Guidance For Industry - Assessment Of Abuse Potential Of Drugs - U.s. Department Of Health And Human Services - 2017 Page 18
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37Contains Nonbinding Recommendations
Animal abuse-related studies generally utilize classic designs that are adapted as appropriate for
regulatory purposes. A sponsor is responsible for proposing and justifying all design parameters
of an abuse-related animal study. If a study is not appropriately designed, the resulting data may
not be relevant to the assessment regarding the abuse potential of the test drug.
Sponsors may propose additional methods of assessing abuse potential, which should include
justifications that demonstrate the scientific validity and reliability of these methods, especially
with regard to assessing drugs with unknown abuse potential.
As described below, each study should incorporate design parameters that facilitate the
collection of data that are consistent with the regulatory goals of the specific study.
1.
General Considerations
Selection of Animals. Typically, abuse-related animal studies are conducted in rats, because this
species has been validated for use in these studies. Although nonhuman primates have often
been used for abuse assessments, the ICH guidance for industry, M3(R2) Nonclinical Safety
Studies for the Conduct of Human Clinical Trials and Marketing Authorization for
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Pharmaceuticals (2010)
(M3(R2) guidance), states that, “When the metabolite profile and the
target for drug activity in rodents are consistent with that of humans, the nonclinical abuse
liability evaluations should be conducted in rodents. Nonhuman primates should be reserved
only for those limited cases where there is clear evidence that they would be predictive of human
abuse liability and the rodent model is inadequate.” The study protocol should justify the
species selected, especially if a non-rodent species is proposed. Typically, a single animal
species is used for animal abuse-related studies. It is appropriate to use animals of both sexes in
these studies. The experimental drug history of the animals (classes of drugs, as well as extent
and recency of exposure) should be provided, if it is known and available, since prior exposure to
drugs may influence responsivity to the current test drug. The number of animals used in the
study should be based on a statistical power analysis in order to ensure that the sample size is
appropriate to detect changes in behavior that can be attributed to the test drug.
Selection of Drug Doses. The doses used in animal abuse-related studies should be selected on
the basis of the specific test being conducted (see below). For regulatory purposes, the doses of
a test drug that will be evaluated in animal abuse-related studies should be derived from the C
max
produced by the highest proposed therapeutic dose, rather than on the basis of characterizing an
entire dose-response curve (e.g., no effect level to incapacitating level). This is because most
animal abuse-related studies are specialized safety studies, not studies that investigate the
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Available at
We
update guidances periodically. To make sure you have the most recent version of a guidance, check the FDA Drugs
guidance Web page at
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