In litigation involving the Food and Drug Administration's (FDA's) approval process for mifepristone (a widely used medication abortion drug), the Fifth Circuit vacated a portion of a lower court order staying the FDA's initial approval of mifepristone. However, the Fifth Circuit affirmed the portion of the lower court's order that stayed the FDA's administrative actions from 2016 (and more recent years) that generally relaxed certain safeguards involving the use of mifepristone.
Overview of FDA's Mifepristone Approval Process (2000 to Present)
As background, the FDA approved mifepristone (under the brand name Mifeprex) in 2000 using a regulation that permits accelerated approval for new drugs that have been "studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful therapeutic benefit to patients over existing treatments" (21 C.F.R. §§ 314.500, 314.520 (Subpart H)). Mifepristone was approved:
With an initial gestational age limit of up to seven weeks.
For use in coordination with a drug called misoprostol, which was already approved at the time.
Subject to restrictions that included an in-person dispensing requirement (initially by doctors in a hospital or similar setting).
In 2002, two of the doctors in this litigation asked the FDA (in a citizen petition) to withdraw its approval, but the FDA denied that petition in 2016.
Began reviewing the REMS for mifepristone to determine whether it should be changed.
In early 2023, the REMS was updated to remove the in-person dispensing requirement and impose a pharmacy certification rule. Under the latter provision, pharmacies that dispense mifepristone must be specially certified by (among other requirements) being able to ship mifepristone using a shipping service with tracking capabilities and designating an authorized representative to manage the certification on the pharmacy's behalf (including to comply with the governing mifepristone REMS program).
Doctors and associations representing doctors brought a lawsuit challenging the FDA's initial approval of mifepristone, and the FDA's subsequent actions, under the Administrative Procedure Act (APA). Earlier this year, a Texas district court granted the doctors' request for a preliminary injunction and issued an order that (subject to a seven-day stay):
Suspended the FDA's approval of mifepristone.
Essentially prohibited mifepristone from being made available in interstate commerce.
The Fifth Circuit stayed part of the Texas district court's order affecting the FDA's initial approval of mifepristone in 2000, but not portions of the ruling that suspended later FDA actions (including the agency's removal of an in-person dispensing requirement).
The Supreme Court later issued a stay of the entire Texas district court's order pending:
The Fifth Circuit's disposition of the appeal.
Any timely requests for the Supreme Court to review the Fifth Circuit's decision.
Mifepristone to Remain Available Under Conditions That Existed in 2016
On appeal, the Fifth Circuit affirmed part of the district court's ruling (regarding the FDA's actions from 2016 and more recent years). However, the Fifth Circuit also vacated part of the district court's ruling concerning the FDA's initial approval of mifepristone from 2000.
Doctors and Medical Associations Had Standing to Sue
On a threshold issue, the Fifth Circuit agreed that the doctors had associational standing based on their injuries resulting from the FDA's actions. Specifically, the Fifth Circuit agreed with the doctors' arguments that they suffered the following injuries:
The doctors were forced to choose between treating patients who experienced complications from medication abortions (which could involve performing surgical abortions to remedy the complications) and violating their conscience rights.
Treating mifepristone patients took away time and resources from the doctors' other patients.
The doctors were exposed to malpractice liability and higher insurance costs from treating mifepristone patients.
The Fifth Circuit rejected the FDA's argument that the doctors could decline to treat individuals who experienced complications from a medication abortion if another doctor was available. In doing so, the court noted the government's contrary positions in 2022 guidance concerning the Emergency Medical Treatment and Labor Act (EMTALA) and litigation challenging that guidance.
The court also concluded that the doctors' injuries were fairly traceable to the FDA's actions from 2016 that expanded access to mifepristone and removed the in-person dispensing requirement.
Regarding the FDA's approval of the generic version of mifepristone, however, the Fifth Circuit held that the doctors failed to show that the generic version contributed to the doctors' injuries. Accordingly, the Fifth Circuit vacated the portion of the district court order that stayed the effective date of the generic version's approval.
Doctors' Claim Challenging Initial Approval Was Time-Barred
Before reaching the merits, the Fifth Circuit addressed the timeliness of the doctors' claim challenging the FDA's initial approval of mifepristone in 2000. The district court ruled that this claim was not time-barred by the six-year statute of limitations—relying on a "reopening doctrine" and equitable tolling theory. (The reopening doctrine essentially permits a plaintiff to challenge an administrative action outside the applicable timely timeline if an agency later reconsiders its original action in a subsequent decision.)
Disagreeing with the district court, the Fifth Circuit concluded that the FDA's regulatory actions in 2016 and 2021 were not a reexamination of its earlier administrative choices that reopened the statute of limitations.
Regarding the FDA's 2016 amendments, the Fifth Circuit concluded that the changes to regulating medication abortion were not a significant departure from the FDA's original approval of medication abortion in 2000. For example, although the 2016 amendments expanded mifepristone's availability, they did not alter the FDA's assumptions regarding the drug's safety and effectiveness. Rather, the court observed, the FDA—in deciding to relax several of the mifepristone REMS in 2016—took as a given the restrictions it had imposed in 2000.
Likewise, the Fifth Circuit concluded that the FDA did not reopen the 2000 approval when it denied the doctors' 2019 citizen petition. The court reasoned that the 2019 petition challenged the FDA's 2016 removal of certain protections but did not ask the FDA to reconsider the underlying approval of mifepristone.
In addition, the Fifth Circuit concluded that the FDA did not reopen the 2000 approval by suspending the in-person dispensing requirement. The court reasoned that suspending this requirement did not involve re-evaluating the underlying approval and was more of an "incremental adjustment" to the original approval.
The Fifth Circuit also concluded that the equitable tolling theory did not apply. The court reasoned that the doctors failed to demonstrate why they could not have filed their lawsuit within the six-year statute of limitations.
As a result, the Fifth Circuit held that the doctors' challenge to the FDA's 2000 approval was time-barred—and that the doctors were not likely to succeed on the merits of that claim.
Preliminary Injunction Analysis: Likelihood of Success on Merits
The doctors had greater success concerning their challenges to the FDA's 2016 amendments and 2021 non-enforcement decision. Here, the Fifth Circuit affirmed the district court, holding that the doctors demonstrated the four requirements for receiving a preliminary injunction, namely:
A substantial likelihood of success on the merits.
A substantial threat of irreparable harm if an injunction is not issued.
A threatened injury that outweighs any harm that will result if the injunction is granted.
The grant of an injunction is in the public interest.
The Fifth Circuit's analysis focused largely on the first of these factors.
2016 Changes to REMS
Regarding the challenge to the 2016 amendments, the Fifth Circuit held that the doctors were likely to succeed on the merits because the FDA failed to consider an important aspect of the issue—specifically, the cumulative effect of the changes. The doctors argued that the FDA failed to consider the combined impact (under its 2016 amendments) of increasing the gestational age, permitting mifepristone to be prescribed by non-physicians, removing the in-person requirement for administering misoprostol and the follow-up appointment, removing a requirement that prescribers report non-fatal adverse events, changing the misoprostol administration method, and changing the mifepristone dose. Although the FDA had evaluated each change individually, the agency conceded that it had not considered the cumulative effect of these changes.
In addition, the Fifth Circuit agreed with the doctors that the FDA ignored a second major issue by failing to consider whether it needed to continue collecting non-fatal adverse events after significantly changing the REMS. The court rejected the FDA's argument that the mifepristone risks were already known—so that continued reporting of non-fatal adverse events was not needed. The court observed that the FDA's easing of mifepristone-related restrictions in 2016 could have affected the risks associated with the drug's use. The court was not persuaded that the drug manufacturer's obligation to report serious adverse events provided the FDA sufficient data to consider mifepristone's risk.
Accordingly, the court held that the FDA likely violated the APA by failing to consider important aspects of the 2016 amendments.
2021 Regulatory Actions
The Fifth Circuit also concluded that the FDA's 2021 non-enforcement decision was arbitrary and capricious. The court reasoned that the FDA relied on:
Adverse event data in the FDA Adverse Event Reporting System (FAERS), which was limited to voluntarily provided data.
Literature that was "not inconsistent" with its decision.
The court noted that—because of reduced reporting requirements under the FDA's own 2016 amendments—the agency could no longer access prescriber data about adverse consequences related to mifepristone. The court reasoned that because the FDA's own actions were the reason for a lack of probative data, the agency could not then cite lack of information in arguing to remove additional protections at a later time.
Irreparable Harm and Balance of Equities
The Fifth Circuit concluded that the doctors were likely to suffer irreparable harm in the absence of a preliminary injunction. As the court noted, there was no legal remedy for the doctors' injuries from having to violate their conscience rights. Even the doctors' economic injuries related to increased liability and insurance costs were irreparable, the court added, given the doctors' inability to recover monetary damages (due to the FDA's sovereign immunity).
The court concluded that the balance of the equities weighed in favor of an injunction.
Stay of FDA's Post-2000 Actions
In sum, the Fifth Circuit vacated the district court's stay order regarding the FDA's:
Initial approval of mifepristone (as likely time-barred).
2019 approval of a generic version of the drug (because the doctors failed to show that they were injured by this action).
However, the Fifth Circuit affirmed the lower court's stay order as to the FDA's 2016 amendments and 2021 non-enforcement decision. In doing so, the Fifth Circuit rejected the drug manufacturer's argument that the stay would be disruptive because of the changes it would need to make to comply with a pre-2016 REMS. The Fifth Circuit indicated that, given the Supreme Court's stay of the district court order, the manufacturer would have sufficient time to prepare for compliance with an earlier REMS.
For now, the Fifth Circuit's ruling will have little effect on the availability of mifepristone. This is because the Supreme Court stayed the district court's order from earlier this year pending disposition of any requests to the Supreme Court to review the Fifth Circuit's ruling.