Segment 4: Technological Approaches to Abuse Deterrence

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Industry is helping to address the opioid abuse problem through innovation, including the development of abuse-deterrent formulations. There are various types of misuse, including taking more medication than prescribed, taking medication that was not prescribed for you, and manipulating medication for the purposes of snorting or injecting. The most common method of abuse is oral administration of intact tablets. As this is the usual route of administration for patients, developing a formulation of a drug that both works when taken by its usual route of administration and that is abused by that same route is very challenging.

There are a number of technological approaches to abuse-deterrent formulations. One involves adding a physical and/or chemical barrier to a formulation to resist manipulation and extraction. Another approach is the use of an agonist/antagonist combination— either adding a bioavailable antagonist to an opioid or adding a sequestered antagonist to an opioid. The method of delivery can also offer resistance to abuse, and unique delivery systems, such as a subcutaneous implant, are being developed. Also being investigated is administering an opioid analgesic as a prodrug, which remains inactive unless taken by mouth and activated via the pH or enzymes in the gastrointestinal system. If the medication is snorted or injected, it would stay as a prodrug and not bind to opioid receptors. New molecular entities are also in development; for example, an opioid receptor agonist that crosses the blood-brain barrier very slowly, which is suitable for purposes of analgesia, but not desirable for abusers. Drug developers may choose to use various combinations of these approaches, as well.

The FDA evaluates the effectiveness of abuse-deterrent formulations via 4 categories of testing. Category 1 is bench testing and is applied to drugs with physical-chemical barriers. For products with physical barriers, this type of testing involves grinding or applying physical force to the product. For products with chemical barriers, category 1 testing involves using a range of solvents at different temperatures. Category 2 involves pharmacokinetic studies in naltrexone-blocked volunteers. Category 3 studies are clinical abuse—potential studies. In these randomized, double-blind studies, drug-liking, nonphysically-dependent volunteers are asked to what degree they liked the administered substance, which could be pure active ingredient, manipulated product, a comparator product, or lactose. Category 4 studies are postmarket analyses evaluating the impact of the product on abuse.

In closing, Jeffrey Dunn, PharmD, MBA emphasized the importance of publishing outcomes data as advances are made, to allow informed decision making. Peggy Johnson adds that the key is having all stakeholders work together to tackle this important public health issue. Quality and value are important in today’s healthcare environment, remarks Burton VanderLaan, MD, FACP. There is a quality gap in this area, one that should be addressed by collaboration among all stakeholders.