ABORTION ACCESS

Did the U.S. Food and Drug Administration Lawfully Remove Requirements for a Drug Used to Voluntarily Terminate a Pregnancy?

 CASE AT A GLANCE

In 2000, the U.S. Food and Drug Administration (FDA) approved mifepristone as part of a two-drug regimen to end an early pregnancy. As part of the approval, FDA imposed certain requirements on the drug’s use. In 2016, FDA relaxed those requirements by extending the approved use from seven weeks to ten weeks, reducing the number of required in-person clinical visits, and allowing certified nonphysician health-care providers to prescribe the drug. Then, in 2021, FDA eliminated the in-person dispensing requirement.

Food and Drug Administration v. Alliance for Hippocratic Medicine and Danco Laboratories, L.L.C. v. Alliance for Hippocratic Medicine

Docket Nos. 23-235 and 23-236

Argument Date: March 26, 2024 From: The Fifth Circuit

by Steven D. Schwinn
University of Illinois Chicago School of Law, Chicago, IL

Introduction
 

Individual doctors, including emergencyroom doctors, and doctor organizations sued the U.S. Food and Drug Administration (FDA), arguing that FDA made the changes without reasoned decision-making, in violation of the Administrative Procedure Act (APA). The United States Court of Appeals for the Fifth Circuit stayed the effective dates of the changes and in the alternative imposed a preliminary injunction.

Issue
 

1. Do the plaintiffs have standing? 
2. Did FDA base its 2016 and 2021 actions on reasoned decision-making? 
3. If not, did the Fifth Circuit grant proper preliminary relief?

Facts
 

Background on Mifepristone

In 2000, after a four-year review of the initial application, FDA approved mifepristone as part of a two-drug regime to end an early pregnancy. (FDA initially approved mifepristone under the brandname Mifeprex, sponsored by Danco Laboratories, LLC, an appellant (along with FDA) in this case.) FDA’s approval called for women using the drug to make three in-person clinical visits: first, to take mifepristone; next, two days later, to take misoprostol, the second drug; and finally, to follow up to confirm the termination of the pregnancy. FDA determined that mifepristone, used this way, was safe and effective for women through seven weeks of a pregnancy. FDA reapproved essentially these same requirements in 2011. (FDA reapproved the requirements as a “risk evaluation and mitigation strategy” (REMS). REMS, which Congress added to the Food, Drug, and Cosmetic Act in 2007, authorizes FDA to issue a “strategy” for drug use whenever FDA determines that such a “strategy” is necessary to ensure that the drug’s benefits outweighed its risks.)

In 2016, FDA approved three changes to the REMS for mifepristone. First, FDA expanded the drug’s approved use from seven weeks to ten weeks. Next, it reduced the number of required in-person clinical visits from three to one. Third, it allowed nonphysician health-care providers who were licensed to prescribe drugs (like nurse practitioners) to prescribe mifepristone. FDA based these changes on numerous studies of mifepristone’s safety and efficacy.

At the same time, FDA also modified a prior provision that required prescribers to report certain adverse events, like hospitalizations and blood transfusions, to the drug’s sponsor. FDA determined, based on “15 years of reporting,” that the requirement to report nonfatal events was no longer warranted, and that this information could be “collected in the periodic safety update reports and annual reports” by the drug’s sponsor—“as with all other approved drugs.”

In support of the 2016 changes, FDA concluded that serious adverse events resulting from mifepristone are “exceedingly rare,” and that mifepristone’s use under the revised conditions would be “safe.” In particular, FDA referenced published studies of tens of thousands of women showing that hospitalization after mifepristone use occurs in between 0 percent and 0.7 percent of cases, and that bleeding requiring transfusion occurs in between 0 percent and 0.5 percent of cases.

In 2019, FDA approved an application for a generic version of mifepristone. The same REMS covers both versions.

In April 2021, FDA announced that it would decline to enforce the in-person dispensing requirement in light of the COVID-19 pandemic. FDA said that the decision “was the result of a thorough scientific review by [agency] experts” who evaluated “clinical outcomes data and adverse event reports.” (Earlier in the pandemic, in July 2020, a federal district court enjoined FDA’s enforcement of the in-person dispensing requirement. American College of Obstetricians & Gynecologists v. FDA, 472 F. Supp. 3d 183 (D. Md. 2020). The injunction remained in place until January 2021, when the Court stayed it. FDA v. American College of Obstetricians & Gynecologists, 141 S. Ct. 578 (2021).) In December 2021, FDA determined that the in-person dispensing requirement was no longer necessary, and in 2023, after this case was filed, FDA removed the in-person dispensing requirement from the REMS. (FDA retained the requirement that only authorized health-care providers can prescribe mifepristone, and only after a patient signed a form that provides information on the drug and instructions on follow-up care, if necessary.)

Challenges to Mifepristone

In 2002, the American Association of Pro-Life Obstetricians & Gynecologists (AAPLOG) and the Christian Medical & Dental Associations (CMDA) filed a citizen petition with FDA asking the agency to withdraw its 2000 approval of mifepristone. FDA denied the petition in March 2016 (on the same day that it approved the changes to mifepristone’s requirements). FDA said that “well-controlled clinical trials supported the safety” of mifepristone in 2000, and that “over 15 years of postmarketing data and many comparative clinical trials in the United States and elsewhere continue to support [its] safety.”

Then, in 2019, AAPLOG and the American College of Pediatricians (ACPeds) filed a citizen petition challenging FDA’s 2016 changes to mifepristone’s requirements, and asking the agency to retain the in-person dispensing requirement. FDA denied the petition in December 2021. Based on the scientific literature, FDA concluded that “the in-person dispensing requirement is no longer necessary to assure the safe use of mifepristone.”

Most recently, in November 2022, the Alliance for Hippocratic Medicine, AAPLOG, CMDA, ACPeds, and four individual doctors sued FDA, challenging its 2000 approval of misoprostol the second drug, used with mifepristone, the 2016 changes, the 2019 approval of generic mifepristone, the 2021 exercise of enforcement discretion, and the 2016 and 2021 denials of the citizen petitions.

The district court stayed the challenged actions. The government and Danco appealed and sought a stay of the district court ruling pending appeal. The Fifth Circuit stayed the district court ruling as to FDA’s 2000 approval of mifepristone, but otherwise left the ruling in place. The Court then stayed the district court stay in its entirety pending appeal.

After additional briefing and argument, the Fifth Circuit vacated FDA’s 2016 and 2021 actions. This appeal followed.

Case Analysis

This case raises three issues. Let’s take them one at a time. (FDA and Danco each submitted a brief. Because their arguments are similar, we refer together as FDA’s arguments.)

Standing

The government argues that the plaintiffs lack standing, because they do not prescribe mifepristone, and because FDA’s actions that allow other health-care providers to prescribe mifepristone “do not require [the plaintiffs] to do or refrain from doing anything.” The government says that the Fifth Circuit was wrong to hold that some of the plaintiffs’ members are injured because they might have to treat women who suffer serious side effects from mifepristone. The government claims that this “statistical” injury has been flatly rejected by the Court.

Moreover, the government contends that the plaintiffs can’t point to a single member who has suffered a sufficient injury for standing, and that the plaintiffs’ proffered injuries are too speculative. (For example, the government asserts that the plaintiffs “cannot identify even a single case where any of their members has been forced to” “complet[e] an abortion for a woman who presents in an emergency room with an ongoing pregnancy.”) In any event, the government claims that the plaintiffs’ standing “theories are independently foreclosed because they rest on the untenable premise that emergency-room doctors suffer an Article III injury whenever they provide emergency care.”

The government argues that the plaintiffs also lack standing because they cannot show that FDA’s challenged actions caused their asserted injuries. “If those injuries occur at all, they will be linked to FDA’s actions only by a long and attenuated causal chain involving independent actions by other providers, patients, and third parties.”

Finally, the government argues that the plaintiffs lack organizational standing. According to the government, “[t]his Court has never accepted [the plaintiffs’] suggestion that an organization can manufacture standing to challenge an agency action merely by expending resources on that challenge.”

The plaintiffs counter that “they are facing multiple concrete injuries” resulting from FDA’s actions. For one, they say that they suffer “conscience harms” related “to taking the life of an unborn child” and their “complicity” in doing so. For another, they contend that “the emergency situations expressly and repeatedly contemplated by FDA cause [them] to divert time and resources away from their labor and delivery practices and increase their malpractice risks.”

The plaintiffs argue next that they can trace their harms to FDA’s actions. They contend that FDA’s 2021 action (removing the initial in-person-visit requirement) “strips away the best opportunity to diagnose dangerous ectopic pregnancies and accurately assess gestational age.” They claim that FDA’s 2016 changes (increasing the gestationalage limit and removing the follow-up-visit requirement) “heighten the risk” that they will have to “participate in elective abortions.”

FDA’s Actions

The government argues first that FDA’s 2016 changes “were supported by an exhaustive review of a record including dozens of scientific studies and decades of safe use of mifepristone by millions of women in the United States and around the world.” The government says that the Fifth Circuit was wrong to vacate FDA’s 2016 actions on the ground that FDA “failed to cite a study examining the combined effect of all the relevant changes.” It claims that there is no basis for such a requirement, and that “in any event, FDA did cite a study that combined the relevant changes.”

The government argues next that it validly changed the reporting requirement for adverse events in 2016. The government claims that this change brings mifepristone “more in line with the reporting mechanism that applies to nearly all other FDA-approved drugs.” It says that it validly dropped the previous reporting requirement “[b]ased on more than 15 years of experience” with the drug, demonstrating that “the drug’s safety profile was well-established and serious adverse events were exceedingly rare.”

Finally, the government argues that its elimination of the in-person dispensing requirement in 2021 was valid. It says that the “actual experience during the pandemic,” among other things, led it to conclude “that the requirement was no longer necessary to ensure mifepristone’s safe use.” Moreover, the government contends that the Fifth Circuit wrongly concluded that FDA used flawed studies. The government asserts that the APA requires FDA “to act reasonably based on the information available,” not to use “perfect data.” The government claims that FDA met this standard here.

The plaintiffs counter that “FDA failed to engage in the reasoned decision-making the APA requires.” They say that FDA’s decision to remove the initial in-person-visit requirement was based on one data set that even “FDA concedes…cannot be used to estimate the incidence of adverse events or indicate the safety profile of a drug” and another set of studies that FDA “admitted…were ‘not adequate’ for that purpose.” Moreover, they contend that FDA lacked important information about the drug’s safety, because it earlier abandoned the requirement that mifepristone prescribers report nonfatal adverse events.

The plaintiffs argue that FDA’s 2016 actions (removing the follow-up-visit requirement, increasing the gestational age, allowing nondoctors to prescribe the drug, and ending the requirement for prescribers to report all serious adverse events) “failed to consider the cumulative impact of removing all these interrelated safeguards at once” and “failed to explain why it could extrapolate safety conclusions for its omnibus changes from studies that did not evaluate the changes as a whole.” They also claim that FDA relied on studies of safeguards (like ultrasound screenings) that “were not included in the approved regimen.”

Preliminary Relief

The government argues that even if the plaintiffs had standing, and even if they might succeed on the merits, “the Fifth Circuit erred in affirming sweeping preliminary relief.” The government says that the district court initially erred in “postponing” FDA’s actions, even though those actions had been “in effect for years.” And it claims that there is no good reason to issue a nationwide halt to FDA’s actions (which “threatens profound harms to the government, the healthcare system, patients, and the public”) when the “asserted injuries are at best attenuated” and when the “claims assert only that FDA failed adequately to explain its actions.”

The plaintiffs counter that the Fifth Circuit’s preliminary injunction is appropriately tailored. They say that all the standards for a preliminary injunction point in their favor. They emphasize that their harms are “irreparable,” and that the injunction would only reimplement the “safety standards that FDA required for 16 years and under which millions of women took mifepristone.”

Significance

Coming just shy of two years after Dobbs v. Jackson Women’s Health Organization, 597 U.S. 215 (2022), overturning Roe v. Wade, 410 U.S. 113 (1973), this case represents a next critical front in the ongoing debates over reproductive freedom. And the stakes are enormous. By 2021, medication abortions accounted for over half of all abortions in the United States. And FDA’s 2016 and 2021 actions made medication abortions even more accessible. Under these actions, women in states that still allow abortion can more easily gain access to medicationabortion drugs. Vacating or enjoining those changes would sharply limit access to abortion nationwide.

But whatever the Court says, this case won’t end debates over medication abortions. For one, FDA’s approval of mifepristone could preempt state laws restricting abortion. If so, women in states that restrict or prohibit abortion, including medication abortion, could still gain access to mifepristone. Cases are now pending in the federal courts but may not work their way up to the Court for some time.

For another, states that are bent on restricting or eliminating abortion continue to look for ways to prevent their residents from receiving abortion drugs through the mail. Many have pointed to the Comstock Act, which prohibits the delivery of contraception and items considered “obscene” through the U.S. Mail. But early this year the Department of Justice opined that the Comstock Act does not prohibit the U.S. Postal Service from delivering mifepristone and misoprostol, because those drugs could be used for purposes other than abortion, and therefore neither the sender nor the U.S. Postal Service can know how the pills will be used. The Department’s opinion drew sharp criticism, suggesting that debates over the Comstock Act have only just begun.

For a third, there is a safe and commonly used (at least internationally) alternative to the mifepristone– misoprostol regimen: a misoprostol-only regimen. While this is not currently approved by FDA, some U.S. telehealth organizations have been reportedly providing a misoprostol-only regimen for several years. We might expect to see more debates and even litigation around misoprostol, regardless of what the Court has to say about mifepristone.

Outside of the ongoing debates over reproductive rights, this case has independent significance for what it might say about FDA’s authority (and maybe about agencies’ authorities more generally). The Fifth Circuit’s ruling marks a truly exceptional break with the deference that federal courts traditionally give to FDA. As the government says, to its knowledge, “this case marks the first time any court has restricted access to an FDAapproved drug by second-guessing FDA’s expert judgment about the conditions required to assure that drug’s safe use.” That’s especially notable, given mifepristone’s exceptional safety record in the United States and abroad.

If the Court affirms the Fifth Circuit, the ruling could have important implications far beyond mifepristone (in particular, with regard to the evidence and methodologies that the Court might allow or disallow FDA to use in approving drugs and establishing their safety standards). And given this Court’s record in recent years of secondguessing agency judgments (and with more cases testing agency decision-making now before the Court), we might not be surprised if the Court similarly second-guesses FDA’s judgments here. But even if so, remember that FDA could have the final word by reapproving mifepristone under whatever standards the Court might set.

ATTORNEYS FOR THE PARTIES

• For Petitioner Danco Laboratories, LLC (Jessica Lynn Ellsworth, 202.637.5886)
• For Petitioners U.S. Food and Drug Administration, et al. (Elizabeth B. Prelogar, Solicitor General, 202.514.2217)
• For Respondents Alliance for Hippocratic Medicine, et al. (Erin Morrow Hawley, 202.393.8690)

AMICUS BRIEFS

• In Support of Petitioners U.S. Food and Drug Administration and Danco Laboratories, LLC 237 Reproductive Health, Rights, and Justice Organizations (Lindsay C. Harrison, 202.639.6000)
• 263 Members of Congress (Boris Bershteyn, 212.735.3000)
• AANHPI, Black, and Immigrant Women’s Organizations (Niyati Shah, 202.296.2399)
• American Civil Liberties Union Foundation, et al. (Julia Heather Kaye, 212.549.2663)
• American College of Obstetricians and Gynecologists, et al. (Shannon Rose Selden, 212.909.6000)
• American Psychological Association and National Association of Social Workers (Steven Henry Aden, 202.741.4917)
• Association of American Medical Colleges (Douglas Harry Hallward-Driemeier, 202.508.4776)
• City of New York and NYC Health + Hospitals, the County of Santa Clara, and Four Other Local Jurisdictions (Richard Paul Dearing, 212.356.2500)
• Disability Rights Education & Defense Fund, et al. (Maria Michelle Uzeta, 510.644.2555)
• Doctors for America and the Reproductive Health Coalition (Christopher John Morten, 212.854.4291) Food and Drug Law Scholars (Robert Allen Long Jr., 202.662.5612)
• Former Military Officials, Civilian National Security Leaders, and Vet Voice Foundation (Carmen Gloria Iguina Gonzalez, 212.763.0883)
• Former U.S. Department of Justice Officials (Alan Evan Schoenfeld, 212.230.8800)
• Freedom from Religion Foundation and American Atheists (Patrick C Elliott, 608.256.8900) GenBioPro, Inc. (John Patrick Elwood, 202.942.5992)
• Honeybee Health, Inc. (Stephanie Leigh Gutwein, 317.237.0300)
• Legal Voice, the National Domestic Violence Hotline, et al. (Matthew Prairie Gordon, 206.359.3552)
• Local Governments and Local Government Leaders (Jonathan B. Miller, 510.738.6788)
• Medical Students for Choice (Jayme Alyse Jonat, 646.837.8455)
• NAACP Legal Defense & Educational Fund, Inc. (Samuel Spital, 212.965.2200)
• National Association of Nurse Practitioners in Women’s Health, American College of Nurse-Midwives, American Academy of Physician Associates, and Association of Physician Associates in Obstetrics and Gynecology (Jonathan K. Youngwood, 212.455.2000)
• National Council of Jewish Women, et al. (Eugene Martin Gelernter, 212.336.2000) New York, et al. (Barbara Dale Underwood, 212.416.8016)
• Over 300 Reproductive Health Researchers (Melissa Goodman, 310.267.4382)
• Over 600 State Legislators (Amanda Shafer Berman, 202.624.2500)
• Patient and Provider Advocacy Organizations (Caroline Lewis Wolverton, 202.887.4107)
• Pharmaceutical Companies, Executives, and Investors (Eva A. Temkin, 202.737.0500)
• Pharmaceutical Research and Manufacturers of America (David Meir Zionts, 202.662.5987)
• Physicians for Reproductive Health (Janice Marie Mac Avoy, 212.859.8182)
• Professor F. Andrew Hessick (F. Andrew Hessick III, 202.374.4634)
• Professors David S. Cohen and Rachel Rebouché (David Samuel Cohen, 215.571.4714)
• Public Citizen and Center for Science in the Public Interest (Nicolas Anthony Sansone, 202.588.1000)
• Reproductive Freedom Alliance (Jaime Ann Santos, 202.346.4034)
• Women Who Have Obtained Medication Abortion Via Telemedicine (Vanessa Kay Burrows, 212.455.2000)
• Women’s Bar Association of the District of Columbia (Candace Nicole Beck, 202.639.8880)

In Support of Respondents Alliance for Hippocratic Medicine, et al

• 145 Members of Congress (Jessica Ring Amunson, 202.639.6000)
• Advancing American Freedom, Inc. (John Marc Wheat, 202.780.4848)
• American Center for Law & Justice (Jay Alan Sekulow, 202.546.8890)
• Americans United for Life (Clarke David Forsythe, 202.289.1478)
• Business Leaders (Jonathan Radford Whitehead, 816.398.8305)
• Charlotte Lozier Institute (Gene Clayton Schaerr, 202.787.1060)
• Democrats for Life of America (Rachel Nicole Morrison, 202.682.1200)
• Dr. Allan Sawyer (Michael Steven Overing, 626.564.8600)
• Dr. Calum Miller (Kristine Lee Brown, 720.285.9552)
• Dr. Grazie Pozo Christie and the Catholic Association Foundation (Megan Marie Wold, 202.879.5000)
• Elliot Institute, Rachel’s Vineyard, and Entering Canaan Ministry (Jay Alan Sekulow, 202.546.8890)
• Ethics and Public Policy Center (M. Edward Whelan III, 202.682.1200)
• Family Policy Alliance and State Family Policy Councils (Randall L. Wenger, 717.657.4990)
• Family Research Council and Martha Shuping, M.D. (Christopher E. Mills, 843.606.0640)
• Former U.S. Attorney General Edwin Meese III (David H. Thompson, 202.220.9600)
• Former U.S. Department of Health and Human Services, U.S. Food and Drug Administration, and White House Officials (James Ruffin Lawrence III, 919.755.1317)
• Gianina Cazan-London MD, Melissa Halvorson MD, and Wagner Faith & Freedom Center (William Wagner, 517.643.1765)
• Heartbeat International (Brennan Tyler Brooks, 336.707.8855)
• Human Coalition, the Ethics and Religious Liberty Commission, and the National Association of Evangelicals (Elissa Michelle Graves, 214.733.3213)
• Jewish Coalition for Religious Liberty (Howard Nathan Slugh, 954.328.9461)
• Judicial Watch, Inc. (Meredith Leigh Di Liberto, 202.646.5172)
• Life Legal Defense Foundation (Catherine Wynne Short, 707.224.6675)
• Mississippi, et al. (Scott Grant Stewart, 601.359.5563)
• Missouri, Idaho, and Kansas (Joshua Michael Divine, 573.751.8870)
• Mountain States Legal Foundation (R. Trent McCotter, 202.706.5488)
• National Hispanic Leadership Conference and the Frederick Douglas Foundation (Mathew D. Staver, 202.289.1776)
• Operation Rescue and West Virginians for Life (Jay Alan Sekulow, 202.546.8890)
• Priests for Life (Robert Joseph Muise, 734.635.3756)
• Prolife Center at the University of St. Thomas (MN) (Teresa Stanton Collett, 651.271.2958)
• Robertson Center for Constitutional Law (Christopher Theodore Holinger, 757.697.6488)
• Secretary David L. Bernhardt (John Clay Sullivan, 469.523.1351)
• Southeastern Legal Foundation and Texas Public Policy Foundation (Thomas Ryan McCarthy, 703.243.9423)
• Stanton International (Erin Elizabeth Mersino, 734.635.3756)
• Students for Life of America (William Bock III, 317.777.7412)
• Susan B. Anthony Pro-Life America, et al. (Heather Gebelin Hacker, 512.399.3022)
• United States Medical Association (Nathan W. Kellum, 901.684.5485)
• Women and Families Harmed by Mifepristone and Former Abortion Providers (Linda Boston Schlueter, 210.274.5274)
• Women Injured by Abortion (Mary Jane Browning, 210.614.7157)
• World Faith Foundation and Institute for Faith and Family (James L. Hirsen, 714.283.8880)