By: Nicholas H. Meza, J.D., M.P.H., Richard Davis, J.D., Theresa DeAngelis, J.D.
On Friday April 21, 2023, the United States Supreme Court granted the application filed by the Food and Drug Administration (“FDA”) and Danco Laboratories, LLC[1] to stay the lower court’s decision in the high-profile mifepristone litigation. The lower court’s decision reversed the FDA’s original approval of mifepristone (issued in 2000) and has created serious obstacles for all entities and individuals involved in the mifepristone distribution supply chain. The Supreme Court’s decision temporarily ensures nationwide access to mifepristone while the merits of the lawsuit are litigated in the Fifth Circuit Court of Appeals. The Fifth Circuit heard oral arguments related to this litigation on May 17th, 2023, and generally expressed sympathy for the parties seeking to limit the sale of mifepristone.
This article provides a summary of mifepristone regulation, the mifepristone litigation, and concludes with implications for entities involved in the manufacture, sale, and dispensation of mifepristone.
I. Background on Mifepristone Regulation
Over 20 years ago, in 2000, the FDA approved mifepristone. The drug blocks the progesterone hormone needed for a pregnancy to continue and is used with misoprostol to end pregnancies through ten weeks gestation. Mifepristone was initially approved under “Subpart H” regulations implemented under the Federal Food Drug and Cosmetic Act (“FFDCA”) to expedite the approval of “new drug products that have been studied for their safety and effectiveness in treating serious or life-threatening illnesses.”[2]
FDA imposed “restrictions to assure safe use” including an in-person dispensing requirement and permitted the drug to be distributed only to prescribers who agreed to dispense it in certain healthcare settings, by or under the supervision of a qualified physician who attested to the ability to accurately date pregnancies and diagnose ectopic pregnancies. Specifically, the restrictions required that mifepristone be used for pregnancies under 50 days gestation, in connection with three in-person office visits,[3] with supervision of a qualified physician, and where all adverse events would be reported. Today, these types of restrictions in connection with FDA drug approval are referred to as Risk Evaluation and Mitigation Strategy (“REMS”).[4]
In 2016, the FDA updated the drug label for mifepristone, expanding use through ten weeks of pregnancy. The FDA also made major changes to mifepristone’s REMS, including: (1) increasing the maximum gestational age at which a woman can use the drug from 49 to 70 days; (2) reducing the number of required in-person office visits from three to one; (3) allowing non-doctors to prescribe and administer the chemical abortions drugs; and (4) eliminating the requirement for prescribers to report non-fatal adverse events from chemical abortion.[5] In 2021, FDA announced “enforcement discretion” to allow mifepristone to be dispensed through the mail during COVID-19. Finally, on January 3, 2023, FDA approved a modified REMS, permanently lifting the in-person dispensing requirement.[6]
II. Mifepristone Litigation
In November of last year, several months after the Supreme Court’s decision in Dobbs v. Jackson Women’s Health Organization,[7] a coalition of doctors and medical associations filed a lawsuit in the United States District Court for the Northern District of Texas to, inter alia, vacate the FDA’s approval of mifepristone, FDA’s 2016 REMS changes, and the 2021 mail order decision.[8]
In essence, plaintiffs argued that the FDA’s approval and subsequent administrative actions with respect to the drug violated the federal Administrative Procedure Act. Plaintiffs argued that: (1) to approve the drug, FDA improperly relied on Subpart H’s accelerated approval because pregnancy is not a life-threatening illness; (2) FDA improperly ignored scientific evidence in approving and setting distribution controls for the drug; and (3) the Comstock Act, an 1873 obscenity law, prohibits the mailing of any medication used for abortion.[9]
In response, the FDA argued, inter alia, that it properly exercised its authority under the FFDCA and applied its scientific expertise when approving and making determinations about mifepristone and that the Comstock Act is inapplicable when the sender of the product intends the product to be used lawfully.
Deciding on plaintiffs’ and FDA’s arguments, on April 7, 2023, Judge Matthew Kacsmaryk issued a preliminary injunction, staying the FDA’s 23- year-old approval of mifepristone. In his ruling, Judge Kacsmaryk found that a preliminary injunction was appropriate due to the “substantial threat of irreparable harm” arising both from claims that the use of mifepristone is dangerous and that the FDA did not appropriately follow its approval processes in approving mifepristone—notwithstanding that FDA has repeatedly said that the use of mifepristone is safe, effective, and that any adverse effects are a “rarity.”
Within the hour of this ruling, Washington federal court judge Thomas O. Rice issued an order in a similar case,[10] which directly contradicted the Texas ruling. Essentially, the Washington ruling ordered the FDA to make no changes regarding the availability of mifepristone in 17 states and the District of Columbia which expressly permit the drug’s use for medication abortions.
Mifepristone’s legality was immediately thrown into question in light of the conflicting rulings. The FDA immediately appealed the Texas District Court’s decision to the Fifth Circuit. The Fifth Circuit stayed the district court’s suspension of FDA’s original approval of mifepristone. But it would not stay the suspension of subsequent updates to the conditions on the drug’s use, which have governed the drug’s distribution for seven years. In effect, the Fifth Circuit’s order permitted mifepristone to remain on the market, but simultaneously made it illegal to send the drug across state lines by eliminating the effective date of the 2016 Major REMS Changes.
The FDA and Danco Laboratories petitioned the Supreme Court for an emergency stay of the district court’s order pending the appeal of the case. The Supreme Court granted the stay of the lower court’s ruling in a short opinion order[11] and sent the case back to the Fifth Circuit for the Fifth Circuit to consider the case on its merits. Thus, the Supreme Court granted the stay of the April 7, 2023 order of the United States District Court of the Northern District of Texas pending the disposition of the appeal in the United States Court of Appeals for the Fifth Circuit and a disposition for a writ of certiorari to the Supreme Court, if such a writ is timely sought. Should the Supreme Court deny certiorari, the stay will terminate automatically. If the Supreme Court grants certiorari, the stay shall terminate upon the Supreme Court’s judgment.
In contrast to the brevity of the majority’s opinion order, Justice Alito wrote a lengthier dissent, finding Danco had not shown that they were “likely to suffer irreparable harm,” in the “presumably short period at issue” where Danco argued primarily that it could not continue to market mifepristone because the drug would be mislabeled, and that distribution could not resume until Danco satisfied certain regulatory requirements. However, according to Justice Alito, this “would not take place, … unless the FDA elected to use its enforcement discretion to stop Danco, and the applicants’ papers do not provide any reason to believe the FDA would make that choice.” Justice Alito cited that the FDA had previously invoked its enforcement discretion to permit the distribution of mifepristone in a way that the regulations then in force prohibited.
As a result of the stay, mifepristone will be available in interstate commerce at least until the Fifth Circuit ruling , which will likely end up before the Supreme Court again.
Most recently, the three-judge panel of the Fifth Circuit heard approximately two hours of oral arguments on May 17th, 2023, including whether plaintiffs could be found to have legal standing by showing they would suffer a real injury if approval of and access to mifepristone remains the same. FDA argued that the plaintiffs waited over two decades after mifepristone’s approval to bring their case. The panel expressed criticism of FDA and sympathy for the plaintiffs generally.
III. Implications
A Fifth Circuit ruling in favor of the plaintiffs would have sweeping effects beyond starkly curtailing or potentially eliminating the availability of mifepristone. Notwithstanding the potential prohibition of patients across the country to access mifepristone, as described by pharmaceutical industry stakeholders in an amicus brief filed with the Supreme Court, “If allowed to take effect, the district court’s decision will result in a seismic shift in the clinical development and drug approval processes, erecting unnecessary and unscientific barriers to the approval of lifesaving medicines, chilling drug development and investment, threatening patient access, and destabilizing the pharmaceutical industry.”[12] Such a ruling would constitute a radical departure from court deference that is given to the scientific and medical judgment of the FDA — the regulatory agency with scientific expertise designated by Congress as the sole regulator of drugs.
This dramatic departure from traditional deference to the FDA ostensibly means that a court can “undo” FDA approval for a drug it “doesn’t like.” For example, the precedent set by such a decision could result in a court undoing the approval of gender affirming drugs/puberty blockers, which are currently being targeted at the state level in the same manner in which abortion-inducing drugs are being targeted.
Pharmaceutical manufacturers could also invoke such a decision as a weapon to challenge FDA approval of competitor drugs. In these ways, the FDA approval process—and medications which are relied on by patients—could be taken off the market due to one judge’s opinion.
Also at issue is whether the Fifth Circuit will apply the Comstock Act to prohibit the mailing of any abortion-inducing drug in the United States. In some respects, such a ruling would provide clarity regarding the legality (or illegality) of interstate dispensing mifepristone, something that mail-order pharmacies and wholesale distributors struggled to monitor as a patchwork of states implement medication abortion bans. On the other hand, should the court rule in favor of the FDA, pharmacies, wholesale distributors and providers will need to continue to monitor state-specific bans and, perhaps, future challenges to such bans as a basis of federal preemption.
Ultimately, the Fifth Circuit has espoused its openness to such a ruling but it remains to be seen whether the Supreme Court would grant certiorari and how the Supreme Court would treat such a ruling. Stakeholders and the public are only left to wait.
[1] Danco Laboratories, LLC is the manufacturer which holds the approved New Drug Application for Mifeprex (mifepristone) Tablets.
[2] 21 CFR § 314.500 et seq.
[3] The first two visits to administer mifepristone and the third to assess any complications and ensure there were no fetal remains in the womb. Specifically, requirements included in-person dispensing by or under the supervision of a qualified physician, dispensing of misoprostol at the provider’s office or clinic, and a follow up visit 14 days later. See generally, https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/information-about-mifepristone-medical-termination-pregnancy-through-ten-weeks-gestation
[4] In 2007, the FFDCA was amended to authorize the FDA to require a REMS for a drug if the FDA deems it is necessary to ensure that the drug’s benefits outweigh its risks.
[5] After the generic version of mifepristone was approved in 2019, one unified REMS was issued for both generic and brand name versions.
[6] Also, in January of 2023, the FDA modified the REMS to provide a process for pharmacies to become certified by the manufacturer of the drug to dispense mifepristone.
[7] 142 S. Ct. 2228 (2022), available at, https://www.supremecourt.gov/opinions/21pdf/19-1392_6j37.pdf
[8] Alliance for Hippocratic Medicine et al. v. U.S. Food and Drug Administration et al., No. 2:22-cv-223 (N.D. Tex. filed Nov.18, 2022).
[9] As a practical matter, the mifepristone litigation as described above applies solely to FDA approval related to brand and generic versions of mifepristone, which are FDA-approved for purposes of inducing a medication abortion. The litigation does not challenge the FDA approvals for other drugs containing mifepristone, such as Korlym, a drug used to treat Cushing’s syndrome.
[10] Washington et al. v. United States Food and Drug Administration et al., No. 1:23-cv-03026 (E.D. Wash. filed Feb. 23, 2023).
[11] Danco Lab’ys, LLC v. All. for Hippocratic Med., 143 S. Ct. 1075 (2023).
[12] See Pharmaceutical Companies et al., Amicus Brief, available at, https://www.supremecourt.gov/DocketPDF/22/22A902/263624/20230414164838799_2023-04-14%20SCOTUS%20Amicus%20Brief%20FINALa.pdf
