FDA’s Dec. 12 approval of Endo International PLC’s new formulation of Opana ER (oxymorphone), which is designed to resist crushing, includes no claim for crush-resistance or abuse-resistance, according to the agency.

That follows the path of other opioids that are formulated to deter abuse but have failed to achieve the claim in labeling. These include Purdue Pharma LP’s revised OxyContin, which contains an excipient to make extraction of the active ingredient more difficult, and Pfizer Inc.’s Oxecta and Embeda, which contain ingredients that make their use unpleasant.

Unlike OxyContin, labeling for the Oxecta and Embeda includes information from studies about their lower likeability. However, the labeling also includes language to limit conclusions that can be drawn from the studies. In the case of Embeda, the labeling notes there is no evidence this “reduces the abuse liability of Embeda.” The Oxecta labeling says there is no clinical significance to the crossover study that found lower likeability for Oxecta compared to immediate-release oxycodone Also see "Pfizer Will Study Oxecta Abuse/Misuse Potential Post-Market" - Pink Sheet, 20 June, 2011..

Approval documents for the new Opana ER were not available as of press time, so full details remain unknown, but the agency said “the labeling for NDA 201655 (OPANA ER) contains no language about crush resistance or abuse deterrence.” There is no requirement or commitment for a post-market study of Opana ER’s impact on abuse, FDA says.

For Oxycontin, Purdue plans to conduct eight studies to demonstrate its drug’s abuse-deterrence Also see "Opioid Abuse Deterrence: Purdue Expects Quick Results On OxyContin, But Cmte. Wonders About Duration Of Effect" - Pink Sheet, 21 October, 2010.. But if the company seeks a broad abuse-resistance claim, they may not be enough. A 2010 advisory committee suggested to FDA that sponsors’ focus should be on limited mechanistic claims, such as crush-resistance or injection resistance Also see "Tamper-Resistance Could Allow New Opioid Formulations To Differentiate Themselves" - Pink Sheet, 1 November, 2010..

To assist in the effort to curtail abuse, an Obama Administration prescription drug abuse plan includes efforts to conduct additional research into abuse-deterrence and non-addictive pain medication formulations Also see "Opioid Sponsors To Get Help Developing Abuse-Resistant Products From FDA, NIH" - Pink Sheet, 2 May, 2011..

Abuse And Generic Aversion In One

Endo reported the U.S. Patent and Trademark Office will issue Patent No. 8,075,872 for the new formulation Dec. 13. The patent will be listed in FDA’s Orange Book and the company expects to have protection for the new formulation until November 2023.

The latest version of Opana ER employs Grunenthal GMBH’s proprietary INTAC technology. That process uses specific excipients and a unique manufacturing process to produce tablets that have crush-resistant properties but retain desired release characteristics. The new formulation was demonstrated to be bioequivalent to the currently marketed Opana ER, facilitating a switch to the new formulation.

The INTAC process produces tablets that are much harder than conventional tablets, Grunenethal says. Attempts to crush the tablet typically leads to deformation and hinders formation of a fine powder, without negatively influencing the extended release properties, the firm says.

No Abuse-Resistance Claim For Endo’s Opana ER Reformulation

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