Early pre-existing anti-drug antibody screening in biotherapeutic development: a cross-company perspective

Pre-existing anti-drug antibodies (pre-ADA) pose a significant challenge in the development of biotherapeutics. This article underscores the importance of early pre-ADA screening in mitigating adverse immune responses and optimizing therapeutic efficacy. Drawing on collaborative insights from three pharmaceutical companies, the paper presents a comparative analysis of pre-ADA assessment strategies, including timing, assay formats, and risk thresholds. It details how each company integrates pre-ADA data into immunogenicity risk evaluation, emphasizing the shift toward earlier screening during lead candidate selection. The article also explores assay-specific considerations, such as detection sensitivity and isotype coverage, and outlines criteria for ranking molecular candidates based on pre-ADA reactivity. By characterizing positive pre-ADA responses and proposing standardized practices, the paper offers actionable guidance for incorporating pre-ADA screening into preclinical workflows. This work highlights the growing relevance of pre-ADA assessments in an increasingly complex biopharmaceutical landscape and advocates for harmonized methodologies to support the development of safe and effective medicines.