GAITHERSBURG, MD 26 June 2009—FDA officials recently acknowledged the enormity of a task that the agency set for itself in February—creating a risk evaluation and mitigation strategy, or REMS, to ensure the safe use of long-acting and extended-release opioid drugs.
"It`s a major undertaking, and it`ll take time," said John Jenkins, director of FDA`s Office of New Drugs, after a public meeting held May 27–28 in Gaithersburg, Maryland, to discuss the development of the REMS.
FDA in February informed manufacturers of 24 products containing fentanyl, hydromorphone, methadone, morphine, oxycodone, or oxymorphone that the development of a REMS is necessary to reduce misuse, abuse, and accidental overdosage associated with the products.
The agency asked the manufacturers to develop a single REMS for the drug class instead of separate programs for each product, and an industry working group has been created to design the program.
Jenkins said the agency is likely to continue meeting with stakeholders affected by the REMS and convene an advisory committee meeting before finalizing the program. He said the agency will also explore whether there are short-term solutions that could be implemented before the REMS is launched.
The REMS process and programs` potential components are described in Public Law 110-85, also known as the Food and Drug Administration Amendments Act of 2007.
The law states that a REMS may include documents such as a medication guide or patient package insert as well as more complex components, like a patient registry or specialized training or certification program for prescribers and pharmacists.
According to the statute, a REMS should not have "unduly burdensome" effects on patient access to medication and should minimize, as much as practicable, the burden on the health care delivery system. But the statute contains no definition of what would constitute an undue burden.
Purdue Pharma Chief Medical Officer Craig Landau, speaking on behalf of the industry working group, said during the May meeting that the opioid REMS "must not interfere with the ability of prescribers and other health care professionals to effectively treat patients suffering with pain."
He said the working group supports a REMS that includes brief, easily understood medication guides to provide patients product-specific information. The working group has also discussed the development of a simplified patient "fact sheet" and tear-off wallet card containing important information about each medication.
Landau said the working group backs the need for education and training for pharmacists and prescribers of opioid drugs. But the group believes strongly that educational content should be provided by professional societies, not the drug industry.
He said the working group has "considered the concept of prescriber certification" but wants to hear the views of prescribers before pursuing this option.
Landau cautioned FDA that the REMS will be of "unprecedented magnitude" compared with other risk-management programs.
Citing data from IMS Health, Landau said that about 20,000 prescribers wrote just over 1 million prescriptions in 2008 for isotretinoin, the highest-use drug currently prescribed and dispensed under an FDA-mandated risk-management program.
During that time, 375,000 physicians wrote nearly 26 million prescriptions for long-acting or extended-release opioids in 2008, Landau said.
Nathan Thompson, director of outpatient pharmacy for the Baltimore-based Johns Hopkins Home Care Group, presented ASHP`s views about the opioid REMS during the first day of the meeting.
In his prepared statement, Thompson urged FDA to exempt inpatient hospital settings from the opioid REMS, because systems already exist in these facilities to lessen the risks associated with the medications.
Thompson also stated that a certification program for physicians and pharmacists who work in hospitals would not have much effect, because these professionals already understand the risks and adverse events associated with opioid drugs.
He stated that the REMS should not include a patient registry or require pharmacists to "police" the risk-mitigation system by verifying, before dispensing an opioid drug, that physicians are certified to prescribe these medications.
Thompson also expressed ASHP`s opposition to devising a REMS that ties prescribers` certification status to their Drug Enforcement Administration (DEA) registration number, a system FDA officials said the agency is considering. Thompson explained that hospital-based physicians are not required to register with DEA.
Ardis Hoven, trustee for the American Medical Association (AMA), told FDA that REMS elements such as mandatory education and certification "must only be used as a last resort" after less-intrusive tools are tried.
Hoven told FDA that requiring certification for opioid prescribers may have unintended consequences, including "physicians opting out of prescribing Schedule II controlled substances, with fewer primary care physicians willing to manage patients with chronic pain."
AMA also opposes mandating within the REMS the use of patient–physician agreements, specific monitoring schedules, and urine tests—practices that Hoven said are already in place in some settings where opioids are used.
AMA was one of several groups that urged FDA to make its decisions on REMS elements on the basis of scientific evidence that the plan will reduce the inappropriate use of opioids without impeding patients` access to the medications.
Jenkins conceded that the ultimate goal of the REMS—no serious adverse events in patients or nonpatients who take opioid drugs—is probably not achievable. But he said FDA remains committed to creating a REMS that "will work and will be workable."
Some meeting attendees were skeptical that a REMS for opioid drugs will function as FDA intends.
B. Eliot Cole, executive director of the American Society of Pain Educators, said that tightening the procedures for prescribing drugs could result in fewer prescriptions being written but no decrease in abuse or misuse.
Cole also reminded FDA that its March 30 decision to ban from the market unapproved versions of morphine sulfate had denied hospice patients access to the concentrated liquid formulations that are critical to end-of-life care [see June 1, 2009, AJHP News].
FDA altered its course on the concentrated oral solutions within days, and Cole said the incident should be a warning to the agency.
"Will we have to create a REMS in three years to undo this REMS? That`s what frightens me," he said.
