woes. Last summer, the government stunned scientists in India and abroad when it announced a bold plan to fast-track a COVID-19 vaccine, made not by Serum but by Bharat Biotech of Hyderabad, with help from the National Institute of Virology. The government’s Indian Council of Medical Research on 2 July 2020 issued a letter that said the “indigenous” vaccine made by Bharat from inactivated virus, called Covaxin, would be ready for “public health use” 6 weeks later, on 15 August—even though it had just entered initial safety, not efficacy, trials.

Some researchers believed nationalism rather than science was work. “Why this one was special is not really clear to me,” says Gagandeep “Cherry” Kang, a vaccine researcher at Christian Medical College, Vellore, who also is on the CEPI board. “Covishield [also] is an indigenous vaccine—it’s made in India.” To Kang and others, Covaxin’s early authorization spotlighted India’s already suspect medical regulatory system. “Ultimately, we want India to be able to make drugs and vaccines for the world, which means the world has to be able to trust what we are doing,” she says.

The 15 August deadline came and went without Covaxin receiving regulatory approval, but in early January, both Indian vaccines received what amounts to an emergency use authorization. In a 3 January interview on India’s popular NDTV, Adar celebrated the decision for Serum, but took a swipe at Covaxin. Only AstraZeneca and Oxford, Pfizer and BioNTech, and Moderna had presented convincing vaccine efficacy data, he stressed. “Everything else has proven to be safe, just like water,” he said. The comment angered Bharat’s CEO, Krishna Ella, who held a press conference the next day and fired back with his own insults about Covishield.

Ella and Adar quickly made peace in a joint statement, and Bharat has since presented preliminary data showing 81% efficacy for Covaxin, better than the AstraZeneca-Oxford vaccine by some measures. But the spat fueled growing vaccine hesitancy in India, adding to doubts fed by an earlier dispute: After a participant in a small trial of Covishield in India filed suit alleging neurological harm and the company threatened to countersue for $13.5 million—20 times more than the man’s suit—because of defamation. The hubbub faded, and Cyrus is unrepentant. “I’m not Jesus Christ to give my second cheek because I was slapped on one,” he says.

However much of a shine the Modi government took to Covaxin, Bharat did not have the production capacity to make enough of the vaccine for the country. Yet India’s first contract with Serum was only made after Covishield received authorization and it was for a mere 11 million doses. Other counties had already locked in hundreds of millions of doses of various COVID-19 vaccines. “The government sort of twiddled its thumbs until the very last moment,” Kang says.

On 1 March, in an image posted on social media and now plastered on billboards across the country, Modi received his first dose of a COVID-19 vaccine. It was Covaxin.

Took my first dose of the COVID-19 vaccine at AIIMS.

Remarkable how our doctors and scientists have worked in quick time to strengthen the global fight against COVID-19.

I appeal to all those who are eligible to take the vaccine. Together, let us make India COVID-19 free! pic.twitter.com/5z5cvAoMrv

— Narendra Modi (@narendramodi) March 1, 2021

A few weeks later, as India’s second wave of COVID-19 began, the vaccine shortage became glaring. “They didn’t plan and now they’re in a panic situation,” says an Indian researcher who has worked closely with the government but asked not to be named. “Suddenly, they want all the doses that are being produced.” The result was the abrupt export halt that has forced Serum to renege on its commitments to COVAX.

Berkley has grown weary of addressing COVAX’s big bet on Serum. “If I had had $12 billion, and held control over the largest biopharmaceutical companies and could force them to make vaccines for me, it would have been a different outcome,” he says. “Serum is a 20-plus–year reliable manufacturer with us, and they had met all of their goals. They’ve not had any quality control problems. But here we are, and they’re not keeping any of their contracts.”

Adar says the burden should not all fall on his company. “I plead with other vaccine manufacturers to provide more doses to COVAX so that the pressure on me is off.”

Swaminathan also wants wealthy countries that have already vaccinated a large percentage of their populations, such as the United States and United Kingdom, to donate doses immediately. “I have always argued within COVAX that we can’t expect India alone to keep supplying [vaccine],” she says.

The pressure on Serum has eased somewhat in recent weeks. New Zealand, France, and Norway all made small donations to COVAX, and the Biden administration said it would give away 60 million doses of AstraZeneca vaccine made in the United States by the end of June. China’s Sinopharm also received an EUL from WHO and started to negotiate with COVAX to provide hundreds of millions of doses. Moderna negotiated a deal with COVAX to sell 34 million doses of its mRNA vaccine in 2021 and 446 million more next year at what the company would only describe as its “lowest tiered price.”

Another huge Indian vaccine company, Biological E., could also address the global need while supplying India with much-needed doses. It has a contract with Johnson & Johnson (J&J) and expects to produce up to 400 million doses this year of its COVID-19 vaccine, which also uses an adenovirus to produce spike but only requires a single shot.

Biological E.’s managing director, Mahima Datla, insists that no matter India’s needs, she will not renege on any deals with COVAX. “We believe all lives our created equal,” says Datla, the representative on the Gavi board for developing country vaccine manufacturers. “I also believe until everybody’s safe, nobody’s safe.” Bharat, which originally planned to produce only 200 million doses of Covaxin a year, is increasing its capacity thanks to a new plant built with a $200 million credit from the Indian government and hopes to more than triple output over the next year.

And Serum may ultimately be able to live up to its promises. The Indian government on 19 April agreed to give it a $400 million credit to help the company boost production to its originally promised 100 million doses of Covishield per month—enough, Serum hopes, to supply both India and the world.

Adar Poonawalla has large ambitions, which his father corralled for many years. “I was a man in a hurry in my 20s and 30s, trying to prove myself, and I wanted to expand very fast, but he prevented me from doing that, and I think prevented me from making a lot of mistakes. He said, ‘Look, you’ve got five vaccines. Why do you need any more, you’re still very profitable, just grow those.’”

Raja Sengupta

But the son is already thinking about the next pandemic. In 2019, Serum opened the $400 million Poonawalla Bio-Technology Park, which doubled the size of the campus. Now, the site is again crowded with cement trucks, cranes, and workers in hard hats adding 28,000 square meters of space to vastly increase Serum’s bulk manufacturing capabilities once more. It will also include a biosafety level-3 lab that can handle all but the most dangerous of pathogens, so Serum can for the first time grow and then inactivate large batches of a virus or bacteria, an old but reliable approach to making a vaccine.

Serum now has clinical trials underway of eight vaccines in development with partners. It sells a monoclonal antibody against rabies and plans to soon make many more of these notoriously expensive medicines at affordable prices for developing countries. Adar wants to expand the business to start selling to the United States and countries in Europe. “We are not treated in the same way that Big Pharma is treated,” he says. “[Governments] don’t see us as a partner they can work with even though we match the same quality, even though we have pricing that would significantly reduce their health care budgets.”

In what may be Adar’s loftiest enterprise, part of the latest construction includes a plant that can quickly switch from Serum’s current products to making vaccines for the next pandemic. “Imagine a dedicated facility, which can handle messenger RNA, viral vectors, anything—fill, finish, store, and dispatch—within 2 or 3 months of pushing a button,” he says.

Adar predicts the pandemic plant could produce 1 billion doses per year, and he hopes governments that never again want to beg for doses and haggle over prices will commit to a kind of annual vaccine insurance payment. Serum’s pandemic facility will guarantee a $3-per-dose vaccine to subscribers, with the number of doses depending on the size of a government’s investment. “This is really the solution for the future,” he says. “There are always going to be emerging diseases.”

Source: Science Mag