The ALERRT ® Instrument: A Quantitative Measure of the Effort Required to Compromise Prescription Opioid Abuse-Deterrent Tablets

Am J Drug Alcohol Abuse. 2017 May;43(3):291-298. doi: 10.1080/00952990.2016.1278006. Epub 2017 Feb 13.

Abstract

Background: US FDA guidance recommends measuring the degree of effort needed to manipulate abuse-deterrent (AD) opioids. The ALERRT® instrument (PinneyAssociates; Bethesda, MD) uses visual analog scales to assess the labor, effort, and resources necessary to physically compromise AD product candidates in standardized settings.

Objective: Use the ALERRT® instrument for testing morphine abuse-deterrent, extended-release, injection-molded tablets (ADER-IMT) 60 and 100 mg and the comparators immediate-release (IR) morphine sulfate 30 mg and extended-release (ER) morphine sulfate 60 mg.

Methods: Four technicians tested the products using 10 household tools. The ALERRT instrument quantified effort (all tools) and time (3 preselected tools) required for manipulation.

Results: Morphine-ADER-IMT 60 and 100 mg were difficult to manipulate, as demonstrated by high scores (mean range, 71.0-99.0 and 77.0-99.5, respectively). IR and ER morphine sulfate were easy to manipulate (low scores; mean range, 2.0-14.8 and 2.3-17.5, respectively). Statistically significant mean differences between morphine-ADER-IMT and comparators' ALERRT scores were observed. Manipulations of morphine-ADER-IMT 60 and 100 mg for 300 seconds failed to produce substantial powdering. Manipulations of IR morphine sulfate (mean range, 65.5-175.8 seconds) and ER morphine sulfate (49.3-163.0 seconds) produced substantial to complete powdering in 92% of tablets.

Conclusions: Morphine-ADER-IMT was extremely difficult to manipulate versus non-AD formulations of morphine. The ALERRT system differentiated the degree of effort for manipulation of morphine-ADER-IMT and non-AD morphine formulations, indicating sensitivity of this instrument as part of Category 1 testing. By measuring the degree of effort required for manipulation, the ALERRT instrument provides an empirical assessment into the relative difficulty of manipulating opioid analgesics for abuse.

Keywords: Abuse-deterrent; morphine; opioids; physical manipulation; tampering.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / administration & dosage*
  • Analgesics, Opioid / chemistry
  • Delayed-Action Preparations
  • Humans
  • Morphine / administration & dosage*
  • Morphine / chemistry
  • Morphine Dependence / prevention & control*
  • Opioid-Related Disorders / prevention & control
  • Substance-Related Disorders / prevention & control*
  • Tablets
  • United States
  • United States Food and Drug Administration

Substances

  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Tablets
  • Morphine