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Regulatory Focus™ > News Articles > 2019 > 7 > FDA Finalizes Revised REMS Modifications Guidance

FDA Finalizes Revised REMS Modifications Guidance

Posted 09 July 2019 | By Michael Mezher 

FDA Finalizes Revised REMS Modifications Guidance

The US Food and Drug Administration (FDA) on Tuesday finalized a revision of its guidance on making and submitting modifications and revisions to risk evaluation and mitigation strategies (REMS).
Specifically, the guidance lays out FDA’s policies for REMS modifications and revisions, including what types of changes the agency will consider and the processes and procedures for submitting those changes to the agency.
The 26-page guidance finalizes an earlier version released for comment in April 2015 that included changes to the section covering submission procedures for REMS revisions in response to amendments to the Federal Food, Drug, and Cosmetic Act under the Food and Drug Administration Safety and Innovation Act (FDASIA).
Under the guidance, FDA explains that REMS revisions consist of editorial changes that do not affect the information in the REMS and materials covering serious risks or safe use of a product and do not change the actions stakeholders must take to comply with the REMS.
All other changes to a REMS are considered either minor or major modifications. According to the guidance, a minor modification may have a limited effect on the REMS information and materials, while changes that have a substantial effect on the REMS are considered major.
For instance, adding or removing a strength or dosage of a product due to an approval or withdrawal of approval would be considered a minor modification, while making changes to a REMS goal or adding new information about a serious risk of a drug would be considered a major modification.
When submitting proposed REMS changes, FDA says that revisions should be submitted as a “REMS Revision” at the time the revisions are implemented and documented in the next annual report for the product.
For REMS modifications, FDA says that sponsors should submit minor modification as a changes being effected in 30 days (CBE-30) supplement, while major modifications should be submitted as a prior approval supplement (PAS).
FDA says it will act on proposed minor REMS modifications within 60 days of receiving a CBE-30. While drugmakers can implement minor modifications after 30 days, FDA says those changes are not considered final until they are approved.
For major modifications, FDA says it will review and act on proposed changes within 180 days and that such changes may not be implemented before they are approved.
For modifications to a REMS due to safety labeling changes, FDA says it will review “conforming” changes within 60 days and modifications “not considered conforming” within 180 days. According to the guidance, conforming changes involve “modifications that transfer the newly approved labeling language into the existing REMS and/or REMS materials” and changes that are not considered conforming apply to “overall programmatic and/or implementation changes to the REMS that result from approved (or ordered) safety labeling changes.”
FDA, Federal Register Notice

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