Assessing monoclonal antibody product quality attribute criticality through clinical studies.

Recombinant therapeutic proteins, including antibodies, contain a variety of chemical and physical modifications. Great effort is expended during process and formulation development in controlling and minimizing this heterogeneity, which may not affect safety or efficacy, and, therefore, may not need to be controlled. Many of the chemical conversions also occur in vivo, and knowledge about the alterations can be applied to assessment of the potential impact on characteristics and the biological activity of therapeutic proteins. Other attributes may affect the drug clearance and thereby alter drug efficacy. In this review article, we describe attribute studies conducted using clinical samples and how information gleaned from them is applied to attribute criticality assessment. In general, how fast attributes change in vivo compared to the rate of mAb elimination is the key parameter used in these evaluations. An attribute with more rapidly changing levels may have greater potential to affect safety or efficacy and thereby reach the status of a Critical Quality Attribute (CQA) that should be controlled during production and storage, but the effect will depend on whether compositional changes are due to chemical conversion or differential clearance.