Immune to Criticism AstraZeneca Debacle Threatens Global Fight Against Pandemic

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The Anglo-Swedish pharmaceutical company AstraZeneca was supposed to supply the world with an inexpensive vaccine against COVID-19. But after a series of mishaps at the company, trust in the substance that was supposed to help end the pandemic is eroding.

By Markus BeckerClaus HeckingJulia MerlotMartin U. MüllerMaximilian PoppAlexander SarovicFritz SchaapJörg Schindler und Janko Tietz

On April 26, 2020, Elisa Granato reported back from the afterlife. “Nothing like waking up to a fake article on your death,” she tweeted. “I’m doing fine everyone.”

Three days earlier, on her 32nd birthday, photos of the Oxford microbiologist were published around the world. They showed a woman with a yellow top smiling in a laboratory as she had a syringe inserted into her upper left arm. It was a small jab for her, but a big one for humanity. The injection marked the start of Europe’s first human trial of a newly developed COVID-19 vaccine.

On April 23, the story of Elisa Granato and the false reports about her death marked the start of a tense and increasingly bizarre dispute over a medication that was intended to vaccinate much of the world.

Developed by a small team of some of the best vaccine scientists on the planet and industrially produced by a pharmaceutical giant with top credentials, Vaxzevria, the new official name of Oxford/AstraZeneca’s vaccine in Europe, has been making headlines for months. But not the kind its makers had hoped for.

At one point, volunteers in the trials were administered different amounts of the vaccine. Then the vaccine was recommended only for people under the age of 65 and then later only for people over 59. Test data proved to be outdated or incomplete. For months, the manufacturer became entangled not only in a political showdown between the European Union and the United Kingdom, but also in inconsistencies that are becoming increasingly difficult to explain away.

As a result, governments around the world have withdrawn all or part of Vaxzevria (which is also known as Covishield in some countries) from use. And even as the third wave grows in momentum as it rolls across Germany and Europe, the number of people and countries saying they want any vaccine but AstraZeneca is growing with it.

What went wrong? DER SPIEGEL’s reporters have reconstructed the events of the AstraZeneca affair in recent weeks. They spoke with employees at the company, interviewed scientists, government officials and doctors. The result is a chronicle of what has become a disaster – not just for the company, but for many countries as well.

How Britain Led the Way in Vaccinations

The saga of Vaxzevria began at the Nuffield Department of Medicine, a research center on the eastern edge of the college town of Oxford. On Jan. 30, 2020, a group of renowned researchers met there, one day before Brexit and a day before the first two COVID-19 cases were registered on British soil, in York, some 300 kilometers (190 miles) away.

For weeks, they had all been watching the news about the outbreak of a new type of virus in Wuhan, China, with trepidation. With Prime Minister Boris Johnson’s government’s energies fully focused on leaving the EU, scientists at Oxford discussed how they could save the world.

Among those at the table that day was Sarah Gilbert, a low-key professor from the neighboring Jenner Institute who experimented with brewer’s yeast in a brewery research lab before becoming a world-renowned vaccine specialist. Gilbert researched vaccines against malaria, Ebola and MERS but had also been preparing for “Disease X,” the next major pandemic that scientists have been anticipating for years.

Gilbert, who had been studying the genetic code of SARS-CoV-2 for weeks, surprised her colleagues that day with the news that she might soon have a vaccine ready. At the time, she was conducting a second series of tests in a Phase I clinical trial for a vaccine against MERS (Middle East Respiratory Syndrome), which is caused by a virus in the coronavirus family. In the vaccine, she used genetically modified adenoviruses that trigger colds in chimpanzees. They serve as vectors to insert the genetic blueprint of typical coronavirus proteins into human cells. The method is relatively new, but has been tested in efforts to fight Ebola.

By March, the Oxford experts had already finished the first batch of the new vaccine, which had been adapted to the SARS-CoV-2 coronavirus. Trials on pigs in Surrey County showed promise. But it had also been obvious for some time that large quantities of the vaccine would be needed. Vast quantities.

So, Oxford began looking for a partner in the pharmaceuticals industry. The first choice was the American pharmaceuticals giant Merck. But with Donald Trump – an erratic “American first” protectionist – sitting in the White House, the British government had reservations about working with the Americans. London pressed for a written guarantee for deliveries but reportedly didn’t get it. That spelled the end of any possible deal with Merck. Speaking later on LBC, a radio station, British Health Secretary Matt Hancock explained that he didn’t want to enter into a contract that would have allowed the Oxford vaccine to be delivered to other countries around the world first. In April 2020, the idea of working with the British-Swedish company AstraZeneca came into play.

Why the Boss Suddenly Took an Interest in Vaccines

When Pascal Soriot took over the helm at AstraZeneca in 2012, the company was at rock bottom. Its share price was plummeting and the company was at risk of losing patents on its medicines. But Soriot managed to turn things around by refocusing AstraZeneca. Instead of implementing cost-cutting measures, he invested in product development. He bought up companies and fended off a takeover attempt by Pfizer in the United States. In keeping with Soriot’s nature, it was a bold strategy, and it paid off. AstraZeneca is now the second-largest company in Britain.

Soriot, 61, learned early on how to assert himself. He grew up in a rough Paris suburb and his father died when he was only 20. Nevertheless, he got into HEC, the Paris business school, and embarked on a career in the pharmaceutical industry.

He is regarded as an overachiever in the industry, a man who works almost around the clock and isn’t afraid of taking risks. As such, it came as little surprise when AstraZeneca’s chief executive announced that his company was planning to tackle the international community’s trickiest task in 2020: that of producing vaccines against COVID-19. And this, even though the pharmaceutical giant has no experience in vaccine research.

At first, the announcement of a partnership with AstraZeneca came as good news for Sarah Gilbert and her team of Oxford scientists. The company, after all, is UK-based and enjoys an impeccable reputation. Soriot also won over Gilbert and her colleagues by making the sweeping promise that AstraZeneca intended to export its vaccine globally at a price between $2 and $5. The company was thus putting itself at the forefront of those wanting to guarantee poor countries swift and equitable access to vaccines. At the same time, however, Soriot also assured the Johnson government that it would supply a large share of the vaccine early and exclusively to Britain.

The deal made sense to Soriot. If he succeeded, he would be assured a place in the history books. Above all else, he would be the man who brought an end to the pandemic. The gain in prestige for his company would also be huge. But staff at the company also say that he didn’t consider the possible consequences of failure closely enough.

A Company Gets Caught Between the Fronts

Soriot approached the vaccine campaign like all of his projects – without hesitation. AstraZeneca guaranteed it would produce 300 million vaccine doses for the EU by mid-2021, as well as 100 million doses for Britain. It was an ambitious goal. Any company would face “massive problems” with an order of such magnitude, says an executive with a Swiss pharmaceutical company.

AstraZeneca is producing Vaxzevria in Europe in at least four factories. Two of them – Oxford Biomedica and Cobra Biologics – are based in the UK. And two others – Thermo Fisher and Halix – are in Belgium and the Netherlands. The plants are operated by subcontractors and not by AstraZeneca itself. And in at least two, things haven’t gone smoothly from the start. Thermo Fisher at first produced less vaccine than expected. And Cobra Biologics wasn’t fully functional until recently.

Dutch health expert Wilbert Bannenberg isn’t surprised by the difficulties with production. He says that hundreds of ingredients are used in vector vaccines like Vaxzevria. And even minor deviations – in raw materials, for example – can render the final product unusable.

By the end of 2020, it had become apparent that AstraZeneca was going to have trouble fulfilling the contracts it had offered. Soriot had to decide who to let down: Britain or the EU, the newly divorced partners.

At this point, a ticked-off prime minister who had done virtually everything wrong that could be done wrong in this pandemic was sitting in London’s Downing Street. Somewhere in between a slew of hair-raisingly bad decisions, he had instinctively made a correct one during the spring of 2020: He set up a vaccine taskforce comprised of renowned scientists and experts. Led by biochemist and venture capitalist Kate Bingham, the force not only set out to organize general-purpose vaccines for Brits, but also to build a real British vaccine industry.

The task force provided production and filling facilities, it pledged the participation of hundreds of thousands of volunteers in clinical trials and the generous assumption of liability risks. In other words, the UK made vaccine developers an offer they could hardly refuse.

How Pascal Soriot Gambled Away Customers’ Trust

Vaxzevria was the third vaccine to be approved in the EU, following those from BioNTech/Pfizer and Moderna. But this autumn, it became clear that AstraZeneca’s studies had been plagued by inaccuracies. Around 3,000 test subjects, for example, received half a dose in their first and then an entire dose in their second vaccination shot. Oxford and AstraZeneca disagreed about whether the half-dose was intentional or accidental. The company drew criticism largely because it basically ended up calculating an average value from the data of different test groups.

The even bigger problem was that too few elderly people were included in the studies. The Standing Commission on Vaccination (STIKO) at the Robert Koch Institute, Germany’s center for disease control, thus initially recommended AstraZeneca only for people aged 18 to 64, upsetting the order of Germany’s priorities for vaccination.

French President Emmanuel Macron, already annoyed by the supply bottlenecks, went one step further. Without any scientific basis, he claimed the AstraZeneca vaccine was “more or less ineffective” in people over 65. From that point on, the vaccine was considered second class in all European countries except the UK.

In the U.S., the vaccine has not yet even been approved, despite the fact that the Trump administration ordered 300 million doses last May. The company seemingly wasn’t totally transparent with the Americans either. It initially concealed the fact that a test subject had fallen ill in the final stages of testing from the U.S. Food and Drug Administration (FDA), resulting in the suspension of the tests. But that wasn’t the last glitch either.

In March, AstraZeneca claimed that its vaccine was 79 percent effective in preventing symptomatic infections. The U.S. authorities, already suspicious, took another look and found there was reason to believe the company had included outdated data, and possibly distorted the results. Anthony Fauci, the country’s leading expert on the pandemic, described it as an “avoidable error.” Once again.

Are these all just blunders and slip-ups that happened in the heat of the moment? And if so, why were they so frequent at only this one company? Or, to put it another way: At what point do individual mistakes add up to a wider-ranging problem?

What the AstraZeneca Crisis Means for the Global Vaccination Campaign

In March of 2021, news began circulating that threatened to destroy trust in AstraZeneca.

In several countries, people vaccinated with Vaxzevria were experiencing vascular occlusions from blood clots in the brain, also known as cerebral sinus vein thromboses. By March 29, the Paul Ehrlich Institute, Germany’s medical regulatory body, had reported that 31 such cases had occurred after 2.7 million vaccinations in Germany. Mostly younger women were affected. Nine died.

Given the challenges the virus poses to governments worldwide, 31 cases in one country were not statistically significant, but it pushed AstraZeneca back into the headlines. Some countries were now at the end of their rope.

On March 31, Germany’s STIKO made the determination that only people over 60 should be given the vaccine. Younger people were to only be given the vaccine after undergoing a risk assessment by their family doctor. Given that Vaxzevria had, for number of weeks, been recommended only for people under 65, it gave the impression of utter chaos.

On Wednesday, the European Medicines Agency for the first time admitted a possible link between the thromboses and Vaxzevria. Nevertheless, the agency continued to recommend the vaccine for all age groups.

Soriot seemed overwhelmed. He struggled to find the right words. He had been stuck with his family in Australia since Christmas. It fit into the picture many had of his company: The captain wasn’t on board the ship.

Then something happened that should never happen in a pandemic: The people who were, until then, mostly afraid of the virus, also became afraid of the vaccine against it. According to a survey, only 23 percent of people in France consider Vaxzevria to be safe, compared to 32 percent in Germany. Norway and Denmark have completely stopped using the vaccine for the time being.

This week, reports of thrombosis and deaths were also now being reported in the UK for the first time. On Wednesday, the British regulatory authority stopped all AstraZeneca vaccines for those under 30, and Oxford University suspended a series of tests on children.

Experts are on the verge of despair. Nina Gatter, a vaccinologist from the western German state of North Rhine-Westphalia, says it is unacceptable that Vaxzevria is now viewed by many patients as a second-class vaccine. “We have to get out of the corona catastrophe, and that is only possible if we vaccinate with all the vaccines that we have.”

At the same time, she is critical of AstraZeneca, arguing that the company hasn’t expressed enough concern about people’s doubts. BioNTech/Pfizer offers video training for vaccinators, publishes informational leaflets in various languages, runs an online chat service for questions and has set up hotlines, but Gatter has found herself googling to find answers to questions about AstraZeneca.

In Europe, growing doubt is already delaying the vaccination campaign. People are being jabbed later than planned, in some cases with a different vaccine.

The consequences could be far worse in other parts of the world. The COVAX initiative, which aims to vaccinate billions of people in mostly poorer countries, is largely dependent on AstraZeneca. While other pharmaceutical companies have only supplied COVAX with a small amount of vaccine or none at all, AstraZeneca has promised hundreds of millions of cheap and easily stockpiled doses for the initiative, which is funded by the World Health Organization and donor countries.

The consequences of this depletion in trust are now visible in South Africa. There, the government has stopped vaccinating with Covishield because it doesn’t provide enough protection against mild progressions of the disease caused by the mutant discovered there. As a result, vaccinations against COVID-19 have also been slowed in the country.

That means the substance that was meant to save the world is, for now, being stockpiled.

Der Spiegel

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