Opioid Abuse-Deterrence Labeling May Be A Long Way Off After Panel Rejects Validity Of Broad Claim

Labeling should be specific, such as a claim for injection-resistance, committee members tell FDA.

A global claim for abuse-deterrence is not possible for opioid drugs, an advisory panel told FDA Oct. 22.

"We need to be talking in highly specific terms. It's injection-resistant. It's snorting-resistant, not it's abuse-resistant," Warren Bickel, Ph.D, M.D., Arkansas Center for Addiction Research, insisted during a joint meeting of FDA's Anesthetic and Life Support Drugs and Drug Safety and Risk Management Advisory Committees.

"Addiction is very malleable," he pointed out. "If you cut off an option, [addicts] will find the next available option that works. That means that as this process of using formulations that make it harder to use, there's going to be dynamic shifts all of the time."

FDA convened the meeting to obtain input on the metrics and surveillance systems needed to support abuse-deterrent claims for opioids ([See Deal]). The panel, however, stressed that labeling should focus on the properties that make each drug resistant to abuse.

The "whole notion of a global abuse-deterrent labeling is false," contended Edward Michna, M.D., Harvard Medical School. "These are tamper-resistant products that may have an impact on the way these things are abused" and that possibility should be the subject of labeling, he said.

FDA already provides that sort of information, noted Division of Anesthesia and Analgesia Products Director Bob Rappaport, who explained that the agency has been using abuse-deterrent because that is a term commonly used in the field.

Although FDA officials occasionally appearing a bit flummoxed by some of the discussion, the agency may appreciate the careful distinctions drawn by committee members about how a product can be labeled, since it often draws such subtle lines itself, often making sure that products carry claims to "reduce the risk of" not "prevent" disease.

Regarding opioid deterrence claims, there is no single way to prevent abuse, John Mendelson, M.D., St. Luke's Hospital, San Francisco, contended. "The problems for each drug are unique and the populations to look at are unique too. You're probably going to have to feel your way inch by inch."

"I would advocate that the sponsors that come forward specify exactly what they mean by resistant, abuse-resistant or deterrent, and prove it. They have to prove that point. That's a high bar but that's their bar to cross."

The Path Forward For FDA And Sponsors

Rappaport suggested to reporters after the meeting that it is not that panel members "don't like abuse-deterrence necessarily. It's that they feel we don't have enough quality data and won't have for some time before we can use that kind of terminology."

The companies most immediately impacted by the advisory committee's recommendations would be King Pharmaceuticals and Purdue Pharma. King's Embeda is an extended release morphine sulfate built around a naltrexone inner core designed to blunt the drug's euphoric effects when it is chewed, crushed or dissolved. An abuse-resistant claim could give a marketing boost to the drug which had $15 million in sales during the second quarter of 2010.

Purdue's reformulated continuous release OxyContin is made to be difficult to break, chew or crush and to form a viscous gel when dissolved. Patients taking the pervious controlled release OxyContin are being transitioned to the new formulation, providing Purdue with a large market share. The company informed the panel that it currently is not seeking an abuse-deterrent claim, but noted it could change that position if data support such a claim.

Both companies discussed early plans for post-market studies to collect information about their drugs' impact on abuse and these were well-received by the committee.

-Cathy Dombrowski ([email protected])