Abuse Liability Nonclinical Studies
Increasing regulatory concern to assess this and other CNS-mediated effects demand specialized neurobehavioral testing strategies that comply with both international health and drug control guidelines. Selecting the key drug and behavioral contingencies to use in the assessment is critical, as poorly designed studies can lead to false positives or underestimated liability that may manifest later in clinical trials or during the post-approval monitoring period.
At Charles River, we understand that the choice of a qualified partner for this function is critical. With our history of responding quickly to industry needs, our facility in Mattawan, MI has been the first CRO to offer fully GLP-compliant abuse liability assays in both rats and large animals in accordance with regulatory guidelines worldwide. We have conducted 100+ drug abuse liability studies, in addition to also conducting nonclinical screening in other standard models, addressing pain and specialized sensory functions, and various psychological and neurological disorders.
Liability Testing Strategies
Amid America’s ongoing opioid crisis, many wonder what role pharmaceutical companies play in helping reduce the likelihood that new medications will be abused.
Charles River responds to your drug abuse and dependence liability testing challenge with:
- Fully GLP-compliant abuse and dependence liability assays in rats and large animals (equipment and study conduct)
- Conformance with international health agency and drug control regulatory recommendations and guidelines
- Customized models to appropriately characterize a wide range of therapeutic targets
Compounds and Assays
- Expertise with compounds that target known major neurotransmitter systems involved in reward/reinforcement (e.g., dopamine, opiate, serotonin, Gamma-Aminobutyric Acid [GABA], acetylcholine, N-methyl-d-aspartic acid [NMDA]), and which may require appropriate behavioral testing
- GLP-validated assays for:
- Self-administration (rat, large animal)
- Drug discrimination (rat, large animal)
- Locomotor activity assessment (rat)
- Dependence potential (rat, large animal)
- Conditioned place preference/aversion (rat)
Additional Specialized Neurobehavioral Evaluations
- Pain/analgesia assessment:
- Tail flick, hot plate, Hargreaves, Von Frey, and writhing assays (rat)
- Tail withdrawal (rat and large animal)
Since pain assessment models should incorporate measures of general motor activity to ensure the selectivity of the NCE and peripheral or CNS pain pathways, we also offer:
- Accelerating rotarod performance (rat)
- Infra-red motor activity monitoring chambers (Kinder Scientific, rat)
- Morris Water Maze (rats)
- Seizure induction/blockade assessment
- Integrative neurological evaluations of objectively verifiable behavioral changes associated with movement disorders, such as
- Parkinson’s disease
- Huntington’s disease
- Dystonia, ataxias, and other paradoxical movement disorders
Center for Drug Evaluation and Research (CDER) (2017). Consulting the Controlled Substance Staff on drug abuse potential and labeling, drug scheduling, dependence liability and drug abuse risks to the public health.
European Medicines Agency (EMA) (2006). Guideline on the non-clinical investigation of the dependence potential of medicinal products.
European Medicines Agency (EMA) (2009). ICH guideline M3(R2) on non-clinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals.
European Medicines Agency (EMA) (2017). European Medicines Agency guidance for applicants seeking scientific advice and protocol assistance.
Food and Drug Administration (FDA) (2017). Assessment of abuse potential of drugs: Guidance for Industry.