On April 7 of this year, it was finally my turn to become one of the millions of Americans to receive their COVID-19 vaccine. After becoming eligible, I scoured websites for appointments, watching several disappear from my digital grasp before finally securing a Pfizer jab at a county drive-through site. When the vaccine was administered through the window of my car, I felt flooded with relief.
As has now become clear, my enthusiasm was not universal. Although epidemiologists agree that universal vaccination is the surest way out of the pandemic, millions of people around the world are “vaccine hesitant” to some degree. Some question vaccines in general, believing (based on no peer-reviewed science) that their harms or side effects are underreported. Others doubt that “new” technologies, deployed this quickly, could be fully safe, or believe that companies or regulators must have “cut corners.” These feelings were sharply amplified by the anxiety of the pandemic and a chaotic political and media environment.
Scientists from Moderna in the lab
In recent months, the emergence of the highly transmissible Delta variant of the virus has caused cases to surge once again, largely among the unvaccinated. Even with lower mortality thanks to new treatments, every new infection risks more than just immediate sickness—the disease’s long-term impacts will only become clear with time.
By now, hundreds of millions of people have received vaccinations, and no evidence has been published of widespread long-term side effects, which typically become apparent within months of receiving a vaccine. The Delta wave has prompted a spike in hospitalizations, but antibody treatments combined with other drugs appear to be reducing mortality compared to past waves before treatments existed. After months of declines, vaccination rates have been ticking up again in response, and Pfizer’s vaccine received full FDA approval for adults on August 23. Moderna has just submitted its own final application.
Even so, should we be more cautious before rolling up our sleeves? In a field known for decades-long development timelines, all of the new pharmaceuticals deployed to battle the pandemic—whether the groundbreaking mRNA vaccines, more conventional jabs, or even the antibody cocktails that help combat active COVID-19 infections—went from first trials to public rollout in record time. The US government’s response was aptly codenamed: progress seemingly came at warp speed.
China released the first sequenced SARS-CoV-2 genome on January 11, 2020, sounding the starter pistol for a worldwide research, development, and logistics effort. Seemingly the entire planet, eager for hope, closely followed the twists and turns of the global pharma industry’s work. Most early-stage research trials are low-pressure, low-attention affairs; now, any tentative result became international breaking news.
To get from a spike protein structure on a researcher’s blackboard to a shot going into my arm at a refurbished dockyard was no easy feat. How did the companies involved navigate the gauntlet of scientific, regulatory, and communications hurdles? How, in an industry more tightly regulated than almost any in the world, did they manage to move so quickly without “cutting corners?” What new collaborations were necessary, both within and across organizations? How did they adapt to the pressure of public scrutiny, maintain unprecedented transparency, and ensure that the public would have every reason to trust the final product? And how will the pandemic change their companies and the industry going forward?
The answer to many of these questions can be found in the cultures at the companies behind these breakthroughs. To find out more, Ethisphere Magazine got in touch with some of the leaders most responsible for stewarding these cultures, the chief ethics and compliance executives at Pfizer, Moderna, and Regeneron. Even considering the knowledge advantages and lucky breaks these companies may have had, talking with these executives made it clear that success wouldn’t have been possible if these organizations hadn’t prioritized ethics, collaboration, and transparency before and throughout the pandemic.
Rady Johnson, Chief Compliance, Quality and Risk Officer, EVP, Pfizer
The Calm Before
In retrospect, it’s difficult to think about December 2019 without some unease, knowing that the coronavirus was already spreading in China. “I was actually in China on business in December of 2019, and there was no discussion at all of COVID-19 going on,” says Rady Johnson, Chief Compliance, Quality, and Risk Officer for Pfizer. The first reports of an “unexplained pneumonia” in Wuhan wouldn’t appear until December 30. Even a few weeks later at the Pfizer’s annual Executive Committee meeting, the virus wasn’t yet a topic of major discussion.
But by early spring, with the virus now circulating in Europe, the United States, and elsewhere, it became clear that COVID-19 was going to become a global problem and not burn out the way that previous near-miss pandemics such as SARS or MERS had. The World Health Organization officially declared COVID-19 a pandemic on March 11. At that point, every company in the industry looked at their own catalog of drugs already approved or in development, and tried to decide how best to help.
Many turned to drugs that were already on the market to treat other conditions, hoping that some might also prove effective at combatting this new threat. But three companies were uniquely positioned to harness years of biotechnical innovation against viruses: Regeneron had developed antiviral monoclonal antibody cocktails, and both Moderna and a Pfizer-BioNTech partnership had the groundwork for mRNA vaccines.
‘Miracles’ Built on Decades of Investment
Some health professionals have lamented the way that the reporting on the scientific response to the virus focused too much on the apparent “miracle” of the new technologies. On the one hand, this crisis was the first time that mRNA vaccines have been deployed, and antiviral monoclonal antibodies are relatively new as well. On the other hand, the widespread impression that these therapies were developed rapidly has contributed to some people’s concerns that that they are either untested or poorly understood. Neither is the case.
While new to the general public, the research underpinning both antiviral antibodies and mRNA vaccines has been going on for decades. In both cases, the innovations that allowed for such seemingly rapid progress were built on years, and sometimes decades, of investment in research in both public and the private sectors.
In the case of REGEN-COV, the monoclonal antibody cocktail produced by Regeneron, the basic science is almost fifty years old, earning key researchers several Nobel Prizes along the way. Monoclonal antibodies are proteins designed to bind to a single virus, cancer cell, or other threat, mimicking those produced by white blood cells. Individual antibodies or antibody cocktails have been used to combat everything from cancers to autoimmune diseases and organ transplant rejection. Regeneron has been perfecting the technology it uses to produce its antibodies over decades against many illnesses. The first antiviral antibodies to receive full FDA approval, which significantly reduced mortality risk from Ebola in patients in the Democratic Republic of the Congo, were also developed by Regeneron. Given that history, the success of antibody cocktails against COVID was no surprise to those who had followed the science.
Beth Holly, SVP, Associate General Counsel and Chief Compliance Officer, Regeneron Pharmaceuticals, Inc.
Nevertheless, in normal times most patients aren’t aware of exactly what kind of technology or therapeutic they’re being treated with. As Beth Holly, SVP, Associate General Counsel and Chief Compliance Officer at Regeneron notes, “People have been taking monoclonal antibodies for quite some time, for example for rheumatoid arthritis. The idea isn’t new, but patients have never distinguished it that way.”
While mRNA vaccines have not been in use by the public before, their history also goes back decades. The technology faced years of skepticism from the research establishment before breakthroughs funded by private sector-led innovation. The New York Times podcast “The Daily” recently exposed millions of listeners to Dr. Katalin Karikó’s valiant struggle to get her research into mRNA taken seriously, going back to the 1980s. Eventually, her work with collaborator Dr. Drew Weissman received just enough funding to reach publication in 2005. Even so, it received a tepid response from the academic community. But the private sector took notice: Karikó and Weissman’s discoveries were patented, bought, licensed, and eventually became the basis of the work done by two new companies specializing in the promise of mRNA treatments—Moderna and BioNTech, where Karikó is now Senior Vice President.
While both Moderna and BioNTech had been pursuing a viable way to bring mRNA to market for years, their efforts had only recently picked up steam; as Nature memorably reported, “five years ago, the RNA technology would not have been ready.” BioNTech’s partnership with Pfizer began in 2018 with an experimental influenza vaccine that was likely still years from market. Similarly, Moderna’s pipeline products were far enough from wide release that they hadn’t yet needed to scale up their risk and compliance controls.
It’s worth noting that in each of these cases, many other companies also had access to the same technology. Monoclonal antibodies are produced by many of Regeneron’s competitors, only a handful of whom also produced COVID treatments. Several other companies designed mRNA vaccines that have either are not showing comparable efficacy, or took much longer to clear the many phases of development. The technology alone didn’t and couldn’t ensure that Regeneron, Pfizer, and Moderna would succeed—and that’s where culture came into play.
A view of a lab where Regeneron’s antibody cocktail was researched
Luck, Bold Moves, and a Flurry of Questions
Each company needed an appetite for a certain amount of risk to push these potentially game-changing technologies. They also had to accommodate the need for collaboration and transparency that followed from these choices.
According to Rady Johnson, Pfizer’s decision to throw its weight behind developing an mRNA vaccine with BioNTech rather than using a more tried-and-true vaccine vector wasn’t actually too complicated. Given the existing partnership, “there was a little bit of luck involved,” says Johnson. Even so, “the scientists who understood its potential felt confident. It was an incredibly bold move. We weren’t sure what would happen, but it was definitely something that we felt confident about.”
Regardless of which technology went into the vaccine development, Johnson says, everyone involved knew that a proactive stance towards transparency and integrity would be vital to reassuring the public. The scientists simply advocated what they felt was the most promising technology, and the rest of the organization mobilized around them to clear the necessary barriers.
For the team at Moderna, there hadn’t been a “more conventional” option, since the entire company was built around the promise of mRNA technology. But that also meant they had another hurdle: the company was still essentially a large start-up, and while it had an open and innovative culture dedicated to transparency, they had not yet needed to build control functions.
Kristin Rand, Head of Corporate Compliance and Global Risk Officer, Moderna
“Before COVID, Moderna wasn’t anticipating having a commercial product for two or three years,” says Kristin Rand, the company’s first Head of Corporate Compliance and Global Risk Officer, hired at the outset of the pandemic once the company decided to pursue its own vaccine trials and prepare for possible commercial rollout. “There was a need to quickly grow a focused, dedicated risk and compliance program. In addition, it was crucial that the company’s commitment to transparency be maintained.”
For the team at Regeneron, there was never a doubt that they could develop a product with a good chance of effectively combatting a viral infection. Having been in the field developing antibodies to combat Ebola since 2014, including a very successful trial during the 2018-2019 Ebola outbreak, Regeneron was culturally and institutionally equipped to rapidly develop and test drugs in a pandemic scenario. “Our scientific leadership has been practicing for this for years. They’ve honed their research tools to be ready to handle an emerging crisis and generate a solution in record time,” says Holly.
Holly remembers the flurry of questions that emerged once it became clear they would develop a therapeutic against COVID-19. “What’s an EUA [emergency use authorization]? Can we get one? How do we get it? How do you market under it?” Although EUAs were explicitly designed to help the U.S. Food and Drug Administration (FDA) provide expedited review of treatments during public health emergencies, the first one had only been issued in 2009 against swine flu, and none had ever been issued for either vaccines or new drug treatments. Navigating the EUA process at the FDA would be just one of several new kinds of scrutiny.