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Before a new
drug candidate can be administered to humans, a series of preclinical
studies must be conducted to characterize the compound.
Regulatory
agencies like the Food and Drug Administration (FDA) have prepared
guidelines on the type of data required for the Investigational
New Drug (IND) application. IND enabling studies are integral
to the IND package and must be completed and included in the submission.
The key components
of the data package are the Pharmacology, Toxicology and Safety
Pharmacology; Adsorption, Disposition, Metabolism, and Excretion
(ADME); and Chemistry, Manufacturing and
Control (CMC) sections of the submission.
QPS' comprehensive
preclinical capabilities allow completion of all the Drug Metabolism
and Pharmacokinetics (DMPK) studies necessary
to support an IND filing. A typical IND-enabling ADME package
to support filing an IND contains data from the following studies:
►Bioanalytical method
validation in two or more species, typically one rodent and one
or more non-rodent species
►Single
dose pharmacokinetics,
dose proportionality and absolute bioavailability in one rodent
and one or more non-rodent species
►Multiple
dose pharmacokinetics in one rodent and one non-rodent species
►Plasma
protein binding in one rodent, one or more non-rodent species,
and human
►in vitro metabolism in
animal and human hepatic preparations
►in vitro CYP inhibition in human liver microsomes
►Mass
balance and routes of excretion in rodents
►Metabolite
profiling and identification in rodents
Some pharmaceutical
and biotech companies also include the following preclinical studies
of their IND-enabling package. Although these studies are not
necessarily required as part of the IND submission, their inclusion
can make the submission data more compelling to support initiation
of the Phase I clinical studies.
►Tissue
distribution by Quantitative Whole-Body Autoradiography (QWBA)
►Protein
and biochemical markers studies for translational medicine
as part of the surrogate end-points
►Toxicogenomic markers
studies also for translational medicine as part of the surrogate
end-points
" Metabolite profiling and identification in non-rodent
QPS also offers
discovery screen as part of the drug candidate selection process.
A typical discovery screen that QPS provides may include:
►Rodent pharmacokinetics
►Plasma protein binding
in one rodent, one or more non-rodent species, and human
► in vitro CYP inhibition
in human liver microsomes
The main differences between a discovery study and an IND-enabling
study are the number of data points or observations, and the acceptance
criteria. Furthermore, due the large number of compounds that
need to be screened, the timeline for completion of discovery
studies is usually within 1 to 2 weeks from compound receipt.
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