Executives Provide Insights on The Future of Drug Development at Virtual DCAT WeekBy
Development of vaccines and treatments for COVID-19 has occurred at an unprecedented pace of scientific innovation. A Pfizer executive tells the story behind how the company brought its mRNA COVID-19 to fruition and how lessons learned may shape the future of drug development, including time to market. Plus, insights from Resilience Inc.’s CEO on manufacturing innovation in drug development.
Gaining expert views
In an executive forum, Executive Insights II: How COVID-19 is Transforming the Future of Drug Development, presented at Virtual DCAT Week, held July 12-16, 2021, Philip Dormitzer, M.D., Ph.D., Vice President and Chief Scientific Officer, Viral Vaccines, Pfizer, explained how the company was able to bring its COVID-19 vaccine to fruition under such accelerated timelines and offered perspectives for the industry on the future of drug development. Rahul Singhvi, Sc.D., Co-Founder, CEO and Director, National Resilience, Inc. and formerly Chief Operating Officer of Takeda’s Vaccine Business Unit and formerly President and CEO of Novavax, a vaccine company, provided insights on the role of manufacturing in the future of drug development. Resilience is a bio/pharmaceutical manufacturing and technology company launched in November 2020 with initial capital of more than $800 million with a specific focus on manufacturing innovation, including for new modalities. The forum was moderated by Patricia Seymour, Managing Director, BioProcess Technology Group, BDO USA LLP. DCAT Week is the premier global event for companies engaged in the bio/pharmaceutical manufacturing value chain and is organized by the Drug, Chemical & Associated Technologies Association (DCAT), a global business development association.
Pfizer’s success factors to a mRNA COVID-19 vaccine
In explaining the key success factors for bringing its mRNA vaccine to fruition, Dr. Dormitzer outlined several key factors, including an earlier partnership with BioNTech, a Mainz, Germany-based bio/pharmaceutical company, in which the companies were collaborating on the development of mRNA vaccines for influenza and later directed their efforts to the development of a mRNA COVID-19 vaccine.
“First, the technology was right. We started working with BioNTech in advance on a flu vaccine. We had teams working together on this technology, and it was relatively straightforward to swap the flu gene to the SARS-CoV-2 gene [the virus that causes COVID-19],” explained Dr. Dormitzer. “Second was a focus of resources. It was made clear from our CEO Albert Bourla that this was going to be the top priority, and all of the resources of the company would be focused. Thirdly, we had in place the infrastructure and expertise to advance vaccine candidates rapidly…Finally, this focus went beyond the company. There were others, including regulators, which had a singular focus of getting a COVID-19 vaccine, so that data were analyzed promptly, submissions were processed rapidly, so everyone worked together to make the vaccine happen.”
Philip Dormitzer, M.D., Ph.D
Pfizer’s/BioNTech’s COVID-19 vaccine was the first mRNA vaccine authorized for emergency use by the US Food and Drug Administration, and it represented a major advance in the application of mRNA technology. Dr. Dormitzer explained that a key difference between mRNA vaccines and traditional vaccines is that most traditional vaccines contain the antigen, part of the virus or bacteria that is used to trigger an immune response. mRNA vaccines do not contain antigens. They contain the instructions for one’s own body to produce the antigen, a fundamental difference compared to most vaccines. Moreover, mRNA vaccines offer certain advantages in that RNA is a platform technology, meaning that the process of analytical development and manufacturing of the RNA is not dependent on the antigen that is being made, explained Dr. Dormitzer. As a new technology, however, he noted that processes and assays had to be optimized, and manufacturing capacity had to be put into place, elements that Pfizer/BioNTech were able to do in order to progress the vaccine.
Although mRNA technology has been a promising area in vaccine/drug development, the success of mRNA COVID-19 vaccines has brought the technology into greater prominence with potential application in other areas. “RNA is a remarkably versatile molecule,” said Dr. Dormitzer. “In addition to other vaccines, RNA can be used to express proteins that replace proteins that are deficient. There are uses for gene editing as well. And there are uses beyond vaccines, such as immuno-oncology…That is just the start of the prophylactic and therapeutic uses in which RNA has potential.”
Manufacturing innovation in new drug development
Rahul Singhvi, Sc.D.
In advancing new vaccine/drug development, being able to manufacturing the vaccine/drug candidate of interest is critical. A key point examined by Resilience’s Dr. Singhvi is the importance of upfront manufacturing investment, particularly for new modalities.
“Bio/pharmaceutical companies are first focused on proof-of-concept and seeing if a drug candidate shows some level of biological activity. Until that is proven, it is difficult for companies to significantly invest in manufacturing,” said Dr. Singhvi. “That is okay when the modalities are well-understood, and we understand how to make those drugs, which is true for small-molecule products and biologicals. But when it comes to very complex molecules, such as vaccines, or newer modalities, like cell and gene therapies, the manufacturing is not fully optimized. So, if we take the same approach of moving early-stage therapies into the clinic, we generally end up with manufacturing approaches that are not fully developed and then you are stuck because you don’t want to change processes that can change the product. For those reasons, he emphasized the importance of upfront manufacturing investment for complex and new modalities.
Future of clinical trials and clinical trial material supply
During the pandemic, bio/pharmaceutical companies, in certain instances, have had to employ decentralized and/or remote/virtual clinical trials due to restrictions, such as limited patient access to clinical settings or difficulty in patient recruitment. The executives were asked from an industry view, if they thought that model of decentralized/remote clinical trials may continue to be of interest and of other lessons learned from the pandemic that can be taken forward.
“I think remote interactions are a real area of interest for the future,” said Pfizer’s Dr. Dormitzer, “Can we conduct clinical trials more efficiently by taking advantage of distributed communications technology and even distributed diagnostics technology in the future? There are innovative lessons learned that we can take in the future, …but they may not be applicable to every project,” he said.
When asked about what changes may be forthcoming in clinical trial material supply, Dr. Singhvi pointed to the value of producing clinical trial materials, even for early-stage trials, using a manufacturing process that is close to the final process. “That is not the normal approach in our industry now where we use a more primitive process early on and then change it to make it more scalable over time. But if we use a platform approach, there is no reason why we cannot have a very strong, solid, robust process upfront, even in the discovery and preclinical stage. The materials produced for Phase I would be representative of what we would see over time, such as in Phase II and forward, which would mitigate the risk and delays. Now there is such a rush to get product into the clinic, the early-stage [manufacturing] processes are generally not well developed.”
Time to market
Given the priority and need for COVID-19 treatments and vaccines, the industry moved forward with an unprecedented pace of innovation and speed in bringing products to market. The speakers were asked of the impact going forward in terms of development timelines and time to market.
“I think that COVID-19 has really changed the benchmark…There are a lot of learnings here,” said Dr. Singhvi. “We talked about upfront investment in manufacturing being one of the success factors and [the value of] collaboration and singular focus. We talked about the regulatory agencies being more flexible in how they helped in developing the clinical protocols. So, I think there are a number of approaches we learned in this COVID experience that will become the norm as we move forward, and my expectation is that using these approaches, we will be able to strengthen the timelines from discovery to commercialization. That doesn’t mean we will take any shortcuts in manufacturing or the clinical trial rigor, but I think, just the way we do things, will allow us to move things forward faster. Having platforms for manufacturing, having better assays developed earlier, having a more coordinated clinical trial program, a more coordinated regulatory paradigm, all of these things will lead to faster development…”
While agreeing, Pfizer’s Dr. Dormitzer also pointed out the pandemic provided for unique circumstances that would not necessarily be replicable in ordinary times. “I think that we can realize some of this acceleration in the future, but some of it is related to the special circumstances of responding to a highly consequential pandemic,” he said.
Manufacturing and new modalities
In looking beyond the pandemic and broader issues in drug development are new modalities, such as cell and gene therapies. Now a niche area, Resilience’s Dr. Singhvi was asked what is required to advance these modalities from a manufacturing view.
“I think cell and gene therapies are part of the future of medicine,…these modalities are coming out because of our understanding of the human genome, a better understanding of our immune system, and just a better understand of human biology,” he said. “But these products, whether they are living cells or viral vectors through which we are delivering genomic payloads or other types of complex vehicles are not that easy to manufacture. For us to be able to take advantage of this incredible biology, these curative medicines, is to invest in better answers for the manufacturing approaches to these types of modalities. Without that investment, without the understanding of the product itself through multiple different types of assays, we will not be able to make or scale them at a cost that is affordable or to apply them to indications that are broader than just a few key rare diseases. The key to take advantage of this incredible biology is to be able to produce these types of products at scale and at yields that are amendable to large-scale production and large deployment of these types of products.”
To achieve this, he emphasized investment in technologies, such as process technologies, analytical technologies, biological engineering, artificial intelligence, and digital. And then applying these technologies in a GMP environment with the ultimate goal of manufacturing these advanced products at higher quality and lower cost.
The future of drug development
To conclude, the speakers were asked how drug development may evolve over the next five to 10 years, including the use of new tools. Pfizer’s Dr. Dormitzer pointed to several potential areas depending on how technology may evolve. He cited potentially greater use of prediction modeling to enable more targeted and focused experiments based on automated ways to examine existing knowledge bases. He also pointed to the possibility of distributed and even, siteless clinical trials, enabled by new technologies of remote diagnosis to enable the administration of large numbers of subjects in more efficient ways.
From a manufacturing view, Resilience’s Dr. Singhvi said the pandemic has proven, distributed or more localized bio/pharmaceutical manufacturing, particularly in areas of the world where manufacturing is limited, is critical. “Technologies that can make that happen in a capital-efficient manner are going to be very important.”