Richard Slauter, PhD, Andrew Augustine, MS, Rachel Goldsmith, PhD
We all need to do Absorption, Distribution, Metabolism, and Excretion (ADME) studies to support an NDA submission, but when does ADME data best support the story we are crafting for the agency? When can it benefit us most scientifically? When can it help us move our program successfully forward?
ADME studies are a vital part of the comprehensive safety evaluation of a new therapeutic entity, whether biologic or small molecule in nature. In vitro ADME evaluations typically inform the nonclinical species selection and give insight into the potential clearance and metabolic profile. All of these data must be confirmed in vivo.
In vivo ADME studies in laboratory animals (rodents, dogs, nonhuman primates, etc.), typically using some form of the radio-labeled therapeutic entity, are required before NDA submission. These in-life studies provide information regarding pharmacokinetics, biodistribution, rates and routes of elimination, metabolites, relative bioavailability, formulation, dosing frequency, exposure, etc. This is all information that can be leveraged at different points in the drug development process to select a lead compound, add value to that compound, enhance the quality of safety studies, or inform decisions about clinical design. The earlier in the drug development pathway that in vivo ADME data are available, the sooner this information can be leveraged in the design of the nonclinical and clinical development plans.
This presentation will focus on the questions around when to conduct the nonclinical ADME studies (pre-IND, Phase I, Phase II, Phase III, pre-NDA) to give the greatest benefit to your program, and how to optimize the design to be most expeditious and cost effective while still delivering the necessary data.