FDA Approves Class-Wide Opioid REMS After More Than Three Years

By Alexander J. Varond –

After more than three years, FDA approved a class-wide Risk Evaluation and Mitigation Strategy (“REMS”) for extended-release and long-acting (“ER/LA”) opioid analgesics on July 9, 2012.  The ER/LA opioid REMS applies to more than 20 companies and 30 products, and while it includes a shared implementation program, each opioid product REMS is to be written and approved as an individual document.

In this post, we first briefly discuss the history of the program’s development and then explain the implications of the new class-wide REMS.

A long road for a rather dull REMS.  On February 6, 2009, FDA sent letters of ER/LA opioid analgesics detailing the need for a new REMS.  During a media briefing on February 9, 2009, FDA officials expressed the agency’s ambitious plan to develop a class-wide opioids REMS and further expressed that the program was “going to be the largest risk management effort [FDA had ever] undertaken.”  Rightly so, FDA announced it was taking on an effort aimed at addressing the nation’s growing prescription drug abuse epidemic.  During the media briefing, FDA also intimated that it was actively exploring requiring mandatory training for prescribers and developing a more restrictive distribution system. 

In February 2009, FDA felt it had a “pretty good outline” of what the REMS should include but took steps to consult with stakeholders, health professionals, and patient advocacy groups about the new REMS.  After collecting information from these groups, FDA planned to write letters to manufacturers and explain the requirements for the new REMS.  Within six months of the letters’ issuance, FDA expected companies to implement the REMS.

More than two years later, in April 2011, FDA finally sent letters to manufacturers of ER/LA opioids detailing its requirements for a new REMS program.  We discussed those requirements here.

Now, more than three years after beginning the opioid REM process, the final REMS is completed and amounts to essentially a mere education and monitoring program.  Additionally, despite FDA’s statement in 2009 that “voluntary programs have not been successful in getting us where we need to go with maintaining access to legitimate patients and dramatically decreasing the serious adverse event reports,” the healthcare professional education provided by the REMS is in fact voluntary. 

It is clear that, in 2009, the agency underestimated both (1) the complexity of creating a program that did not adversely affect patients in need of pain management and (2) the difficulty associated in creating a class-wide REMS program with many manufacturers.  FDA also miscalculated its authority to create a mandatory training program (FDA later considered its ability to create a mandatory training system but decided that it would need a grant of legislative power to create such a system).

Moreover, FDA did not anticipate the resistance (here and here) it would receive from healthcare professionals and patient advocacy groups against mandatory training or restrictive distribution systems.  These groups urged the agency not to require a REMS that was overly burdensome or jeopardized patient access to ER/LA opioid analgesics.

FDA’s decision not to impose mandatory education on prescribers or patients highlights the agency’s “step-wise approach” and emphasizes the difficulty it faces in reducing prescription drug abuse while maintaining access to patients with legitimate needs.  Moreover, the approximately 41-month timeframe it took to develop the LA/ER opioid analgesics REMS program reveals the difficulty FDA faces in coordinating class-wide and shared REMS programs of this nature.

FDA’s Blueprint for a house it’s not completely satisfied with.  Under the approved REMS, drug manufacturers are required to pay accredited continuing education ("CE") companies to independently develop and provide voluntary 2-3 hour ER/LA opioid training programs to prescribers in accordance with FDA’s “Blueprint for Prescriber Education for Extended-Release and Long-Acting Opioid Analgesics.”

The training will focus on developing prescriber knowledge about ER/LA opioid analgesic therapy in the following categories: assessing patients for treatment; initiating therapy, modifying dosing, and discontinuing use; managing therapy; counseling patients and caregivers about safe use; general drug information about ER/LA opioid analgesics; and specific drug information.  Additionally, prescribers will be counseled on how to recognize evidence of and potential for opioid misuse, abuse, and addiction.

Manufacturers will also be expected to provide a patient counseling document for prescribers to give to patients, helping prescribers to properly counsel patients on their responsibilities for using ER/LA opioid analgesics safely and an updated one-page Medication Guide that pharmacists will include when dispensing the drug that contains consumer-friendly information on the safe use and disposal of the medicines.

The first CE programs must be offered to prescribers by March 1, 2013.  FDA also expects 25% of the nation’s estimated 320,000 prescribers to be educated by year one, 50% by year two, and 60% within three years.  The REMS includes additional assessment metrics which include the number of grants awarded to CE providers, the number of prescribers trained, patient knowledge of risk information, and the effect on access to patients with legitimate needs for ER/LA opioid analgesics.

During the announcement of the REMS, Margaret Hamburg, Commissioner of FDA, and R. Gil Kerlikowske, Director of National Drug Control Policy, expressed a desire that these efforts to curb prescription drug abuse would be bolstered by future legislation to make opioid analgesic training mandatory.