Applying a Toolbox to a Platform
Platform approaches to production and purification have been popularized by the emergence of mAb therapeutics. Matteo Costioli, Ph.D., associate manager for downstream processing at Merck Serono, described what he calls a “toolbox approach” for mAb purification platforms.
The toolbox idea can be thought of as adding versatility to manufacturing platforms, and thereby reducing costs. An example is the three-column platform for mAbs. Rather than stick with expensive unit operations like protein A capture, Merck Serono process engineers evaluate older, trusted technologies or new ones with the idea of plugging-and-playing them when the need arises.
“The main goals of our approach are to reduce costs, shorten timelines, and increase process knowledge,” said Dr. Costioli.
Regardless, this is a major undertaking involving significant behind-the-scenes development and probably some in-process tweaking as well. “Toolboxing” requires first identifying different purification technologies, matching them to processes on molecules, and testing with different mAbs under different conditions.
When a similar situation arises down the road—a highly hydrophobic protein or one that tends to aggregate—Merck Serono reaches into its toolbox, pulls out the right operation, and applies it. The company is accumulating a database of techniques and conditions, which it hopes to apply to its future bioseparations projects.
“Everything will be tested, known to work, and suitable for including in the separation platform,” pointed out Dr. Costioli.
His Prague presentation specifically focused on a process that involves precipitating impurities in-line with the bioreactor, then capturing on a cation exchange column, or capturing and clarifying in one step using a novel expanded bed adsorption technology.
Originally developed by Upfront Chromatography and now exclusively owned by DSM Biologics, the so-called second generation expanded bed adsorber has applications in food and feed industries as well as pharmaceuticals. Its main claim to fame is reducing two unit operations (harvest, capture) to one at high yield and throughput.
So why haven’t biotech companies been knocking down Dr. Costioli’s door to get a piece of these cost-saving technologies? “There’s always a balance between the effort you have to put in at the beginning, to change a technology, and the benefit at the end,” he said.