High ionic strength dissociation assay (HISDA) for high drug tolerant immunogenicity testing.

Antidrug antibody (ADA) assessment may be challenged in studies that involve the administration of high doses of biotherapeutics and/or with long half-lives. In such cases, ADA assays with optimized drug tolerance are desired. We evaluated the use of MgCl to develop high ionic strength dissociation assays in two investigational examples (bridging enzyme-linked immunosorbent ADA assays) to attain high drug tolerance while maintaining best possible structural integrity of ADAs. Both ADA-bridging assays treated with MgCl showed improved drug tolerance and higher signal-to-blank values compared with overnight incubation or acid treatment. The use of MgCl treatment in ADA-bridging assays provides a sensitive, drug tolerant and easy-to-use alternative in cases where acid dissociation is not possible or unwanted.