Earlier this week, the U.S. Food and Drug Administration (FDA) released guidance on the definition and processing of submissions for modifications and revisions to approved pharmaceutical risk evaluation and mitigation strategies (REMS). REMS are strategies to manage a known or potential serious risk associated with a drug or biological product. FDA has the authority to require REMS on the part of a manufacturer if the agency finds that a safety strategy is necessary to manage a known or potential serious risk associated with a drug.
The recently-released guidance is meant to clarify what types of changes to REMS will be considered modifications, and what types of changes will be considered revisions. The distinction is important, as there are different procedures and timelines for the submission and review of modifications versus revisions. Revisions are defined in the new guidance as editorial changes, correction of typographical errors, and changes in the application holder name or address. The new guidance provides a hierarchical definition for modifications: minor modifications are those that “may nominally affect the risk message, and/or nominally change the REMS requirements;” major modifications are those that “may substantially affect the risk message and/or substantially change the REMS requirements.”
The guidance details the varying submission procedure for each of the three types of updates. Minor modifications must be submitted as a CBE-30 supplement. Changes submitted via CBE-30 supplements may be implanted by the application holder 30 days after FDA receipt of the supplement. Major modifications must be submitted as a prior approval supplement (PAS). PAS-proposed changes must be approved by the FDA before implementation. Under the proposed (and currently non-binding) portion of the guidance, REMS revisions may be submitted in an alternative manner. The guidance dictates that such submissions be titled “REMS REVISION” and include components such as a detailed description of the changes to the REMS along with clean and redlined versions of the original and revised REMS.
The portion of the guidance regarding modifications to previously-approved REMS is immediately binding, as such guidance may be implemented following notification to the Secretary of HHS under the Food, Drug & Cosmetics Act. The guidance setting forth the submission procedures for REMS revisions, however, will be binding only once the guidance is final – which will not occur until after the required notice and comment period has elapsed.
FDA has requested comments by June 8, 2015 on the proposed portion of the guidance. The guidance, with the non-binding portions shaded in grey, can be accessed on the FDA’s website; electronic submissions may be made at http://www.regulations.gov
