FDA laid out general guidelines for a class-wide Risk Evaluation and Mitigation Strategy for opioid pain products during a closed-door meeting March 3, and urged manufacturers to work collaboratively to help develop a proposal as soon as possible.

The agency invited 16 manufacturers of marketed extended-release opioids to meet with high-level agency officials at FDA's campus in Silver Spring, Md. to discuss plans for the class-wide REMS (¹ Also see "Record-Setting REMS: FDA’s Classwide Opioid Program Will Be “Massive”" - Pink Sheet, 16 February, 2009., p. 4).

Among the ² manufacturers invited to the meeting were King Pharmaceuticals, which markets Avinza (morphine); Purdue ( OxyContin /oxycodone and MS Contin /morphine); Endo ( Opana /oxymorphone); and Ortho McNeil/Janssen ( Duragesic /fentanyl). All invited companies sent at least one representative.

FDA officials struck a collaborative tone at the meeting, participants said, urging cooperation both between the agency and drug sponsors, and between companies in developing a class-wide REMS.

The two-hour meeting was chaired by Office of New Drugs Director John Jenkins. FDA spent 30 minutes on presentations from Division of Analgesics, Anesthetics, and Rheumatology Products Director Bob Rappaport, Deputy Director Sharon Hertz and Office of Regulatory Policy Director Jane Axelrad. A large number of FDA staff were also in attendance.

Hertz presented possible elements for the REMS, including a Medication Guide, elements to assure safe use and an implementation system. After the conclusion of the presentations, FDA then took 90 minutes for a question-and-answer session.

Next Steps And A Possible Timeline

FDA will now evaluate industry's comments to determine next steps. Officials did not specify a timeline for completing the REMS, except to say that the agency hoped to have a plan in place as soon as possible.

But given the number of steps involved, it will be many months before a final plan can be hammered out - and likely may not be completed before the end of 2009.

The manufacturers' meeting was the first in a series of closed-door sessions with various stakeholders. FDA will later meet with other federal agencies, patient and consumer advocates, representatives of the pain and addiction treatment communities, and health care professionals.

FDA is also planning a public meeting in late spring or early summer; no specific date has been set. An advisory committee meeting may also be necessary, the agency said.

Challenges In Creating A Class REMS

One challenge will be creating a single REMS that can cover a range of opioids with different abuse attributes. Some manufacturers argue that opioids on the lower end of the pain management continuum (like methadone) may have the same potential for abuse as those on the upper end (like oxycodone).

Manufacturers are also making the case to FDA that their existing risk management plans may be sufficient to prevent abuse, and that additional steps could bar access to legitimate pain patients.

But FDA is convinced a more extensive effort will reduce the potential for opioid abuse. Despite past risk management efforts, the agency says, "the rates of misuse and abuse, and of accidental overdose of opioids, have risen over the past decade."

A single REMS will help reduce the burden on an already-overtaxed health care system, and FDA has pointed to the Accutane (isotretinoin) iPLEDGE system as an example of how companies can work together (³ Also see "The Downside Of REMS: An Over-Taxed Health Care System – FDA’s Jenkins" - Pink Sheet, 16 February, 2009., p. 3).

The regulatory and commercial significance of a class REMS for opioids cannot be understated. While FDA has required risk management plans for other classes, the size of the opioid market - 21 million prescriptions per year - will put that REMS at orders of magnitude greater than current plans.

It is also the first time that FDA has talked about a class-wide REMS that has elements to assure safe use. Fluoroquinolone antibiotics have a class Medication Guide, putting them at the lower end of the REMS spectrum. FDA is also working on class REMS for erythropoietin, anti-epileptics and antidepressants.

- Kate Rawson (k.rawson@elsevier.com)

FDA Kicks Off Opioid Class REMS Discussion; Asks For Industry Collaboration

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