Saturday, October 24, 2009

FDA Delays Opioid REMS; Will Industry Snooze?

After much angst and turmoil, the U.S. Food and Drug Administration (FDA) is delaying for a year their mandate to the pharmaceutical industry to develop Risk Evaluation and Mitigation Strategies (REMS) for certain opioid analgesics. A question now is, having received a wake-up call that the FDA means business when it comes to safeguarding these products, will industry take constructive action on their own or merely press the snooze button for the coming year?

By way of background, last May the FDA convened a public meeting to gather input on developing REMS programs specifically for extended-release and long-acting opioid analgesic formulations, followed by a public comment period ending June 30, 2009. REMS would be intended to ensure that the benefits of these drugs continue to outweigh risks associated with: (1) their improper use in non-opioid-tolerant and inappropriately selected individuals; (2) abuse, (3) misuse, and (4) overdose. REMS would likely include elements to ensure that prescribers, dispensers, and patients are aware of and understand the risks and proper use of these products.

Now, the FDA has effectively delayed their final decisions regarding REMS by reopening and extending the comment period to October 19, 2010 “in light of continued public interest in this topic and to provide an opportunity for all interested parties to provide information and share views on the matter.” The actual reasons behind this extension — a reprieve of sorts — are not publicly known. The FDA had already received at least 1,255 comments from individuals and various stakeholder groups; mostly expressing concerns about placing severe restrictions on these vital analgesics, but many were constructive and wishing to comply with FDA directives in a rational manner. Perhaps, the FDA realized that they did not have adequate and accurate data to fully assess the situation or that there could be seriously negative unintended consequences of their mandates regarding opioid-REMS, but this is speculation.

Meanwhile, last July a new buccal-soluble fentanyl product (Onsolis®) to treat breakthrough cancer pain was approved with a REMS program that is so egregiously restrictive [see blogpost of 7/17/09] that, according to feedback we have received, it is questionable whether it will be prescribed. And, a recommended REMS program to accompany Exalgo® (a new extended-release hydromorphone product awaiting final approval) is only slightly less restrictive [see blogpost 9/26/09]. Both of these programs seem to belie the FDA stipulation and promise that appropriate REMS will “adequately manage the risks of these products without unduly burdening the health care system or reducing patient access to these medications.” Yet, last August, King Pharmaceuticals’ EMBEDA™ product (a tamper-resistant extended-release morphine sulfate and naltrexone hydrochloride combination product) was FDA-approved with a reasonable “interim REMS” consisting of a medication guide and special communications sent to prescribers [see blogpost 8/14/09]. So, what may happen during the coming year in terms of the fates of the existing opioid REMS, new opioid product approvals by the FDA, and the shape of “interim REMS” to come is anyone’s guess right now.

The added year could be a boon to the pharmaceutical industry if they use the time to seriously address issues surrounding opioid safety on their own, essentially making pressure coming from the FDA superfluous. Industry now has an idea of what an opioid-REMS program could consist of, albeit the two current examples are far from desirable from all perspectives. Various pharmaceutical firms and stakeholder organizations have already formed working groups to address the opioid-REMS mandate and, hopefully, they can come up with practical approaches that truly will manage risks while also preserving patient access to opioid analgesics. We encourage them to continue their work in earnest and arrive at concrete and rational plans during the coming months.

Interested persons have until October 19, 2010 to submit comments to the FDA:
Title: “Risk Evaluation and Mitigation Strategies for Certain Opioid Drugs; Notice of Public Meeting; Reopening of Comment Period.” Docket ID#: FDA-2009-N-0143.
> Submit written comments to: Division of Dockets Management (HFA-305); Food and Drug Administration; 5630 Fishers Lane, rm. 1061; Rockville, MD 20852.
> Submit electronic comments by going to and clicking on the “Submit Comment” tab.
> For further information call 301-796-3448; or e-mail: