On September 30th, FDA issued draft guidance, “Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments and Proposed REMS Modifications”. While much of this draft guidance is a codification of what’s already been happening in practice over the past 2 years, there are a few interesting surprises (depicted in bold below) for those working in the REMS space to contemplate. This is the fourth in an ongoing series of blog articles about this important document.
Our first three articles covered the background of FDAAA and REMS, an overview of a REMS submission and greater detail about the “Proposed REMS”, and “REMS Supporting Document” components of the REMS document submission. This article covers the section of the guidance about “REMS assessment and modification submissions” and “communicating with FDA”.
REMS assessments must be submitted according to the agreed Timetable for Submission of assessments. REMS assessments may also be voluntarily submitted with or without a proposed modification to the REMS at any time. Any proposed modification must include an assessment of the REMS (presumably as evidence to justify the proposed modification).
FDA may also determine that new information indicates that an element of the REMS should be modified. At that time, the manufacturer must assess the REMS and, if agreed, that assessment may be a statement that the element together with the proposed modifications would be adequate to achieve the purpose.
Proposed modifications may include:
- Enhancement or reduction to the approved REMS
- The addition, modification, or removal of a REMS element
- Additions or modifications to the Assessment Timetable
- A proposal to eliminate assessments after the 3 year assessment
Any proposed modification, including changes to materials, must be submitted as a proposed modification in a new prior approval supplemental application and must not be implemented until the modified REMS is approved.
Each proposed modification submission should show:
- The complete previously approved REMS plus all proposed modifications highlighted
- Updated REMS Supporting Document (either as a new document referencing prior document or a modified document with changes highlighted) with the rationale and description of proposed modifications and their impact on other REMS elements
- Future guidance will provide more information on assessments and modifications of approved REMS
Communicating with FDA regarding REMS may involve submissions (e.g., initial REMS, REMS assessments, and proposed modifications), written correspondence (e.g., other REMS submissions), and questions directed to FDA regulatory project managers.
Submissions may include:
- Proposed REMS may be included in the initial submission of an original or supplemental application or as an amendment to an existing original or supplemental application. Supplemental applications that include a proposed REMS or proposed modifications to an approved REMS should be submitted as prior approval supplements.
- Assessments of approved REMS may be submitted at any time and as required in the Timetable for Submission of assessments. An assessment alone (i.e., without proposing a modification) is not considered a supplemental application.
- REMS assessments with a proposed modification should be submitted as either a new supplemental application or included in a related supplemental application at time of submission or as an amendment
- A supplemental application for a new indication for a product with an approved REMS must include a REMS assessment unless the drug is not subject to section 503b and the REMS includes only a Timetable for Submission of assessments. The supplemental application for the new indication should include the required REMS assessment and may propose modifications to the REMS.
A proposed REMS and proposed modifications to an approved REMS should be submitted using FDA templates and include electronic versions as both pdf and Word processed document.
Document identification specifications for proposed REMS, assessments and modifications of approved REMS, and other REMS submissions are described in the guidance.
Other REMS submissions that are not part of proposed REMS, modifications, amendments, or assessments may include:
- Requests for information about what to include in a REMS
- Requests for information about the REMS assessment plan
- General correspondence about an approved REMS
- Other submissions
Such correspondences should prominently identify content with the words “REMS – Other”.
Questions about REMS should be directed to regulatory project managers within the relevant Office of New Drugs Review Division, Office of Generic Drugs, and in the Center for Biologics Evaluation and Research.
The guidance includes a glossary of terms and a REMS template with an example of a fictitious drug.
In a subsequent posting, we will be describing a preliminary review and interpretation of the draft REMS guidance, as well as opportunities for enhancement.
Stay tuned…