Revised labeling for Purdue Pharma LP’s reformulated OxyContin (oxycodone HCl controlled-release) approved by FDA on April 16 allows the company to market the drug with a claim for reduced abuse by injection and snorting and eliminates the possibility of generic competition based on the original formula.

“In vitro data demonstrate that OxyContin has physicochemical properties expected to make abuse via injection difficult,” labeling says, while data from both the in vitro and clinical studies “indicate that OxyContin has physicochemical properties that are expected to reduce abuse via the intranasal route.”

FDA issued the first abuse-deterrent claim for an opioid based on what available data say about the new formulation compared to the old formulation, CDER Deputy Director for Regulatory Programs Douglas Throckmorton told reporters.

“We believe that in aggregate, those data predict a significant impact to reduce abuse by the intranasal and injection routes of abuse, and we think that that’s valuable and something that was worth including in labeling. Going forward, we’re going to be applying a similar standard to new data for other products as they become available to us for review,” he said.

As the science evolves and the agency better understands how products can be developed and assessed for abuse reduction, he noted, the agency would like to establish “a bright light standard” for reviewing abuse deterrence. In the meantime, it is a matter of looking at the data, the value presented and a drug’s predicted impact in the real world, he said.

Epidemiologic Studies Not Yet On Label

Revised labeling includes a description and results of in vitro and clinical studies that support the reformulation’s abuse deterrence. In vitro tests showed that “relative to original OxyContin, there is an increase in the ability of OxyContin to resist crushing, breaking, and dissolution using a variety of tools and solvents” and this finding also is true “relative to an immediate-release oxycodone,” labeling notes.

The studies also found that when placed in an aqueous environment, the reformulation also “gradually forms a viscous hydrogel (i.e., a gelatinous mass) that resists passage through a needle.”

A randomized, double-blind, placebo-controlled five-period crossover pharmacodynamic study with 30 recreational opioid abusers who had a history of intranasal drug abuse found less liking for reformulated OxyContin.

Participants gave nasally administered finely crushed reformulated OxyContin a numerically lower mean and median drug liking score than nasally administered finely crushed original OxyContin or powdered oxycodone HCL. On the question of whether they would take the drug again, finely crushed reformulated OxyContin had a lower mean and median score than the other two drugs.

Of patients who received both finely crushed reformulated OxyContin and finely crushed original OxyContin, 12 had no reduction in liking for the reformulation versus the original; 16 had some reduction in likely; 10 had a reduction in liking of at least 30% and eight had at least a 50% reduction in liking. Relative to powdered oxycodone HCl, 12 had no reduction in liking for the reformulation, 15 had some reduction in liking, nine had at least a 30% reduction in liking and six had reduced liking of at least 50%.

Reviewers also looked at data from epidemiologic studies. Although “the quality of [those] data were not adequate to support inclusion in the labeling, we did feel that there was a general trend that was supportive of the other findings in that this product is now likely to be deterrent of abuse by the intravenous and nasal routes,” Bob Rappaport, director of the Division of Anesthesia, Analgesia and Addiction Products told reporters.

Purdue continues to provide the agency with data from a variety of on-going epidemiologic studies Also see "Opioid Abuse-Deterrent Labeling Claim Decision By FDA Could Come Soon" - Pink Sheet, 15 April, 2013..

Opana Generics Still A Question Mark

In the wake of its approval of an abuse-deterrent claim for reformulated OxyContin, FDA will remove original OxyContin from the Orange Book and will not approve ANDAs based on the original version.

FDA is taking that action based on a determination that Purdue removed original OxyContin from the market due to reasons of safety or effectiveness. That decision denies several citizen petitions that asked the agency to declare the withdrawal was for other reasons Also see "FDA’s Opioid To-Do List Could Redefine Pain Market For Brands, Generics" - Pink Sheet, 18 February, 2013..

The initial formulation “poses an increased potential for abuse by certain routes of administration, when compared to reformulated OxyContin,” FDA explains in a Federal Register notice scheduled for publication April 18. “Based on the totality of the data and information available to the agency at this time, FDA concludes that the benefits of original OxyContin no longer outweigh its risks,” the agency says.

FDA’s decision on OxyContin indicates generic manufacturers will have to keep up with their reference products in terms of abuse-deterrence, something left unclear in January guidance ([A#14130109004]). In the case of OxyContin, generics could be delayed until 2025 if patents on the reformulation hold up.

The decision also offers hope to Endo Pharmaceuticals Inc. that it can put off competition to Opana (oxymorphone HCl) if it can gain an abuse-deterrent claim for its reformulated version ([A#14121203008]).

Purdue noted after the relabeling approval that it is working to add abuse-deterrent technologies to morphine, other formulations of oxycodone, and a once-daily hydrocodone bitartrate.

OxyContin Revised Labeling Expects Less Abuse Via Injection, Snorting

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