The concept in developing an abuse-deterrent formulation (ADF) is similar to that of developing any new opioid. General goals include producing a drug that is safe and effective for the intended population, one that does not easily cause serious harm to the potential abuser, and a medication that is economically feasible.10
The only additional component added to the development of an ADF is that it must also deter abuse by potential abusers.
Research aimed at finding reliable data on the most commonly abused drugs and their preferred routes of administration by abusers can be very helpful in determining which drugs need an ADF and which characteristics the new drug will most likely exhibit. The National Addictions Vigilance Intervention and Prevention Program (NAVIPPRO) database was created to track drugs of abuse, their current popularity, and their preferred method of use by abusers.11
The NAVIPPRO database further breaks down each drug of abuse into percentages showing the drug’s use within the previous months and the routes by which it is most often abused. A thorough examination of this database would help the pharmaceutical industry to focus on the drugs of abuse that cause the most concern and to identify routes of delivery that new formulations should specifically strive to deter. For example, after a review of the database, it would be simple to conclude that investing large amounts of time and money into developing a new formulation of hydrocodone that deters injection would be a waste of resources, because only 1% of hydrocodone users inject the drug.11
After an innovation for an ADF is under development, the next step is to show that the drug is safe and effective for the treatment of pain and that it deters abuse. The current “gold standard” in clinical trials is to compare the abuse liability of a new opioid or opioid formulation with that of an opioid of known abuse liability in volunteers who have a history of previous drug abuse.10
If the trial shows a low abuse liability within this population, the abuse liability in the general population can also be expected to be low.
Clinical trials can lead manufacturers to make FDA-approved implicit or explicit claims, which can be included in the product’s labeling. Implicit claims may indicate that the new formulation might
have some impact on abuse but has not yet been proven.10
Explicit claims may be made when clinical trials establish that the new formulation has been shown to deter abuse.10
These claims and any materials promoting the new formulation, although they are closely monitored by the FDA, are among the few incentives that drug companies receive for investing their time and money in products that some would consider unnecessary or that would serve only to protect the public from itself.
One method of creating an ADF is to add a pharmaceutical or a chemical component to the opioid. An example is the addition of naloxone to decrease the user’s response to an abused substance or to provide an adverse reaction when the user alters the formulation. This type of modification is made in an attempt to decrease the abuse quotient of the particular opioid formulation. Another method is to deter the user’s ability to physically alter the drug’s original manufactured form to extract the active ingredient through various methods, such as crushing, chewing, or mixing with a solvent, such as alcohol.8
This article discusses available opioids that include abuse-deterrent mechanisms as well as such agents currently in development.