“Where the magic happens” – inside BioNTech’s innovative vaccination plant
It starts producing one of the most innovative vaccines in the world in a small room, empty but for a work table, bottle holder and bioreactor. However, within two days, the 50-liter genetic material produced will be sufficient for the owner of the 8 m coronavirus.
Six months ago, 300 workers at a plant in the German city of Marburg never worked with a ribonucleic acid or messenger mRNA. They developed antibodies against cancer for Novartis in Switzerland. BioNTech then bought the plant to increase production in one of the only vaccines the world counts to end the pandemic.
Now, the entire team is trained to produce BNT162b, the first approved mRNA vaccine, developed in collaboration with the US pharmaceutical group Pfizer.
“No one has done that before,” said Valeska Schilling, head of processing at BioNTech. “It was really motivating for us: we’re at the frontier of science.”
Although the factory produces mRNA quickly, local technicians have to go slow – they can’t disturb the calibrated filtered air that flows from the ceiling to the floor. They look like astronauts, dressed in blue suits and white antistatic medications. If you didn’t know they were on the edge of nanomedicine, you might think they were dressed up for science fiction movies.
This time, the scene is staged: BioNTech is showing journalists throughout the facility so the mRNA manufacturing room is not completely sterile. The liquids in the bottles are just water; materials to get the most sought after vaccine in the world are expensive.
Manfred Brunen, head of manufacturing science and technology at the factory, said the DNA templates used for making mRNA and the actual bottles of enzymes are not so different. “It simply came to our notice then. That’s it, “he said.” It’s not very exciting. “
But it’s science, as well as the scale at which it works.
The Marburg facility has a modest exterior: it is only 1,800 square meters and looks like a block of flats. However, Pfizer and BioNTech plan to produce about a quarter of the 2.5 billion doses taken this year. By comparison, the building at Pfizer’s facility in Kalamazoo, Michigan, covers more than 90,000 square feet at the site where it was vaccinated and packaged.
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The size of the Marburg plant reflects how small mRNA-based drugs can be produced. Most common vaccines are grown by weak viruses inside chicken eggs, which are sterilized by hundreds or thousands of eggs, or in cultured cells, inside large metal cylinders that look like a brewery.
Much research has been done on the miniaturization of vaccine production, said Anne Moore, a senior professor of biochemistry at Cork University, who specializes in vaccine development. In the case of vaccines that use cell cultures, i.e., how AstraZeneca and Johnson & Johnson vaccines are made, conventional methods are necessary.
When BioNTech arrived in Marburg, staff stored 2,500-liter steel containers that were once used for cell culture; the stairs were so high to reach the summit.
RNA-based vaccines reproduce the genetic code of a pathogen – in this case, the hair protein of the coronavirus. Then the cells of the body learn to produce antigens against it. Because it is molecular, substances can be manufactured on a much smaller scale. “It doesn’t mean that mRNA vaccines can cure all diseases, but it’s working for the coronavirus,” Moore said.
In Marburg, the vaccine is created in four phases. It starts in one of two small rooms where technicians pour DNA and enzymes into bottles in bioreactors. This requires a specialized workbench equipped with a live air filter to ensure cleanliness.
“It may take eight to nine hours to transfer everything to that bioreactor,” Brunen said. “Some steps need to be done at a very specific time; so you start the reaction and then you stop the reaction.”
Looking at the bioreactor, it is difficult to understand how sophisticated the process is. It looks like a steel drum fed with pipes and pumps and is equipped with a huge plastic bag. Vaccine manufacturers require a lot of these specialized bags, so everyone needs to check for leaks or damage.
The substance is then poured into drums that filter out excess “soup” of enzymes and DNA, leaving mRNA behind.
The purified mRNA is then sent to four chambers, each equipped with the same steel vessel and pump. The pump “looks like shoe boxes,” Schilling explained, adding, “The magic happens there.”
To be able to enter cells in the body without breaking down, it must be introduced into fat droplets called lipid nanoparticles of mRNA, which are only 0.1 microns in diameter. Pumps “shoot” RNA and lipids together efficiently.
It takes 13 days to complete a batch. The part that requires more time is being tested: each batch needs to be examined for a few weeks and quality controlled. This is also the one that uses most of the facility space – the labs only take up a floor and a half.
Once approved, the batches are shipped in refrigerated trucks to partner facilities across Europe for the “fill and finish” phase. The vaccine is re-checked and then inserted into the vials.
Under normal times, it took about a year to set up the new plant. But workers in Marburg and German authorities approved the facility in weeks. Regulators saw every step – they were eager to learn technology, Schilling said.
Schilling is amazed at how fast his team has moved. But that’s still not fast enough for his family and friends: “Everyone asks: how? Can you be faster?”