On the site that also houses the National Institute for Public Health and the Environment (RIVM), a few hundred meters from the meeting rooms where the so -called crisis meetings took place during the Corona Pandemie, there is a brand new building. During the festive opening on January 30, the employees of Vaccin producer Bilthoven Biologicals (BBIO) are beaming with a glass of champagne in their hand. Yet they hope to never have to use this factory for the purpose for which it was actually built.
BBIO, located in the wooded area of Bilthoven, at Science Park Utrecht, is one of the largest producers of polio -vaccines in the world, but has recently started a new function: making vaccines against a future, still unknown pathogen. That can be a new variant of Corona, or bird flu, or an infectious disease that we don’t know at all. The question is not whether a new pandemic will break out, scientists say, but when, and what kind of one. And if the moment is there, then in this so -called Pandemic preparedness facility, at the initiative of the European Union, at least 300 million doses of vaccines per year can roll off the band.
This factory is a tangible result of the hard lessons drawn from the Coronapandemie. One of them: Europe was not well prepared for the large -scale rollout of vaccines. “The problem was not when developing suitable vaccine candidates, which went very fast and good,” says Jurgen Kwik, the chairman of BBIO. “When scaling up the production capacity and making raw materials, the buffers and media that are needed to make the vaccine, the process ran to the filling bottles and the stoppers that go on the ampoules. Almost everything was a lack of worldwide.”
So in 2023 the European Commission devised a plan: EU FABa network of companies that can make vaccines quickly and on a large scale with a whole European supply chain. That became Bilthoven Biologicals, together with three factories in Spain, one in Ireland and one in Belgium. Because it is still unknown to what pathogen it will be the best, and what type of vaccine protects against it, the EU concluded contracts with producers of different types of vaccines. In Belgium and Ireland, mrna vaccines are made, so-called protein vaccines in Spain, and in Bilthoven there is many years of experience in making viral vector vaccines. These are vaccines that use a harmless virus to bring a piece of genetic code of the pathogen into the body. The Coronavaccins of Astrazeneca and Janssen were such vector vaccines.
Shifting world order
“It is good to see that after the pandemic there is no sitting still, and it is now being thought ahead. With this factory on the watch flame you win months in the next pandemic,” says Hans Schikan. Between 2021 and 2022 he was appointed as special envoy Coronavaccins by the Ministry of Health, Welfare and Sport (VWS) and was instructed to find out how still the vaccine production from the Netherlands could be accelerated. His painful answer was: that is not possible in such a short term. The Netherlands simply does not have the production facilities. And moreover: the global supply chain was hidden, with all the geopolitical tensions that that entails.
“In one fell swoop, the global vaccine requirement from five to six billion punctures a year shot to double, only for coronavaccins. The delivery time of some materials increased to more than a year.” That scarcity encouraged everyone-for-sea mentality, Schikan saw. “American parts no longer left the country under the name of America First. Boris Johnson was considering a raid at Halix in Leiden to ‘come and pick up a batch of Astrazeneca vaccines’ because he thought the United Kingdom was entitled to it. Vaccines produced in India were not allowed to cross the border and Europe itself also threw all kinds of barriers to prevent vaccines from being able to be exported outside Europe. ”
The entire supply chain has already been mapped out
That was then. But since a few months, the cards on the world stage have again been a lot of guns. The US President Donald Trump announced the departure of the United States from the World Health Organization (WHO) just after his inauguration. China has been threatening for months with a trade war with Europe. The power relationships between the US and Russia are shifting and a war is raging on the European continent. In short: the need for Europe to fall back on itself is growing day by day.
Jorrit van Hoorn, business developer at BBIO, points to a closed box containing hundreds of filling tops that will soon have to close the ampoules. He doesn’t even have to check it, because he knows for sure: these caps come from a factory in Europe. “In some cases, stocks are already present in Bilthoven, such as this box.” According to Van Hoorn, agreements have been made with the supplier for other materials, raw materials and semi -finished products. This keeps the required amount of the material behind for the vaccine factory and can deliver it when needed. “The entire supply chain has already been mapped out and the contracts with all suppliers have been signed.”
Factory ‘keep warm’
Although the facility is built for a crisis to be breaked out, that does not mean that until then the light is out and the door locked. On the contrary. When NRC You can look inside at the end of February, the final preparations will be made to run the facility. The building is divided on the ground floor into two so -called cleanrooms. In one room, cells are grown, in the other room, full of bins, cupboards and boilers, the vaccine is made in large quantities. On the first floor are all technical and air installations that clean the production space below.
In the laboratory, a laboratory technician is already struck in a green suit with an overall, hairnet, safety glasses and gloves over it. “The processes are tested and started step by step,” says Claudia Tietz. She was at the head of the development of the factory.
The European Commission made a hard requirement, she says: the factory must be continuously ‘kept warm’: the machines must run. That means that other vector vaccines are made ‘in peacetime’, “also to keep our staff trained, and all certificates and licenses up-to-date,” says Tietz. What kind of vaccines will that be? “That is not yet clear,” says Jurgen Kwik, who himself has also attracted a sterile suit. “It would be the most logical that it will be a vaccine from our parent company in India, because we already have the knowledge about it. But we are also talking to other parties, for example that of the new vaccine against shingles.”
Now this factory has already been reserved
But vaccine developers who use the Pandemic Preparedness Facility do do so under a strict condition: the production stops as soon as the European Commission gives the order for vaccine production. The factory must be converted within three months to do what it is intended for. “With that, the European Commission is supposed to do exactly what went wrong during Corona,” says vaccinologist Ben van der Zeijst, former head of vaccines of the RIVM and former director of the former Dutch Vaccin Institute (NVI). “At that time, all kinds of parties seized the production capacity for vaccines at lightning speed. Now this factory has already been reserved.”
This is how it will go: if the WHO calls out a global health crisis, all kinds of commercial parties and universities will develop vaccine candidates, as happened during Corona. On the basis of scientific advice, the European Commission will choose the most suitable candidates and link the developers to one of the suitable EU FAB factories. “If it is a vector vaccine, the developer will end up with us,” says Kwik. “There are already contracts ready to arrange the ‘tech transfer’. That is the transfer of the vaccine recipe and all knowledge about the production process. We will then make the vaccine in large quantities on behalf of that developer.”
Sockets on the ceilings
Being able to switch quickly is interwoven in the design of the factory. Unobtrusive, but crucial, for example, that all devices are on wheels. And the sockets are not in the wall, but hang on the ceiling. “Broadly speaking, the production process of all vector vaccines is the same, but we do not yet know what kind of vaccine we will make,” says Claudia Tietz while walking around in the sterile space. “This factory must be flexible to be able to adjust steps in the process: change a centrifuge device from place or insert an extra filtration step somewhere. For example, with the wheels and the floating sockets you can exactly connect each device to the spot in the process where it is needed.”
The development of a viral vector vaccine is in a number of standardized steps. First in the laboratory, the DNA or RNA of the pathogen is brought into a harmless virus. Huge amounts of cells are then grown in cylindrical bioreactors. In those cells, the virus can multiply in a few days. What remains is a thick liquid that looks like a red soup containing millions of virus particles. After this ‘upstream process’, in which more and more is made of the virus, the ‘downstream process’ follows: in a number of purification and filtration steps all impurities are removed from the liquids, so that a pure and concentrated virus product remains. That only needs to be filled in small ampoules. That happens in a building a little further. The ‘bulk vaccine’ is brought to the filling facility in large plastic bags. That goes with golf carts and small cars, because the terrain is so large that the paths have street signs.
At a subsequent pandemic, the facility will be able to produce at least 300 million doses per year, but according to Kwik that could be much more. “Whether that is enough for all Europeans, and whether those vaccines will also go to low and middle income countries, we do not yet know. In this phase it is mainly about starting quickly. If the next pandemic is at the door, this time you have to be in-house to start producing right away.”