FDA issued its long awaited draft guidance, “Format and Content of Proposed Risk Evaluation and Mitigation Strategies (REMS), REMS Assessments and Proposed REMS Modifications”, on September 30. While much of the guidance is codification of what’s already been happening in practice over the past two years, there are a few surprises (indicated here in bold) for all of us working in the REMS space to contemplate. This is the first in a series of blog posts about this important document.
This draft guidance document covers the background of FDAAA and REMS relative to RiskMAPs and deemed REMS, the format and content of a REMS submission (proposed REMS and REMS supporting documents), the content of REMS assessments and proposed modifications of approved REMS, and communications with FDA (identifiers and process). It also provides a glossary and an example of a REMS document for a fictitious drug. Future guidance will be issued for ANDA submissions, more details about REMS assessments and proposed modifications to an approved REMS.
A proposed REMS is required if FDA determines it is needed for a new entity to ensure that the benefits of a drug outweigh the risks, if FDA becomes aware of new safety information for an approved product, and/or for some products with a previously approved RiskMAP. Manufacturers may also submit a proposed REMS voluntarily without being required to do so; if FDA determines that a REMS is not required in such cases, the manufacturer may still undertake voluntary risk management measures performed outside of a REMS.
REMS and their ancestor RiskMAPs are very close cousins. As stated by FDA “many of the principles that were included in the RiskMAP guidance are embodied in the FDAAA REMS provisions”. A product that would have previously been approved with a RiskMAP will instead be approved with a REMS. Products previously approved with a Medication Guide or patient package insert will now need a REMS. But, other than the RiskMAPs that were deemed REMS, other approved RiskMAPs and approved Medication Guides or patient package inserts will remain as RiskMAPs, unless a REMS is needed in the future. ANDAs will have either RiskMAPs or REMS, depending upon the status of the reference drug.
A REMS must include a timetable for assessment and one or more other elements. Assessments must occur at a minimum of 18, 36 and 84 months. Elements may include a Medication Guide, a patient package insert, a communication plan to healthcare providers, and/or elements to assure safe use. An element to assure safe use must include goals and may include implementation systems to monitor, evaluate, and improve implementation.
In addition to required assessment, manufacturers may also voluntarily submit an assessment and proposed modification to an approved REMS at any time. Modifications may enhance or reduce the approved REMS and could include:
- More or less frequent assessments
- Additional, modified, or removal of one or more elements
Likewise, FDA may determine that new information indicates that assessments or elements should be added, modified, or removed.
Content of a REMS submission should include a concise “proposed REMS” and a more expanded “REMS supporting document”, which explains the rationale and supporting information about the proposed REMS. The proposed REMS should describe the goal and proposed elements, with all proposed materials appended, and follow the template on the FDA website. Likewise, a template for the REMS supporting document can be found on the FDA website.
In subsequent posts, we will cover Section III – Content of a Proposed REMS Submission and REMS Supporting Document, Section IV – REMS Assessment and Proposed REMS Modification Submissions and Section V – Communicating with FDA Regarding REMS.
Stay tuned…