Risk Evaluation and Mitigation Strategies (REMS)

By: Claudia Manzo, director, Office of Medication Error Prevention and Risk Management, Office of Surveillance and Epidemiology, Center for Drug Evaluation and Research

Risk evaluation and mitigation strategy (REMS) programs focus on preventing, monitoring, and/or managing a specific serious risk(s) associated with certain drugs by informing, educating, and/or reinforcing actions to reduce the frequency and/or severity of a particular adverse event(s). As discussed in Part 1, there are several key participants who play important roles in the medication use process for drugs that are subject to REMS.

REMS programs for certain drugs have recently undergone major changes resulting from drug companies needing to change vendors (often referred to as REMS administrators) who implement REMS programs. The changes to the affected REMS, in some cases, significantly changed how stakeholders interact with the programs.

Implementation Challenges with REMS Programs

Claudia Manzo

While FDA can require drug companies to implement certain requirements under a REMS that support the safe use of the drug, the law does not authorize the agency to require specific methods or standards for implementing these requirements.

The differing approaches that companies take leads to the lack of standardization in how REMS programs are implemented. Due to gaps in data exchange there is difficulty in communication and coordination of efforts amongst stakeholders within a REMS program. The lack of standardization and integration into the health care delivery system has led to stakeholder burden and barriers to patient access to drugs with REMS.

There has been little incentive to adopt standard approaches to implementing REMS requirements, including how the requirements can be integrated into existing health care delivery system workflows or health information technology (HIT) systems and no unified way to transmit or share REMS data between REMS stakeholders.

Opportunities to Address REMS Challenges and Potential Solutions

Our vision is that REMS activities will be fully integrated into the clinical workflow for health care professionals. Innovative approaches are needed to keep up with current and future technologies that are being implemented or already in place in the health care delivery system. The use of data standards will facilitate exchange of REMS requirements and REMS information between stakeholders as well as help us gather more accurate and complete REMS data. To address some of the standardization challenges and to improve communication and compliance around REMS requirements, CDER developed the Format and Content of a REMS Document Guidance for Industry and initiated the REMS Structured Product Label (SPL) project.

Standardizing REMS information using SPL

Stakeholders observed the older REMS document format was not standardized or structured, and generally could not be easily searched, queried, or managed. SPL can be used to capture and present REMS information in a format that is easily shared with stakeholders and readily incorporated into health information technology. Stakeholders suggested use of SPL as a standard that may allow for a centralized, standardized REMS information repository.

As a result of this stakeholder feedback, we developed the guidance, “Providing Regulatory Submissions in Electronic Format - Content of the Risk Evaluation and Mitigation Strategies Document Using Structured Product Labeling.” This guidance describes the format requirements for the electronic submission of the content of a REMS document. This guidance also describes how the agency will implement requirements for the electronic submission of REMS documents as part of submissions under new drug applications, abbreviated new drug applications, and certain biologics license applications. All REMS documents submitted to FDA on or after December 28, 2022 must be in SPL format and include:

1. REMS documents associated with a new REMS;
2. REMS documents submitted as part of REMS modifications; and
3. REMS documents that are already in SPL format must remain in SPL format.

Arranging of REMS content and elements to assure safe use into SPL is a major first step in standardizing REMS into a granular, computable format. As REMS sponsors submit and update their REMS documents into SPL, SPL will allow for downstream users, such as drug information resources and health systems, to more readily identify REMS drugs and incorporate the REMS requirements into end user systems like electronic health records and pharmacy information management systems.

REMS Integration Use Case

Through the Health Level 7 International (HL7®) CodeX® REMS Integration Use Case, FDA is supporting the use of open data standards. The use case ultimately aims to reduce the burden associated with REMS implementation and improve efficiency, improve the quality of REMS data for feedback and evaluation, and optimize safe medication use and health outcomes. FDA is supporting the use of open data standards. The use case ultimately aims to reduce the burden associated with REMS implementation and improve efficiency, improve the quality of REMS data for feedback and evaluation, and optimize safe medication use and health outcomes.

Importance of Stakeholder Input during the Development and Modification of REMS Programs

It is important that REMS stakeholders be able to access the right data at the right time in order to carry out their tasks efficiently and effectively. FDA remains committed to systematic evaluation and improvement of REMS program implementation, informed by stakeholder feedback throughout the lifecycle of a drug—and the shared mission of ensuring that patients continue to have access to safe and effective therapies.

In March 2023, we opened a public docket requesting feedback on factors the agency should consider when reviewing proposed changes to third party vendors, often known as REMS administrators, resulting in proposed modifications to a REMS. FDA is interested in feedback on any stakeholder input that should be received by the sponsor for a proposed change in a REMS system and how long stakeholders need to transition to a new REMS system. FDA is also requesting feedback on what the agency, drug sponsors, and/or REMS administrators should consider before implementing changes including possible testing of the system, how to evaluate if change was successful and how to plan for system failures.

The comment period ends July 21, 2023.

FDA’s highest priorities are patient safety, patient access to medications, and continuity of care. We are championing and actively exploring innovative technologies to facilitate a standardized approach for the completion of REMS requirements within the prescribers and pharmacists’ workflows.