In November 2016, the EMA released draft guidance for sponsors planning early clinical trials with investigational pharmaceuticals, in response to a recent clinical study in which healthy volunteers experienced unexpected serious neurologic toxicity, including death (Kerbrat et al, 2016). In the first half of 2017, sponsors have received queries on EU Clinical Trial Applications that align with the revised draft guideline. Through the International Consortium for Innovation and Quality (IQ) and an EU pharmaceutical trade organization (EFPIA), industry has collaborated with EMA regulators, providing comprehensive, science-based written comments on the draft guideline. Further, a face-to-face workshop provided a forum for joint discussion of potential impacts on pharmaceutical development, and risk-based guideline revisions were proposed. In parallel, IQ/DruSafe member companies recently published a manuscript on their nonclinical approaches to progress small molecules to early clinical trials, concluding that following current nonclinical practices support clinical trial participant safety while advancing in the development of important new medicines (Butler et al, 2017). This conclusion is reinforced by an IQ/DruSafe nonclinical to clinical translational database indicating that absence of toxicity in animal studies predicts similar clinical outcomes (manuscript in preparation). All stakeholders agree that in cases where there is higher uncertainty regarding nonclinical to clinical translation, a more conservative approach to clinical trial design is warranted. Given the rapid evolution of pharmaceutical safety evaluation, health authorities and industry must continue to jointly engage to ensure that testing paradigms and regulatory guidance evolve in line with emerging science without impeding development of new medicines.