The Food and Drug Administration (FDA) held a public meeting on May 27 and 28, 2009, to obtain input on developing Risk Evaluation and Mitigation Strategies (REMS) for certain opioid drugs. The REMS process was recently authorized by Congress in the FDA Amendment Act. The agency accepted written and electronic comments until June 30, 2009. Numerous pain management, medical, and pharmacy organizations submitted comments. The REMS process is intended to ensure that the benefits of these drugs continue to outweigh certain risks. The FDA reports that it has long been concerned about adverse events associated with this class of drug and has taken steps in cooperation with drug manufacturers to address these risks.
The FDA announced the following discussion points for the meeting.
REMS are an FDA-developed strategy to ensure that the benefits of certain opioid medications continue to outweigh the potential serious risks. The proposed REMS requirements include the following:
‐ health care providers have specific training or experience;
‐ pharmacies and practitioners be specially certified;
‐ certain opioids be dispensed to patients only in certain health care settings;
‐ safe utilization be documented using laboratory tests; and
‐ patients prescribed these opioids be enrolled in a national registry.
The FDA held an “Opioid Analgesic and REMS Stakeholder Meeting” on May 4, 2009, with 44 panelists across various facets of health care and regulatory agencies to discuss the role of medical education and REMS.
The FDA is seeking public comments on the following questions:
‐ What are the education requirements of prescribers and clinicians who dispense opioid medications to ensure adequate education on the potential risks?
‐ What are the education requirements of patients, and should prescriber-patient agreements be included?
‐ What additional fundamentals are required to minimize risks associated with the use of approved opioids?
‐ The breadth and depth of the REMS—how extensive should the REMS restrictions be; should distributors and other health care providers be included in the controls; are there existing systems that could be utilized?
‐ What challenges need to be overcome before the FDA can implement a single and shared system for all stakeholders involved?
‐ What metrics should the FDA use to assess the success of REMS?
The FDA announced that it will conduct two further meetings, one for pharmacists and one for patients and patient advocates, as well as the public meeting on May 27–28. Once these meetings are completed, the FDA will finalize their REMS programs for manufacturers to utilize as they research and market their drugs.
David Craig, PharmD, a member of the Journal Editorial Board, the immediate past chair of the American Pain Society (APS) Pharmacotherapy Special Interest Group (SIG), and a member of the APS Board of Directors attended the hearings on behalf of the APS. He is preparing a more detailed report on the REMS process and the meeting for the December issue of the Journal (Volume 23, Number 4). Dr. Craig reports the following impressions from the meeting.
Despite the many views presented by the approximate 75 presenters, the ideal way to conduct and measure the outcomes associated with a FDA-mandated Opioid REMS policy is still unknown.
Approximately a half dozen bereaved parents, including a pharmacist who runs a radio talk show in Tampa FL (see http://www.banoxycontin.com), vocally demanded that the FDA ban OxyContin immediately because of the public health crisis and opioid addiction that it has caused.
The FDA has recently been required to develop a REMS for any drug it deems to have safety issues, but lacks the authority to many of the good suggestions made during the meeting (requiring prescribers to have education tied to their DEA controlled substance registration, reduction of drug availability for nonpatients).
Opioid REMS is unfortunately NOT likely to reduce opioid related deaths within the United States. However, this policy may “squeeze the balloon” and simply shift the demand to illegal substances such as heroin, etc. This is an important “metric” that could be tracked by evaluating either the number of heroin related overdose deaths or the number of patients referred to the Emergency Departments with either proven or suspicion of heroin overdose within the United States.
The opioid REMS is a requirement by Congress which gave the FDA authority to require a REMS (FDAA Act of 2007) fueled by the Public's wishes to do something about the rising use and overdose deaths currently associated with the increased availability and use of prescription opioids.
The FDA is in a precarious situation because of its responsibility to ensure the safety of any person prescribed an approved drug, but lacks the authority nor does it have the available tools to make a successful Opioid REMS; at least any tool that has demonstrated efficacy in this regard.
It is likely that all opioids (long and short acting) may be included within the proposed REMS policy. Many of those who spoke, including the APS and the Pain Care Forum—which includes many other professional pain and pharmacy organizations, have made this clear in their recommendations.
According to what the FDA has said publicly thus far, this policy will likely include an educational requirement for providers, and pharmacists.
The American Pain Society (APS) established two working groups that submitted recommendations to the FDA docket prior to the June 30th deadline to assist them in developing measurable outcomes (Metrics) and recommendations for mandatory prescriber and pharmacist education surrounding prescribing/dispensing of opioids.
The FDA has prepared four free Webinars and PowerPoint presentations to explain the opioids REMS. The agency seeks to hear broad input from all stakeholders, including prescribers of opioid drugs. The first Webinar explains the goals of the initiative and the need to maintain access to the drugs while limiting their misuse and abuse. The second program explains the regulatory history of the drugs, and current misuse and abuse issues. The program concludes with the FDA indicating it will require extended-release oral opioids, methadone for pain management, and transdermal fentanyl to establish REMS. These online presentations are accessible at https://webmeeting.nih.gov/p53364025/; https://webmeeting.nih.gov/p59178873/; https://webmeeting.nih.gov/p51598115/; and https://webmeeting.nih.gov/p57998755/.
The future of opioid regulation clearly will change. Hopefully, sufficient input from concerned professionals, citizens, and professional societies will guide the regulatory process to provide balanced benefits and risks.