Legal Challenges to the FDA Approval of Medication Abortion Pills

Medication abortion has emerged as a major legal front in the battle over abortion access across the nation. Since the Supreme Court’s Dobbs ruling on June 24, 2022, four new cases have been filed in federal courts specifically regarding aspects of the FDA’s regulation of medication abortion. These challenges, some in the early stages, could affect the availability of abortion medications in the short and long term. At the heart of these cases is the FDA’s authority to approve drugs, whether courts can reverse the FDA’s decisions, and if states can impose additional restrictions beyond what the FDA requires. The case that has gotten the most attention recently is Alliance for Hippocratic Medicine (AHM) v. FDA, filed in November 2022, a challenge to the FDA’s decision to approve mifepristone, the first medication taken as part of the medication abortion drug regimen and to include misoprostol in the medication abortion regimen. The plaintiffs in this case contend the FDA did not act within its authority and that an 1873 anti-obscenity law, the Comstock Act, prohibits the mailing of any medication used for abortion.

The outcome of this case could have ramifications for access to medication abortion throughout the country, including in states where abortion is legal and protected. For the first time, the court is being asked to essentially overturn the approval of a drug, in this case one that has been safely used by more than 5.6 million people since it was approved in 2000 with a long record of safety and effectiveness. This issue brief focuses on the major claims in the AHM case, as a decision is expected soon, but many of the issues raised will also be relevant to the other abortion cases involving the FDA and its role in approving and regulating mifepristone.

Background on the FDA’s approval of Mifepristone

Mifepristone, often referred to as medication abortion pills, RU-486, or the abortion pill, was approved by the FDA over 20 years ago as a medication that can safely and effectively end pregnancy. A regimen of mifepristone, followed by misoprostol, a drug that is also used to treat ulcers, manage miscarriages, induce labor, and assist with IUD insertions, is an FDA approved protocol for abortion during the first 70 days, or up to 10 weeks, after the first day of the pregnant person’s last menstrual period. It is estimated that in 2020, medication abortions accounted for just over half of all abortions in the US. The drug regimen terminates pregnancies successfully 99.6% of the time, with a 0.4% risk of major complications, and an associated mortality rate of less than 0.001 percent (0.00064%). The FDA initially approved mifepristone with some conditions on who and how it can be dispensed in 2000, and over the years the FDA has amended these restrictions. (Appendix Table 1). The plaintiffs in the AHM case are challenging the FDA’s initial approval of mifepristone on procedural grounds, as well as the 2016, 2019 and 2021 changes to the drug’s safety program as being beyond the FDA’s authority.

Subpart H

When the FDA initially approved mifepristone, it did so under a provision called “Subpart H,” a set of regulations implemented to expedite the approval of “new drug products that have been studied for their safety and effectiveness in treating serious or life-threatening illnesses,” like those to used treat HIV. The FDA approval process for mifepristone, however, was not expedited, as it was approved more than four years after the original application was filed. In the case of mifepristone, Subpart H was originally used to restrict the dispensing to prescribers who agreed to dispense it in certain health care settings, by or under the supervision of a qualified physician who attested to the ability to accurately date pregnancies and diagnose ectopic pregnancies. The drug was not available for distribution at retail pharmacies.

Risk Evaluation and Mitigation Strategy

The FDA Amendments Act of 2007 (FDAAA) added a new section (Section 505-1) to the Federal Food, Drug, and Cosmetic Act (FFDCA) authorizing the FDA to require a Risk Evaluation and Mitigation Strategy (REMS) for a drug if the FDA deems it is necessary to ensure that the drug’s benefits outweigh its risks; it also revises the terminology for eligibility for the drug from treating a “serious or life threatening illness” to permitting the FDA to require a REMS for drugs intended to be used for a “disease or “condition.”

Congress also deemed all drugs with existing restricted-distribution programs (Section 909 of the FDAAA), including mifepristone, to require a REMS. Congress required sponsors of such “deemed” drugs to submit a proposed REMS to the FDA — which mifepristone’s sponsor did. The FDA approved the initial REMS for mifepristone in 2011, which required in-person dispensing by or under supervision of a certified physician, the dispensing of misoprostol at the provider’s office or clinic, and a follow-up visit 14 days later. In 2016, the FDA updated and approved a new evidence-based regimen and drug label for mifepristone. This updated regimen expanded the use of the mifepristone/misoprostol regimen from 49 days to up to 70 days (10 weeks) of pregnancy. In addition, the provider certification requirement was broadened from being limited to physicians only to include other advanced practice clinicians (e.g., nurse practitioners and physician assistants) who can meet the REMS requirements. The FDA approved the generic version of mifepristone in 2019 and issued a unified REMS for both the generic and the brand-name medication. In April 2021, the FDA decided to exercise enforcement discretion for the in-person dispensing requirement during the public health emergency. In December 2021, when the FDA rejected the plaintiffs’ citizen petition, the FDA removed the in-person dispensing requirement for mifepristone and expanded the distribution to include certified pharmacies in addition to certified clinicians. On January 3, 2023, the FDA updated the REMS approving the protocol for certification of pharmacies, allowing those that have been certified by the manufacturers to dispense mifepristone directly to patients (eliminating the requirement that it can only be dispensed directly to the patient by the certified provider).

The Legal Challenge to the FDA’s Approval of Mifepristone

In the case, Alliance for Hippocratic Medicine v. FDA, (filed November 18, 2022 in the US District Court for The Northern District of Texas Amarillo Division presided over by a Trump Administration appointed judge), the plaintiffs are challenging the FDA’s approval of mifepristone on many grounds. (Table 1) The plaintiffs are the Alliance for Hippocratic Medicine (a newly formed anti-abortion advocacy coalition); the American Association of Pro-Life Obstetricians and Gynecologists; the American College of Pediatricians; and the Christian Medical and Dental Associations, as well as three individual doctors (Shaun Jester, D.O., Regina Frost-Clark, M.D., Tyler Johnson, D.O., and George Delgado, M.D.)

As with any lawsuit, the plaintiffs first need to show they have legal standing by demonstrating they have an injury, and that they have filed this action within six years of the FDA’s action, the statute of limitations.

Do the plaintiffs have standing?

The plaintiffs, the Alliance for Hippocratic Medicine, the AAPLOG, the American College of Pediatricians and the Christian Medical & Dental Associations, contend that they have members in Texas and around the country who have treated and will continue to treat women and girls who have experienced a complication from medication abortion. In addition, the associations assert that they have suffered organizational harms from the FDA’s approval of mifepristone because they have spent time and resources to conduct their own studies and analysis, and to educate their members about the dangers of medication abortion. Anyone challenging the actions of a federal agency must demonstrate that they are within the “zone of interests” protected or regulated by the statute in question. The plaintiffs contend that they are within the FDCA’s zone of interests, meaning their interests are protected by the statute. The plaintiffs who are individual doctors are suing on their own behalf and on behalf of their patients, citing that the Supreme Court has held that medical providers have third-party standing to invoke the rights on their patients. Interestingly, in his dissenting opinion for June Medical Services v. Russo, Justice Alito called into question the precedent that allowed abortion providers to challenge abortion restrictions on behalf of their patients.

The Government argues that none of the plaintiffs have established an injury-in-fact or that they are within the “zones of interest,” which is necessary to establish standing. While the plaintiffs are not regulated by the FDA and do not prescribe mifepristone, the plaintiffs claim they will have to treat patients who suffer from complications from mifepristone and therefore have less time and resources to treat other patients. The Government argues this reasoning is speculative. Furthermore, they claim this approach to standing could open the door for any doctor to challenge the FDA’s approval of any drug that causes adverse events.

Have the plaintiffs filed this lawsuit within the statute of limitations?

There is a six-year statute of limitation to challenge any federal agency action. Anyone challenging an agency action is also required to exhaust their administrative remedies before initiating litigation seeking judicial review. FDA regulations specifically require challengers to file a “citizen petition” before any legal action can be filed in a court. In 2019 the plaintiffs filed a citizen petition asking the FDA to undo a 2016 revision of the REMS for mifepristone, which had changed the gestational limit for taking the drugs from 49 days to 70 days (10 weeks), expanded the provider certification requirement beyond physicians to include advance practice clinicians (e.g. nurse practitioners and physician assistants), and eliminated the requirements for in-person administration of misoprostol and for an in-person follow-up examination. The Government’s position is that the statute of limitations bars the plaintiffs from raising any issues not included in their 2019 citizen petition. This petition did not contest the underlying approval of mifepristone established in 2000. The plaintiffs maintain that the statute of limitations resets every time the FDA has modified the restrictions for mifepristone.

WHAT ARE THE PLAINTIFFS’ CLAIMS?

If the plaintiffs make it through these two hurdles, they are challenging the FDA’s approval and subsequent modifications of the dispensing requirements for mifepristone as being beyond the FDA’s authority based on the FFDCA statute. The plaintiffs are asking the court to find the FDA acted beyond its authority to initially approve mifepristone using Subpart H and that the FDA’s initial approval and subsequent actions to regulate mifepristone were not supported by sufficient evidence of safety and efficacy. The plaintiffs have cited their own studies to reach their conclusion that mifepristone is not safe. It is an unprecedented request to ask a court to block the FDA’s prior determination that a drug is safe and effective (Table 1).

Table 1: Summary of the Plaintiffs’ and the Government’s Positions Alliance for Hippocratic Medicine v. FDA
Claim: FDA’s approval of mifepristone in 2000 violated the Administrative Procedures Act (APA) because the FDA Lacked the authority to use subpart H
Plaintiffs’ Position: The FDA fast tracked the initial approval of mifepristone. The use of Subpart H was not proper because pregnancy is not an illness.	Government’s Position: FDA’s original approval of mifepristone, which occurred more than four years after the new drug application was submitted to the agency did not involve an ‘’accelerated review.” The preamble to Sub-part H regulation makes clear that it was intended to be used for “conditions” as well as illnesses. FDA extensively reviewed the scientific evidence and determined the benefits of mifepristone outweigh any risks. FDA relied on Subpart H to place certain restrictions on the manufacturer’s distribution of the drug product to assure its safe use.
Claim: The FDA’s approval of and subsequent actions to regulate mifepristone were not supported by sufficient evidence of safety and efficacy and did not meet federal pediatric assessment requirements, violating the APA and Federal Food, Drug and Cosmetic Act
Plaintiffs’ Position: The FDA’s initial approval and subsequent actions to regulate were not supported by sufficient evidence. The FDA did not consider the impact on the pediatric population. The FDA’s denials of two citizen petitions were unreasonable and not supported by the administrative record.	Government’s Position: FDA extensively reviewed the scientific evidence and determined the benefits of mifepristone outweigh any risks. The FDA’s conclusion that studies in pediatric patients were not needed is consistent with the pediatric rule regulations. The FDA’s determinations are entitled to significant deference. The FDA denied the citizen petitions based on its scientific review of the evidence clearly demonstrating mifepristone’s safety and efficacy.
Claim: The FDA’s approval of mifepristone and subsequent modifications violated the Comstock Act.
Plaintiffs’ Position: This act should be read literally to prohibit the mailing of any drug used to terminate an abortion.	Government’s Position: The plaintiffs are barred from raising this issue because they failed to raise it in the administrative proceedings. This law has been amended by court precedents and administrative actions and does not apply to mailing abortion drugs when the sender has no reason to believe they will be used unlawfully.

Does the Comstock Act impede the distribution of abortion medications?

When the Comstock Act was passed in 1873, it made it illegal to send “obscene, lewd or lascivious,” “immoral” or “indecent” publications or other materials through the mail. It also banned the mailing of any articles that could be used as contraceptive or to cause abortions. The plaintiffs in this case contend that the Comstock Act should be read literally. The plaintiffs cite a section of the Act as prohibiting the mailing or delivery by any letter carrier of “[e]very article or thing designed, adapted, or intended for producing abortion” and “[e]very article, instrument, substance, drug, medicine, or thing, which is advertised or described in a manner calculated to lead to another to use or apply it for producing abortion, ” and a separate section as prohibiting the use of “any express company or other common carrier” to transport abortion drugs in interstate or through foreign commerce. They are seeking to block the distribution of drugs for abortion (mifepristone and misoprostol) to clinics, doctors, and hospitals, as well as to patients, on grounds that the Comstock law makes it illegal to send these through the mail or other carriers.

However, the Government contends that because the plaintiffs failed to raise the Comstock argument at any stage of the administrative proceedings, they are therefore barred from raising it now. In addition, the Government contends that the plaintiffs’ Comstock argument fails on the merits. Although Congress has not amended the abortion provisions in the statute, prior court cases and administrative actions have limited the reach of the Comstock Act. In December 2022, the US Department of Justice’s Office of Legal Counsel issued an opinion, concluding that the Comstock Act does not prevent the mailing of medication for abortion for legal use.

Possible Rulings and Implications

Depending on the ruling, the case could affect the availability and distribution of mifepristone. More broadly, if the court allows the plaintiffs to have standing, the door may be opened for future litigation brought by doctors and organizations challenging the FDA’s approval of other drugs. Similarly, if the court does not restrict the plaintiffs’ challenges to what they included in their 2019 citizen petition, then other litigation may be brought beyond the six years statute of limitation period that challenges agencies’ actions without first exhausting administrative remedies.

Possible Ruling 1: FDA Approval of Mifepristone Violated the APA

The federal court could find that the FDA did not apply a lawful review process for its initial approval of mifepristone in 2000. It would be unprecedented for a Court to rule that the FDA did not properly approve a drug, much less one that has a safety and effectiveness record over more than two decades. While the availability of mifepristone for abortion could be blocked following such a ruling, it is likely, based on the research, record and clinical trials, that the drug would be reapproved by the FDA. This would, however, force those who seek abortion to use a less effective medication abortion protocol with misoprostol only in the interim. The court could also rule that the FDA acted beyond its authority by including misoprostol in the two-drug regimen for medication abortion. However, because misoprostol is currently used for medication abortion off-label, it is not clear how this ruling would impact the availability of misoprostol.

If the court suspends the FDA’s approval of mifepristone, with or without finding that the FDA acted improperly by including misoprostol, clinics will likely respond by switching to using a higher dose of misoprostol alone, but that is less effective (estimated to be between 80% and 100% effective) than using mifepristone and misoprostol together (99% effective). Misoprostol along can also cause more side effects, including pain and bleeding than the combination regimen. In addition, patients experiencing a miscarriage will also need to switch to using only misoprostol. This ruling will likely have implications far beyond abortion. This action would open the door for other actors to potentially sue to block the approval of existing or new drugs that may be deemed as controversial such as vaccines or treatments for conditions that are at the crosshairs of culture wars. Manufacturers may be reluctant to bring to market certain new drugs or treatments if they are concerned that a court ruling could block the approval of the drug in the future.

Possible Ruling 2: FDA 2016 Revision of the REMS Violated the APA

The court could limit the plaintiffs’ arguments to those they included in their 2019 citizen petition, which challenged changes to the conditions of use and restrictions on the distribution of mifepristone. The 2019 petition asked the FDA to “[r]etain” the 2011 REMS and its in-person dispensing requirement, and to “restore and strengthen elements of the [mifepristone] regimen and prescriber requirements approved in 2000” to: (1) limit mifepristone’s use to 49 days gestation; (2) require the drug to be administered by or under the supervision of a physically present and certified physician who has ruled out ectopic pregnancy; (3) require three office visits; (4) include a contraindication for patients who do not have convenient access to emergency medical care; (5) require reporting of certain adverse events to FDA; and (6) require additional studies If the court grants the plaintiffs’ request to roll back the requirements for the gestational age for which the regimen is approved and limit the pool of clinicians who could be certified to dispense the drug therefore constraining abortion access for those in states that have not banned abortion. This would effectively eliminate the new evidence-based protocols the FDA has established which removed the in-person dispensing requirement, permitted telehealth abortions, and established the process for pharmacies to become certified to dispense mifepristone.

Possible Ruling 3: The Comstock Act Blocks Distribution of Medication Abortion Pills

If the court rules in favor of the plaintiffs finding that the Comstock Act prohibits the mailing of mifepristone and misoprostol, the distribution channels for both drugs could be effectively shut down, and access to the drugs will become limited over time. This would affect not only the mailing of the drug to patients through telemedicine but could also limit the distribution of the medication to hospitals, clinics or clinicians. Misoprostol is used to treat ulcers, and mifepristone is used to treat Cushing’s Syndrome. Both drugs are used for miscarriage management. Patients who need these drugs ,for these conditions, many of whom are women, could potentially have limited or no access. If the court ruling relies narrowly on the Comstock Act, there would not likely be broader ramifications for the FDA’s authority to regulate other drugs and be limited to medication abortion. It is conceivable that if it reaches the Supreme Court on appeal, the Court could leave intact the FDA’s current authority to review and approve drugs, but rule in favor of the plaintiffs, based on the Comstock Act reasoning that it’s the responsibility of Congress, not the Court’s, to repeal the Comstock Act if it’s no longer valid. This ruling could create large barriers for patients to access medication abortion across the country, even in states where abortion is legal. Even if the ruling does not find that the FDA’s approval of mifepristone was improper, a ruling based on the Comstock Act would severely limit distribution of the mifepristone and misoprostol.

Other Cases Involving the FDA and Medication Abortion

While many have focused on the AHM case, there are several other cases in the federal court system that relate to aspects of the FDA’s regulation of mifepristone. Now that states are permitted to ban abortion, new questions have arisen regarding the intersection of federal and state authority when it impacts access to abortion.

Federal law preempts state law, but some are questioning how the new state authority to regulate or ban abortion intersects with the Federal FDA’s authority to regulate drugs. There are currently two cases in federal court challenging state abortion prohibitions and restrictions on federal preemption grounds. The maker of a generic mifepristone medication, GenBioPro, Inc., is challenging West Virginia’s total abortion ban, and an ob-gyn, Dr. Amy Bryant, is challenging the abortion restrictions in North Carolina, which include requirements that mifepristone be dispensed in person by a physician following a state-mandated counseling session and a 72-hour waiting period. In both cases, plaintiffs argue that the FDA’s authorization and regulation of mifepristone preempt state law banning the use of the medication or regulating its use more strictly, and given this, enforcement of the state laws should be blocked. If these lawsuits are successful, people living in states where abortion is banned could access medication abortion.

In addition, the Oregon and Washington Attorneys General joined by 10 other Attorneys General are also challenging the FDA’s decision-making about mifepristone. but rather than challenging the FDA approval process, the plaintiffs are calling to question the FDA’s decision to impose restrictions on prescribing and dispensing mifepristone through the Risk Evaluation and Mitigation System (REMS). The case filed by the Oregon and Washington Attorneys General in the US District Court in the Eastern District of Washington could result in a conflicting ruling from the AHM case. Ultimately, the Supreme Court could decide the role of the courts to review the FDA’s decisions, and how much deference the agency should be given.

Conclusion

No matter how the district court rules in the AHM case, the parties will likely appeal to the 5th Circuit Court of Appeals and then to the Supreme Court. The case, as well as others about medication abortion, raise questions about the role of the courts in reviewing the FDA’s findings about a particular drug. While most of the focus since the Dobbs ruling has been on the impact of that ruling on those who live in states that ban or greatly restrict abortion, the outcome of these medication abortion cases could also affect the availability of medication abortion to people in who live in states that protect abortion access. Furthermore, these cases could also have far-reaching implications for the FDA’s authority to continue to regulate not only mifepristone, but a wide range of other drugs that could be perceived to be controversial today and in the future.