LAKE BUENA VISTA, FLA. – The “Guidance for Industry” issued by the Food and Drug Administration last year has encouraged a systematic approach to the development and testing of opioid abuse-deterrent technologies that can be credited with spurring innovation, according to two pain specialists.
“Clinicians trying to understand these products are going to have to get used to hearing about likability studies and other types of evaluations that measure the efficacy of deterrence,” reported Jeffrey A. Gudin, MD, director of pain and palliative care, Englewood Hospital and Medical Center, New Jersey. He suggested that the outline provided by the FDA has been instrumental in defining standards with which different types of strategies can be compared.
At least eight opioids with abuse-deterrent properties already are on the market. Those include a product with a reservoir of the opioid-antagonist naloxone, which is designed for release in the event of tampering; pills constructed with complex polymers that produce a viscous gel when crushed or dissolved to prevent injection or snorting; and a tablet in which the opioid is accompanied with an aversion product. If the tablet is crushed, the aversion product mixes with the opioid, producing discomfort.
Four types of studies are recommended to evaluate abuse-deterrent strategies in the FDA manual for industry. Those include laboratory manipulation studies, pharmacokinetic studies, clinical abuse-deterrent studies, and postmarketing surveillance. The clinical abuse-deterrent studies are the ones that test likability. According to Dr. Gudin, those studies enroll drug-experienced recreational users who test whether pleasurable effects can be derived from the product despite the mechanism for deterrence.
Fulfilling the criteria for effect abuse deterrence “does not mean that the product is abuse proof,” cautioned Martin E. Hale, MD, an orthopedic surgeon and pain management specialist in private practice in Plantation, Fla. Rather, the goal is to provide a sufficient obstacle that the epidemic of opioid abuse and opioid-related deaths can be turned around. “Creating these types of deterrents may help,” Dr. Hale said.
Typically, addicts are seeking an immediate high, which is a very different goal from control of pain symptoms, according to Dr. Gudin. He reported that preventing the rapid onset of euphoria is one of the abuse-deterrent strategies being pursued. He cited one product in clinical development that requires 5 days before it crosses the blood-brain barrier. Such a product, he said, “would still work for the chronic pain patient, but it is not so good for the individuals who wants to get high.”
Not surprisingly, opioids with abuse deterrence cost more than those without, but the effort to remove this obstacle to encourage wider use is being addressed at the level of state legislatures, Dr. Gudin said. By his count, laws have been proposed in 30 states calling for third-party payers to make opioids with abuse deterrence available at the same cost as products without this technology. Four states have passed this legislation already, and an additional four have made passage contingent on studies demonstrating a change in risk of abuse.
In an informal poll at the meeting, a sizable majority of the attendees agreed that they would prefer to prescribe an opioid formulated with an abuse deterrent, particularly if third-party coverage was assured, but Dr. Gudin, like Dr. Hale, emphasized that no deterrent technology is foolproof.
For preventing inappropriate use of opioids, “abuse deterrence is just another tool in the toolkit,” Dr. Gudin said. He cautioned that all the other strategies aimed at keeping opioids out of the hands of abusers still should be employed. He predicted that most ER/LA opioids soon will have some form of abuse deterrence, and the same types of technologies are likely to offered in immediate-release opioids as well. Requiring third-party payers to provide reimbursement would accelerate the transition.
“Let’s face it, what is the downside if payers say they will work with you,” Dr. Gudin said.
Dr. Gudin reports a financial relationship with Teva, and Dr. Hale reports a financial relationship with Purdue.
The meeting was held by the American Pain Society and Global Academy for Medical Education. Global Academy and this news organization are owned by the same company.