Usage Examples
- We submitted the proposed REMS with the NDA because FDA raised hepatotoxicity at the pre-NDA meeting.
- Our REMS has no ETASU, so pharmacies do not have to be certified before they dispense.
- The 18-month REMS assessment is due off the REMS approval date, not off the annual report cycle.
What is Risk Evaluation and Mitigation Strategy (REMS)?
Risk Evaluation and Mitigation Strategy (REMS) is an FDA-mandated drug safety program that imposes enforceable conditions on prescribing, dispensing, or patient monitoring whenever FDA determines those conditions are necessary to ensure a drug's benefits outweigh its risks.
Risk Evaluation and Mitigation Strategy exists because a serious risk is usually a reason to control how a drug is used, not a reason to reject it. Section 505-1 of the Federal Food, Drug, and Cosmetic Act, codified at 21 U.S.C. 355-1, lets FDA require a strategy whenever the agency determines one is necessary to ensure that the benefits of the drug outweigh the risks. That makes risk management a condition of marketing rather than a recommendation.
Risk Evaluation and Mitigation Strategy covers the conditions surrounding use of a drug, not the drug itself. A REMS may require a Medication Guide distributed to each patient when the drug is dispensed, a communication plan to health care providers, elements to assure safe use such as prescriber or pharmacy certification, and a timetable for assessing whether the strategy is working. A REMS does not change the approved indication, the dosing, or the manufacturing controls.
Risk Evaluation and Mitigation Strategy is applied as a submitted, assessed, and enforceable program rather than a document. The proposed strategy goes in as part of the application, or within 120 days of FDA notification when the agency requires one after approval based on new safety information. Assessments follow a statutory minimum timetable of 18 months, 3 years, and the seventh year, and either FDA or the responsible person can propose modifications.
Not to be confused with
- Medication Guide
- a Medication Guide is one component a REMS may require, developed for distribution to each patient under part 208. The REMS is the enforceable program; the Medication Guide is a single deliverable inside it.
- ETASU (elements to assure safe use)
- ETASU are the restrictive subset of REMS components FDA may impose only where they mitigate a specific serious risk. Every ETASU sits inside a REMS, but a REMS can exist with no ETASU at all.
- Pharmacovigilance
- pharmacovigilance detects and evaluates safety signals across a product's life. A REMS is the enforceable intervention FDA imposes once a risk is judged serious enough that labeling alone will not carry it.
- Boxed warning
- a boxed warning changes what the approved labeling says about a risk. A REMS changes who is allowed to prescribe, dispense, or receive the drug, and creates a misbranding exposure when its requirements are missed.
REMS obligations sit on the responsible person named in the application. These are the statutory anchors.
What you must do
- 1Submit a proposed REMS as part of the drug application when FDA determines a strategy is necessary to ensure the benefits of the drug outweigh the risks21 U.S.C. 355-1(a)
- 2Submit a proposed REMS not later than 120 days after FDA notifies the application holder that a strategy is required post-approval on the basis of new safety information21 U.S.C. 355-1(a)
- 3Develop and distribute the required communication elements, including a Medication Guide under part 208 given to each patient when the drug is dispensed, and a provider communication plan where FDA determines one supports implementation21 U.S.C. 355-1(e)
- 4Implement only those elements to assure safe use FDA requires, keeping them commensurate with the specific serious risk and not unduly burdensome on patient access21 U.S.C. 355-1(f)
- 5Meet the assessment timetable, with assessments at 18 months, 3 years, and in the seventh year after the strategy is initially approved21 U.S.C. 355-1(d)
- 6Comply with every REMS requirement arising under subsections (d), (e), and (f); non-compliance by the responsible person renders the drug misbranded21 U.S.C. 352(y)
Common mistakes
Treating the REMS as marketing collateral rather than a compliance obligation
a drug subject to an approved REMS is misbranded the moment the responsible person fails to comply with a requirement under subsection (d), (e), or (f) of 21 U.S.C. 355-1. The exposure attaches to the product itself, with no requirement that a patient was harmed.
Proposing certification and enrollment systems reflexively
FDA may impose elements to assure safe use only where they mitigate a specific serious risk, and the statute requires them to be commensurate with that risk and not unduly burdensome on patient access. Sponsors who volunteer restrictions build access friction and running cost they then have to unwind through a REMS modification.
Running assessments off the wrong clock
the statutory minimum timetable runs from the date the strategy is initially approved: 18 months, 3 years, and the seventh year. Teams that fold REMS assessments into an existing periodic safety reporting cadence discover the 18-month date has already passed, which is a compliance failure under subsection (d) and therefore a misbranding trigger.
When This Matters
- We submitted the proposed REMS with the NDA because FDA raised hepatotoxicity at the pre-NDA meeting.
- Our REMS has no ETASU, so pharmacies do not have to be certified before they dispense.
- The 18-month REMS assessment is due off the REMS approval date, not off the annual report cycle.
Frequently Asked Questions
Yes. FDA can require a REMS after approval if it becomes aware of new safety information and determines a strategy is necessary to ensure the drug's benefits outweigh its risks. The application holder then has 120 days from FDA's notification to submit a proposed REMS.
