SEKISUI XenoTech is proud to have made contributions to the paper entitled, “Considerations from the IQ Induction Working Group in Response to Drug-Drug Interaction Guidances from Regulatory Agencies: Focus on CYP3A4 mRNA in vitro response thresholds, variability, and clinical relevance.” This paper, prepared by the IQ Induction Working Group of The International Consortium for Innovation & Quality in Pharmaceutical Development (IQ) and found in the journal Drug Metabolism and Disposition, provides recommendations, that although do not supersede any regulatory guidance at this time, do guide pharmaceutical companies on how to conduct CYP induction studies.
Major recommendations of the manuscript include:
- CYP induction should continue to be evaluated in three separate human donors in vitro
- In light of empirically divergent responses in rifampicin control and most test inducers, normalization of data to percent positive control appears to be of limited benefit
- Two-fold induction, with concentration dependence, is an acceptable threshold for positive identification of in vitro CYP3A4 mRNA induction
- To reduce the risk of false positives, in the absence of a concentration dependent response, induction ≥ 2-fold should be observed in more than one donor to classify a compound as an in vitro inducer.
IQ “is a technically-focused organization of pharmaceutical and biotechnology companies with a mission of advancing science and technology to augment the capability of member companies to develop transformational solutions that benefit patients, regulators and the broader R&D community.” To augment this group, the Induction Working Group takes a data driven approach to “move towards a better understanding of the overall regulatory approach to induction-based DDIs in the guidance from the EMA (+FDA and PMDA).”
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