SARS has a mortality rate of 20-30 times of COVID. For the next pandemic what will we do? Head of the Centre Robin Davies talks with Richard Hatchett from the Coalition for Epidemic Preparedness Innovations (CEPI) about the work they are doing with the support of Australia and other countries to invest in research, production and distribution of vaccines to fight MERS, SARS and COVID. What are lessons for responding to emerging infectious diseases and the growing threat they pose to global health security?
“We're a little over a year and a half into our relationship with this virus, and we've already delivered according to WHO, somewhere on the order of three and a half billion doses of vaccine, which is miraculous. No one would have predicted, you know, by the middle of 2021, that 3.5 billion doses of vaccine would have would have been delivered…but it’s not fast enough.”
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Tags: #COVID19, #EndPandemics, #COVAX
Contain This - Richard Hatchett
Vaccine, investment, COVAX, development, pandemic, manufacturing, diseases, countries invested, partners, funds, production, focused, important, doses, support
Robin Davies, Richard Hatchett
We're a little over a year and a half into our relationship with this virus, and we've already delivered according to WHO, somewhere on the order of three and a half billion doses of vaccine, which is miraculous. No one would have predicted, you know, by the middle of 2021, that 3.5 billion doses of vaccine would have would have been delivered.
Welcome to Contain This. I'm Robin Davies from the Indo Pacific Centre for Health Security. Today, I'm joined by Richard Hatchett from the Coalition for Epidemic Preparedness Innovations. Richard, you're perhaps one of the busiest people I know. We're really pleased to talk to you today. Australia has been a strong supporter of CEPI since 2019, with a total investment of AUD$12 million. Richard, thanks for joining us.
Now we'll spend a lot of time, of course, talking about COVID vaccines today. But before we do that, I wanted to take you back really, to the beginning. And talk a bit about the purpose of CEPI, the Coalition for Epidemic Preparedness Innovations. It's an organisation that very few people were aware of only two years ago, now it has become a household name. It's playing a central role in COVAX. So, it's been a fascinating journey. But could you tell us a bit about how CEPI started what its original purpose was?
You’re right. Our profile has certainly increased dramatically as a response to the pandemic. So CEPI was established in the wake of the Ebola epidemic to develop vaccines against emerging infectious diseases. Initially, we were focused on epidemic diseases, so diseases that WHO had identified as presenting epidemic threats, diseases like Ebola, but also Lassa Fever, MERS, Nipah, which is of course related to the Hendra virus that occasionally pops up in Australia.
We were working on those diseases when we got the first reports of a new outbreak in China, and we had really only very recently developed our emergency response protocols. I mean, we'd spent several years building the organisation up, we weren't quite three years old, when the first reports emerged about the outbreak in Wuhan, and we really dialed up our alert posture quite quickly in the first week of January. And then as things unfolded over the next couple of weeks and we were observing the response in Wuhan, and watching the numbers begin to rise around the middle of the month, we decided very rapidly to sponsor the development of vaccines against the new virus. And we moved very rapidly to do so. And ultimately, were able to establish a, you know, a large, both geographically and in terms of the technology, diverse portfolio of vaccine candidates and we've been pushing those forward ever since.
I think one of the unique things about CEPI, is that we focus both on the development of vaccines against emerging infectious diseases and on ensuring access for all populations, to those vaccines. And in the COVID response, we use our investment of funds for research and development to secure access commitments to what ultimately became the COVAX effort to distribute vaccines globally.
So before CEPI was created there were somewhere between 15 and 20 existing product development partnerships, a lot of them working on the development of drugs for neglected diseases. How would you say that the CEPI model differs? Is it more end to end for example?
I think it differs in a in a couple of important ways. CEPI, in its aspect as a Product Development Partnership - and it is a Product Development Partnership. It was focused on a category of problem - epidemic disease. And so we weren't limited by geography. We weren't limited to a specific defined disease, but we were focused on a problem. And so we were striving to develop capacities to respond to that problem in all of its sort of ‘protean’ manifestations.
I think the other thing that's different about CEPI is that we were set up as a as a coalition to bring together stakeholders to address that category of problem. And so we bring together countries that invest in CEPI, and that partner with CEPI; we bring together philanthropies, the private sector has a has a very important role in the CEPI coalition, and we also work with civil society partners. And that big tent approach, trying to bring all of the actors together and in a way trying to serve as a fair or neutral broker to balance the incentives for everyone to participate has been a very important part of our success. It's a big challenge obviously, but I think it really defines CEPI as an organisation.
How do you make choices about where to put your funding across a portfolio?
Before COVID, you know, we, we had a, you know, reasonably long list of diseases that present epidemic threats. WHO had 10 or 11, diseases on their list of so called priority pathogens. We did down select from that list to really work on five or six different diseases and we wanted to work on diseases where vaccines, we thought were an important part of the capability set that we needed.
One of the diseases that we worked on before COVID was the Middle Eastern Respiratory Syndrome, or MERS, which I think many of your listeners may be aware is caused by a Coronavirus that is actually related to COVID. And so we had allocated about USD$140 million into a set of five different vaccine candidates working against MERS, one of which was from the University of Queensland. When COVID emerged, we turned those partners who were working on MERS vaccines - we thought they were well positioned to work on COVID. And so we invited many of them to work on COVID vaccines. There has not been any licensed Coronavirus vaccines and we weren't sure which approach was likely to be successful. And so we wanted to have a technologically diverse portfolio using a variety of different approaches to vaccine development. And so we invested in DNA vaccines, we invested in mRNA vaccines, we invested in protein-based vaccines and vaccines delivered through viral vectors. We really wanted to spread our bets, because we didn't know which ones would succeed and which ones would succeed fastest. We wanted to make sure we have a lot of shots on goal. The other way we diversified our risk - and this has proved to be really important was we anticipated the risk of vaccine nationalism - we anticipated that countries would buy up vaccine supplies when they knew which vaccines were successful. So, in addition to having a diversified portfolio in terms of technology, we also wanted to have a diversified portfolio in terms of the geography of the vaccine developers. And from some of the vaccines, we also invested in transferring the technology to additional countries so that we had a really broad spread in the hopes that we would be able to secure access to vaccine from somewhere, whatever the circumstances were, and we've seen a lot of the things that we were concerned about. I don't know that we were completely successful in avoiding some of the pitfalls, but we certainly were aware of them in advance.
Can I ask a question about financing, both on the income and expenditure sides of the ledger, I guess, but then, what you get for your funding when you invest in a particular vaccine, what sort of commitments are extracted from the relevant industry partners.
Sure, the way CEPI is financed, is through contributions from donors, and the vast majority of our donors now are countries. Quite a few have become first time investors during the COVID epidemic. I think we started with about eight countries prior to COVID and that number has gone up substantially. We take those funds and we've secured around $USD2.4 - 2.5 billion of contributions since CEPI was established in 2017. And about two thirds of that has come during the response to COVID over the last year and a half. We take those funds and we establish contracts with our vaccine development partners. We also fund centralised laboratories, we fund some work on epidemiology. I mean, there's some non-vaccine development related activities that we fund but the major focus of our investments are in supporting actual vaccine development activities. In writing the contracts, which describe the development program and establish sequential stages of investments, we don't just turn over the complete amount of money upfront - we invest stage by stage and the partners have to demonstrate progress to get to the next stage of funding. But we also ask for access commitments. And that can mean different things on different projects. And let me focus mainly on COVID, because I think it's most relevant in COVID.
With our COVID partners, we asked for commitments of doses if the vaccine development programs were successful to the global allocation facility. So what that meant was that if our vaccine development programs were successful, COVAX would have right of first refusal to purchase vaccines, essentially we were securing a place at the front of the queue for the COVAX facility.
Let's talk about COVAX. Now, the COVAX facility brings together CEPI, Gavi - the Vaccine Alliance, and the World Health Organization, and really also UNICEF as the delivery partner. How would you sort of define CEPI's particular role within the overall division of labour in COVAX?
COVAX was designed to provide an end to end enterprise in the interest of global vaccine equity. And by bringing those organisations together, we've assembled this mechanism, which, through the R&D investments that CEPI makes, has its own portfolio of vaccine candidates that are moving forward. Many of us, many of the candidates that CEPI invested in – Moderna, AstraZeneca – most prominently, have now delivered vaccines that are available in emergency use.
The candidates that are in the R&D portfolio are providing vaccine through procurements which are conducted by Gavi, which provides the diversified pool of vaccines that COVAX can deliver.
WHO plays a very important role, obviously, in the international regulation of those vaccines through the emergency use listing procedure or the pre-qualification procedure, that essentially provides a seal of good housekeeping to vaccines that they've been appropriately regulated and are ready to use for many countries that don't have strong regulatory systems. And WHO also has developed an allocation procedure. Then of course UNICEF has tremendous logistical capabilities and both Gavi and UNICEF and WHO, for that matter, have worked with providers in countries to ensure that they're able to receive and deliver and use the vaccines that are provided. So, by bringing those organisations together we've created this end to end facility. Within that facility CEPI’s role is obviously focusing on research and development, and making sure that we have the vaccines that we need to fight this virus.
Something that I've often wondered about is the division of labour in relation to vaccine manufacturing. So how do you divide labour on support for manufacturing?
Well, you’ve picked up on a really important point there, Robin, there was a seam in the system that we put together, which is that there is no organisation that was directly focused on supporting and ensuring the large scale manufacturing of vaccines. And it sort of fell between the cracks and so CEPI had to step up into that role. And it's changed the nature of our activities and it's been a hugely important part of the response to the pandemic - it's one of the most challenging aspects of vaccine development, obviously. And we have made substantial investments, hundreds of millions of dollars to support, particularly the scale up and the technology transfer of successful vaccine candidates, which was not something that was originally envisioned as being part of CEPI's role. But I think, by virtue of our experience during the pandemic, it is become something that we will be doing going forward.
I wanted to ask you about the 100 day vaccine manufacturing, development and production initiative, which CEPI has put forward, which has been endorsed by the G7 - the general idea being that from the point where a need is identified for a vaccine, it can be developed, authorised and manufactured in adequate quantities within 100 days. Just going back a year, from a donor perspective, from the perspective of an organisation that invests in product development. It was such a different world at that time: vaccine investments were very rarely successful, the R&D process could take 10 years or more, and most of the shots at goal failed. And that was one of the reasons why many donors were more inclined to invest in drugs and diagnostics rather than vaccines. Once your portfolio of COVID vaccine candidates took shape, there was still an assumption that maybe none would succeed, maybe one or two would succeed. But now here we are, with a significant number of effective safe and effective vaccines, and the real constraint is manufacturing. So, it's a completely different world. But nevertheless, do you think that 100 day goal, as opposed to what has been, let's say, 3 or 400 day goal for COVID vaccines? Do you think that is feasible?
I do think it's feasible. I think it I think it's a stretch goal. I think it will require concerted effort and focus to achieve it. When the pandemic started, when I was talking about a 12-18 month timeline last January to delivering vaccines, that sounded preposterous. And yet, look at where we are, we're a little over a year and a half into our relationship with this virus and we've already delivered according to WHO, somewhere on the order of 3.5 billion doses of vaccine, which is miraculous. No one would have predicted by the middle of 2021, 3.5 billion doses of vaccine would have would have been delivered. That said, and as fast as the vaccines were developed, it was actually 326 days from release of sequence to the UK regulators emergency authorisation of the Pfizer vaccine. You know, that hasn't been fast enough. We've now got over 4 million documented deaths - probably the actual number of deaths worldwide is maybe 10 or 12 million or even more at this point - a devastated global economy, trillions of dollars of economic losses, so 326 days is miraculous, but not good enough. And the question we asked ourselves was; had we faced a even greater threat, I mean SARS, the mortality rate of SARS, is probably somewhere on the order of 20 to 30-fold higher than the mortality rate for COVID. If we faced a SARS that had the infectiousness of COVID, what would we do? I think there are a lot of lessons learned about the vaccine development efforts. One of the most important lessons in my mind is the value of the prior research on developing MERS vaccines and SARS vaccines which allowed us to design what have proved to be very highly effective vaccines.
I think the overall success rate of the vaccines has been remarkable, and I think a lot of that is because we had a pretty good understanding of the category of threat we were facing with coronaviruses. Making further investments to broaden our ability to respond with the same rapidity to any future threat, no matter what barrel family it comes from, I think is a critical part of enabling the 100-day goal. We also learned a lot about clinical trials, how those could be streamlined and essentially you can roll from a phase one to a phase two to be almost directly into a phase three clinical trial. We've learned about how we might design those late stage clinical trials for maximum efficiency, and I think we have seen some really interesting examples of the ingenuity and creativity that regulators can bring to their work in a crisis without compromising evaluations of safety or evaluations of efficacy. But we have to think about how we want to regulate under that environment, and that's a big global project. That's the reason that I was so glad when CEPI was conceptualised and taken up by the G7, and put at the centre of their pandemic agenda – to have them embrace it and try to figure out how to implement it - I think it is a hugely important step for the world.
Can I finish by just asking you to reflect on the future of CEPI and perhaps a little bit the future of the broader COVAX facility?
Yes, CEPI has been transformed through our response to the pandemic. I think we may have almost tripled in size in terms of number of staff, our remit has expanded to include manufacturing, we helped conceptualise and create COVAX - which has not yet achieved its goal in terms of promoting vaccine equity, but I think represents an improvable and necessary model for the future - and I think a COVAX-like facility will become a permanent part of the global Emergency Preparedness and Response architecture. I think if it's adequately prepared and funded, it will in the future contribute much more successfully to ensuring equity of access at the very beginning of availability.
I think CEPI as it moves into this new, hopefully post pandemic world, there'll be new institutions, new regional arrangements and a heightened focus on national health security. And I think CEPI, as an organisation that operates internationally, needs to position itself to facilitate all of those efforts, all of that investment is critically important. We can't control all of that investment, but we can bring groups and people together and we can help them understand how their individual investments can add up to greater preparedness for the world, and we'll obviously be working very closely with other international partners like the WHO and of course Gavi and UNICEF and many of the other partners that we have worked with. It's a very challenging, but very exciting time to be working in this space.
My name is Richard Hatchett. I'm the Chief Executive Officer of the Coalition for Epidemic Preparedness Innovations or CEPI. And Robin, I just want to thank you and the Indo Pacific Center for Health Security for having me on the podcast and for all your support of our work. It's been a terrific partnership.
Thank you Richard. That was Richard Hatchett, the CEO of the Coalition for Epidemic Preparedness Innovations or CEPI, talking about the organisation's critical work towards global vaccination coverage for COVID-19 and also other diseases we could face in the future. Please join us again in two weeks’ time for another episode of Contain This.