Yesterday, the FDA announced that it has sent letters to the manufacturers of both generic and brand name opioid based products that they may be required to have a Risk Evaluation Mitigation Strategy (REMS), which the agency now has the authority to require of manufacturers under the auspices of the Food and Drug Amendments Act 0f 2007 (FDAAA). According to the FDA page posted on this issue, the affected opioid drugs are formulated with fentanyl, hydromorphone, methadone, morphine, oxycondone and oxymorphone.
The FDA has set what is the first in a series of three meetings for March 3, in an effort to gain input from all stakeholders and is going to schedule a public meeting later on this Spring to get input from a wider set of stakeholders, turning what has already been a quite lengthy process into an even longer, and forgive me, painful process.
Since REMS became part of the FDA's duties, it seems that the agency and manufacturers have struggled with the concept, particularly as it relates to opioids. In November 2008, the FDA held two advisory meetings where the Anesthetic and Life Support Drugs Advisory Committee met jointly with the Drug Safety and Risk Management Advisory Committee to consider two proposed opioid based products for approval and to consider the REMS that would go along with them. The first was for Remoxy and the second for Embeda, controlled-release and extended release products respectively. The transcripts for these meetings have not yet been posted, despite the considerable length of time since the meetings (November 13 and 14). Pain Therapeutics received a Complete Response Letter and King Pharmaceuticals received notice that the PDUFA date was being extended. (Note, King acquired Alpharma, the developer of Embeda.) It was clear during the two days' worth of meetings, that the committees were less concerned about the abuse potential of Embeda than they were of Remoxy.
But a Complete Response Letter is supposed to suggest a "pathway to approval" – if the FDA is still gathering information on REMS for opioid based products, it raises a question whether any pain killer that is opioid based can gain approval for now.
This is a difficult situation. Extended and controlled release pain products are of great interest to those who suffer from chronic pain, as they might be to those that abuse them. The FDA is employing an abundance of caution to develop a REMS program, for which they might be faulted were it not for the fact that there are many in Congress who are always willing, and even anxious, to use the deliberations of the FDA as a baseball bat whenever handy. Therefore, caution on the part of the agency is warranted. However, the interests of not only the patients and the treaters is at stake, but there is a public policy issue at stake as well in keeping the incentive for manufacturers in this area. Why develop complicated systems of extended pain relief if the product is going to lose valuable patent time while a REMS system is devised. It is important to instill greater momentum into this process. And it is important for manufacturers to go into FDA with some very clear, well thought out and creative REMS programs to begin with, not relying solely on yesterday's RiskMAP thinking.
For some REMS background and how REMS differ from, or incorporate the old RiskMAPs, you may want to listen to a podcast on Eye on FDA posted on January 6 where I interviewed Jane Axelrad, J.D. Associate Director for Policy for the Center for Drug Evaluation and Research (CDER) and Dr. John Jenkins, Director of the Office of New Drugs. Though opioid REMS were not discussed, it provides some insight into the FDA's evolution of thought. It was also in that interview that they stated that they would be open to the use of some new media in support of risk mitigation, particularly YouTube.