Mammalian Cells: Still the Workhorses
Mammalian cell culture remains the workhorse expression platform at CMOs, in large part due to the popularity of monoclonal antibody treatments. Like many contractors, Laureate Pharma works exclusively with mammalian cells, generally for the manufacture of clinical trial materials. Laureate’s product mix includes 75% monoclonal antibodies, 15% fusion proteins (usually containing antibody fragments), and 10% other therapeutic proteins.
The company’s largest bioreactor is 2,500 L, with a 2,000 L working volume, but Laureate is considering adding 5,000 L tanks to accommodate commercial-scale manufacturing. That decision will ultimately depend on economic conditions and anticipated demand for that level of capacity. “Many of our clients, which are small biotechs, are having trouble raising money and are cutting back on the number of batches,” explains Michiel Ultee, Ph.D., vp, process sciences.
Nevertheless, Dr. Ultee recognizes that gains in cell-line productivity and trends toward lower dosing and more potent biopharmaceuticals may solve the capacity problem for Laureate “without us having to go to larger bioreactors.” Laureate is, in fact, speaking with one customer with a Phase III molecule about producing commercial-scale batches.
But mammalian cells are by no means the alpha and omega of biomanufacturing. “There’s still plenty of work to do in microbial systems, particularly for smaller protein drugs,” notes Harold Ross, vp, process development for KBI Biopharma. One of the more versatile CMOs in terms of expression platforms, KBI specializes in process development and manufacturing through Phase II in bacterial, yeast, mammalian, and insect cells.
Ross believes that volumetric productivity numbers from mammalian cell lines can be misleading, since cells are engineered in every conceivable manner for specific products (mostly monoclonals), only to be assessed honestly in terms of specific proteins and expression systems. “That’s what people are generally referring to when they mention yields of 15 or 30 grams per liter. These cells have been selected and engineered specifically to withstand high antibody concentrations.” Expression of non-mAb proteins can, and often are, much lower.