REMS Modifications and Revisions: A Retrospective from the Past 12 Months

With the new year comes the prospect of change, as well as an opportunity to reflect on the past year.  And, welcoming change can lead to meaningful growth.  That is particularly valid when it comes to REMS modifications and revisions.

According to the FDA¹, REMS revisions are limited to editorial updates, corrections of typographical errors, and changes to the application holder’s name or address. These revisions pertain to the REMS document and/or associated materials, but do not alter the risk message or other REMS requirements.

In contrast, REMS modifications involve changes to the approved REMS and are categorized based on their potential impact on the risk message and/or REMS requirements. Proposed REMS modifications are classified into two categories: minor and major modifications. 

Minor modifications are those that may have a nominal impact on the risk message or make minimal changes to the REMS requirements and are submitted as supplements.  These modifications are considered moderate changes under FDA recommendations.  Major modifications, on the other hand, are changes that may significantly alter the risk message or substantially modify the REMS requirements, including updates to the REMS website used by stakeholders.

2024 REMS Activity

In reviewing the FDA’s REMS Dashboard², 2024 saw the largest number of updates to approved REMS in the past five years. Like all changes, some are straightforward while others are painstakingly complex.

What all these adjustments have in common is the goal to improve the REMS experience for all stakeholders. 

Editorial Updates were far and away the highest quality of changes. Impacting nearly 25% of approved REMS, these changes included minor clarifications in wording and sponsor information (i.e. manufacturer trademark, address updates). These are intended to clarify the presentation of REMS information. 

Another primary reason for 2024 changes was the continual goal to reduce burden. The Agency and sponsors work together to recognize where adjustments to website functionality or workflow can alleviate the responsibilities to prescribers, pharmacies and/or patients. These updates are frequently welcomed by REMS stakeholders, and frequently are identified by participants as part of their daily REMS tasks. 

Labeling updates are commonplace for any medication, and REMS products are no exception. Minor updates to indication, dosing, or safety information require a revision to the REMS; significant changes to the safety information may require a modification.

The least common reasons for change in 2024 were new indications, application ownership and notification of discontinuation of a product. These changes were focused on content, website banners, and sponsor name changes.  

REMS updates can mean a multitude of things. Several were form and process updates for pharmacies. Additional reasons included updates to audit requirements, which monitor compliance with the REMS rules as well as assessing the effectiveness of the program.  Modifications for shared REMS may require longer timelines, as the various regulatory teams will entail more review and approval time.

Another driver for REMS updates can be a change in REMS Administrator. This requires a very concentrated focus on stakeholder impact as it relates to the REMS platform, call center contacts, and processes to conduct verification.

Impact of REMS Modifications

Regardless of the specific nature of the changes that occurred in 2024, each adjustment was implemented with a singular, overarching goal in mind: to enhance the safety and well-being of REMS patients. These changes, whether they involved modifications to safety communications, new REMS Administrator, or compliance requirements, all were carefully designed to address emerging insights and evolving patient needs. 

The longer a REMS is in place, the more valuable real-world data is gathered, proving a deeper understanding of the potential risks associated with the treatment. This continuous accumulation of information allows for more informed decisions, leading to more targeted and effective safety measures. 

Lastly, sponsors acknowledge that feedback from REMS stakeholders – including healthcare providers, pharmacies, and patients – is crucial for the ongoing progression of REMS. These stakeholders play an essential role in identifying potential areas for improvement, allowing for the refinement of safety measures. This feedback is then shared with the FDA for finalization of modifications. Through this ongoing feedback and adaptation process, REMS can be fine-tuned to provide optimal safety while still allowing patients access to necessary treatments. 

This article was written by Christine Manley, REMS Director, Pharmacovigilance at MMS. For questions regarding this article, email info@mmsholdings.com.

References

1. Risk Evaluation and Mitigation Strategies Modifications and Revisions | CENTER FOR DRUG EVALUATION AND RESEARCH
2. REMS Dashboard | FDA