IND Enabling Studies
IND enabling studies include a list of assays recommended by the United States F.D.A. to apply for the status of an Investigational New Drug (IND). Once the status of Investigational New Drug is secured, companies can proceed to clinical trials, making an approved IND one of the most important steps in drug development.
IND Enabling Studies Overview
The goal of the IND application section on pharmacology and toxicology (PT) is to show with safety and pharmacokinetic data, that the drug candidate is safe for clinical trials. According to the F.D.A., these studies may be done in vivo or in vitro. Because of the advances in in vitro assays over the past 20 years, along with the time and cost savings seen when running in vitro studies, more companies are successfully submitting IND applications with in vitro data than ever before.
How IONTOX Supports Companies Applying For the IND
IONTOX supports companies applying for the IND with a combination of in vitro assays and data interpretation. In addition to providing a detailed final report for each study, IONTOX will suggest follow-up studies to improve the likelihood of F.D.A. acceptance when necessary.
IND Enabling Assays
| IONTOX Recommended Assays For The IND (Based On F.D.A. Guidelines) |
|---|
| Caco-2 Permeability Unidirectional - Caco-2 Cells •2 concentrations, 3 replicants, 1 time point •LC/MS/MS endpoint |
| Caco-2 Permeability Bidirectional - Caco-2 Cells •2 concentrations, 3 replicants, 1 time point •LC/MS/MS endpoint |
| CYP Induction - Hepatocytes •4 concentrations, 4 target CYPs, 1 time point •mRNA expression or enzyme activity/cytotoxicity endpoint |
| CYP Inhibition - Microsomes/Supersomes •3 concentrations, 4 target CYPs, 4 time points •LC/MS/MS or fluorescence endpoint |
| Metabolic Stability - Microsomes/Blood/Hepatocyte Model depends on molecule type •2 concentrations, 3 replicants, 2 time points •Disappearance of parent over time LC/MS/MS endpoint |
| Metabolite ID - Specialized Bioanalytical dependent on metabolite •2 concentrations, 3 replicants, 6 time points •Typically LC/MS/MS combined with a secondary method endpoint |
| Plasma Protein Binding - Human Plasma/Equilibrium Dialysis •2 concentrations, 3 replicants, 4 time points •LC/MS/MS endpoint |
| Reaction Phenotyping - Determines which CYP enzymes contribute to metabolism: Microsomes •2 concentrations, 3 replicants, 2 time points •LC/MS/MS endpoint |
| Blood Partitioning - Human Plasma/Equilibrium Dialysis •2 concentrations, 3 replicants, 4 time points •LC/MS/MS endpoint |
| Transporter Interactions - Transfected Cell Models •13 transporters, 2 concentrations, 3 replicants, 1 time point •LC/MS/MS endpoint |
| Cytotoxicity - (ATP, LDH, or MTT) specialized assays available on request •1 species, 6 concentrations, 3 replicants, 1 time point •Endpoint depends on assay |
| Hemolysis - Fresh RBCs, Hemoglobin Release •1 species, 6 concentrations, 3 replicants, 1 time point •Hemoglobin spectrometry |