The US Food and Drug Administration (“FDA”) finalized a revised guidance on making modifications to risk evaluation and mitigation strategies (“REMS”). The document, entitled “Risk Evaluation and Mitigation Strategies: Modifications and Revisions Guidance for Industry,” defines the types of changes to approved REMS, how applicants should submit changes to approved REMS and how the FDA will process these submissions.
The guidance divides proposed changes into subcategories based on a consideration of their degree of effect on the information provided in the REMS related to the serious risks of the drug, the safe use of the drug, and/or the actions that the applicant, patients, providers and other stakeholders must take to comply with the REMS. The subcategories are as follow.
Revisions: REMS revisions are editorial changes that do not affect the information contained in the REMS document and/or materials concerning the serious risk of safe use of the drug, and the actions the enumerated parties must take to comply with the REMS. REMS revisions would include, for example, updates to application holder’s name or contact information, and correction of grammatical errors.
Minor Modifications: Minor REMS modifications are changes that have a limited effect on the information contained in the REMS document and/or materials concerning the serious risk of safe use of the drug, and the actions the enumerated parties must take to comply with the REMS. Minor REMS modifications would include, for example, adding approved new strength or dosage information, and adding an authorized generic.
Major Modifications: Major REMS modifications are changes that have a substantial effect on the information contained in the REMS document and/or materials concerning the serious risk of safe use of the drug, and the actions the enumerated parties must take to comply with the REMS. Major REMS modifications would include, for example, adding or removing a REMS goal, or adding a new indication that may alter the serious risks of the drug for the new patient population.
The guidance indicates that a “REMS Revision,” which is similar to drug correspondence, should be submitted at the revision is implemented and should be documented in the subsequent annual report. REMS Revisions do not require FDA action, and, consequently can be implemented following FDA receipt of the document. Proposed Minor REMS modifications should be submitted as “changes being effected in 30 days” (“CBE-30”) supplements, and they will be acted on within 60 days of receipt. Applicants can implement those modifications in 30 days, but they are not considered final until approved by the FDA.
Proposed Major REMS modifications should be submitted as a prior approval supplement (“PAS”), and they will be acted on within 180 days. These proposed changes may not be implemented until they are approved.
This guidance updates a prior guidance with the same title, issued on April 7, 2015.