You might think a Pfizer vice president overseeing key processes in the production of his company’s COVID-19 vaccine would know how clinical studies were going, but access to such information could violate insider-trading laws.
So Paul Mensah, a University of Virginia chemical engineering alumnus, learned like most Americans the morning of Nov. 9 how the thing that consumed his days and nights for eight months was really going to work.
“I heard it on the news,” Mensah recalled of the day Pfizer announced the vaccine proved more than 90% effective in Phase 3 trials. “And when I came to my computer, there was an email from our CEO and our head of research sharing the excitement about the data.”
Then, his wife and children were there hugging him – and not just in congratulations. They were thanking him, too, for his efforts to make a vaccine available. It was a feeling Mensah did not take for granted, in spite of 5 a.m. conference calls and 17-hour days glued to his computer.
Mensah, who earned his Master of Science and Ph.D. at UVA in 1997 and 1999, respectively, oversees Pfizer’s bioprocess research and development and drug supply group. The group is responsible for the development and manufacturing of drug substances, which are the active ingredients in pharmaceutical products. In Pfizer’s COVID-19 formulation, that ingredient is the messenger RNA upon which the vaccine is based.
“I can speak for my group, and perhaps everyone at Pfizer, that working on the vaccine is personal, and in many ways, a privilege as well,” Mensah said. “It’s personal because all of humanity needs the vaccine. But it’s also a once-in-a-lifetime opportunity where you can look back and say you helped with this pandemic, and the efforts were successful. It’s been hugely inspirational and hugely motivational.”
Mensah is among a group of UVA Engineering faculty, alumni and students who have important roles in the fight against COVID-19. They are attacking the pandemic from all angles – investigating antiviral drugs, tracking data and protecting supply chains of vaccines, tests and treatments from those who would do harm.
Michael L. King, who received his Master of Science in chemical engineering at UVA in 1976, is a professor of practice in the department and a retired Merck and Co. vice president. He also is a subject matter expert in vaccine development and distribution for the Bill & Melinda Gates Foundation, a leader in global efforts to end the pandemic.
Like Mensah, King understands the reality that vaccinating about 80% of the world’s nearly 8 billion people is the only way to stop COVID-19. So do chemical engineering alumnus Drew Biedermann and student Nick Seyler.
Biedermann earned his B.S in chemical engineering at UVA in 2017 and now works in the chemical engineering lab of professor Chris Love at Massachusetts Institute of Technology; Love also happens to be a UVA alumnus with a bachelor’s in chemistry. Seyler is a fourth-year chemical engineering and biology undergraduate.
What unites these individuals – apart from ties to UVA’s Department of Chemical Engineering – is they’re all runners in the race to inoculate the world against COVID-19. Here are their stories.
Michael L. King
On Feb. 21, 2020, King flew to Seattle to meet with colleagues from the Gates Foundation. King, who joined the UVA chemical engineering faculty in 2007 after 32 years at Merck, went to Seattle to discuss how he could help the foundation’s response to COVID-19, which still had not been declared a pandemic.
In April, the World Health Organization, the European Commission, France and the Gates Foundation launched the Access to COVID-19 Tools Accelerator, a collaboration of governments, businesses, scientists and non-governmental and global health organizations. The accelerator’s mandate is to speed up development, production and equitable access to COVID-19 tests, treatments and vaccines.
The vaccines pillar, called COVAX, is chartered under the World Health Organization, and two of its ACT Accelerator partners, the Coalition for Epidemic Preparedness Innovations and Gavi, The Vaccine Alliance. COVAX is an association of more than 185 member nations established to develop a portfolio of COVID-19 vaccines with the goal of ending the acute phase of the pandemic. COVAX, guided by the principle that no one is safe until everyone is safe, plans to distribute 2 billion doses to the most vulnerable people by the end of 2021.
King worked with the Gates Foundation and the Coalition for Epidemic Preparedness Innovations figuring out where to focus resources among hundreds of vaccine programs. He began by surveying 300 organizations worldwide to identify high-capacity manufacturers, and matching vaccine developers to antigen researchers in academia, such as Biedermann and Love. Ultimately, vaccinating enough people worldwide to contain COVID-19 will require many manufacturers and numerous technologies.
In mid-summer, King joined a multidisciplinary investment committee that manages allocations of funds under COVAX’s Research, Development and Manufacturing Workstream. He also serves on the committee’s Technical Review Group, which brings manufacturers, regulators and other stakeholders together to rapidly overcome common challenges.
“We workshop best practices for things like storage or labeling, so everybody’s not reinventing the wheel,” King said.
From his home office – where a Dr. Anthony Fauci bobblehead adorns the desk and photographs from his travels during easier times line the walls – King sits at a virtual table with people oceans away hashing out supply chains and regulatory approvals and manufacturing capacity. The hours can be long and stressful, but broken up by occasional levity, he said.
Once, King was leading a meeting of 40 or so people when a dog in New York wouldn’t stop barking. A dog on the West Coast started barking back. Far from being annoyed as the canines’ owners frantically tried to quiet them, someone said, “No, let’s hear what they have to say.”
“It just kind of broke the tension,” King recalled.
For King, seeing so many people work behind the scenes for the common good is heartening.
For example, to address glass vial shortages, developers agreed to retool for multi-dose packaging – cutting glass requirements by an order of magnitude, King said. Garnering that kind of cooperation isn’t automatic, though.
“To be effective, you have to understand other people’s perspectives, use your technical knowledge but also learn theirs well enough to find the sweet spot between the two,” he said, “and be an active listener. To get things done, leadership and teamwork are as important as technical skills.”
The pandemic response provided an excellent case study for students in King’s spring vaccines course, “Bioproduct and Bioprocess Engineering.” His role in COVAX gave students a unique perspective as events unfolded, so much so that he plans to revise the course content around COVID-19.
COVAX also reunited King with many colleagues from his time at Merck, whose expertise he relied on then, as he does now.
“It’s a small community, but we know and trust each other, and we work well together,” King said. “My students can see that maintaining professional networks is very important to be successful, so when things come up, they can always reach out to the right people.”
Andrew “Drew” Biedermann and J. Christopher Love
The Love Lab at MIT has worked with the Gates Foundation since 2017 to make extremely low-cost vaccines by investigating how to automate the first steps of manufacturing – finding materials in the lab likely to produce a strong immune response and modifying the materials to be ready for manufacturing. It was Valentine’s Day when the foundation called: Could Love and his students apply their ideas to a COVID-19 vaccine?
“We’re developing more efficient ways of making vaccines, and one thing that goes hand-in-hand with that is speed,” said Biedermann, a former Rodman Scholar and a 2017 Outstanding Student Award winner, one of UVA Engineering’s highest undergraduate honors. “We think a lot about technologies that allow us to quickly develop new vaccine candidates.”
The team works on subunit vaccines, which use a piece of a protein from the virus – the antigen – to trigger the immune system to produce antibodies against the virus. One way they speed up the process is by using a fast-growing yeast host to produce a protein. The faster the protein-expressing yeast cells grow, the sooner the researchers can test the protein’s potential to spark an immune response, allowing them to move quickly through candidates.
One overarching goal is to build a system for on-demand drug development. The concept originated as a U.S. Department of Defense project a decade ago, and drew the attention of the Gates Foundation for its potential to produce vaccines for pennies per dose.
COVID-19 presented the perfect test case that nobody really wanted – and it meant Biedermann was one of the few graduate students who stayed behind in the lab when most of MIT shut down in March.
“There was a particularly poignant moment when I talked to the two undergrads that I’m working with, because they were getting sent home, and we were trying to figure out what that means,” Biedermann said. “By the end of the week, only four of us were left, working two on, two off. It was like that for two or three months. It was kind of surreal to get up every day and try to push the work forward a little more.”
The Gates Foundation pairs Love’s team with partners around the world who can take the lab’s candidates to the clinical stage. Within 28 days, Biedermann and his colleagues had materials, including the yeast host they used to produce the protein for the vaccine candidate, ready to transfer to a company in India to begin manufacturing.
That first vaccine component is part of a candidate advancing in clinical trials, while others are being tested for efficacy in animals, a precursor to transferring the materials to a manufacturer.
“This is where the Gates Foundation has been incredible. Working with folks like Mike [King], they’ve put together a broad network of partners and individuals who are contributing to how to advance several of these ideas forward,” said Love, MIT’s Raymond A. and Helen E. St. Laurent Professor of Chemical Engineering.
King, an expert in how to bring a drug to market, provides feedback to Love’s team in areas including experiment design and translating their findings to manufacturing partners for smoother transfer of the technology, Love said.
Recalling how hard it was to ship materials to India because of travel disruptions in the early days of the pandemic, Love said developing small regional manufacturing capability could be the next thing to think about.
“If you could download the blueprints of how to do it, that’s very different than having to ship cells and parts around the world. It might allow for faster distribution. There are some interesting potential uses and future readiness that the kinds of technologies we’ve been developing might impact,” Love said.
Seyler’s first summer internship disappeared because of COVID-19. When he managed to replace it with one at Lonza Group, he was just happy to land a gig with a global leader in pharmaceuticals and biologics manufacturing. What he didn’t know was that the Lonza plant in Portsmouth, New Hampshire, – where he was headed – was being outfitted to produce millions of doses of the Moderna mRNA-1273 vaccine.
Moderna, the U.S biotech firm that partnered with the National Institutes of Health to develop a COVID-19 vaccine, struck a manufacturing deal with the Swiss company in May for billions of doses.
In New Hampshire, Seyler found himself tracking the arrival of new lab equipment needed to manufacture the vaccine and helping to establish maintenance plans.
“I have gotten to have input on some of the decisions that set the precedent for equipment maintenance for the entire project, which is pretty exciting,” Seyler told UVA Today in August.
While Seyler was back at UVA for the fall semester, Moderna released its Phase 3 clinical trial results, just days behind the Pfizer announcement. The vaccine proved nearly 95% effective, and was granted an emergency use authorization by the U.S. Food and Drug Administration on Dec. 18, a week after the FDA approved Pfizer’s vaccine for emergency use.
“I never thought I would have the chance to do anything close to as important as this, especially this summer after my first job was canceled at the last minute. It has been an amazing experience,” Seyler said.
From the time China published the genetic sequence of the virus to the day Pfizer and BioNTech, its German partner, announced the first vaccine to work in rigorous clinical trials, 307 days went by.
“Vaccine development typically is a years-long effort,” Mensah said. “We didn’t have years. Our CEO, Albert Bourla, impressed upon us, the only thing that should stand in our way is the science. In most pharmaceutical investment, you do it by stage. In this case, everything had to be done in parallel, but in such a way that we didn’t cut corners.”
When the pandemic broke out, Pfizer and BioNTech were already partnering on a flu vaccine using BioNTech’s messenger RNA technology. The mRNA approach has long been studied, but has never been tried until now.
Despite the head start, the challenge for Mensah and his colleagues was staggering: Develop a vaccine for a new disease and produce 100 million doses in nine months and 1.3 billion by the end of 2021. To get it done requires a “meticulously choreographed high-wire act,” as the Washington Post reported in detail.
It’s financially risky, manufacturing a drug before it’s proven, let alone getting past regulatory approvals. But that’s what Pfizer and dozens of vaccine developers are doing worldwide to beat this virus – typically with massive investment or purchase guarantees from governments and organizations such as COVAX to recover their costs. That’s how drug makers could move so fast on safe, effective vaccines – they go through the same exacting steps, just not in the normal sequence.
On Dec. 14, a critical care nurse became the first person in the U.S. to receive the Pfizer-BioNTech vaccine. The United Kingdom began administering the vaccine on Dec. 8.
At Pfizer’s St. Louis plant, Mensah’s home base, one of his groups manufactures DNA containing the genetic code for the spike protein found on the coronavirus’ surface. This protein is the mechanism the virus uses to invade a host. The encoded DNA then goes to Mensah’s group in Andover, Massachusetts, where it is transcribed to create the mRNA drug substance. The mRNA substance instructs the recipient’s cells to produce the spike protein, triggering the immune system to produce antibodies that protect against the virus.
The mRNA drug substance is purified before handing it off to another Pfizer group that formulates the substance into lipid nanoparticles, which is the vaccine’s delivery mechanism. At each step, the materials are analyzed for quality assurance.
Messenger RNA technology is potentially a much faster route to producing vaccines in the future than current methods, which often rely on growing viruses in big vats or in chicken eggs as the first step. The new technology has challenges, though. The formulations are inherently unstable to varying degrees, necessitating special handling particular to each manufacturer’s product.
Pfizer designed temperature-controlled thermal containers to ensure the vaccine stays frozen between minus-60 and minus-90 degrees Celsius during shipping. Each shipment is equipped with GPS-enabled thermal sensors the company can monitor for signs of trouble. On top of that, the Pfizer/BioNTech and Moderna vaccines, require two doses, three and four weeks apart, respectively, for full protection. The vaccines can cause mild side effects in some people, such as fatigue or low fever. Lastly, no one is sure how long the protection lasts.
Pfizer and BioNTech were not able to reach 100 million doses by the end of 2021, but Mensah was unfazed.
“No one thought [making a new vaccine this quickly] was going to be achievable. It’s never been done. You know, one of the things that we have going on is ‘science will win,'” Mensah said, referencing a Pfizer ad campaign. “We’ve been able to prove that. Science is winning.”
Maybe so, but it took human effort on a global scale. That’s what impressed him most.
“The human spirit,” Mensah said. “Seeing how much people have been willing to give has been an incredible experience.”