Inappropriate use of prescription opioids is a major public health challenge, prompting the U.S. Food and Drug Administration (FDA) to issue a draft guidance document aimed at helping industry create new formulations of opioids with abuse-deterrent properties.
Released in January, “Guidance for Industry: Abuse-Deterrent Opioids—Evaluation and Labeling” provides recommendations for conducting studies to prove that a particular formulation contains abuse-deterrent properties. It also explains how the FDA will review the results and determine which labeling claims to approve.
This announcement is “one component of our larger effort to prevent prescription drug abuse and misuse, while ensuring that patients in pain continue to have access to these important medicines,” Douglas Throckmorton, MD, deputy director for regulatory programs in the FDA’s Center for Drug Evaluation and Research, said during a teleconference.
According to the FDA guidance, opioid analgesics can be abused in a variety of ways:
- Swallowed whole;
- Crushed and swallowed;
- Crushed and snorted;
- Crushed and smoked; or
- Crushed, dissolved, and injected.
With the science of abuse deterrence being relatively new, the FDA plans to take a flexible and adaptive approach. That’s because the analytical, clinical, and statistical methods for evaluating formulation technologies are still evolving.
“Physicians should care about this because the government is regulating prescribing practices more directly than in the past, especially with pain drugs,” says Daniel Carpenter, PhD, a Harvard University government professor and author on FDA pharmaceutical regulation. “The FDA and federal agencies are going to be leaning more heavily upon physicians.”
To date, the majority of current abuse-deterrent technologies have not been effective in preventing the most widespread type of abuse—ingesting a number of pills or tablets to reach a state of euphoria.
—Daniel Carpenter, PhD, Harvard University government professor and author on FDA pharmaceutical regulation
Science points toward ways that formulations can help thwart abuse. For instance, adding an opioid antagonist can hinder, limit, or defeat euphoria. An antagonist can be sequestered and released only upon the product’s manipulation. In one such scenario, the substance acting as an antagonist could be clinically inactive when swallowed, but then would become active if the product is crushed and injected or snorted.
“The guidance describes advice for the development of abuse-deterrent opioids and does not describe practice guidelines,” says Christopher Kelly, an FDA spokesman. However, he adds, “[FDA] urges all prescribers of extended-release and long-acting opioids to participate in the training under the Risk Evaluation and Mitigation Strategy (REMS).” The first REMS-compliant training is expected to become available by March 1.
Such a strategy is intended to manage known or potential serious risks associated with a drug product. The FDA requires it to ensure that the benefits of a drug outweigh its risks.
Manufacturers of opioid analgesics have worked with the FDA to produce materials for the REMS program that would inform healthcare professionals about safe prescribing. Continuing-education providers also are designing accredited training. (For more information, listen to this NIH podcast about training to help providers prescribe painkillers properly.)
Prescribers are advised to complete a REMS-compliant program through an accredited continuing-education provider for their discipline. They should discuss the safe use, serious risks, storage, and disposal of opioids with patients and caregivers each time they prescribe these medicines. It’s also essential to stress the importance of reading the medication guide they will receive from the pharmacist at drug-dispensing time.
Whether the FDA’s industry guidance for the development of abuse-deterrent opioids will make a difference remains to be seen, according to Carpenter. The addictive potential of opioids has created “a kind of public health epidemic,” he says. “It’s not an infectious epidemic in the sense of the flu, but it’s socially and behaviorally infectious and very destructive.”