FDA Releases Opioid Class-Wide REMS

By William T. Koustas –

On Tuesday, April 19, 2011, after years of debate and several public meetings, FDA released the final Risk Evaluation and Mitigation Strategy ("REMS") it will require for all extended-release opioid medications.  The final REMS was issued as part of the White House’s multi-agency plan to reduce prescription drug abuse.  FDA has been working on a class-wide opioid REMS since at least February 2009, when it invited sponsors of extended-release opioid products to a private meeting.  Seventeen months later, in July 2010, FDA released its draft of a REMS for extended-release opioid products. 

In a letter to sponsors of extended-release opioid products, FDA states that it has “become aware of substantial numbers of postmarketing reports of abuse, misuse, addiction and overdose resulting in fatalities associated with [extended-release] opioid drugs.”  Letter from Bob A. Rappaport, M.D., Post-Approval REMS Notification, April 2011.  FDA considers this “new safety information,” which allows it to require sponsors to implement REMS under section 505-1 of the Federal Food, Drug, and Cosmetic Act. 

The REMS consists of a Medication Guide, elements to assure safe use ("ETASU"), and a timetable for submission of assessments.  The ETASU includes an education program for prescribers and materials that the prescribers can use to educate patients regarding the safe use, storage, and disposal of extended-release opioids.  Part of this program appears to include educating prescribers about the potential use of a “Patient Provider Agreement.”  The education program should be conducted through a continuing medical education provider and include information on opioid prescribing, product specific information, and patient counseling.  Prescribers must also obtain proof that they have successfully completed the education program.  The patient education materials must include, among other things, a Medication Guide and information on how to properly take an opioid, report adverse effects, and store opioids.  The materials released by FDA also mention a  “Patient Treatment Agreement,” although its use by the prescriber appears to be optional.

The timetable for submission of assessments is at least six months, 12 months, and annually after the REMS is approved.  Assessments should include the following:  the number of prescribers having completed the education program; an independent audit of the quality of the education materials used to train prescribers; an evaluation of patient and prescriber awareness of the risks associated with extended-release opioids; a surveillance plan to monitor misuse and abuse of opioids, including surveillance in various risk groups and settings; and evaluations of drug utilization and prescribing behaviors.  The FDA recommends that the sponsors of extended-release opioids cooperate to establish a single system for monitoring these assessments across all extended-release opioid products.

Sponsors must submit a proposed REMS based on the requirements described above within 120 days of the date of the notification letter.  Interestingly, FDA notes that prescriber education is not mandatory under the REMS, but FDA is working with other federal agencies and Congress to make it mandatory by linking prescriber education to training required by the Drug Enforcement Administration.  FDA expects the REMS to become effective by early 2012.