Of all the activities that constitute a bioprocessing operation, a good argument could be made that the most critical step involves optimizing cell-line development.
That was one of the main messages delivered at CHI’s “Bioprocessing Summit”, in the late summer.
Jesús Zurdo, Ph.D., head of innovation for biopharma development at Lonza Biologics, discussed the challenges and advantages of various strategies for minimizing high attrition rates related to “dwindling R&D productivity and spiraling development costs,” and the resulting cost pressures on process development for microbial fermentation and mammalian cell culture.
According to Dr. Zurdo’s model, risk may enter the picture anywhere during development, including preclinical studies, human testing, or manufacturing.
“Because we get involved early in the development process, we are often the first to notice issues in the form of low yield, aggregation, low chemical stability, immunogenicity, and immunotoxicology,” he said.
Dr. Zurdo’s approach to assessing “developability” involves in silico computational methods to predict productivity, aggregation, stability, and immunogenicity. This helps investigators select, from a collection of potential candidates, a molecule optimized with respect to these properties.
Next he examines, through in vitro and ex vivo assays on cultured human cells, immunogenicity-related events such as T- and B-cell activation and cytokine secretion. The objective of this two-pronged is not to characterize the molecule fully, but to select optimal candidates with low risk of stability and immunogenicity issues.
“Once you are comfortable with biological activity, you can select the lead molecule based on all these assays,” he added.