Failure to evaluate REMS risk early can create avoidable launch risks, including compressed implementation timelines, increased costs, and delayed market entry.
By Melissa Landers, Founder and Vice President, Shepherd Safety Services at Two Labs
Here is a situation that plays out more often than it should. A manufacturer submits its New Drug Application (NDA), the FDA accepts it, and the launch team turns to final preparations. Then, weeks before the expected approval, the FDA determines that the product will need a Risk Evaluation and Mitigation Strategy (REMS) before it can go to market. One requirement, raised late, can move a launch date back by months, and in some cases, close to a year.
A REMS is a safety program the FDA requires for certain products to keep a drug’s benefits and risks in balance and support safe use. The agency usually calls for one during the review of an NDA or a Biologics License Application (BLA), as it weighs the risks identified during development. The requirement itself can be manageable, but the trouble is that most teams do not plan for one, so by the time FDA raises the issue, there is little room left to respond well.
Why REMS catches teams off guard
REMS is a small corner of drug safety. In recent years, more than 10% of novel applications to FDA received a REMS as part of their approval, only 72 of the more than 20,000 prescription drug products on the U.S. market carry one1,2,5,6. Because REMS programs are uncommon, so is deep experience with them, even among people who have spent years in regulatory and drug safety roles. A team can have many successful launches behind it and still have almost no direct experience designing and operating a REMS.
That gap shows up in predictable ways. Manufacturers may miss the early signs that a REMS could be coming, and they may not set aside the time or budget to develop, implement, and operate one. Timelines get compressed, and in the worst cases, FDA extends the products Prescription Drug User Fee Act (PDUFA) date by three months, delaying commercial launch of the product.
It also helps to know where the most common risks sit. REMS is rare across all marketed drugs, but the odds climb for the kinds of products many emerging manufacturers are working on now, including biologics, cell and gene therapies, psychedelics, and other complex modalities. A team that assumes a REMS will not apply may be relying on the overall average instead of its own product’s risk relative to recent FDA precedents.
Reading the early warning signs
The signs are usually there to read. While the FDA determines the need for a REMS on a case-by-case basis, existing programs provide useful precedents for understanding the types of risk that may warrant one.
Some risks show up as recurring themes across therapeutic areas. Liver-related risks, such as hepatotoxicity and drug-induced liver injury (DILI), appears in approve REMS for multiple therapeutic areas and drug classes. Other risks follow the drug class, as with cardiac myosin inhibitors, due to the risk of systolic dysfunction and subsequent heart failure.
The most common themes are compiled in Figure 1, taken from the FDA’s documentation of the 72 currently approved REMS. When a development team sees risks like these in its own product, that is the point to bring in REMS expertise, before the issue turns into a late-breaking surprise during FDA review.
Not every risk lines up with a known theme, which is what makes some products’ REMS likelihood harder to predict. The FDA evaluates benefit and risk based on factors such as the clinical significance and likelihood of a drug’s benefits and the likelihood and medical importance of its risks. That assessment is made on a product-by-product basis, and words like likelihood and medical importance leave significant room for judgment.
The FDA’s 2019 guidance gives general direction on when a REMS is necessary3, but a specific read on a given product usually takes a REMS specialist. Professionals with a breadth and depth of REMS experience and knowledge can take a data-driven approach to determining an individual product’s REMS risk. By anchoring these analyses in data, not opinions, manufacturers are able to cut through internal politics and opinons to understand the REMS potential and plan accordingly to avoid downstream complications that negatively impact launch.
When REMS likelihood is moderate or higher, the first decision is whether and when to engage FDA in REMS-related discussion. When a risk fits a clear theme, such as liver toxicity, the sensible move is to raise it with the FDA prior to submission and submit the REMS along with the NDA or BLA. That preserves the time needed to design a program that supports safe use while minimizing REMS burden on patients, prescribers, and pharmacies. Submitting proactively can also prevent a three-month target approval date extension, since adding a REMS during NDA or BLA review counts as a major amendment to the application.4
What waiting really costs
The launch impact is more than just the three-month extension to the approval timeline. It is also about the time necessary to develop a high-functioning REMS program and associated regulatory documentation. FDA consistently provides direction on REMS late in the review cycle, typically mid-cycle or later, because the need for a REMS is based on the risk-benefit profile resulting from the clinical portion of the review process.
In recent years, most REMS approvals occur two to four months after receipt of first REMS-related FDA feedback7. Given this short window, playing wait-and-see with FDA limits the manufacturer’s time to strategically design a REMS program, create the regulatory documentation, negotiate program requirements with the Agency, and set up a REMS technology and call center solutions.
A REMS program developed under significant time pressure typically results in more burdensome program requirements because speed drove the design instead of quality. When a REMS is developed in a hurry, there is less opportunity to consider how each decision will affect patients, prescribers, and the overall usability of the program.
Minimizing REMS burden on the healthcare delivery system and patients is critical to success at launch and beyond. The number and complexity of REMS requirements directly impacts prescriber willingness to prescribe a therapy with a REMS program, which ultimately limits patient access to these products.
To mitigate these risks to program success, at a minimum, the manufacturer should draft the REMS documentation and determine what it would take to operationalize the program. Having this documentation in their back pocket provides manufacturers with some degree of insurance if FDA requires a REMS for product approval.
A stronger insurance policy is to start building the administrator system and call center that will bring the REMS to life. A REMS requires a custom-configured system, usually a database, a website, and a contact center, and these can take three to eight months to stand up. Paying to configure a system that may not be needed may feel like waste, but it is a relatively small investment when weighed against the cost of a delayed or poor-quality launch.
Design the program around the patient
Having a contingency plan for a potential REMS can make a big difference to launch success because small REMS design choices can have an outsized effect on access. Consider how often a REMS can require prescribers to submit documentation of safe use conditions, like labs, to the program. While it is the patient who must obtain the labs, it’s their prescriber who must interact with the REMS on the patients behalf to document safe use conditions necessary to start and stay on treatment. Precedents show that some prescribers decide that the paperwork creates too much downstream burden to justify becoming REMS-certified to prescribe the drug. As a result, their patient either cannot access the therapy or must seek another certified prescriber.
Taking this example a step further, it is not just the requirements that create barriers to access; often, it is how the requirements must be completed.
If a program requires prescribers to enter lab results on a recurring schedule, for example, the system should make that process as straightforward as possible. Giving each prescriber a dashboard that displays their patients, rather than requiring them to search for each patient again every month in the REMS system, can save time and help prevent the requirement itself from becoming an unnecessary barrier.
Safe use comes first, always. Minimizing administrative burden so that it does not stand between a patient and their therapy is also critical, and the two objectives do not have to compete when both are considered from the beginning. Early experience matters, too. If a prescriber or patient encounters significant friction when first interacting with a REMS program, that experience can shape their perception of the program even after improvements are made.
Make REMS part of the launch plan
A manufacturer that does not plan for a possible REMS can end up facing two difficult options. It can protect quality and lose time to market by taking the time needed to design, negotiate, and configure a high-quality program. Or it can protect the timeline and risk giving patients and prescribers a program that was put together too quickly and creates unnecessary friction.
Neither trade-off is required. A REMS can be planned for, designed, and built so that it does not derail the launch or create unnecessary barriers for patients, as long as the work starts early enough. Whatever the risk profile of a product, simply hoping a REMS will not be required is not a plan. Bringing in REMS expertise early to assess the potential for a REMS and prepare accordingly is the more dependable route.
Note: The list of REMS themes is not exhaustive and is current as of August 28, 2026. For currently approved REMS and their risks, go to https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm.
How Two Labs can help
Shepherd Safety Services at Two Labs works with manufacturers on REMS and other post-marketing safety programs, including risk management plans, controlled access programs, and patient registries. We help teams plan a program, build it, and run it, from the regulatory writing through the website and contact center that patients and prescribers actually touch.
Our work runs across REMS strategy, program build and administration, and program management. We have supported more than 20 REMS programs, including more than 10 shared-system consortia, and we bring that experience to each product rather than fitting the product to a template. If a REMS could be in your product’s future, the time to prepare is before the FDA puts it on the table. Talk to Two Labs now to understand your REMS risk, or schedule a meeting with our REMS specialists to discuss whether a REMS likelihood analysis is the right next step for your product.
The list of REMS themes is not exhaustive and is current as of August 28, 2026. For the current list of approved REMS and their risks, see https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm.
Sources
- “Approved Risk Evaluation and Mitigation Strategies.” U.S. Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm. Accessed 08/28/2026.
- “Fact Sheet: FDA at a Glance.” U.S. Food and Drug Administration. https://www.fda.gov/about-fda/fda-basics/fact-sheet-fda-glance. Accessed 08/28/2026.
- “REMS: FDA’s Application of Statutory Factors in Determining When a REMS Is Necessary. Guidance for Industry.” April 2019. U.S. Food and Drug Administration. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/rems-fdas-application-statutory-factors-determining-when-rems-necessary-guidance-industry. Accessed 08/28/2026.
- “Code of Federal Regulations: Title 21, Chapter I, Subchapter D, Part 314, Subpart B.” National Archives. https://www.ecfr.gov/current/title-21/chapter-I/subchapter-D/part-314/subpart-B/section-314.60. Accessed 08/28/2026.
- “FDA REMS Public Dashboard.” U.S. Food and Drug Administration. https://fis.fda.gov/sense/app/ca606d81-3f9b-4480-9e47-8a8649da6470/sheet/6840df68-c772-45f1-bc4f-39d8b04cbfc1/state/analysis. Accessed 9/21/2026.
- “Novel Drug Approvals at FDA.” U.S. Food and Drug Administration. https://www.fda.gov/drugs/development-approval-process-drugs/novel-drug-approvals-fda. Accessed 9/21/2026.
- “Risk Assessment and Risk Mitigation Review(s).” 2023-2025. U.S. Food and Drug Administration. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm. Accessed, 9/21/2026.
About the Authors
Melissa Landers
Founder and Vice President,
Shepherd Safety Services at Two Labs
Melissa Landers has more than 25 years of management consulting experience, with 22 in the biopharma industry. She is focused on supporting regulatory, medical affairs, and commercial launch leadership teams in developing and executing REMS programs, post-marketing safety requirements, process improvements, launch strategies, and complex program management. Prior to joining Shepherd Safety Services at Two Labs, Melissa was a managing director in the Risk and Program Management Advisory Group at Syneos Health Consulting. Melissa holds a bachelor’s degree in journalism, with an emphasis on marketing and public relations, from the University of Georgia.