RESUMO
INTRODUCTION: In 2015, IQ DruSafe conducted a survey of its membership to identify industry practices related to in vitro off target pharmacological profiling of small molecules. METHODS: An anonymous survey of 20 questions was submitted to IQ-DruSafe representatives. Questions were designed to explore screening strategies, methods employed and experience of regulatory interactions related to in vitro secondary pharmacology profiling. RESULTS: The pharmaceutical industry routinely utilizes panels of in vitro assays to detect undesirable off-target interactions of new chemical entities that are deployed at all stages of drug discovery and early development. The formats, approaches and size of panels vary between companies, in particular i) choice of assay technology; ii) test concentration (single vs. multiple concentrations) iii) rationale for targets and panels selection (taking into account organizational experience, primary target, therapeutic area, availability at service providers) iv) threshold level for significant interaction with a target and v) data interpretation. Data are generated during the early phases of drug discovery, principally before in vivo GLP studies (i.e., hit-to-lead, lead optimization, development candidate selection) and used to contextualize in vivo non-clinical and clinical findings. Data were included in regulatory documents, and around half of respondents experienced regulatory questions about the significance of the results. CONCLUSION: While it seems that in vitro secondary pharmacological profiling is generally considered valuable across the industry, particularly as a tool in early phases of drug discovery for small molecules, there is only loose consensus on testing paradigm, the required interpretation and suitable follow up strategies to fully understand potential risk.