A contract research organization perspective on secondary pharmacology: current practices, panel selection, and emerging needs for interpretation.

Secondary pharmacology has become an established component of modern drug discovery and nonclinical safety assessment, supporting the early identification of off-target activities that may contribute to unintended pharmacological clinical effects. Although current regulatory guidance does not prescribe specific panel compositions, secondary pharmacology data are commonly expected to support first-in-human submissions and non-clinical safety assessments. However, practices remain heterogeneous with respect to panel design, assay format, testing strategy, and data interpretation. This perspective provides a contract research organization (CRO)-based overview of current secondary pharmacology practices, based on anonymized operational data from more than 550 sponsor organizations and contextual insights from voice-of-customer activities and routine scientific interactions. Standard catalog panels accounted for more than 90% of panel use and were favored across sponsor categories, whereas customized panels were used less frequently and mainly to address specific scientific or safety questions. Small panels (≤50 targets) were the most commonly used format. Binding assays remained the predominant screening modality, particularly for early compound triage, while functional assays were mainly applied for follow-up characterization or tiered testing strategies. Panel selection was influenced by regulatory considerations, historical experience, target coverage, operational constraints, and project-specific needs. Our analysis highlights ongoing challenges related to dataset sufficiency, regulatory expectations, and the biological interpretation of secondary pharmacology data. Greater harmonization of testing strategies, interpretation frameworks, and regulatory guidance will be important to maximize the value of secondary pharmacology in drug discovery while supporting implementation of the 3Rs principles.