In April 2015 the FDA published Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling in which nonbinding recommendations were presented to drug sponsors on how to demonstrate that a given formulation has abuse-deterrent properties. In return for meeting a number of specific endpoints, the FDA may permit sponsors to propose labeling that sets forth the results of in vitro studies that appropriately characterize the abuse-deterrent properties of their product(s).
Because opioid products are often manipulated for purposes of abuse by different routes of administration or to defeat extended-release (ER) properties, most abuse-deterrent technologies developed to date are intended to make manipulation more difficult or to make abuse of the manipulated product less attractive or less rewarding. Abuse-deterrent properties are defined as those properties shown to meaningfully deter abuse, even if they do not fully prevent abuse. The term abuse is defined as the intentional, non-therapeutic use of a drug product or substance, even once, to achieve a desirable psychological or physiological effect.1
The FDA guidance document describes three categories for premarket testing of abuse-deterrent formulations:
Category 1: Laboratory-based in vitro manipulation and extraction studies;</ol>
Category 2: Pharmacokinetic studies;
Category 3: Clinical abuse potential studies
Category 1 studies would appear to be the most important because, according to the FDA guidance document, the results of Category 1 studies may influence the design of Category 2 and Category 3 studies.
For more than a decade, PDRC has been assisting drug sponsors with what the FDA today is describing as Category 1 laboratory-based in vitro testing of abuse-deterrence properties. In 2005, Robert Bianchi of PDRC co-authored an article in a DEA journal with industry colleagues that reported a laboratory-based manipulation and extraction study of pseudoephedrine products4. Since 2005, similar studies using “kitchen chemistry” techniques developed by Mr. Bianchi have been conducted on abuse-deterrent formulations of opioids.
As a pioneer in the laboratory-based in vitro study of abuse-deterrent formulations, PDRC has enjoyed a long partnership with National Medical Services (NMS) Laboratories, one of America’s largest and most respected DEA-registered forensic laboratories.
PDRC is prepared to work with drug sponsors who plan to propose abuse-deterrent information for the labeling of their product(s) in conducting the appropriate Category 1 laboratory-based in vitro manipulation and extraction testing recommended by the FDA. In cooperation with NMS scientists, PDRC will design the appropriate protocol of tests, work side-by-side with the NMS chemists to conduct experiments and collect the data, and then provide sponsors with a candid and confidential interpretation to assist in proposing labeling information to the FDA.
(1)Smith S M, Dart R C, Katz N P, et al. 2013. Classification and definition of misuse, abuse, and related events in clinical trials: ACTTION systematic review and recommendations. Pain, 154:2287-2296