Manufacturing of one of many world’s most modern vaccines begins in a small room, empty however for a workbench, a bottle rack and a bioreactor. But inside two days, the 50-litre batch of genetic materials made shall be sufficient for 8m coronavirus jabs.
Six months in the past, the 300 employees at this plant within the German metropolis of Marburg had by no means labored with messenger ribonucleic acid, or mRNA. They developed most cancers antibodies for Switzerland’s Novartis. Then BioNTech purchased the plant to ramp up manufacturing of one of many handful of vaccines the world is relying on to finish the pandemic.
Now, the whole workforce is educated in producing BNT162b, the primary accepted mRNA vaccine, made in partnership with US prescription drugs group Pfizer.
“No one has achieved this earlier than,” mentioned Valeska Schilling, BioNTech’s head of processing. “It was actually motivating for us: we’re on the fringe of science.”
Although the manufacturing unit produces mRNA rapidly, its technicians should go gradual — they can not disturb the calibrated filtered air that blows from ceiling to ground. They appear to be astronauts, wearing blue fits and white anti-static boots. Should you didn’t know they have been on the frontier of nanomedicine, you would possibly suppose they have been dressed for a science-fiction movie set.
This time, the scene is staged: BioNTech is exhibiting journalists across the facility, so the mRNA manufacturing room is just not utterly sterile. The liquids within the bottles are simply water — supplies for the world’s most extremely sought vaccine are too costly to waste.
Manfred Brunen, head of producing science and expertise on the plant, mentioned the true bottles of DNA templates and enzymes used to make mRNA don’t look so totally different. “You’d see some swirls. That’s it,” he mentioned. “Not very thrilling.”
However the science is — as is the dimensions at which it operates.
The Marburg facility has a humble exterior: at simply 1,800 sq m, it seems like a squat block of flats. But it’s meant to supply a few quarter of the two.5bn doses Pfizer and BioNTech pledged this yr. By comparability, the constructing at Pfizer’s facility in Kalamazoo, Michigan, the place the vaccine is made and bottled is greater than 90,000 sq m.
The Marburg manufacturing unit’s dimension displays how small mRNA-based drugs could be produced. Most standard vaccines are made by rising a weakened virus both inside hen eggs, which means tons of or hundreds of sterilised eggs, or in cell cultures, inside giant steel cylinders that appear to be these at a brewery.
Lots of analysis has gone into miniaturising vaccine manufacturing, mentioned Anne Moore, a senior biochemistry lecturer at College Faculty Cork, who specialises in vaccine improvement. However for vaccines utilizing cell cultures, which is how the AstraZeneca and Johnson & Johnson vaccines are made, standard strategies are obligatory.
When BioNTech got here to Marburg, the employees stowed away the two,500-litre metal vats as soon as used for cell cultures — so tall that they had staircases to succeed in the highest.
RNA-based vaccines reproduce the genetic code of a pathogen — on this case, the coronavirus spike protein. The physique’s cells then be taught to supply antigens towards it. As a result of it’s molecular, substances could be manufactured on a much smaller scale. “It doesn’t imply mRNA vaccines can resolve each illness nevertheless it’s working for coronavirus,” Moore mentioned.
At Marburg, the vaccine is produced in 4 levels. It begins in considered one of two small rooms the place technicians pour the bottles of DNA and enzymes into the bioreactors. This requires a specialised work bench, fitted with intense air filtering to make sure purity.
“It takes possibly eight to 9 hours simply to switch all the pieces into that bioreactor,” Brunen mentioned. “Some steps should be carried out at a really particular second — so that you begin a response, then cease a response.”
Trying on the bioreactor, it’s exhausting to fathom how subtle the method is. It seems like a metal drum fed with tubes and pumps, and lined with an enormous plastic bag. These specialised luggage are in excessive demand by vaccine makers, so each should be checked for leaks or harm.
Subsequent, the substance is poured into drums that pressure out the leftover “soup” of enzymes and DNA, forsaking the mRNA.
Subsequent, the purified mRNA is distributed to 4 rooms, every fitted with an identical metal vessels and pumps. The pumps “appear to be shoeboxes”, Schilling defined, including: “That is the place the magic occurs.”
In an effort to enter a physique’s cells with out breaking down, mRNA must be encased in fats droplets known as lipid nanoparticles, simply 0.1 micron in diameter. The pumps successfully “shoot” the RNA and lipids collectively.
It takes as much as 13 days to formulate a batch. The extra time-consuming half is testing: every batch wants just a few weeks of research and high quality management. That is additionally what makes use of many of the facility’s house — labs alone take up just one and a half flooring.
As soon as accepted, batches are shipped in refrigerated vehicles to accomplice services round Europe for the “fill and end” stage. The vaccine is checked once more, then put into vials.
In regular occasions, establishing a brand new plant would take a few yr. However Marburg employees and the German authorities acquired the ability accepted in weeks. Regulators watched each step — they have been desirous to be taught the expertise, too, Schilling mentioned.
Schilling is amazed how rapidly her workforce has moved. However that’s nonetheless not quick sufficient for her household and buddies: “All people asks: how’s it going? Are you able to be sooner?”