FDA Standardizing REMS Re-Enrollment Procedures

Common registration site for participants in REMS was endorsed by several panel members during a joint meeting of the Drug Safety and Risk Management and Dermatologic and Ophthalmic Drugs Advisory Committees.

FDA is developing a standardized policy on how frequently participants in Risk Evaluation and Mitigation Strategy programs should re-enroll and recertify in order to keep their participation current.

The policy is part of FDA efforts to standardize REMS programs in response to stakeholder complaints about the burden on the health care community that results from varying requirements among REMS (Also see "REMS Reform Looks To Be Theme Of PDUFA V: Stakeholders Call For Standardization, Earlier Notice" - Pink Sheet, 19 Apr, 2010.).

FDA risk management analyst Reema Jain mentioned the policy during a Dec. 1 meeting of the Drug Safety and Risk Management and Dermatologic and Ophthalmic Drugs Advisory Committees, convened to discuss the impact of REMS with elements to assure safe use on patient access, the health care delivery system and safe drug use.

She said such a policy would make managing re-enrollment and recertification easier, but gave no details about what the policy might entail.

Class-wide Hopes

Another path to standardization is shared REMS implementation systems for drugs in a therapeutic class with a class risk, Jain pointed out, and FDA is looking to the single systems created for brand products with generic versions as the guide.

An example of a shared system is the iPLEDGE program put into place by Roche and generic manufacturers of acne medication isotretinoin, a potent teratogen and another discussion topic at the meeting (Also see "REMS Refinement: Does iPLEDGE’s Evolution Have Lessons For Opioids?" - Pink Sheet, 29 Nov, 2011.). Panel members overall were impressed with that program, but made several suggestions to decrease the burden on patients.

FDA cannot require manufacturers to share a REMS system. But sponsors of long-acting/extended-release opioids have accepted that road to implementing their products’ REMS, which FDA expects to approve by the beginning of 2012 (Also see "Opioid REMS: Sponsors Share Implementation, But Also Give Up Some Control" - Pink Sheet, 25 Apr, 2011.).

FDA also suggested that approach for immediate-release transmucosal fentanyl products and provided sponsors with templates for a patient-prescriber agreement and an enrollment form, as well as the REMS document (Also see "FDA Standardizes REMS Documents For Certain Fentanyl Products" - Pink Sheet, 7 Jan, 2011.).

Standardization, Or A Dozen Models?

Panel members supported making it easier for stakeholders to meet REMS requirements, but several noted the difficulties of standardization.

Enrollment in REMS should be a one-stop process, Mary Maloney, University of Massachusetts, Worcester, suggested. There should be a single system for physicians to register for all REMS, she said. “We need to have a general registration that then will allow me to specify which of the programs I want to participate in.”

Elaine Moratto, University of Colorado, Denver, supported Maloney’s suggestion. But, she pointed out, it raises the question of “who is accountable, who owns, who’s going to fund this cross-fertilization of ideas across therapeutic categories?”

The ideal would be a national system “that kind of helps to whip this together,” she noted. But since sponsors are focused on their own drug and negotiating their own REMS, this way of operating is not conducive to dong big, informative work to design a single system.

An inherent problem in developing a system across therapies is “each company is incentivized on their own product, not to come up with a national solution for everyone.”

Chairman Lewis Nelson, New York University, cautioned against expecting standardization to be universal. “There’s just enough nuance difference” between drugs that differences in the elements will be necessary, he said.

And REMS have multiple stakeholders, he pointed out, and each group has its own issues. “Creating some sort of real single model that’s going to standardize everything is going to be impossible.”

Rather, Nelson suggested, as many as a dozen models may be needed to serve as standards for various components of the REMS and the REMS will be crafted according to the issues of the particular product.

Making Standardization Fair

Standardization may be the goal for those in the health care delivery system but it could prove painful to get there.

During the public comment period, Anita Ducca of the Healthcare Distribution Management Association pointed out that in the case of the transdermal immediate-release fentanyls, wholesalers already have instituted programs to accommodate REMS for Cephalon Inc.’sActiq and Fentora, ProStrakan Group PLC’sAbstral, Meda Pharmaceuticals Inc.’s Onsolis and Archimedes Pharma Ltd.’s Lazanda (Also see "Abstral REMS Sets Stage For Risk Reduction Plans For Similar Fentanyls" - Pink Sheet, 17 Jan, 2011.).

“Therefore, the possibility exists that after distributors have gone to considerable length, including dedicating resources, to complying with these REMS,” there may need to be “modifications at additional cost in order to participate in the class-wide REMS.”

While a unified set of requirements for drugs with common characteristics is the goal, “Developing one REMS for some of the drugs and then moving to include those same drugs, plus others, into a potentially different REMS, is not quite the approach to fair standardization we had in mind.”