New opioid drug approval comes with full-featured REMS program

Published on: 
Pharmaceutical Commerce, Pharmaceutical Commerce - July/August 2009,

Approval marks an innovative buccal drug-delivery mechanism, as well as signaling how FDA might approach REMS for all opioids

The news highlight: FDA has approved Onsolis (fentanyl buccal soluble film), which is manufactured by Aveva Drug Delivery Systems (Miramar, FL) and marketed under license from BioDelivery Sciences International Inc. (Raleigh, NC), by Meda Pharmaceuticals Inc., based in Somerset, NJ. The drug is an innovative thin film containing fentanyl that sticks to the inner cheek of the mouth, dissolving in 15-30 min. It is intended to provide relief from pain flareups for cancer patients who are already using another opioid to manage stable, constant pain.

The background: Onsolis is the most recent product approval of an opioid that came after FDA announced in Feburary that it would require Risk Evaluation and Mitigation Strategies (REMS) for most types of long-acting or extended-release opioid pain products. The agency has held meetings with manufacturers, kept a comment period open until the end of July, and is currently evaluating the information it has received.

FOCUS on transmucosals


The REMS approved for Onsolis is called FOCUS (Full Ongoing Commitment to User Safety), and FDA stated that a similar program will be set up for other transmucosal fentanyls, including Cephalon’s Actiq and Fentora products. Under the FOCUS REMS, a patient registry will be maintained, and a restricted list of approved distributors, pharmacies and physicians will be permitted to supply or prescribe the product. The prescriber will originate a scrip which is faxed to the pharmacy (and then followed with a hardcopy sent “via courier”), and the pharmacy dispenses the product—again, via courier—directly to the patient’s home.

[The all-paper prescribing feature of the REMS is something of a slap against the all-electronic Controlled Substances Ordering System, or CSOS, set up several years ago by DEA, on top of being yet another roadblock, caused by controlled substances, to e-prescribing. But the all-paper process might be interpreted as FDA’s understanding of the serious risk of the transmucosal fentanyls’ availability to the public.]

The REMS also includes a boxed warning in the medication guide, and a registration and training process for physicians, pharmacies and distributors.

FDA was quite explicit that the structure of the Onsolis REMS “is independent of FDA’s effort to develop REMS for extended-release and high potency opioids,” drawing a distinction between the transmucosals and the other opioids. “The REMS for Onsolis was specifically tailored to that drug and should not be viewed as a model REMS for long-acting and extended-release opioid products,” said Douglas Throckmorton, MD, deputy director of CDER. “Developing the comprehensive REMS for these other products is a complex undertaking. We will take the time necessary to review all of the public comments and will proceed in a deliberate manner toward the mutual goals of patient access and patient protection.”

However, the potential (or actuality, in the case of Purdue Pharma’s Oxycontin and other extended-release opioids) of abuse is one of the drivers for establishing REMS for these products. The fact that it is even possible to set up a restricted, but national, distribution program for the drugs, and that FDA can now mandate (as opposed to recommend) a REMS-type program sets the precedents.