FDA Announces First Class-Wide REMS for Opioids

By Bill T. Koustas –

On February 9, 2009, FDA (or “the Agency”) announced it has invited the sponsors of opioid drug products to a private meeting in March in order to begin the process of developing Risk Evaluation and Mitigation Strategies (“REMS”) that will impact 24 opioid products from 16 different sponsors.  This will be the first class-wide REMS program instituted by FDA.  While sponsors of investigational opioids are not immediately affected, the meeting outcome and eventual REMS will undoubtedly affect their products as well.      

According to FDA, the risks that the REMS is intended to mitigate are: (1) the use of certain opioid products in patients who are not opioid tolerant; (2) abuse; and (3) accidental and intentional overdose.  The Food and Drug Administration Amendments Act of 2007 (“FDAAA”) gives FDA the authority to require REMS for approved products when it becomes aware of new safety information and determines that a REMS is necessary to “ensure the benefits of the drug outweigh the risks of the drug,” but has no express provisions authorizing class-wide REMS. FDC Act § 355-1(2).  The Agency, however, has broad discretion in determining what constitutes “new safety information” and would likely defeat a challenge that it failed to make the requisite finding for each individual drug.  While FDA’s public statement regarding this issue notes that the Agency “recognizes the need to achieve balance between appropriate access and risk mitigation,” it is unclear what REMS elements will be required for this class of products.  In a call with the media, Dr. John Jenkins, Director of the Office of New Drugs, indicated that the REMS may include added labeling and patient monitoring among other elements to assure safe use.

According to FDA’s announcement, the opioid drugs affected by this announcement include both brand name and generic products that contain fentanyl, hydromorphone, methadone, morphine, oxycodone and oxymorphone.  The meeting described in the letter signed by Dr. Bob Rappaport, Director of the Division of Anesthesia, Analgesia and Rheumatology Products, is scheduled to take place on March 3, 2009 at 3:30pm on FDA’s White Oak campus.  Implicitly acknowledging that developing class-wide REMS for these drug products is complicated and potentially controversial, the Agency noted in the announcement that it is also planning to hold several meetings with other federal agencies, non-government organizations, patient and consumer advocates, pain and addiction treatment advocates and other health care professionals and stakeholders.  Additionally, the Agency is planning a public meeting on this issue in late spring or early summer to permit more public participation.  FDA expects to inform the sponsors of the affected opioid products regarding the required REMS after the public meeting. 

FDA will likely consult with the Drug Enforcement Administration ("DEA") on the class-wide REMS.  The Controlled Substances Act and DEA regulations require that manufacturers and registrants of controlled substances maintain effective controls against diversion and compliance with REMS could arguably be viewed as a part of this duty.  Manufacturers will need to consider that DEA will evaluate compliance with REMS as a factor in determining ongoing compliance with DEA requirements.