Category | Large molecule
Vaccine development is a lengthy process—it is expensive, attrition is high, and to get a licensed vaccine to everyone, it takes multiple candidate iterations. Vaccine development for pandemics and epidemics is risky, and due to the novel nature of viruses, certain unknown factors can derail a vaccine program. For example, the Zika outbreak—some epidemics can taper off before a vaccine is fully developed. There is a level of uncertainly not only if/when a vaccine gets approved, but if it will still be in high demand. Producing a pandemic-scale stockpile of vaccines that aren’t being used because a pandemic tapered off, could be financially devastating to a vaccine manufacturer.
From long and expensive development timelines, to the novel nature of viruses like COVID-19, combatting a pandemic in the pharmaceutical industry is particularly challenging. Fortunately, despite this reality and the desperate era of COVID-19, many brilliant minds, sensical regulatory agencies, and cutting-edge technologies have brought the first COVID vaccines to market. The road to living in COVID-free world is still long, but the speed at which these vaccines were developed and brought to the people is quite miraculous.
For context of how speedy the industry and regulators responded, here’s a brief timeline of COVID-19 and its vaccine(s):
The effort contributing to this speedy response to the global pandemic is an excellent example of innovation and private/public sector collaboration. From the day the WHO characterized COVID-19 as a pandemic, it took pharma companies and regulators just under a year to have a vaccine approved and ready for distribution; reducing the usual five to 10-year vaccine development time—which doesn’t even include manufacturing and distribution.
While joint private/public sector initiatives like Operation Warp Speed have driven the availability of COVID-19 vaccines, what is done during the development phases fuels the effort. “Vaccine development is a complex and costly undertaking that is incredibly risky”—most “vaccine candidates fail during preclinical and Phase I development.” And the rough, estimated cost of developing a vaccine—before any applications are submitted to regulatory authorities to actually license a vaccine—is over $0.5 billion. From determining the medical need, demand, and technical feasibility, all the way down to a successful Phase III—the time, resources, and risks of developing a vaccine before even preparing the application for approval, is long.
Like many aspects of life, COVID-19 has changed things, likely forever and it is up to pharmaceutical companies—both large and small—to reassess how they strategize the development of vaccines. And while strategies must change, every vaccine should fulfill these fundamental, base-level requirements:
While the above qualities must also be present for a successful vaccine, getting there is another story. As previously mentioned, the approximate decade-long, traditional approach to vaccine development is complex and most candidates fail during the initial development phases. This begs the question—how have vaccine developers been able to get multiple vaccines approved in just under a year?
When it comes to vaccine development there are two approaches—or platforms—developers can utilize: traditional platforms or new generation platforms. And both have certain pros and cons as it pertains to manufacturing and the end-product.
Most current and licensed vaccines for human use are either virus- or protein-based vaccines. “The virus-based vaccines can consist of inactivated virus that is no longer infectious, or live-attenuated virus… Protein-based vaccines can consist of a protein purified from the virus or virus-infected cells, recombinant protein or virus-like particles.”
Traditional vaccine platforms are tried and true approaches to vaccine development and are already present in the market. They have strong and robust historical data and many of them have relatively simple formulation. Despite being familiar and having these positives, traditional vaccine platforms have their fair share of cons. For example, traditional vaccine platforms require a dedicated facility for biosafety monitoring and must have a study that demonstrates the virus will not regain virulence.
There is certainly a place for traditional platforms for vaccine development. From smallpox to polio, many vaccines have been developed by traditional platforms and many diseases/viruses have been eradicated. However, the limitations of traditional vaccine platforms make them less ideal for trying to develop a vaccine quickly, in response to a pandemic.
Unlike traditional platforms, new generation vaccine platforms can go off genetic sequence information alone. DNA and RNA-based platforms only require laboratory synthesis, not culture or fermentation—there isn’t a need for a dedicated biosafety facility as there is no handling of infectious material. This speeds vaccine development exponentially and most COVID-19 vaccine clinical trials have utilized a new generation platform for this very reason. Furthermore, vaccines based of viral vectors offer a high level of protein expression, long-term stability, and can introduce a strong immunic response.
Though new generation vaccine platforms are ideal during a pandemic, they have own fair share of challenges. RNA’s are sensitive and need something to preserve them. To help perverse the RNA, lipid nanoparticles are used which adds quite a bit of complexity. Furthermore, RNA-based platforms are poorly stable at room temperature, making the need for sub-zero storage and supply chain monumentally important—most need to be stored at -70 degrees Celsius. Additionally, DNA-based developed vaccines could require special medical devices to administer the vaccine.
Despite the challenges of new generation vaccine platforms, its’ more streamlined process and approach is just what developers needed to get out a COVID-19 vaccine, fast. If developers went with traditional platforms, a vaccine wouldn’t be out for mass consumption for almost a decade. This reality makes the cons and added complexity of new generation platforms all the more worth it.
Aspects like vaccine platforms are a crucial consideration when it comes to vaccine development amidst a pandemic, however, it’s merely the tip of the spear of all the other complex and crucial considerations. The whole vaccine development playbook is being re-written and pharmaceutical companies and scientists are working relentlessly to bring life-saving vaccines to the people quicker, all while not sacrificing vaccine quality, safety, or efficacy.