Biography
Biography: Chung J D
Abstract
The need to characterize glycosylated biologics in terms of the compositions and specific potencies of their underlying molecular species was recognized nearly 30 years ago when the first biologics entered clinics. However, little progress in improving the characterization of glycosylated biologics has been made. It continues to be widely presumed that manufactured heterogeneous biologics can be adequately characterized by qualitative descriptions of product quality and sample average measurements of biological activity. When quantitative activity-composition studies are performed, empirical or black box methods are used, often leading to more questions than answers. Recently Zhan and Chung reported on a molecular mechanistic mathematical framework that was based on classical ligand-receptor biochemistry and was developed specifically to analyze the effects that different afucosylated IgG1 forms have on Fc-Fc gamma RIIIa binding activity. Using data published in the public domain by the Roche organization, they were able to extract valuable biochemical property information embedded in the data, thus dissecting the contributions of concentration and biochemical property differences between the different IgG1 forms to sample average activity. Such information and methods had hitherto evaded the drug development community. Their study demonstrates that computational methods provide access to important product characterization information embedded in readily generated data and thus expands the totality of evidence associated with heterogeneous IgG1s. Since the methods of Zhan and Chung are directly applicable to characterizing a variety of currently-marketed, follow-on and newly-approved IgG1s, the use of mathematical methods based on established mechanisms in ligand-receptor biochemistry should be of interest to all parties engaged in biologics research.