Titers, Protein A Issues Overblown?
Eric Grund, Ph.D., senior director, biopharma applications GE Healthcare believes that the buzz over rising protein titers is over-blown. Titers have been rising steadily for a decade, he argues, and bioprocessors have had more than sufficient opportunity to respond with larger, or in many cases, more-efficient separations. Moreover, higher titers have been accompanied, generally speaking, with raw product material that is more concentrated and of higher-quality, which has enabled simpler downstream processing, for example, by cutting the number of purification steps.
Dr. Grund, also a steadfast supporter of protein A capture, believes that to propose precipitation or cation exchange capture is nothing but an attempt to fix something that already works phenomenally well.
“It’s naïve to say protein A is too expensive, and therefore, must be replaced. Protein A does most of the purification work for mAb processes, providing a product that is 99% pure. Precipitation cannot come close to that and provide a safe product.”
Dr. Grund notes that the plasma protein industry, which traditionally has used precipitation to produce IgG and albumin, is moving more and more toward chromatography-based purifications because “that is what makes these products highly pure, reproducible, and safe.”
Moreover, he feels that protein A’s reliability as a platform technology is a huge advantage. “If you have 20 mAbs in your pipeline, you can purify them all without too much trouble.”
Manufacturers of blockbuster products, says Dr. Grund, will always look for cost advantages through lean and six sigma approaches, and through optimizing utilization of plant resources. But that is not justification for abandoning tried-and-true methodology that generates safe products. “Of course some monoclonals can probably be prepared using methods developed in the plasma products industry years ago, but I’m not certain you’ll get the same level of purity or yield as you will with protein A capture.”