Dr. Stephen Thomas, who helped develop vaccine candidates for diseases such as Ebola, Zika and MERS, discusses the challenges involved in accelerating development during a pandemic.
When I served in the U.S. Army as a physician-scientist, I was assigned to Thailand, and there is one patient I remember vividly. He was only about 8 years old, lived on a farm in the northern part of the country, and was in the hospital with a serious brain infection. His infection was caused by the Japanese encephalitis virus (JEV), which he’d caught from a mosquito. If he survived, he was destined to live his life with severe and debilitating neurologic abnormalities. Even worse – this tragedy could have been avoided. Thailand had a safe and effective JEV vaccine and worked extremely hard to routinely immunize all its children, but this child had been missed.
The heartbreaking situation reminded me what my friend and mentor, Dr. Bruce Innis, told me as I embarked on a career in vaccine development, “Vaccines don’t save lives, vaccination saves lives.” He should know, Dr. Innis has helped successfully develop more than 15 vaccines, including the JEV vaccine licensed in the U.S.
Developing vaccines is a complex process driven by the fundamentals of biology, biomanufacturing and engineering, and innovation. Vaccine concepts are explored, and prototypes first tested in the lab. Scientists then test the safety of the vaccine on animals and, if results are promising, clinical trials involving people begin. It can take years to develop a vaccine, and something that works well in the lab may not fare as well in people. We need to keep this long, complicated, uncertain process in mind as we hear news emerge about vaccine candidates for the Covid-19 pandemic.
The U.S. Food and Drug Administration reviews and decides whether a vaccine candidate is suitable for experimentation in humans. Although the agency does consider the results of animal studies, much of its review focuses on how the vaccine is manufactured, and whether the process is scalable. Manufacturing at scale (hundreds of millions of doses) is important because it is not enough to demonstrate a vaccine is safe and has clinical benefit, you need a system in place to make sure the vaccine is accessible, and people are actually vaccinated.
The entire process can take up to ten years, sometimes longer, and can cost up to a billion U.S. dollars, sometimes more. Even in times of a public health emergency it is difficult to advance a vaccine from concept to the marketplace. I played key roles in developing candidate vaccines for Ebola, MERS-CoV, and Zika, and despite the human suffering caused by these diseases, despite their international focus, and despite considerable investment from governments and the pharmaceutical industry, only one of those vaccines (Ebola) has been licensed.
The World Health Organization (WHO) attempts to expedite global vaccine development efforts by facilitating coordination and communication, using tools like their ‘vaccine pipeline tracker.’ In an unfortunate but recurring pattern, numerous vaccine candidates always populate the tracker initially as outbreaks unfold and the money flows but, invariably, developers move on and drop off as resources and interest dries up. It is unclear how the WHO’s role and influence will change if the U.S. severs ties and withdraws its people and funding from Geneva.
Many developers with promising vaccine candidates become permanently stalled in their development process because they cannot afford the costs of required testing. Others experience significant bottlenecks when trying to access the limited biomanufacturing facilities specialized in producing vaccines suitable for human use. Even large pharmaceutical companies with generous financial coffers and in-house capabilities face sizeable opportunity costs by pursuing epidemic outbreak projects. They are forced to borrow staff and other resources from current projects to support new development teams, thereby stalling ongoing projects and the introduction of vaccines against other human diseases.
Facing such programmatic headwinds, how is the U.S. government going to execute its Covid-19 vaccine development plan, Operation Warp Speed? Compared to the U.S. government responses for Ebola, MERS, and Zika, many elements of the operation are status quo, especially in the areas of development and manufacturing. The Covid-19 vaccine effort, however, looks to employ new approaches in the hopes of reducing project timelines. For example, utilizing the Department of Defense to deploy, distribute, and administer vaccines could support the rapid immunization of sizable populations.
Another new approach is the expanded role of the federal government in the private-public partnerships that have defined the Covid-19 vaccine development space. Operation Warp Speed directs that the federal government will decide on the vaccine development pathways and the pharmaceutical companies will not, “…decide on their own protocols.”
How will industry manage the risks and costs of developing a Covid-19 vaccine, while relinquishing considerable developmental command and control to the government?
The successful past performance of private-public partnerships in vaccine development leave me very encouraged for the prospect of a safe and effective Covid-19 vaccine. My expectations are measured and cautious, however, given the difficult realities of public-private coordination, risk sharing, and industry finding the balance between meeting public health needs and revenue goals. As with any ambitious and audacious plan, the devil is in the highly complex details.
There is no doubt the federal government has numerous very experienced vaccine developers, and it was my privilege to work with many of them during my Army career and I continue to do so today. But vaccine development involves numerous teams working together and requires close coordination, not only between government agencies (this is hard enough), but with Congress and the academic and private sectors.
Achieving harmony in these relationships has been difficult in the past because the mission scope and incentives for the government and the private sector are different in many important ways. John Young, Pfizer’s chief business officer, was recently quoted saying Pfizer would not seeking government funding (even after they were selected by U.S. government as a finalist for funding) because their focus was speed and they, “…didn’t want to … spend a month negotiating with the U.S. government.”
The government is focused on protecting the Nation and its citizens. The pharmaceutical industry cares greatly about public health, but also answers to shareholders. Committing millions of dollars to high-risk ventures is a daily occurrence in the life science industries but that risk is carefully calculated, as is the financial upside. In some cases, such as with Merck’s Ebola and GSK’s malaria vaccines, companies embark on development projects despite understanding there will be financial losses, but these situations are the exception. How will industry manage the risks and costs of developing a Covid-19 vaccine, while relinquishing considerable developmental command and control to the government?
Why does it matter who controls the development plan? Because they determine how the vaccine will ultimately be used and by whom, thereby defining the market. If protocol designs are restricted to meet U.S. or largely Western agendas, industry may lose out on accessing a global Covid-19 vaccine market, perhaps the biggest vaccine market, – which means billions would be left without a vaccine and industry would be left without a good way to recoup its investment.
Many companies jump into the vaccine development pool during epidemics and pandemics, but few possess the required financial staying power to see projects to completion.
There is also the issue of who will own the intellectual property (IP) generated during the collaboration. IP protections are major drivers of revenue streams and recovery of research and development investments. Members of Congress are already waging war on drug and other pharmaceutical pricing and profits. More than a few members wish to also revamp provisions in U.S. Code, like the Bayh-Dole Act, to limit industry’s exclusive rights to IP developed using U.S. taxpayer dollars.
The government may contend, some say rightly, that if U.S. taxpayers are paying the development bill, the U.S. must be guaranteed an immediate return on its investment – such as preferential vaccine access and/or pricing. But this concept of “America first,” is not playing well. Paul Hudson, the CEO of French vaccine juggernaut Sanofi Pasteur, was quickly corrected by the French government when he implied the U.S. may be entitled to preferential Covid-19 vaccine access due to its financial investment.
Heads of prominent non-governmental organizations, governments, and industry convened this spring to discuss the topic of vaccine access and the result, expressed by Dr. Tedros Adhanom Ghebreyesus, WHO Director-General, was that, “Countries, health partners, manufacturers, and the private sector must act together and ensure that the fruits of science and research can benefit everybody.”
Once a vaccine is available, manufacturing and distribution activities will need to be sustained and licenses and certifications maintained long after the U.S. government has moved on to the next problem. These activities represent millions of dollars in expenditures every year. The pharmaceutical industry executes these tasks on a routine basis but without the financial upside of global market access and IP rights, how will they be incentivized? Many companies jump into the vaccine development pool during epidemics and pandemics because it is the right thing to do for public health. But few possess, or tolerate, the required financial staying power to see the project to completion.
My experience leaves me little doubt that developing a safe and effective Covid-19 vaccine is feasible. The unprecedented scope of coordination between, and among, U.S. government agencies and industry is reassuring that the process can move fast, maybe even approach very fast, but that’s slightly slower than warp speed.
Last week it was reported that the government identified five companies it believes have the highest likelihood of delivering a safe and effective Covid-19 vaccine, including Moderna, AstraZeneca, Johnson & Johnson, Merck, and Pfizer. But numerous questions remain about how the relationship between the development partners will continue to be mutually beneficial long enough to not only realize the development of a vaccine but to witness lives saved through vaccination.