Opioid REMS: Sponsors Share Implementation, But Also Give Up Some Control
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Now that FDA has unveiled what it expects in a Risk Evaluation and Mitigation Strategy for long-acting and extended-release opioids, sponsors will be scrambling to write the REMS for their individual products and put together the shared components and implementation system envisioned by the agency. FDA has a brisk implementation schedule. The firms have 120 days from April 19, the date the REMS were requested, to provide REMS proposals and a common REMS supporting document. The agency expects to approve the REMS by the beginning of 2012 so they can be put into effect (see (Also see "Implementation Timeline For Opioid REMS And National Rx Abuse Plan" - Pink Sheet, 25 Apr, 2011.)). The common effort will be conducted by the Industry Working Group formed by sponsors after FDA announced its intention to impose the REMS and has continued to meet since submitting a REMS proposal in 2010 (Also see "Opioid REMS: Industry Group Would Add Communication Plan To FDA's Proposal" - Pink Sheet, 22 Jul, 2010.). A robust structure of subgroups was created around topics, such as prescribers, patients, operations and technology, and will remain in operation. On the must-do list is coming to an agreement on how to structure an entity that can move forward to put the REMS and shared educational and assessment provisions in place (see related story, (Also see "REMS Assessments For Opioids Will Require Data From Across Health System" - Pink Sheet, 25 Apr, 2011.)). The sponsors will have to design a governance system for the program that can survive the addition or departure of large sponsors. Deciding how to share the costs will not be an easy task for the IWG, which currently has 21 members of varying sizes and LA/ER opioid sales. Four companies are participating in the group in addition to sponsors of the drugs for which FDA is requiring the REMS (see (Also see "A Longer List Of Long-Acting/Extended-Release Opioids Needing A REMS" - Pink Sheet, 25 Apr, 2011.)). These are Apotex, Cephalon, DAVA Pharmaceuticals and Ranbaxy; it seems reasonable to conclude that each has plans to enter the long-acting opioid market. The cost of implementing the REMS will not be negligible as sponsors pay for prescriber training, Medication Guides for physicians, as well as pharmacies, and the infrastructure to assess whether the REMS is having an impact on opioid abuse and misuse. Can 21 Firms Work As One? One of the major challenges confronting the sponsors is getting so many companies to agree, Marc Hoffman, vice president of science and medical affairs at Covance, said in an interview. To implement the REMS, "the first thing they're going to have to do is arrive at a collective understanding" of what FDA wants, he noted. Covance designed and managed the iPLEDGE program that restricts prescriber, patient and pharmacy access to all versions of isotretinoin. Roche has taken Accutane, the brand product, off the market, but generic makers of the drug continue to operate the program. In the April 19 letters to the sponsors asking for a REMS proposal within 120 days, FDA provided an extensive list of information expected to be included in the educational programs to be provided to physicians and patients (see chart, (Also see "A Quick Look At The Long-Acting Opioid REMS" - Pink Sheet, 25 Apr, 2011.)). But those are just headings and there is room for interpretation, Hoffman pointed out. Companies are "going to have to assure that they can agree on the central message." In addition to the core presentation about pain management in general and selecting the right medication for individual patients and discussing how to avoid abuse and misuse, FDA has called for a second component of the educational material to discuss individual products. The educational materials are to be presented in a non-promotional fashion. Sponsors will "have to make sure that in addition to these [materials] being non-promotional – so no claims – that they're also worded in such a way that no one company arrives at a competitive advantage or disadvantage. So I think that that's going to be a significant challenge that they're going to have to hammer out," Hoffman said. "The level of detail, and again trying to make sure that nobody sneaks in promotional information – time of onset, duration of effect, those types of things – where somebody could actually gain some kind of competitive advantage by this being disseminated by all, is still going to be tricky." A Four-hour Call To "Scratch The Surface" Determining the implementation system will be a major task, Hoffman said. "That's probably a four-hour call or conversation, even to scratch the surface as to what the parameters are." It is in the interest of all parties – health care professionals, patients and industry – to have a single system, he said. "You want to avoid duplication of effort at any and all costs." And while the REMS is being implemented to protect public health, FDA does not want a system that limits patient access or dissuades prescribers from prescribing, he continued. "This for the people who really need it, so that's going to be a real problem." Risks With Success Or Failure The burden that firms are feeling in implementing the REMS could be even greater if Congress fails to enact legislation that would require physician education as a prerequisite to registration with the Drug Enforcement Administration (see related story, (Also see "Does Mandatory Opioid Prescriber Education Go Far Enough? Congress Might Say No" - Pink Sheet, 25 Apr, 2011.)). If the DEA registry system can't be used – or even if the system as envisioned fails to curb abuse or overdoses – FDA might require tighter controls than the REMS currently includes. So sponsors would have a keen interest in establishing an education program that is as strong as possible, without creating the undue burdens on the system that FDA has been working hard to avoid. That kind of balancing act is no easy task: Fail to reduce adverse outcomes and FDA will likely make the program more restrictive; succeed, and FDA might look to this kind of system when faced with safety problems from widely used products, regardless of how expensive the measures have been to implement. |