In 2007, Congress expanded the FDA’s post approval authority with the Food and Drug Administration Amendments Act. Specifically, the act allowed the FDA to institute Risk Evaluation and Mitigation Strategies (REMS) for new and already approved drugs. REMS plans add communication, certification, and monitoring requirements for drug usage. Since 2007, the FDA has created and maintained REMS for medication with “serious safety concerns to help ensure the benefits of the medication outweigh its risks.”[1] The FDA currently holds 60 active REMS plans and 206 have been released.

Some REMS plans focus on communicating risks to doctors and pharmacists. For example, the most recently released REMS plan for the drug Blincyto followed this form. Blincyto is a bispecific monoclonal antibody targeting the CD19 antigen on B cells. The drug is administered intravenously to treat a form of acute lymphoblastic leukemia. From 2014- 2022 the Blincyto REMS plan included a communication plan to alert healthcare providers, pharmacists, and professional societies of life-threatening risks such as Cytokine Release syndrome (CRS) and Neurological Toxicities.[2] 

In comparison, many REMS plans include requirements for administration by only certified health care facilities that are adequately trained to counsel patients and monitor patients for adverse events.[3] For example, the REMS plan for Lemtrada requires prescribers, healthcare facilities and pharmacies to enroll and become certified to prescribe or dispense the drug. Lemtrada is administered intravenously to treat relapsing multiple sclerosis. Like Blincyto, it is a monoclonal antibody. The need for certified facilities may limit the availability of the drug. While there are 3 facilities in Palo Alto certified to administer the drug, there are no certified facilities south of Palo Alto along the coast of California until you reach the greater Los Angeles area.[4] In Nebraska, a state of almost 2 million people, there are only 4 certified facilities. In areas far from one of the certified centers, patients may not have access to the drug. 

The limited access story demonstrated by Lemtrada is not unique. In 2022, Ameet Sarapatwari and colleagues published a qualitative study of patients and caregivers of those patients receiving drugs with REMS programs. Of those interviewed 54% reported burdens unrelated to insurance during their course of treatment.[5] Burdens included the need for travel that may be outside of public transportation or patient transport service ranges. One conclusion of their study was the need to improve the quality of REMS plans to promote efficient medication access. Specifically, the authors recommend the FDA “require manufacturers to routinely report the number and location of certified providers and should require more active provider recruitment in underserved areas.”[6]

Are there ways to balance the need to protect patients from adverse effects without limiting the access to drugs? One option may be to fashion more REMS plans like the modified REMS plans for one of the medical abortion drugs, Mifepristine. On January 3, 2023, the FDA permanently removed the in person dispensing requirement for Mifepristine in favor of a new pharmacy certification requirement. The in person dispensing requirement was previously lifted on a temporary basis at the start of the COVID-19 pandemic.

The American College of Obstetricians and Gynecologists (ACOG) has long advocated for the removal of strict REMS requirements in large part because of the barriers to access they created that disproportionately affected people of color and people living far from health care professionals.[7] 

The Mifepristone model could be a creative solution to similar barriers to access for other medications as well. Virtual proscribing decreases some of the burden on taking a REMS drug. Rather than a patient needing to find a local doctor who is certified to prescribe a drug or a patient requesting their physician become certified, the physician can refer the patient to a certified physician virtually. If a drug can be taken at home, mail-order pharmacies can help provide access for patients in remote areas. The Mifepristone model does not remove all barriers, however, because it does not remove the certification requirement for pharmacies that dispense the drug. If drug safety depends on in person administration, patients will still need access to a certified facility. 

As we develop, test, and approve novel drugs, REMS plans will continue to be necessary to facilitate safe use of medication with serious safety risks. In developing REMS plans, the FDA should also consider how the plans limit access to medication and should consider creative solutions like virtual prescribing to increase healthcare equity. 

[1] https://www.fda.gov/drugs/drug-safety-and-availability/risk-evaluation-and-mitigation-strategies-rems

[2] https://www.accessdata.fda.gov/drugsatfda_docs/rems/Blincyto_2017-07-12_Full.pdf

[3] https://www.accessdata.fda.gov/scripts/cder/rems/index.cfm?event=RemsData.page (56 [93%] include “elements to assure safe use’ (ETASU). REMS with ETASU typically require clinicians or health care settings to become certified prior to prescribing and to participate in additional REMS activities, such as training, patient counseling, and monitoring.)

[4] https://www.lemtradarems.com/locator/calloutsearch

[5] https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788241

[6] https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2788241

[7] https://www.acog.org/clinical/clinical-guidance/practice-advisory/articles/2023/01/updated-mifepristone-rems-requirements