As the world reacts to the SARS-CoV-2 pandemic, one of the most pressing questions is “When are we going to get a vaccine for this disease?” Scores of pharma companies have jumped into ramping up manufacturing capacities and developing vaccine candidates for COVID-19. But we’re not likely to see a successful vaccine until 2021 or later, causing many to wonder how the process can possibly take that long.
DDN spoke with Amélie Boulais, vaccine platform marketing manager at Sartorius Stedim Biotech, to learn about some of the obstacles that stand between our present circumstances and a vaccine for SARS-CoV-2.
DDN Magazine: What are some of the most pressing challenges for companies that are attempting to create a vaccine for COVID-19?
Amélie Boulais: One of the first obstacles is deciding on an antigen and [a] platform for the vaccine candidate. There is no precedent for what will work best against this virus, so the industry is working on a variety of different approaches. So far, we have seen traditional viral vaccines, recombinant proteins, viral vectors, and mRNA and DNA emerge as some of the leading strategies.
Companies also need to consider how to ramp up manufacturing to an unprecedented speed, if their vaccine candidate is deemed safe and efficacious during clinical trials. To ensure availability of a vaccine in 2021, vaccines developers are already working on setting up production capacity. This means they will take a huge financial risk of producing a vaccine before the outcome of the clinical trials.
DDN: Why are we looking at a wait time of around 18 months before the first COVID-19 vaccine could become available?
Boulais: A time of 18 months is already a very ambitious target. Vaccine development usually takes 10 years. Speed should not compromise efficacy nor safety. The vaccine must undergo extensive testing, and this will take several months. Researching, developing, testing, manufacturing and distributing a novel vaccine is a long and complex process. To focus on just two of these stages, there are inherent development and clinical trial challenges that cannot be readily bypassed.
On the development front, this vaccine will need to be safe and effective in every demographic category, regardless of age, gender or comorbidities. That’s difficult to achieve and to prove—especially as we’re starting from scratch. The industry is better prepared for a new influenza vaccine, for example, because seasonal influenza occurs every year. There is a template to build off of. With SARS-CoV-2, there were no vaccines in development before this year, so everything from the platform to the antigen must be scrutinized.
When it comes to clinical trials, vaccine studies are lengthy for several reasons. The vaccine will be administered to healthy people, who are then are monitored over time to determine whether they contract the disease. So, it’s not like treating a disease—we’re waiting for the person to be naturally exposed to the virus. Regulatory bodies are working to accelerate these clinical trials where possible, but patient safety must come first. That’s particularly challenging at this scale: to identify a side effect that occurs in 0.01 percent of the population, tens of thousands of patients will need to be identified, enrolled, inoculated and followed for results.
DDN: What are some of the bioprocess process management challenges that may crop up while a therapy undergoes the production process?
Boulais: Production will need to be scaled up quickly, so developers will need to strike a strategic balance between speed and overall process productivity. A number of solutions are available to accelerate process development, such as high-throughput development tools and experiment software that is designed to allow for a systematic approach to process development. Process intensification technologies can be implemented to compensate [for] low productive cell lines or limit the size of bioreactors during scale-up.
Process robustness is also important as production is scaled up, and should not be compromised by speed. This can be achieved through advanced sensors and process analytical technologies that may be combined with data analysis. Multivariate data analysis can be used to build statistical models to get an overview of the data, identify the reasons of deviations, and predict the properties of data. This can help to accelerate scale-up and de-risk tech transfer, while ensuring process robustness.
DDN: Approximately how long will it take to ramp up manufacturing of a vaccine once one is developed?
Boulais: It is hard to say for sure at this time. Given the urgency, a lot of effort and money is being invested in the rapid scale-up of manufacturing. Some have proposed the idea of establishing large-scale manufacturing for promising candidates before they have been approved. [This] would likely waste of billions of dollars producing vaccines that will never be used. However, it would also give the world a head-start on manufacturing the vaccines that do prove effective. We also know that manufacturers will need to rely on single-use technologies because they can be implemented and validated much faster than traditional stainless-steel facilities. These technologies are flexible, so they can keep up with the changing demand that is likely to come with vaccines. It is also important that developers work with an experienced bioprocessing partner that can ensure a quality supply of single-use technologies.
The production of the COVID-19 vaccine will rely on partnership. Vaccine developers do not have time to build manufacturing capacities dedicated to COVID-19 manufacturing. They will partner with established vaccine manufacturers and contract manufacturing organizations that already have production capacities for similar processes and are heavily based on single-use technologies. This is why the vaccine candidates based on manufacturing platforms, such as viral vectors or mRNA, are so attractive. Once the vaccine is launched out of these existing repurposed facilities and is successful, the companies might consider building dedicated production capacities.
DDN: What do you find most pressing to work on, to ensure the success of a vaccine against COVID-19?
Boulais: Vaccine development has traditionally taken longer than 18 months, so this is an ambitious goal. There are still no approved vaccines for HIV (identified in 1981), SARS (outbreak began in 2003) and MERS (outbreak began in 2012). Developers and manufacturers are working as quickly as they can to develop a vaccine against the virus, but it is important to also maintain safety and efficacy standards. Partnership among universities and start-ups with promising candidates, established vaccine companies with experience in running clinical trials and regulatory filling, [and] contract manufacturing organizations and suppliers is essential to bring a vaccine to the market quickly. We need to bring all of our expertise together.