REMS Programs Explained: How the FDA Manages High-Risk Medications

When a drug can save lives but also cause serious harm-like birth defects, organ failure, or deadly blood disorders-the FDA doesn’t just slap on a warning label and call it a day. Instead, it puts in place something called a REMS program. These aren’t simple warnings. They’re complex, legally required systems designed to make sure patients get the medicine they need without putting their lives at risk. As of November 2025, there are about 120 active REMS programs covering over 185 drugs in the U.S., mostly for cancer treatments, multiple sclerosis, and rare autoimmune conditions.

What Exactly Is a REMS Program?

REMS stands for Risk Evaluation and Mitigation Strategy. It’s a formal safety plan the U.S. Food and Drug Administration (FDA) can require for certain prescription drugs. The goal? Let patients access life-saving medications that would otherwise be too dangerous to approve. REMS programs were created in 2007 under the Food and Drug Administration Amendments Act (FDAAA). Before that, the FDA used to handle high-risk drugs like thalidomide and isotretinoin with patchwork rules. Now, there’s a standardized, enforceable system.

Every REMS has one core purpose: to make sure the benefits of the drug clearly outweigh its risks. The FDA doesn’t use REMS lightly. It only steps in when the potential harm is serious enough that standard labeling-like the tiny print on a pill bottle-isn’t enough.

The Four Key Parts of a REMS Program

Not all REMS are the same. Some are simple. Others are so complex they slow down prescriptions for weeks. But every REMS includes at least one of these components:

• Medication Guides - These are printed handouts given to patients with each prescription. They explain the biggest risks in plain language. About 78% of REMS programs require them. For example, the guide for lenalidomide (Revlimid) warns pregnant women that even one dose can cause severe birth defects.
• Communication Plans - These are messages sent to doctors and pharmacists. They might come as letters, emails, or safety alerts. About 62% of REMS include these. The FDA and drugmakers use them to update providers on new safety data or changes to the program.
• Elements to Assure Safe Use (ETASU) - This is the strictest layer. It’s required in about 45% of REMS programs. ETASU means extra steps before a patient can get the drug. These might include:

1. Doctors must be certified to prescribe the drug.
2. Pharmacies must be specially approved to dispense it.
3. The drug can only be given in certain settings, like a hospital or infusion center.
4. Patient must be enrolled in a registry to track outcomes.
5. Pregnancy tests must be done before each dose.

For drugs like pomalidomide (Pomalyst) or alemtuzumab (Lemtrada), these steps are non-negotiable. A pharmacist won’t fill the prescription unless the prescriber is certified, the patient’s pregnancy test is in the system, and the pharmacy is on the approved list.

Who Runs REMS Programs-and How Much Do They Cost?

The drug manufacturer is responsible for designing, funding, and running the REMS. That means the company pays for everything: training materials, online portals, staff to verify certifications, patient registries, and even the cost of training doctors. The FDA doesn’t pay a dime.

A 2023 FDA analysis found the average annual cost of running one REMS program is $2.7 million. For a company with five high-risk drugs, that’s over $13 million a year-just for safety compliance. And it’s not just the drugmaker. The whole healthcare system pays too. Pharmacies spend hours verifying each prescription. Clinics hire extra staff to manage paperwork. Patients wait longer for their meds.

Overall, REMS-related costs across the U.S. health system are estimated at $1.2 billion per year. But the FDA says that’s a bargain. They estimate REMS prevent about $8.4 billion in healthcare costs from adverse events-hospital stays, emergency care, and long-term damage.

Why REMS Programs Cause Delays and Frustration

For patients, REMS can feel like a maze. One survey found 42% of people prescribed a REMS drug experienced delays getting their medication. Why? Because every step requires human action:

• A doctor has to complete a 45-minute online certification course just to prescribe lenalidomide.
• The pharmacy has to log into a secure portal to check if the doctor’s certification is still active.
• Patient must bring in a recent pregnancy test-sometimes within 7 days of the prescription.
• The drug can only be picked up from a specialty pharmacy, which might not be nearby.

Pharmacists on Reddit’s r/pharmacy thread say REMS adds 15-20 minutes per prescription. One wrote: “I’ve had patients cry because they drove 40 miles only to find out their doctor wasn’t certified.”

For oncology clinics, it’s worse. A 2023 survey by the American Society of Hematology found 68% of hematologists spend more than five hours a week just managing REMS paperwork. That’s time taken away from patient care.

REMS Blocks Generic Drugs-And That’s a Big Problem

One of the biggest criticisms of REMS is how it blocks cheaper generic versions of drugs. When a brand-name drug has a REMS, the generic maker can’t get samples to test its product unless the brand company agrees to share them. Many brand companies delay or refuse, saying they need to protect patient safety.

A 2024 Health Affairs study found 78% of generic manufacturers reported REMS-related delays averaging 14.3 months before they could launch their version. That means patients pay higher prices for years longer than they should.

For example, the REMS for the multiple sclerosis drug Lemtrada required hospital administration and strict monitoring. Generic makers couldn’t get samples for years. Even after approval, the REMS rules made it hard for community pharmacies to stock the generic version.

Legislators are pushing for change. The 21st Century Cures Act Reauthorization (2022) now requires the FDA to create a process for generic companies to get samples faster. A proposed 90-day review window could help, but it’s still not in place as of late 2025.

What’s Changing in REMS? The Modernization Push

The FDA knows REMS is broken in places. Too many steps. Too many paper forms. Too many portals. So they’re trying to fix it.

The REMS Modernization Initiative, launched in 2023, aims to:

• Standardize certification forms across all REMS programs.
• Replace paper registries with electronic systems that auto-update.
• Create a single dashboard where doctors and pharmacists can check all REMS requirements in one place.
• Use real-world data-like hospital records and pharmacy claims-to measure if REMS is actually working.

By Q3 2025, the FDA plans to launch a public REMS Dashboard showing which programs are effective, which are too burdensome, and which should be removed. So far, only three REMS have been discontinued since 2007. The last one, for Zeposia (used for multiple sclerosis), was removed in March 2023 after data showed the risks were manageable with standard labeling.

Experts like Dr. Rachel Sherman, former FDA deputy commissioner, say future REMS will be smarter. Instead of blanket requirements for every patient, they’ll use data to target only those at highest risk. For example, if a patient’s blood tests show no signs of liver damage, they might not need monthly check-ups anymore.

What Patients and Providers Should Do

If you’re prescribed a drug with a REMS:

• Ask your doctor: “Is this drug under a REMS? What do I need to do?”
• Make sure your pharmacy knows how to handle REMS drugs. Not all pharmacies are certified.
• Keep copies of your certification forms and test results. Don’t assume your doctor’s office has them.
• If you’re delayed, call the drugmaker’s REMS support line. Most have one.

For providers:

• Use the FDA’s REMS@FDA website to check if your REMS requirements changed.
• Don’t skip certification-even if you’ve done it before. Expiry dates matter.
• Advocate for electronic systems. Paper is slowing you down.

REMS isn’t perfect. But it’s the best tool we have to balance risk and access. The goal isn’t to make life harder-it’s to make sure no one dies because a drug was given without the right safeguards.