Key takeaways:
- Internal FDA documents consistently affirmed the safety of mifepristone over more than a decade, despite ongoing public controversy and litigation.
- Regulatory decisions around the mifepristone REMS evolved incrementally, shaped by evidence review, external events such as the COVID-19 pandemic, and statutory constraints.
- FDA staff scientists’ recommendations were largely evidence-based and varied by context, while occasional divergence from scientific review reflected higher-level regulatory or political considerations.
According to a new qualitative analysis published January 12, 2026, in JAMA, investigators provided a detailed examination of how the FDA has regulated mifepristone for over 10 years based on thousands of internal agency documents collected via the Freedom of Information Act. Overall, from 2011 to 2023, FDA oversight for mifepristone has been largely shaped by scientific evidence and a “cautious regulatory approach led by scientists at the agency,” the study authors noted, although continued debate surrounding the Risk Evaluation and Mitigation Strategy (REMS) remains.1
Background on mifepristone and FDA oversight
Mifepristone, a progesterone receptor antagonist with antiglucocorticoid activity, is most widely used in combination with misoprostol for pregnancy termination. It is also approved for the control of hyperglycemia in adults with endogenous Cushing syndrome who are not candidates for curative surgery. According to the study authors, consensus exists among the United States and international professional associations that “mifepristone is effective for pregnancy termination and that serious complications, such as heavy bleeding or sepsis, are very rare.”2,3
However, since its initial FDA approval in 2000, mifepristone has been subject to heightened regulatory oversight and intense scrutiny, despite broad consensus among professional associations and regulatory authorities that it is effective and that serious complications are very rare.1
The authors reviewed 5,239 pages of FDA documents spanning June 2011 to January 2023, including sponsor-submitted REMS assessments, internal FDA reviews, memos, and regulatory correspondence. Their analysis focused on the FDA’s rationale for establishing, maintaining, modifying, or removing specific regulatory elements over time, identifying 5 key moments in the history of the mifepristone REMS program.
Five key moments of mifepristone regulation
The first occurred in June 2011, when mifepristone was formally transitioned into the REMS framework following passage of the Food and Drug Administration Amendments Act. At that time, the FDA largely carried forward restrictions that had existed under an earlier regulatory pathway, formalizing them as Elements to Assure Safe Use, including prescriber certification, restricted distribution settings, and documentation of safe-use conditions.
In October 2013, FDA leadership requested a reevaluation of whether the REMS was still necessary. Internal reviews concluded that “the overall safety profile of Mifeprex has not changed over the last 6-7 years and is consistent with current product labeling.” Nonetheless, FDA scientists ultimately recommended maintaining the REMS, citing limited clinician familiarity with medical abortion and concerns about distribution challenges.
A third inflection point followed a sponsor-requested label change in 2015 that proposed extending gestational age limits and modifying dosing and prescriber qualifications. After reviewing clinical evidence and 16 years of postmarketing safety data, the FDA concluded that “overall, the rate of deaths and SARs is acceptably low,” approving the label changes in 2016 while retaining several REMS elements.
The COVID-19 pandemic prompted renewed scrutiny of in-person dispensing requirements in 2020 and 2021. Internal FDA memos acknowledged that telemedicine could achieve the goals of counseling and documentation, and staff scientists recommended enforcement discretion during the public health emergency. Although the agency initially opposed litigation challenging the requirement, it later adopted a policy of non-enforcement and formally removed the in-person dispensing mandate in 2021.
The final key moment came with a comprehensive REMS reassessment in November 2021. FDA reviewers again affirmed the drug’s safety, citing the absence of new safety concerns and extensive published evidence. The agency ultimately replaced in-person dispensing with a pharmacy certification system while retaining prescriber certification and a patient agreement form.
Across these regulatory milestones, the authors identified consistent themes. Internal FDA scientists repeatedly affirmed mifepristone’s well-characterized safety profile, grounding recommendations in evidence rather than ideology. Although isolated instances suggested divergence between scientific review and leadership decisions, the overall regulatory trajectory reflected cautious, incremental adjustments rather than abrupt shifts.
The authors concluded that mifepristone’s regulatory history illustrates how the FDA has navigated drug safety oversight in a highly politicized environment, emphasizing scientific evidence while balancing statutory obligations, external pressures, and evolving clinical practice.
References:
- Dilek S, Rosen J, Levashkevich A, Sharfstein JM, Alexander GC. The US Food and Drug Administration’s regulation of mifepristone. JAMA. Published online January 12, 2026. doi:10.1001/jama.2025.23091
- Spitz IM, Bardin CW, Benton L, Robbins A. Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med. 1998;338(18):1241-1247. doi:10.1056/NEJM199804303381801
- Gatter M, Cleland K, Nucatola DL. Efficacy and safety of medical abortion using mifepristone and buccal misoprostol through 63 days. Contraception. 2015;91(4):269-273. doi:10.1016/j.contraception.2015.01.005
