IND-Enabling ADME Studies

Before a new drug candidate can be administered to humans, a series of preclinical studies must be conducted to characterize the compound. Investigational New Drug (IND) enabling studies are integral to the IND package and must be included in the submission. Key components of the data package include pharmacology, toxicology and safety pharmacology, ADME and CMC sections of the submission.

QPS’ comprehensive preclinical capabilities allow completion of all ADME studies necessary to support an IND filing. A typical IND-enabling ADME package contains data from the following studies:

• Bioanalytical method validation in one rodent and one or more non-rodent species

• Single- and multiple-dose pharmacokinetics, dose proportionality and absolute bioavailability in one rodent and one or more non-rodent species

• Plasma protein binding tests in one rodent, one or more non-rodent species and in human

• In vitro metabolism in animal and human hepatic preparations

• In vitro CYP inhibition in human liver microsomes

Some pharmaceutical and biotech companies also include the following preclinical studies in their IND-enabling package. Although these studies are not required for submission, their inclusion can make the submission package more compelling to move a compound into Phase I clinical studies.

• Mass balance and routes of excretion in rodents, including biliary excretion in rats

• Metabolite profiling and identification in rodents and non-rodents

• Tissue distribution by Quantitative Whole-Body Autoradiography (QWBA)

• Protein, biochemical and toxicogenomic marker studies for translational medicine, as part of surrogate end-points

Once a compound is moved into the clinical phase, QPS continues to support ADME studies such as ex vivo protein binding determination and metabolite identification and quantification in clinical study samples.