ZAPI’s work can help dramatically speed up the development and approval of new shots for COVID strains, but also flu, malaria and other infectious diseases
Bringing a new vaccine to market takes a long time because manufacturers have to prove that their vaccines not only work, but that they’re beyond reproach, safety-wise. Each application for authorisation requires years of data generation that adheres to strict definitions and guidelines set out by medicines regulators.
But in recent years, pharma companies have been experimenting with ‘platform technologies’ that can speed up this laborious licensing process. Platform technologies is a term borrowed from the world of computing, but when applied to medicines development, can refer to any technology, whether it’s a mechanism, delivery method, or cell line, that we can use as a base for producing different medicinal products.
The partners in the ZAPI project, recognising that such a platform is essential in the face of recurring but unpredictable threats of emerging zoonotic disease outbreaks, started working on a plug-and-play vaccine and antibody production platform in 2015. Their platform allows the immunogen of a new virus to be plugged in to produce millions of doses of new doses within months.
How ZAPI has affected EU law
The ZAPI partners not only built the technical platform (and put it into practice when COVID19 struck), they also worked the regulatory side, having launched the project knowing that legislative changes would be needed to make it possible for vaccine manufacturers to employ such ‘surge production’ technologies in the future. Setting out in the very beginning of the project to work closely with the European Medicines Agency (EMA), they have influenced the updated legislative guidelines for veterinary medicine products that will be applicable in all EU countries from 28 January 2022, thus likely shaving years off future authorisation applications.
“What was missing from the legislation,” says Dr Joris Vandeputte, president of the International Alliance for Biological Standardization (IABS) in Lyon, “was the principle of surge production, and that’s what we were working on. So we were communicating with the regulators early to make sure this was included in the updated European veterinary medicine regulation so that, with a limited amount of scientific safety and efficacy data, things could move very quickly in the face of a disaster like a pandemic.”
This is important because if a pharma company wants to develop, manufacture and sell a new medicinal product, they have to look at the definition in the most recent relevant regulation. The regulation lists all the requirements and guidelines, and until now, there were no guidelines for vaccines based on platform technologies, whether protein-based, DNA or mRNA-based, viral or bacterial vector-based vaccines.
The ‘master file’
ZAPI’s intention was to show the platform could work to ramp up production in the face of a pandemic, and to open the door to wider acceptance of modern genetically-engineered products, something that had faced resistance among some national governments. What’s included in the law now is the concept of a vaccine platform technology master file. This file is to be part of the application submitted to the regulator that remains unchanged, regardless of the antigen or genetic material that the developer ‘plugs in’ to the platform. As such, it needs to be approved only once, potentially cutting years off the process.
“That means that there is no need in the licensing procedure to re-discuss the safety of the platform. It’s done,” says Dr Vandeputte. The vaccine developer only has to insert the new immunogen for the new disease, and then go on with final product testing.
“This is really incommensurable, what ZAPI has done here. The big added value is not only the principle, it's also the fact that we have prepared the regulatory authorities. We are sure that thanks to this technology, in six months we can generate not millions, but billions of the antigens needed for vaccines.”
It offers hope for speedier turnaround for annual flu shots, too. “The WHO announces sometime in the springtime what the next dominant virus strain be, and then the manufacturers can start to manufacture and the license goes relatively quick. In theory, this can be used for anything, as we have a good definition of the right protective immunogen,” adds Dr Vandeputte.
Putting minds at ease about safety
All signs indicate that the ZAPI surge manufacturing principles and platform master file will make their way into the equivalent law that concerns the production of human medicines, currently under revision. “Now, the team at EMA responsible for human health legislation are also looking at the results of our platform technology proposal, and how it works in the veterinary context, and we would not be surprised if there is a copy-paste into the human regulation as well,” says Dr Vandeputte.
The benefits go beyond speed alone. According to Dr Carmen Jungbäck, who works alongside Dr Vandeputte as deputy work package leader in ZAPI, as secretary to IABS and IABS-EU, and former head of veterinary vaccines at IABS. “People were very concerned about the safety of COVID19 vaccines. There was a lot of discussion among the public about it. We can have more confidence in new vaccines that come from platforms.”
“Instead of having to rely on emergency use authorisations, which are temporary, the platform is already established, meaning you can go directly to full authorisation. That's something we can foresee for the future. It’s not something that’s very easy to explain to the general public, but I think it can help build confidence in vaccines generally.”
A modular vaccine development process
According to Dr Vandeputte: “Pharma companies are expanding their platform technologies for malaria, for example, using the same principle that we have established in the ZAPI platform. Malaria is a very difficult vaccine, but it could go very quickly.”
“This is a very important point,” adds Dr Jungbäck, “The platform could be extended to diseases that are prevalent in low- and middle- income countries that cannot pay for expensive research. Malaria is a good example of that.”
According to Dr Vandeputte, “Another advantage is that we have the capacity to implement a modular vaccine development process: you could produce the platform in Europe but you can produce the gene or the antigen somewhere else, and you can insert or mix it, for example in a developing country. The principles and also the legal framework are ready. It did not exist before.”