A Data Driven Strategy for Implementation of Singlicate Analysis in Ligand Binding Assays Used for the Determination of Anti-drug Antibodies to a Multidomain Biotherapeutic.

A stepwise, data-driven approach for Anti-Drug Antibodies (ADA) singlicate assays has been developed to evaluate the feasibility of singlicate ligand binding assay (LBA) method development, qualification and validation to support our clinical programs. With initial precision runs in method validation and subsequent statistical analysis to directly compare duplicate and singlicate formats, our results indicated no meaningful difference in assay precision between duplicate and singlicate. Consequently, the rest of the ADA method validation proceeded with singlicate analysis yielding acceptable validation results. The validated ADA assay in singlicate has been employed to support a Phase I study. The appropriateness of singlicate analyses is further supported by Signal-to-Noise (S/N) data from the three tiers of the confirmatory positive samples, which showed strong correlation in S/N values.