The growth of therapeutic monoclonal antibodies continues to accelerate due to their success as treatments for many diseases. As new therapeutics are developed, it is increasingly important to have robust bioanalytical methods to measure the pharmacokinetics of the circulating therapeutic monoclonal antibodies (mAbs) in serum. Ligand-binding assays such as enzyme-linked immunosorbent assays (ELISA) utilizing anti-idiotypic (anti-ID) antibodies against the variable regions of the antibody, are a sensitive and specific bioanalytical method routinely used to measure levels of therapeutic antibodies in a biological matrix. Screening and selecting optimal reagents and assay format are critical steps in the development of robust assays. An additional complication exists for soluble circulating drug, mAb targets that could interfere with the anti-IDs binding to the therapeutic mAb resulting in underestimation of total drug concentrations. Therefore, the selection of anti-IDs and the assay format that are not impacted by soluble antigen is paramount to development of a successful pharmacokinetic (PK) assay. We have developed an automated workflow and scoring system that allows for ranking of candidate anti-IDs on a variety of criteria. A primary generic automated indirect ELISA was utilized to shortlist the anti-IDs that need to be labeled and screened in pairs. A secondary screen using a sandwich ELISA with labeled-anti-ID pairings tested multiple PK assay formats to identify the best anti-ID pairing/PK assay format. We demonstrate the use of automation and a scoring system that allows for screening of anti-IDs and identification of the most robust PK assay format in a significantly reduced timeframe compared to standard approaches.