Gerhard Gross, Head of Drug Metabolism Lundbeck Pharma
New guidances like the FDA MIST guidance and the ICH-M3 guidance present new challenges to the ADME discipline, as they imply definitive knowledge and quantification of key metabolites earlier in development to avoid potential delay of development programs. Both guidances provide clear criteria about which metabolites have to be covered in tox species and provide decision trees for further activities. The guidances and their overall impact is discussed, current industrial approaches will be outlined. As the criteria and the contents between the two guidances differ, both guidances will be compared, potential weaknesses will be outlined and industrial approaches and strategies will be outlined. Examples of current approaches will be provided and the Lundbeck MIST approach will be discussed in detail. The application of newer in vivo models in the area like the “humanized mouse” will be presented also.