Category One Abuse-Deterrent Testing

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


Syringeability is an important property to evaluate and compare to reference listed drugs. (Photo courtesy of National Medical Services Laboratories)


Extraction of formulations in alcohol and commonly available solvents. (Photo courtesy of National Medical Services Laboratories)

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