Risk identification, risk assessment, and risk management of abusable drug formulations.

There is a demand for pharmaceutical products with reduced abuse liability. These products must meet three tests to be successful. They must be safe for patients, be less likely to injure the abuser, and be less desirable for abuse by established drug abusers relative to existing products on a dose for dose (milligram-equivalent) basis. There is a need for standardization of the evaluation of abusable pharmaceuticals in the various stages of drug development from preclinical animal studies to postmarketing surveillance. Formulations with reduced abuse liability must: (1) be tested using standard animal, benchtop, and human pharmacokinetic methods that allow interpretation, (2) sufficiently reduce the recovery of abusable drug substance, or contain another ingredient to deter abuse, (3) not alter drug activity for patients in an undesirable or risky way, and (4) have an accurate pre-approval estimation of their reduced abuse liability, which is validated by adequate epidemiologic post-approval surveillance.