Which obstacles are most likely to delay a Covid-19 vaccine, and how can we prepare to overcome them? That's the focus of an extensive recent report by Ezekiel Emanuel and Topher Spiro of the left-leaning Center for American Progress (CAP).
In the latest episode of Radio Advisory, host Rachel (Rae) Woods talks to Emanuel—senior fellow at CAP, vice provost for global initiatives and chair of the department of medical ethics and health policy at the University of Pennsylvania, and former advisor to President Barack Obama—about the daunting road ahead.
As Emanuel emphasizes, the world has never manufactured and distributed a vaccine at the extraordinary scale and speed demanded by the novel coronavirus: "[It's] like asking, 'Zeke Emanuel, we would like you to make a billion pair of jeans,'" he says, adding, "I wouldn't know where to start."
But the truth is, Emanuel does know where to start: He has thought more deeply about the roadblocks to vaccine manufacturing and distribution than nearly anyone else. And in this wide-ranging, candid conversation, he shares concrete ideas for how stakeholders throughout health care can accelerate the day when every American is vaccinated. (While Emanuel references his political affiliations, keep in mind that Advisory Board is a nonpartisan institution.)
Read a lightly edited transcript below, or download the podcast to hear the full conversation.
Rachel (Rae) Woods: There is no shortage of news reporting on the progress made towards a vaccine, but I'm not convinced that the average American, or even the average health care leader, understands just how big of a challenge this is for our industry or for our country. So, I want to start off a little bit big picture here. Let's imagine it's a year from today, and America still doesn't have widespread access to an effective coronavirus vaccine. What's the single biggest thing that went wrong?
Ezekiel Emanuel: First of all, you have to ask yourself, "Is there a vaccine that's effective out there? Does one exist?" I presume the answer is, "Yes. There is one that exists. And it's just that it hasn't been manufactured, put in vials, distributed, and administered." And it's one of those steps that just hasn't been successfully completed.
So, in this hypothetical, let's assume that we've got a vaccine that we've proven works—the question is then, "What's it going to take to get from having that proof to actually getting shots in arms? What are all the steps that are needed? And where are the most likely places that the process could go awry?" Because most of us, and certainly I as a physician, didn't know. And so my team and I explored this in our report by interviewing manufacturers, the packagers, the glass companies, the needle makers, the syringe makers, the pharmacies and all the people who'd normally administer these things.
Woods: So your point is that there isn't one thing that's going to go wrong. There's a lot of things that could potentially go wrong. But I do want to follow your guidance and assume, for the sake of this conversation, that we have access to a vaccine. Frankly, that is where most of the conversation is happening in the news. Everybody's latched on to point number one, and that's finding that viable vaccine. I want to focus on the other 21 issues that you point out.
Emanuel: Look, even if it's not the AstraZeneca-Oxford one, or the Pfizer one, or some other one, it will be one of them. We've got so many shots on goal. Something is going to work, unless it's really impossible, like HIV—but no one thinks it's going to be impossible. Even people who are die-hard skeptics such as myself don't think it's impossible. So, we're going to have something, even if it takes a little longer than everyone expected.
The issue is, after you've got it, then you have to manufacture it. And each one of these different types of vaccines require different manufacturing capacity. Some are fermented, some are based on producing the RNA, etc.
Woods: That's exactly right. Making enough of the vaccine is a completely different challenge. The parts required to ship it, store it, administer it, and distribute it in hopes of reaching that herd immunity. When it comes to supply chain, I'm curious if there are two to three things that you really want to make sure our audience understands about why it is so hard to make what could be a half a billion doses of this vaccine.
Emanuel: Well, let's go to step one. A lot of the players in this game have never manufactured a vaccine, period. And most vaccines, by the way, are not made in billion level quantities each year, because you don't need that level. So this is a big demand. That's like asking, "Zeke Emanuel, we would like you to make a billion pair of jeans." I wouldn't know where to start.
So, aside from some companies like Johnson & Johnson and Merck, who have a lot of experience making vaccines, production is a big problem. And you can see that there are many, many partnerships with the Serum Institute of India (SII), which is the largest producer [of vaccines], also a very cheap producer. But the problem is, is SII overselling its production?
Now, I'm not privy to information about the Serum Institute, but I would say that they produce so many vaccines, I often wonder if what's happening is they're a little like the musical, The Producers. They got capacity. And they're selling the capacity over and over and over again, in part because they don't expect everyone to pan out. So SII might be thinking, AstraZeneca bought a bunch of capacity, but if that doesn't work, we'll shift capacity to Pfizer or whomever.
That may be true. It may turn out not to be true. But I can't believe they have the capacity for a billion more doses just idly sitting by, or that they can add it so quickly that they can add 67%-75% more capacity than what they're doing today for Covid-19. Everything I know about the drug industry and the vaccine industry is they run very close to their limits. They have not overbuilt. And that's good. It's good for efficiency. It's bad for, "Wow, we have to produce 7.8 billion doses here." Well, you don't have spare capacity. How are we going to do that?
Woods: When we talk about supply chain at Advisory Board, there's a sense of whack-a-mole. You figure out how to solve for some piece of the supply chain in one part, only to create a problem somewhere else. What are you hearing from manufacturers, from distributors, even from the policymakers, about anything they're trying to do proactively to avoid some of those supply chain ripple effects?
Emanuel: So, first of all, everyone says, "We would never compromise on one vaccine"—let's call it measles, mumps, and rubella—"for Covid-19. People need to have both. And we're going to ensure both." No one will publicly say, "Yes. We're going compromise that other vaccine."
On the other hand, unless we plan better, there very well could be shortages. One shortage that surprised me, personally, and is potentially rate-limiting stuff, is the glass vials. I didn't understand before doing this project that it's not regular old glass—it's special glass, and there are not hundreds of manufacturers for this type of glass out there. There's Corning in the United States. There's a German company and an Italian company.
Now, one of the companies we talked to said, "We want to build an American plant, but the U.S. government hasn't come to us. If they're willing to take the risk and finance it, we're willing to set up the plant and produce a bunch of glass vials for them for Covid-19." So, glass vials could potentially be a rate-limiting step if they can't actually get those production lines up and running.
Another step I was blown away by and totally shocked by is "fill-finish." Now, I think I know something about health care, but I'd never heard of this before. But fill-finish is when you take the vaccine you've made, and you have to put it into those glass vials in super sterile conditions. You have to make sure that there's no bacterial or viral or fungal contamination at all. And the factories that do that are 100 times more sterile than a hospital operating room.
And currently, the world is running at 85% plus capacity of fill-finish. And every vaccine player in the game that we talked to mentioned that this fill-finish capacity was a major concern of theirs. They really, really wanted Washington to finance the building of two or three additional factories. What they told us is, "Look. Those take two or three years." Now look, Covid-19 is not going to be gone in the first wave. But if we start now and build two or three more factories, that buffer would be very good for the world, especially as we're very likely to be developing more vaccines for other things.
Woods: And this is exactly why your report advocates for immediate government intervention. But, in an honest moment, when I speak with clinical executives, with the people who are seven months into the fight against coronavirus, none of them are under the impression that there is going to be some sweeping change that happens with the federal government, at least not in the immediate future. So they're all rightfully looking for something they can do; they want some control and some agency over what they can do to help facilitate the path to a safe and accessible vaccine.
So I want to ask you to put yourself in the shoes of a health system leader, or a medical group leader. Is there anything those folks can start doing today to increase the likelihood that they are ready to administer vaccines once it's finally ready?
Emanuel: They're at the end of the line. They're at, "We've got a vaccine. It's in the glass vial. It's shipped. It's in your office or your hospital system. You have to now administer it. And you have to do it in an efficient manner. And remember, at least for the early vaccines, there could be multiple does—so you not only have to do this in an efficient manner, you have to do it multiple times over in an efficient manner." (Now, Merck is trying to develop a one dose option, precisely because of this problem.) But this means, in all likelihood, you have to give it to Mrs. Jones tomorrow, and then 28 days later you have to give it to Mrs. Jones again. And you have to make sure you know which one she got, and you have to get her back in. That is a huge challenge.
It's a huge psychological and logistical challenge. And you have to prepare for that. How are you going to do the outreach to all your patients or your community? So part of what you should be investing in is, how can we be sure our community is going get Covid-19 vaccine when we get it, and make sure that we have the capacity to go down the priority list? Are we training the right people? Do we have the right capacities? Are we going to set up tents and do it that way? You know, one of the things I've advocated for is going house to house—we don't traditionally do that in the United States, but other countries do. They don't wait for people to come to you. You go to people.
So, if you're in a city—let's say, Houston—and I were the mayor, I'd say, "Let's call the hospital systems in. Let's divide up the city. You're responsible for this. You're responsible for that." You know, the vaccine's going to be paid for by the government, so you need to be responsible for this community. So we're going to make a deal: You're responsible for your community, and your performance is going to influence how I, or my successor, is going to review your next request." I think that's a very important kind of planning that can go on now.
Woods: That's right. And I think that it's relatively uncontroversial the way that you've laid out prioritization for the vaccine—start with first responders, health care workers, essential workers, high-risk populations, and then the rest of us. I think the message for health system leaders is, "You've have to figure out how much of those tiers are actually in your service area and your community," because, in my opinion, the two worst things that can happen is, 1) it creates so much competition that people are hoarding a vaccine, even if it exists and even if it can be distributed, or 2) you haven't accurately accounted for demand and you run out.
Emanuel: Well, I don't want to get political here, but we've seen with the Trump administration that the distribution of personal protective equipment (PPE) was not done in an efficient, effective way. It should have been, if you had 500 employees, you got 500 face masks. No. Sometimes you got 17,000 face masks. And it made no sense why you got the big number and this other group that had more people got a smaller number.
So I think that has to be done pretty carefully. I keep saying it's not too early to plan. Say something is approved in January or four months from January. You might not get it tomorrow, but that's six months from now. You have to get ready now—and getting ready is going to take a lot of oomph.
Woods: It's interesting you bring up some challenges that revealed themselves in the earlier stages of actually combating Covid-19. PPE is absolutely one of them. But the other that comes to mind was actually Covid-19 tests and getting the answers to those tests—that was a patchy effort, at best. And I fear that some of the same challenges are going to come up when it comes to getting a vaccine.
So, your report references this network of locations that should be created to give regular people access to a vaccine. When it comes to things like partnerships, schools, community centers, religious institutions, who should we be thinking about when it comes to making a Covid-19 vaccine accessible?
Emanuel: I always like to put this in context. Each year, 45% of adults get a flu vaccine, round about. We're going to have to get closer to 70%, 80% or 90%, of Americans getting this vaccine.
Woods: Could we pause and talk about that for a moment? Because there's some new research...
Emanuel: No. I don't want get into it, and I'll tell you why. There is new research, and behind it is a paper about vaccination coverage required to establish herd immunity against influenza from before, where they're calculating various parameters. And there are lots of variables that no one controls—what actually is the Rt, or transmission rate at a given time? So it's a lot of estimates, and it's hard to know with any precision. How effective is the vaccine? We're going to know in the trial population, but not necessarily in every population—say, younger teenagers versus more elderly people. And that's going to vary a lot, and that obviously will determine your coverage level. And that gives you a sort of isometric plot.
Woods: What I hear you saying is that the science is changing, and that we're living in this world that's so far beyond best practices that maybe it comes back to your point about planning now. And if we plan for 660 million doses, then at least we're covered, versus saying, "Herd immunity can actually happen at 45%," and then not having enough in reality. Is that fair?
Emanuel: That's fair. And it's very hard to see that 45% is the right number. I mean, that's the biggest variable. Not only don't we know what the Rt actually is—we only have a range—but it also depends upon how effective this vaccine is going to be.
Woods: Let's come back to this idea of getting it in the arms of everyday Americans, and how we can do that. You were about to talk about the kind of community network that we can build here.
Emanuel: Yeah. So, when you talk to Walmart or CVS or Walgreens, they do a portion of what we do normally. I think CVS says it does 20 million. So, 20 million is 10% of the minimum amount. Now, that's a big number, don't get me wrong, but it's not a big percentage of what we need to accomplish. You add on Walmart, Walgreens and a few other spots, physician offices, all that, and that's still not that big. What we have established in the past is a very haphazard patchwork system of administering vaccines. We don't make it easy.
Just think about it: You spend time going and waiting, and then you get a pain in your arm, so you don't feel better afterwards—you feel worse. And you're telling me that I have to do this twice? So I think you have to make it really really easy. That's why I've been a big advocate of bringing it to people's homes. Our substitute in America for bringing it to people's homes is to do it at work or school or places where people are already.
You know, at my institution, UPenn, in a normal year, we line up outside the facility for our annual flu shot. I remember going last year, and it was this long line, and I asked the person who was administering how long it was going to be—it looked like it would take an hour or two. And she said, "Oh, it will be three minutes." I said, "Three minutes. There is no way." She said, "Talk to me on your way out. Okay?" And she was absolutely right. They had it down to four minutes. And that's the reason everyone was lining up, because it didn't take that long.
So we have to make it like that. It has to be easy. It has to be fast. It has to be convenient in your neighborhood. And I think we're not there yet with this pandemic. And then, you have to be able to record the person so you can contact them and make sure they show up for the second dose.
Woods: In the example that you gave about lining up, that really takes the burden off of the patient. It's something that happens in a couple of minutes. It's a normal part of going to work or going to school that day. Of course, we're living in a pandemic where most folks are still at home.
But honestly, what that brings to mind for me, is the question of how clinical leaders can make sure that folks in historically underserved communities, those who aren't going to travel long distances, maybe those who don't even have a regular primary care provider, how are we going to make sure the vaccine gets into the hands of those vulnerable patients? Do you have any thoughts there?
Emanuel: Yeah. They have to hook up with either communities that they have not worked with or community organizations that they've worked with on different things, and work on the vaccine. So, set up a facility at churches, at Boys and Girls clubs, at places that are literally in the community that needs to be vaccinated, so people can be vaccinated there, and they don't have to travel to your hospital. First of all, you don't want all that traffic. And second, it's probably not a hotsy-totsy idea to bring everyone in. You need to do your best to bring this to people where they spend their time.
I would say the other thing that you can see from the testing situation is hours of availability, right? Try to get a test on a weekend. Places are open nine to noon. There's actually a place I was looking in Philadelphia open half an hour—half an hour on Saturday? That's it?
So again, we have to change our paradigm so that we're open from 6 a.m. to 11 p.m. You know, some people are on the night shift. Some people are just getting off the night shift. You have to make it available. We have to put ourselves in other people's shoes. It has to be as easy as possible. You have to do everything you can to remove barriers.
Woods: So we're discussing how we can get this vaccine into the arms of everyday Americans—but what about the people who don't want to get a vaccine? One of the most alarming statistics I've seen on this is that 35% of Americans say they won't get a Covid-19 vaccine even when it's available. What should health care leaders do to combat this kind of fear and hesitation?
Emanuel: I would say political leaders need to be very visible about getting their shot. Right up front, they need to show they're willing. We need to get celebrities and influencers, whatever the hell they are, to do this as well, very visibly. You know? We have to make it a positive valence on doing this. You need to get people who the public recognizes and trusts in some way. That is going to be critical. And I think that is going to be one of the key elements.
Are we going to overcome everyone's resistance? No. Employers can maybe make their workers get the vaccine if they're private. Even public, I guess the University of California has said its students and its faculty and staff will have to be vaccinated. That's true for lots of stuff. You can't come to University of Pennsylvania without getting a list of vaccines. But we may still fall short with that.
And I think once you've got tens of millions of people, not a lot of adverse reactions, you know, the attitude will change. What I worry about is that not only will the attitude change, but the interest in the vaccine once it ceases to be such a big threat may dissipate. We saw this with H1N1. At the start, it was like, "Oh yeah. Absolutely. We've got to get it." And then, you know, it's like, "It passed, so I'm not getting it."
Woods: That's right. And you referenced this historical example of Elvis actually getting a polio shot on the Ed Sullivan Show. And I don't know what that looks like today, maybe the TikTok version of that is for 2020.
But this is another area where it strikes me that clinical leaders can really step in. People trust their physician. And I'm curious for your take as a doctor, how can clinicians actually get ahead of some of this medical information? How do they become part of the marketing that this is something that everyone should be doing?
Emanuel: You're 100% right. Doctors and nurses are critical to this. And I do think that, inside their community, they have to be made available. And health care organizations have to utilize them. And I think, frankly, medical societies, local medical societies, need to take an initiative and be very responsible about this.
Woods: So, of course, the work doesn't actually end at this point yet either. Even when a vaccine arrives and when it starts getting distributed to the people, the next challenge, which you've actually referenced a couple of times, is tracking and monitoring who's getting vaccinated, what outcomes are we observing, and have they come back for their second dose.
Again, this is where I think a lot of health care leaders are looking for some agency and some control. So let's pretend for a moment that there isn't going to be a trusted and transparent tracking system that comes from the government. What do you recommend health system leaders do?
Emanuel: They're going to have to create their own tracking system of the patients who they know, and make it work in their community. And again, I think this is the larger community—not every hospital should make its own little widget. You need to all come together and make one widget that everyone in the same city or same metropolitan area is going to use.
Woods: Have you heard any examples?
Emanuel: No, but I think this is a situation where maybe the dominant payer in a community can do it. Or, you know, if you have a state or regional Blue, for example, or maybe you have the mayor of a city take the lead. Those are the kinds of things that have to happen.
Woods: Now, when FDA actually approves a vaccine, we know that it is going to face some pretty intense scrutiny. Things like, "Was it rushed? Was it actually based on good data? Did political pressure play a role here?" And those questions could be pretty intense, especially if, as President Trump has suggested, a vaccine becomes ready right around election day. So, I want to fast forward to that day when the FDA announces that a vaccine got approval. Are there specific factors that you'll be looking at to determine whether the agency made the right move, or perhaps not?
Emanuel: The key variables are going to be how many people in the control group got Covid-19 versus the vaccinated group. And did they confirm not only that they clinically had it, but that they had it via laboratory test, PCR? That is going to be critical, to have that data and make it transparent, so everyone can look at it. But that's not all you're interested in.
You're also interested in side effects. And what you're going get at that point are very short-term side effects—two to four months. So you're going to want to look at, "What side effects did people experience? How severe were those side effects? And how did they break down by the placebo group versus the vaccine group—what's the differential? How much more did people who got the vaccine experience?"
And God willing, it will be small. But we should remember, it'll be small, but the total number of people who got a vaccine in these studies will be 30,000 or so. And we're going to try to vaccinate 300 million. So let me remind people. For every person who was in the trial, we're going to do 10,000. That dramatically increases the risks of problems. So there are problems you'll see in the trial, but there will inevitably be problems we will see only when we do larger numbers of people.
Now, Tony Fauci told me once that the great vaccine maker of the 20th century, while we all know Jonas Salk, was actually a guy named Maurice Hilleman. Maurice Hilleman saved more people in history than anyone else. He developed all the vaccines, including many for Merck. And he said he did not sleep easily when he introduced a new vaccine until three million people had experienced it—it was at that point, he felt, that they would see every side effect they were going to see.
Woods: And how many are included in Phase III trials typically?
Woods: Yeah. So, much less than three million.
Emanuel: Right. Much less. So even the 3 million number is 100 times the clinical trial number. So safety is a big concern. You're giving it to healthy people who haven't seen Covid-19 and aren't likely to.
Woods: And this is exactly why it is so important that we have a mechanism to actually track not just whether someone got their first and second dose, but what reactions are occurring, especially as more and more Americans get the vaccine.
Woods: So, Zeke, I think it is easy to look at the long list of challenges that you've outlined and feel pretty discouraged. I will admit that that was my initial reaction upon reading it. So, I'm curious. Is there something that gives you confidence, that gives you hope in the face of this incredibly daunting task that's ahead of us?
Emanuel: I can only be political, but faith in a new administration. Look, this is a managerial logistical challenge. You have to look at everything we outlined. You have to talk to the critical industries at each node. And you have to figure out how to solve that problem. And you have to be systematic and go down the list, doing the most difficult challenges that we've discussed, the glass, the fill-finish, etc., first.
That's not brain surgery, but it is a big, complicated endeavor. Can we do those big complicated endeavors? Absolutely. That's what gives me faith that it could happen. Enough people getting the vaccine, that's what worries me. And there could be some social discord because people who want it can't get it. But I think that's a solvable problem.
Woods: Well, Zeke, considering everything that we've discussed today, and perhaps even what we haven't touched on, what's the one thing that you want to make sure health system executives are focusing on right now?
Emanuel: You can't do it alone, and don't try to do it alone. You have to partner and partner effectively, and probably partner effectively with people who you've traditionally considered your competitors. In this endeavor, you have to bury the hatchet, collaborate, and make this collaboration work more efficiently.
Woods: Zeke calls the path to designing and distributing a coronavirus vaccine one of the most challenging initiatives ever undertaken. And keep in mind, this isn't something that's simply going to be handed to us. There is a role for every player in the health care industry to make sure that we can package, ship, and administer a coronavirus vaccine to 300 million Americans, even if we have to do that twice. So if you have questions about what role your organization can play on the global race to a vaccine, remember, we're here to help.