Challenges in the Development of Prescription Opioid Abuse-deterrent Formulations

Abstract

Opioid analgesics remain the cornerstone of effective management for moderate-to-severe pain. In the face of persistent lack of access to opioids by patients with legitimate pain problems, the rate of prescription opioid abuse in the United States has escalated over the past 15 years. Abuse-deterrent opioid products can play a central role in optimizing the risk-benefit ratio of opioid analgesics--if these products can be developed cost-effectively without compromising efficacy or creating new safety issues for the target treatment population. The development of scientific methods for assessing prescription opioid abuse potential remains a critical and challenging step in determining whether a claim of abuse deterrence for a new opioid product is indeed valid and will thus be accepted by the medical, regulatory, and reimbursement communities. To explore this and other potential impediments to the development of prescription opioid abuse-deterrent formulations, a panel of experts on opioid abuse and diversion from academia, industry, and governmental agencies participated in a Tufts Health Care Institute-supported symposium held on October 27 and 28, 2005, in Boston, MA. This manuscript captures the main consensus opinions of those experts, and also information gleaned from a review of the relevant published literature, to identify major impediments to the development of opioid abuse-deterrent formulations and offer strategies that may accelerate their commercialization.

The role of human drug self-administration procedures in the development of medications

“…), the abuse liability of the active compound, and knowledge of the patterns of abuse and/or tampering of the currently marketed formulation (Grudzinskas et al, 2006;Katz et al, 2007;Wright et al, 2006). In addition, it may be advisable, when feasible, to conduct a study for each type of potential abuser relevant to the test compound.…”

Impact of Intravenous Naltrexone on Intravenous Morphine-Induced High, Drug Liking, and Euphoric Effects in Experienced, Nondependent Male Opioid Users

“…[2] Abuse of prescription drugs, including opioid analgesics, has increased substantially since the mid-1990s, [3][4][5][6][7][8] creating a need for products that are a less inviting target for abuse. [9][10][11][12][13] Among US Department of Health and Human Services, FDA, Center for Drug Evaluation and Research recommendations is the call for drug manufacturers to ''modify opioid painkillers so that they are more difficult to tamper with and/or combine them with agents that block the effect of the opioid if it is dissolved and injected.'' [14][15][16] Naltrexone hydrochloride is an orally available opioid antagonist that competitively binds to m-opioid receptors and reduces the euphoric effects of m-opioid agonists, such as morphine.…”

Designing a tool allowing for a standardized assessment of resistance to drug diversion

“…The first, drug abuse, can be defined as 'the intentional self-administration of a medication for a nonmedical purpose such as altering one's state of consciousness, e.g., getting high' [2][3][4]. Abusers commonly tamper with drug products prior to administration.…”

“…Some laboratories developed tamper-resistant formulations to try to avoid these problems of drug product diversion, [3,[16][17][18][19][20][21][22][23][24][25][26][27], (offering some type of physical resistance to crushing, chewing, snorting) [28][29][30] or abuse deterrent formulations (formulations that have added excipient to reduce the attractiveness of the product for abusers) [2,[31][32][33]. Nevertheless, tamper-resistant dosage forms do not avoid these problems; and more specifically, they cannot prevent the ingestion of high doses required to obtain some effects.…”

“…The problem for healthcare authorities is now to assess new formulations developed to limit the risk of diversion of administration mode and/or chemical submission so as to determine to what extent these risks are limited [2,3,7,13,16,[18][19][20]22,25,27,[36][37][38][39][40][41][42][43][44][45][46][47]. Recently, the FDA published a draft guidance for industry for the evaluation and labeling of abuse deterrent opioids.…”