The expansion of the Merck Serono Biotech Center in Corsier-sur-Vevey has made it one of the world’s largest and most technologically advanced production facilities for biopharmaceuticals.
Monoclonal Antibody Production
The figures are impressive: 120,000 L of bioreactor capacity, 65 km of new piping, 10,000 m2 of additional production and cleanroom facilities, 2700 m2 for logistics and support, storage space for 4500 pallets, a new wastewater treatment plant for fully biological treatment of 1200 m3 of wastewater, and 2500 m2 of 12 m retaining walls on the production site.
The Center will produce large amounts of active ingredients for biopharmaceuticals, especially for Merck’s cancer drug Erbitux®, a wide range of biosimilars and Rebif® (interferon beta-1a), a second messenger used in multiple sclerosis treatment, producing them in animal cells and releasing product into the surrounding culture medium, from which they are harvested and purified.
Because only a tiny amount is administered to each patient, production volumes are very small. "It only takes a couple of kilograms of Rebif® to supply the entire world market," says Jens Regelin, Head of the Merck Serono Biotech Center. "By contrast, therapeutic antibodies for targeted cancer therapies such as Erbitux® are produced by the ton or hundreds of kilograms, as dosages can be much as 18,000 times higher than for Rebif®”.
At the expanded Merck Serono Biotech Center, process development and production are neatly dovetailed. Process development begins in the Cell Sciences Department, where the gene with the blueprint for producing the biopharmaceutical is introduced into the animal cells. The next task is to select cell lines that produce the therapeutic protein in high yields and outstanding quality. These cell lines are then handed to Process Development, which determines the optimal conditions for cultivation and purification.
All of this is part of the development of a fully commercial production process. Since 2011, robots have been used to simultaneously test as many parameters in parallel as possible, using a minimal amount of cells. As a result, the number of cultures tested in one year rose six-fold. Similarly, plant engineering software and automation ensure that all of the production processes are closely monitored and controlled.
Project Specifications for GEA
Supply: fermenters/bioreactors for microbial and cell fermentation: up to 20,000 L, sterile design, high performance control system with visualisation, tested and qualified.
Fermentation: design, automation, manufacturing, assembly, FAT, qualification of 8 x production reactor skids (15 kL), 8 x feed vessels (3 kL), 2 x harvest tanks (17 kL) and 18 x heating/cooling systems.
Filtration: design, manufacturing, assembly, FAT, qualification of 2 clarification skids (6 x depth filter, 5 x media filter, 1 x sterile gas filter) and 2 break tank skids (1 x 3 kL break tank, 2 x heating/cooling units, 2 x sterile gas filters).