REMS programs explained

As of early November 2026, FDA's REMS@FDA database¹ listed 68 active Risk Evaluation and Mitigation Strategies. Fifty-six of them, 82 percent, include what the law calls elements to assure safe use, the restrictions that can require a certified prescriber, a certified pharmacy, a lab result or a patient registry before a prescription is filled, according to FDA's REMS data page². The other 12 consist only of a communication plan.

Fourteen of the 68 are shared systems, single programs that cover a brand drug and its generic copies under one set of rules. The newest, for thalidomide, was approved on September 2, 2026.

A REMS changes how a prescription moves through the system. It can decide which pharmacy may dispense a drug, what paperwork a prescriber files and what a patient signs. For generics the stakes are specific: federal law requires a copy of a REMS drug to carry the same safety program, and the way brand and generic makers share that program has been a recurring regulatory issue. This explainer covers what the 2007 law created, the six restrictions it allows, how generics fit, and what oversight reviews have found.

What the 2007 law created

Congress created REMS in the Food and Drug Administration Amendments Act of 2007⁹, signed September 27, 2007. The same law reauthorized the prescription drug user fees for another five years. Section 901 added section 505-1 to the Food, Drug, and Cosmetic Act, codified at 21 U.S.C. 355-1⁸, and it took effect 180 days after enactment.

FDA describes a REMS³ as a drug safety program for certain medications with serious safety concerns, and notes that only a few medications require one. It can require a REMS when it decides one is necessary to make sure a drug's benefits outweigh its risks. Its guidance on the statutory factors¹⁰ explains how it weighs that call. A REMS can include a Medication Guide or patient package insert, a communication plan for health professionals, and elements to assure safe use. Every REMS also carries a timetable for assessments. The statute's minimum calls for one by 18 months, one by three years and one in the seventh year after approval.

REMS apply only to prescription drugs and biologics. FDA's REMS FAQ⁴ says they do not apply to over-the-counter medicines, and that without a REMS, the drugs that have one "would not be approved or would be withdrawn from the market." Most labels carry their safety information in the prescribing information and, for some drugs, a boxed warning. FDA's overview of REMS requirements⁵ notes that all Medication Guides are approved as part of a drug's labeling, but only a small number are part of a REMS (GxRadar explains the difference in its piece on Medication Guides).

Over its life the program has been busier than the current count suggests. FDA's REMS dashboard page⁷ says the agency has approved more than 300 REMS and over 700 modifications since 2008. Many were later released, which is why only 68 remain.

The six elements to assure safe use

Subsection (f)(3) of the statute lists the restrictions FDA can impose. Its examples, from FDA's own descriptions⁵, show how they work in practice.

Congress also put limits on FDA. The restrictions must not be "unduly burdensome on patient access to the drug," must be compatible with established distribution and dispensing systems, and, under paragraph (f)(8), may not be used by a brand holder "to block or delay approval" of a generic or a 505(b)(2) application. That last clause was the backdrop for the CREATES Act, which GxRadar covers in a separate piece on access to brand samples.

For patients, the visible effect is often where a prescription can be filled. FDA's page on REMS participants⁶ says some REMS drugs can only be given in hospitals or infusion centers, some are available only through certain pharmacies, and others can be filled at a regular pharmacy. That is one reason many REMS drugs end up at specialty pharmacies. A pharmacist or prescriber can say which steps a particular program requires.

How generics fit in

A REMS does not stop generic competition. FDA's FAQ⁴ answers that question directly: when a drug has a REMS, any generic must also have one, either through a shared system with the brand or a separate program with the same goals.

Subsection (i) of the statute⁸ sets the rules. A generic approved under an abbreviated new drug application is subject only to some parts of the reference drug's REMS: the Medication Guide or patient insert, any packaging or disposal requirement, and any elements to assure safe use. For that last part, the generic may use a single, shared system with the brand or a "different, comparable aspect" of the safety elements. FDA can require a shared system if it finds no comparable alternative would work. FDA, not the generic maker, carries out any communication plan for the generic.

That "different, comparable" option came from a 2019 amendment, Public Law 116-94, which replaced the earlier rule that generics use a single shared system unless FDA granted a waiver. FDA had laid out how it viewed those waivers in a 2018 draft guidance on waivers¹², published the same day as a draft guidance on developing shared systems¹¹. A year earlier, FDA proposed in a 2017 draft guidance¹³ that members of a shared system file their REMS documents through a single Type V drug master file. In 2023, FDA finalized a standard format for REMS documents¹⁴.

The 14 shared systems on the list

REMS@FDA names single-product programs after the brand and shared systems after the molecule or class. GxRadar's tally of the database¹ in November 2026:

Source: GxRadar tally of REMS@FDA¹, November 2026. All 14 include elements to assure safe use.

Communication-only programs tell a different story. Eleven of the 12 REMS without safe-use elements belong to denosumab, its reference product and its biosimilars, each listed separately. Biosimilars follow their own pathway, which GxRadar describes in how biosimilars differ from generics.

What oversight reviews found

In February 2013, the HHS inspector general reported that FDA lacked comprehensive data¹⁵ to tell whether REMS improve drug safety. The OIG counted 199 REMS approved from 2008 through 2011, 99 of them still required in 2012. Of 49 REMS it examined, FDA had determined that seven met all their goals. Nearly half of the company assessments lacked information FDA had asked for, 10 arrived late, and FDA's reviews took longer than its 60-day goal for all but one. The OIG's recommendation tracker shows two of its recommendations, including one that FDA seek authority to enforce its assessment plans, closed as implemented on March 31, 2025.

FDA's FAQ⁴ says it can release a REMS, or drop parts of one, when assessments show the extra measures are no longer needed. New risks can also push the other way: FDA's quarterly safety-signal postings¹⁶ list "development or modification of a REMS" among the actions a signal can lead to.

The database keeps moving. The bosentan shared system was updated on October 27, 2026, and the isotretinoin program on October 7. FDA's data files² also flag a caution for anyone counting: the active and inactive status in the historical download file "is not accurate," and FDA says it is working on a fix. GxRadar's generic approvals data shows when copies of REMS drugs reach the market.