A rolled-up sleeve and a brief jab: That’s all it took to make history in December. The world watched as the first doses of the Pfizer-BioNTech vaccine were administered, first in the U.K. and then followed quickly by the United States. In the months since, more than 265 million people around the world have received one or more doses of a COVID-19 vaccine.
These outcomes, literally years ahead of what experts expected, represent the most potent pharmaceutical response to a global health crisis ever mustered. But this triumph of biotechnology also signals a huge change for the for-profit industry currently engaged in figuring out the problem of how to produce enough vaccine doses to keep up with demand.
In January 2020, as the pandemic was brewing, the vaccine industry was dominated by four big companies: GlaxoSmithKline, Merck, Sanofi, and Pfizer. More than a year later, the picture has changed. Only one of these four companies has so far won the race to develop a COVID-19 vaccine: Pfizer, whose messenger RNA (mRNA) vaccine was found to provide 95% protection when used in a two-dose regimen. The company anticipates approximately $15 billion in revenue from its vaccine in 2021, which will represent nearly 30% of company revenue overall.
In the meantime, others—Moderna, AstraZeneca, Novavax—once on the periphery of market awareness, have become household names, and countries like China and Russia are developing homegrown vaccine industries. As COVID-19 starts to look like it’s here to stay, their success signals a sea change in the highly consolidated industry.
“For the pandemic, Pfizer is clearly going to be the leader in vax sales globally this year,” says Patrick Bell, a health care analyst at S&P Global. Moderna, a small biotech company catapulted into the limelight after producing an mRNA vaccine whose effectiveness is on par with Pfizer’s, is “going to enter as potentially No. 2,” Bell says. The company anticipates $18.4 billion in total product sales this year.
A changing industry
Making vaccines is costly and time-consuming, and vaccine revenues in any given year tend to be relatively small. Vaccines are a high-volume, low-price commodity, says David Kaplan, a health care analyst at S&P Global. “That has led to a lot of companies exiting the market,” he says. Before the pandemic, vaccines were a $33 billion industry, representing only 3% of the global pharmaceutical industry. The Big Four produced about 90% of the revenue in this sector.
Despite its small contribution to pharma industry revenues, the vaccines segment—like biotech more generally—has seen significant technological change in the past 30 years, which has driven remarkable growth, experts say. New vaccines for human papillomavirus (HPV) and shingles, for example, as well as improved vaccines for everything from influenza to measles, created a significant market.
But prior to the pandemic, the industry was in danger of getting stuck in a plateau between innovations. From the research and clinical trials needed to develop a successful vaccine candidate to the scale-up challenges of producing vaccines, companies need to invest billions of dollars. And there’s risk at most stages of the process: There’s no guarantee that primary research, which can take years, will lead to a successful vaccine or that demand once the vaccine is approved will be sufficient enough to make the vaccine worth producing.
Under normal circumstances, technological change in this environment can take decades. But because of the urgency of the COVID-19 pandemic, governments and industry poured funding into the search for a vaccine. A high level of collaboration between industry, governments, and academia has produced multiple successful vaccines in record time, in the process catapulting vaccine technology, and the connections required to produce it, into the future.
The development of nascent mRNA technology, which an international cohort of scientists and investors had been working on for more than 30 years, is the main example of this phenomena. “COVID has helped to accelerate some of the mRNA technology which was under development but would otherwise have proceeded at a slower pace,” says Bell.
Operation Warp Speed, the U.S. government’s $10-billion COVID-19 vaccine development initiative, created the environment that produced Moderna and Pfizer’s innovative vaccines. Moderna received about $1 billion in direct support as well as significant logistical support, while Pfizer received the government’s commitment that it would buy approximately $2 billion worth of its vaccine if successful.
Moderna, a small biotech company whose IPO was only in 2018, was in a unique position to leverage the funding environment created by Operation Warp Speed. Without the funding and expertise provided by Operation Warp Speed, it’s unlikely that a small biotech company could have mustered the funding for rounds of clinical trials and refinement of its drug candidate.
The company, together with other vaccine hopefuls, partnered with the National Institutes of Health to produce multiple vaccine candidates that would progress along the same trial lines. Its vaccine came out on top.
The race to develop vaccine candidates
The broader pharmaceutical industry has struggled to maintain momentum and preserve reputation over the past three decades during which mRNA technology was being developed. The COVID-19 pandemic offered the conditions to improve on both fronts: Companies immediately turned to their available stock of treatments to see if anything worked against the disease (nearly all available treatments weren’t useful) and dipped into stores of PPE for image-boosting opportunities to donate the scarce protective equipment to hospitals, care homes, and others in desperate need.
The big prize, though, was a vaccine. Literally hundreds of COVID-19 vaccine candidates went into development around the world in the course of 2020, many with the support of governments. “A very distributed development of the vaccine took place,” says Devendra Mishra, executive director of Bio Supply Management Alliance.
Mishra’s organization, which brings together members of the entire biotech supply chain, started producing a newsletter early on in the pandemic to help its members keep track of what was going on. As early as May, that newsletter started sharing material about the burgeoning race to develop a vaccine.
By the end of 2020, more than 200 vaccine candidates were still in development. The number of vaccines currently being used around the world is nearing double digits. The newest, developed by Johnson & Johnson’s pharmaceutical arm, Janssen, received an emergency use authorization (EUA) from the U.S. Food and Drug Administration on Saturday.
The difficulty of developing new vaccines is illustrated by the fact that only one of the Big Four has so far succeeded in producing a working vaccine against COVID-19 on the abridged timeline. “Merck has abandoned plans on two of their vaccine candidates,” says Bell. “GlaxoSmithKline and Sanofi were working together on one, and they still are.” While the GSK-Sanofi vaccine could hit the market eventually, it’s not arriving soon, he says. GSK has also partnered with CureVac, a German biopharma company, to work on a next-generation mRNA vaccine.
Distribution challenges
While the distributed nature of vaccine development definitely contributed to the number of vaccines developed against COVID-19 in a short time, the demands of vaccine production on a mass scale—combined with unprecedented disruptions in the logistics network that transports raw materials and vaccines around the highly globalized pharmaceutical industry—have thrown the supply chain into disarray.
“The COVID-19 pandemic exposed the vulnerabilities of the supply chain of life sciences. It showed where our links are weak,” says Mishra.
The technology and raw materials needed to produce vaccines must be certified to good manufacturing practice (GMP) standards. The expense of production at this high standard means that the resources of biotech companies tend to be fully leveraged. The problem of finding additional capacity to manufacture literally billions of doses of vaccines has accelerated an ongoing shift in the dynamics of the pharmaceutical supply chain, although it remains to be seen if this shift will endure in the long term.
Depending on considerations like production scale, pharmaceutical companies either construct the facilities to make their products in house or they rent capacity from contract development and manufacturing organizations (CDMOs). “It has been very good for the CDMOs,” says Bell. He and Kaplan coauthored a report last year in which they noted that CDMO gains may endure even after initial vaccine production demand has subsided. The organizations allow small biotech companies to manufacture their products without the overhead of maintaining an in-house facility that will frequently not be in use. The pandemic has led to more focus on producing vaccines and medicines domestically, however, and industry-watchers anticipate that Big Pharma may continue to leverage CDMO capacity in response to pressure to produce vaccines in-country.
During the pandemic, pharma companies that haven’t produced a successful vaccine have agreed to share their in-house capacity with those who have. Most recently, President Joe Biden announced Merck’s intent to produce the Johnson & Johnson vaccine, radically increasing supply.
But collaborating isn’t always simple. “One of the problems is that each company has built their manufacturing facilities to what they need for their product, and sometimes there isn’t overlap,” says Alyson Kelvin, a virologist at Dalhousie University. And the pandemic doesn’t mean the need for other critical medications has stopped: Drugs for other conditions are just as necessary as ever. Still, Kelvin emphasizes that “out of the box thinking” has allowed companies to collaborate and make as many doses of the vaccine as possible, even in unconventional circumstances.
The critical last mile of the supply chain figures into pharmaceutical companies’ considerations as well. Governments need stable supply with good forecasting to initiate mass vaccination campaigns—something that companies have struggled to provide in this new context, says University of Waterloo management sciences professor Hossein Abouee Mehrizi. But he’s optimistic that the supply issues already encountered are just growing pains. “I am pretty sure companies are going to scale up, and we’ll get much more supply than we have now,” he says.
The COVID-19 pandemic response has kick-started a new era in the vaccine industry, one that will likely be shaped by diversification.
“I do think it’s true that we’ll probably see a more fragmented market coming out of COVID than going into COVID,” says Kaplan.
In the past, it was most common for small companies like Moderna to be purchased by Big Pharma once their product was at a promising stage. But, in this case, demand occurred just as Moderna was in the right place to exploit its innovation and keep its name. What that means in the longer term for companies like Moderna and other small innovators like Novavax and Inovio has yet to be seen, but their innovations may allow them to bypass the acquisition stage and enter the market as more significant players in their own right.
Major uncertainty remains regarding how long COVID-19 vaccines themselves will remain profitable. But as the virus continues to mutate and infections continue to occur, it’s appearing more and more likely that vaccines for COVID-19 will be necessary for some time to come, whether because people will need booster shots or because mutated strains will necessitate revaccination. “The question is, is it going to be pandemic or is it going to be endemic,” says Mehrizi. “At this point, it seems like it’s not going to end as fast as I thought in the beginning.”
