The Innovation and Quality (IQ) consortium is comprised of 41 member pharmaceutical companies. Within this framework are Leadership Groups which focus on various aspects of Drug Development. The Drug Metabolism Leadership Group created an Induction Working Group (IWG) to address specific aspects of regulatory Drug Drug Interaction (DDI) guidances related to enzyme induction. The intent of the IWG is to propose changes to current DDI guidances, using data to support recommendations. Based on preliminary interactions within IQ member companies and with the EMA, the following topics were selected for further consideration; down-regulation of inducible enzymes, CITCO as the positive control for CYP2B6 induction, CYP2C induction, significance of 2-fold increases in mRNA to trigger a confirmatory clinical study, and recommendation of 72h for in vitro induction incubations. The results of a survey within IQ member companies and some of the data used to support recommendations from the IWG will be presented. Survey respondents confirmed that down regulation is not atypical. Once confirmed that the decreases in mRNA and/or enzyme activities are not due to cell toxicity or time dependent inhibition of activity, other explanations were less obvious. The relevance of down-regulation observed in vitro to clinical outcome remains uncertain and strategies to address such observations do not currently exist in most companies. Typically the signal for CYP2C9 mRNA upregulation is much lower than for CYP3A4 induction. Based on co-regulated pathways and correlations of induction observed in vitro and in vivo, CYP3A4 induction can be used as a gauge of clinical relevance of CYP2C9 induction. Thus only potent inducers of CYP3A4 need to be clinically evaluated for increases in CYP2C9. While CITCO is a direct constitutive androstane receptor (CAR) agonist and phenobarbital (PB) activates the receptor through an indirect mechanism, of the human hepatocyte donors evaluated, CYP2B6 induction did not occur without co-induction of CYP3A4. Together with the requirement to evaluate 3 human hepatocyte donors, the IWG consider that the likelihood of missing a CAR mediated response would be negligible and recommend that PB can still be used. Data have also been generated evaluating in vitro induction assay variability and robustness, thresholds for positive and negative signal and clinical relevance of in vitro CYP3A4 data, using a large dataset of both prototypical and proprietary compounds. Additionally, mRNA and enzyme activity measurements over a time-course of induction of CYP1A2, CYP2B6, and CYP3A4 have been derived to recommend preferred time points and minimum incubation time(s) that would be helpful for cytotoxic compounds and which would retain acceptable sensitivity and a consistent DDI assessment.