Using a manufacturing platform developed to prevent the transmission of disease during blood transfusions, IDRC staffers are working with the faculty of several departments at CSU to test an internally developed vaccine candidate dubbed SolaVAX. If it shows promise, the IDRC's BioMARC -- winner of the 2019 Colorado Manufacturing Award for Bioscience/Medical Manufacturer of the Year -- will help transition the vaccine to mass manufacturing.
CompanyWeek recently spoke with Dr. Raymond Goodrich, executive director of the IDRC, about the initiative in the context of the ongoing pandemic, and how a vaccine will progress from research to manufacturing at a global scale.
CW: How has the IDRC been involved in fighting the COVID-19 pandemic thus far?
RG: The IDRC is made up of a couple different components. One of those components is housing facilities that allow us to handle agents like SARS-CoV-2, which is the causative agent of COVID-19. That means the people and the facilities -- and the knowledge of how to operate those kinds of facilities and the types of techniques to use -- exist.
That really is part of the vision of making the investments to create these kind of facilities, so that when something comes along like this, we're not scrambling to develop the methodologies and develop the know-how and train the people, we already have those capabilities in place and we can apply them to attacking the problem that's at hand.
I think what unfolded here, relative to the IDRC's involvement, is very much along those lines of realizing that mission and realizing that vision that went into the creation of the facility. Because we have the facilities and we have the people who are trained to work with these kinds of agents, we were able to get samples of the virus that were isolated very early on, in the February time frame. We were able to grow it up in culture systems and optimize some of those cell culture methods to increase the yields, which is always an important part of developing new therapeutics, vaccines, and diagnostics. You have to have a sufficient amount of the agent to work with and to evaluate.
Then we were able to apply some of the knowledge that we have about methods to inactivate these viruses. Some of that was applying know-how on my part from what I've done in the field of transfusion medicine for several decades, looking at ways to prevent transfusion-transmitted infections and utilizing photochemical methods to prevent to transfusion-transmitted infections and being able to two and two together and say, "Some of those methods may apply for us to treat products and create inactivated vaccines that might be useful in being able to treat or prevent the disease."
So I was able to work with one of my great colleagues here, Dr. Richard Bowen, who's a long-term CSU professor, a veterinarian PhD who really has an incredible history of working on these kind of issues with emerging diseases and developing animal models to study emerging diseases, and testing new therapeutics, new diagnostics, and new vaccine candidates. So it was just a great combination of being able to utilize some of the know-how that we had in the facilities with people like Dick Bowen, and we recruited other folks like Dr. Mark Stenglein, who's an expert on next-generation sequencing techniques and methodologies to help us characterize what the inactivated virus actually looks like and how to optimize that by understanding the nature of the inactivation chemistry and how that is creating the inactivated virus; and Dr. Marcela Henao Tamayo, who heads our flow cytometry core lab and is doing studies looking at the response mechanisms that animals have when they're vaccinated with vaccines like this.
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Dick's group was able to demonstrate that the hamster is a very good model for the disease. Once you have a vaccine candidate, if you don't have an appropriate test system to study it in, it's not of much use. So Dick's group -- and this is something that they've done quite extensively with Dr. Izabela Ragan and Dr. Angela Bosco-Lauth, with Dick and the students in his group -- were able to demonstrate that hamsters contract the disease, that they produce the virus in large quantities, that they develop a lung pathology that is very similar to the lung pathology -- severe bronchial pneumonia -- that appears in COVID-19 patients, so many of the characteristics, but not all, that you see with the disease. That could be a good model for us to test the vaccine.
Once we had that established, once we knew how to grow it, once we demonstrated we could inactivate it and we could show that the chemistry was behaving the way we thought it would at the molecular level, we were ready to test it in animals. About three weeks ago, we started our first vaccine challenge study in hamsters, a group of 40 animals. It's a 10-week protocol, so we really won't have data until the end of May, beginning of June. We'll collect data, we'll look at the immune response and at the protective mechanisms if we're seeing protection, and we'll see how effective the vaccine is in protecting against challenge with the native virus. Also importantly, we'll see if there are any side effects due to vaccination. If anything adverse happens in the animals because of giving them the vaccine and then challenging it with the live virus.
Those are the steps that really need to be taken, and if all of that is successful, one other asset that we have here, and again is built with that same framework and that same concept of creating the environment where this work could advance, is we have the BioMARC operation as part of the IDRC. BioMARC is a group that functions like a contract development and manufacturing operation in a nonprofit environment. We work with government labs, we work with private industry organizations, we work with other academic groups. We basically transition technologies or concepts that are developed from the basic science and on the laboratory side into processes you can scale up -- and you can scale up in a way that's consistent and compliant with good manufacturing processes that are required by the FDA and other regulatory bodies around the world. So we can move this from a laboratory environment into an environment that helps us make the transition to scaling and doing the process in a way that's compliant with what you need to do to make products available for human clinical testing. Our plan allows us to make that transition under one roof.
CW: How unique is that? Are there other facilities that have these capabilities in both research and production?
RG: Absolutely. . . . Certainly in the private sector, there are other groups that are capable of doing this, where that's their business. In the public sector, there are a few as well: besides government labs, the Regional Biocontainment and the National Biocontainment Laboratories. We are a part of that network. Back in the mid-2000s, there were 13 of these sites established in the United States. Colorado State was one of them, as a Regional Biocontainment Lab, with the idea of creating this capacity. I think one of the pieces that was unique here, that I've seen at least -- I wasn't here at the time -- is that there was the vision here to say, "We really want to integrate all aspects of what the development process looks like." We have faculty labs. At the IDRC, we have the Research Innovation Center. That has faculty labs where faculty investigators and students who are doing research. That's co-housed with private industry labs where there are organizations, private-sector groups, that come in and they rent space, they place people there, and they're doing research. The idea was to synergize the discovery, the invention, and the innovation, the collaboration, and create an environment where those kinds of interactions could take place, where both groups -- the private sector and the public sector -- could benefit to the advantage and to the benefit of the public that we all serve.
Because if we can find ways to solve problems collectively, from the public side and the private side, then we're really fulfilling a public mission, which is to find new therapeutics for diseases, to find new diagnostics, to find new vaccines that resolve problems like we're currently facing with COVID-19. You need that private sector/public sector interface and interaction in order to really see this all the way through. I don't believe that either group would be able to take these concepts or ideas all the way on their own. So this was an environment that was created at the Research Innovation Center where the Regional Biocontainment Lab is located, and then taking that a step further to say, "Can we move discovery from the bench into the practical side of: How do we scale this up? How do we manufacture?" That's where BioMARC came into play.
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[This model] has been really successful here at Colorado State, and it's really a credit to the people who envisioned this. You have the public sector, you have the private sector, you have the manufacturing capacity, and you put that all into one environment where you have that ecosystem of invention and innovation to really be utilized for the benefit of the public, and delivering products and services that make a difference in people's lives.
CW: You mentioned that the IDRC was able to react very quickly because you had the necessary resources and expertise at your fingertips. How much more accelerated is this than the usual process with other microbes that have come across the workflow at the IDRC?
RG: I think things are very accelerated here because we're living in a time with COVID-19 that the world has not seen for at least 100 years. We had some near-misses with Ebola, with Zika, with Chikungunya, with dengue. Those impacted large regions of the world and populations, and they were severe diseases. I think here in the United States in many other cases, we dodged bullets. The world dodged bullets with Ebola and SARS and MERS. But nature is persistent and keeps trying and keeps finding ways to overcome some of the natural barriers that exist that prevent the spread of these diseases. It was only a matter of time until something like COVID-19 came along. Since it's so unprecedented, what we're seeing, what we're experiencing, it's a moment in modern human history that I don't think many of us will forget in our lifetimes, and perhaps our children's lifetimes as well.
That demands a response that is proportional if we're going to get in front of it, if we're going to get on top of it. I think what you're seeing around the world, just in the actions people are taking and the steps we're taking to try and limit and prevent it from the size and scope of the 1919 flu pandemic, the same kinds of steps are being taken in what we're doing from a research standpoint.
I made a comment to a colleague just the other day that it's amazing to me just how much collaboration and how much dialogue is taking place now. Just from my own personal experience, I'm interfacing with new colleagues that I've met just within the last couple of months and brainstorming with them on ways to resolve some of these problems. For example, we've established a relationship with National Jewish hospital. They have strengths and capabilities, we have strengths and capabilities, and we're bringing those together. We're working with the Colorado COVID-19 Convalescent Plasma Project Consortium to try and bring capabilities that we have together with capabilities that they have.
You can find scientists, physicians, healthcare providers, and people in the public and private sectors coming together to really work on trying to solve this problem. It's amazing to me the pace at which that is occurring and the magnitude at which it is occurring. It's certainly unprecedented, I would say, in my lifetime in my career for how quickly these things have mobilized and how much energy is really being put into trying to solve this problem at a global level.
CW: What's next for the COVID-19 work at the IDRC? What's the timeline and calendar moving forward?
RG: I'm asked the question a lot: "When will we have a vaccine?" It's not just about this one, but more in general. I think Dr. Fauci has done a good job of describing the process and the steps that are required. He's given timelines saying 12 to 18 months. I know people hear that and they say, "Why does it take so long?" I think in reality, he's probably already knocked two to three years of what it would normally take if we were not in a pandemic situation. That's remarkably fast.
There's a reason it can't be tomorrow. The first rule for anyone who develops products for human beings is do no harm. That's the mantra of physicians, but I think it's also the code of anyone who works in a field that products go into human use must have. The attitude they have is do no harm, first and foremost.
The worst thing we could do is rush something and create a vaccine or create a therapeutic or create a diagnostic that doesn't work the way we think it should and create problems that magnify the issues we already have. Testing is required, evaluation by independent bodies is required, in order to make sure that we're doing something that is not just effective but also safe when it's administered to people, and that takes time. It takes time, it takes effort, but I'm very confident that everyone working is hard as they can towards that end.
From the IDRC perspective, we're not just trying something that we developed in-house. We're working on that absolutely, but we're working on supporting other efforts with the capabilities that we have. We are a public institution, and our role and our goal is to assist anyone and everyone who has a reasonable approach and has something that could help in this situation.
We can't do everything -- we would love to -- but we try as much as possible to support all efforts that we can that are reasonably trying to look at ways to develop new vaccine candidates of different structure and function, even some opportunities that are going on here at CSU, but including groups that are outside CSU. Here at CSU, Dr. Gregg Dean's group is working on a candidate based on some studies he's done over the last several years with a lactobacillus delivery platform. There are other examples like that, so it's not meant to be a one-trick-pony approach. I personally don't believe there's going to be just one solution that solves the problem. To attack something of this magnitude, you're going to have to have many approaches, whether they're therapeutics, vaccines, or diagnostics or combinations of all of the above in order to get on top of this.
CW: You said the BioMARC facility could be used to inform the scaling of a vaccine on a global level. Tell me a little bit more about what that looks like in practice.
RG: The first step is growing the virus. You can grow it in tissue culture flasks in small volumes. The next step is you've got to take it up to where you're doing one-liter or five-liter batches in bioreactors. Despite how good something may look in a tissue culture flask, there is always a transition and a challenge to scale that size up to something that's a much larger volume. There are ways to overcome some of those problems that have been developed other vaccines over the years that have similar issues, but you never know which one approach or which combination of approaches are really going to be required until you get into that work with the actual agent that you're going to grow. So that's the first step.
Then, scaling the inactivation process, that's where we feel this particular method that we're using has some advantages, because we're repurposing, in essence, existing equipment, existing disposables, and existing materials that are already approved for human use in this application to do the inactivation. So of all the parts of the process, that's probably the one where we have the most knowledge about and the most confidence in relative to doing scale-up and further development. But the procedures have to be verified, the procedures need to be validated, the assays that are used in an application have to be verified and validated, SOPs have to be written -- those things take time and effort. Then, the downstream side when you have the inactivated virus is formulating it, getting it purified, getting it concentrated, and oftentimes there are losses in the process that occur as you go through the purification and concentration steps where you get it down to where it's in a vial ready to be used in a vaccine administration.
This is not something that would be unique to this virus -- it happens with every vaccine candidate to some degree -- and there are a variety of methods and processes that people have developed to overcome that. Which combination of them are the right ones to use here? You don't really know until you get into doing the work. That's really what BioMARC does. BioMARC can take the scale of production to, say, 20 liters or 200 liters. If we want to make this at scale that would address the needs more broadly, you may need multiples of that -- much larger production volumes, much more larger production batches. That's not something BioMARC does. BioMARC does that transition in the early stage, maybe it can produce something on the order of 1,000 vials of 2,000 vials of a vaccine that could be used in, say, a phase I trial. But when it transitions to needing more and going to larger and larger production, there are many different groups out there that have the capacity to do that, and those would be the groups that would be sought as partners or as owners of the concept that has been developed within CSU and within the BioMARC environment.
You will never see a product that we work on that has a Colorado State University label on it. You will never see a product that has a BioMARC label on it. We will facilitate and move those processes through. Our goal, again being a public entity and one that is focused on serving the public, is really to find ways to make these things possible and hopefully groups in the commercial sector, private industry sector will be able to take that ball once we get it to a certain point and move it over the finish line to get it to the point where people could actually be using it, because there's still a lot of work that needs to be done after we get through these initial stages.
CW: If SolaVAX shows promise in clinical trials, will it move over to the private sector once the process is honed at BioMARC and other facilities?
RG: Exactly. The unique thing here with what we're doing is oftentimes an organization will come to us and they will say, "We have this idea. We think this is how we want to make it. Can you go and figure out how to do it at scale and how to do it compliant with GMP?" The difference here is we're taking an idea generated internally at CSU and bringing it to BioMARC and asking those same questions.
CW: If it proves successful, how would SolaVAX get passed on to the private sector? What is the mechanism for that?
RG: That's usually done through the IP that exists on the products and technology. Those are all filed, owned, and assigned to Colorado State University, and the negotiations and things that are done take place through the Colorado State University Research Foundation. Again, the idea is that these are created with the use of public funds, so the benefits should come to the people of the state of Colorado and the people of the United States if it has commercial utility.
You know, in this particular case, it's hard to say. When you have a pandemic like this, it could also be the case that the government says, "We need to find a way to get everyone who needs the vaccine to get the vaccine." So I'm sure there will be government programs and approaches that will be used to make sure that those who want it, those who need it, those who should have it, that it's available to them. Again, that's further down the road, and we have to make sure that it works and that it's safe to begin with. That's first and foremost, and that's where we are right now.
CW: Any other comments?
RG: We're really pleased to be able to put people to work on these issues on behalf of the public and the stakeholders. That's why these facilities exist, that's why we're here doing what we do, that's why many of us chose these kinds of professions, so I'm very proud of my colleagues and the people who are engaged in this work, and other related work. There's a lot more going on here at Colorado State than just what is happening at the Infectious Disease Research Center. That includes people working on making ventilators available, people working on ways to make personal protective equipment more available to the public and to healthcare workers. There are people involved in the screening of healthcare and first-line personnel to make sure that they're not being exposed or exposing others. There's a tremendous amount of work. I'm very proud of what CSU is doing as a whole contributing to this, and I'm sure that story can be told at many other institutions here in Colorado, groups like National Jewish, CU Anschutz, CU Boulder. It really is remarkable to see how many people are coming together to collaborate and to try and put heads together to the end of overcoming this problem.
Eric Peterson is editor of CompanyWeek. Contact him at firstname.lastname@example.org.