Scientists from industry and academia gathered in October to discuss biomanufacturing trends and technologies at “Cell Factories of the Future,” a symposium held at Rentschler Biotechnologie’s main facilities in Laupheim, Germany. The symposium was the first in a new series of specialized conferences.
Stefan Schlatter, Ph.D, associate director of upstream development at Boehringer Ingelheim (BI) presented a talk on BI-HEX® (Boehringer Ingelheim High Expression), a platform for optimizing CHO production of monoclonal antibodies “from DNA to commercial process.”
BI-HEX commits resources early in development to scaleup, process performance, and product quality. The focus is clone selection, but BI-HEX extends through commercial production, downstream processing, and formulation, leaning heavily on BI’s experience with CHO and mAb production.
“It’s an experience-based platform, a concept for the entire process consisting of preferred conditions and operations culled from our understanding of cell culture over the last several decades.”
BI-HEX reportedly results in specific productivity averaging more that 100 pg/cell/day, or final titers of about 8 g/L, for standard fed-batch cultures. The conditions are not widely publicized, but Dr. Schlatter said “the concept is no secret. The key is to achieve high productivity with high quality consistently and predictably, not just once and then selling it.”
BI-HEX supports BI’s own products but is also offered commercially, either as a full development service or up to the clone selection step. BI can also assume post-approval manufacturing, where it leans on its experience from the development stage.
Readers may wonder how sponsors, particularly development-stage companies, can afford to devote significant resources to preclinical molecules when most will fail anyway during clinical testing. That, said Dr. Schlatter, is a misrepresentation of what BI-HEX is about.
“Our slogan, ‘do it right the first time,’ can be misinterpreted. It doesn’t mean to cover every detail in the beginning, but to conduct development in such a way that steps need not be repeated or re-done later at larger scale. Do things in a way that they do not need to be redone later.”
With respect to cell-line development, arguably the critical step, Dr. Schlatter described the process as “commercially enabling.” He said BI takes great care during clone selection, paying extra attention to stable, highly productive, consistent and well-characterized cell lines with impurity profiles that facilitate purification.
“All three factors—scalability, productivity, and quality—factor into the decision of which clone is best.” These attributes are often balanced against each other, e.g., a high producer that does not scale, or a highly scalable cell line with high concentrations of a troublesome impurity. “The clone we select must be one that we can work with for the entire life cycle of the product.”