Key Takeaways:
- A hearing on a motion for preliminary injunction in Alliance for Hippocratic Medicine v. U.S. Food and Drug Administration challenging Food and Drug Administration's ("FDA") approval of mifepristone is scheduled for today.
- The government's response details the decades-long history of safety and effectiveness data supporting FDA's actions with respect to this drug and raises several issues of justiciability.
- If the preliminary injunction is granted, access to the most common regimen for the medical termination of early pregnancy could be halted, even in states where abortion remains legal.
The legal status of mifepristone and misoprostol, drugs legally prescribed by physicians since 2000 for the medical termination of early pregnancy, may soon be decided by a federal court in Texas in a lawsuit known as Alliance for Hippocratic Medicine v. U.S. Food and Drug Administration. The plaintiffs – four medical organizations and four doctors – have asked the court in their complaint (filed November 18, 2022) to overturn all of FDA's reviews and actions with respect to mifepristone since 2000 and render mifepristone and misoprostol unapproved drugs, effectively disregarding the federal drug approval process that recognizes FDA's scientific expertise in making such a decision. The plaintiffs have filed a memorandum in support of a motion for preliminary injunction with the court challenging the procedural integrity of FDA's review process as well as the underlying safety and effectiveness data relied upon by FDA to approve mifepristone in 2000 and subsequent changes to the labeling in 2016. The defendants – FDA, FDA Commissioner and other FDA officials, the Department of Health and Human Services (DHHS) and the DHHS Secretary – have filed a response opposing the motion for preliminary injunction in which they detail procedural adequacies, FDA's authority to review and approve drugs as mandated by Congress, and the extensive 23-year history of safety and effectiveness data supporting all of FDA's actions regarding the use of mifepristone.
A hearing on the motion for preliminary injunction is scheduled for Wednesday, March 15, 2023, at 9 a.m. in the District Court for the Northern District of Texas, Amarillo Division, before Judge Matthew J. Kacsmaryk. In his Hearing Order, the Judge identified the following seven areas of interest to the court:
- Standing (referring to the right of the
plaintiffs to bring this action):
- associational, organizational, zone of interests;
- Reviewability (referring to the scope of
issues the court is permitted to review):
- reopening doctrine, Heckler v. Chaney, exhaustion;
- Subpart H (referring to the federal
regulations governing certain FDA approvals):
- history, text, applicability, and implementation;
- Agency Decisions (referring to FDA's
decisions):
- restrictions, labels, elements, and conditions;
- Harm (referring to alleged harm suffered
by the plaintiffs):
- irreparability, deference, and third-party interests;
- Public Interest (referring to the interest
the public has in the matter):
- public health, police power, and FDA policymaking; and
- Remedies (referring to the permissible
relief the court may provide):
- injunction, vacatur, withdrawal, and/or suspension
The Judge will allow only two hours per side to address the
issues.
The holder of the approved new drug application for Mifeprex
(mifepristone), Danco Laboratories LLC, has also been permitted to
intervene in the case and filed its own opposition to the plaintiffs' demands,
citing two-plus decades of safety and effectiveness data and
information and multiple FDA evaluations. Numerous amicus
curiae ("friend of the court") briefs have been
filed in support of both sides. Amicus briefs have been filed by 22 states and several organizations in support of the
plaintiffs' motion. Amicus briefs in support of the FDA, filed
by 21 states and the District of Columbia, American College of Obstetricians and
Gynecologists, American Medical Association and other medical
professionals: and 19 FDA law scholars, highlight the extensive
safety profile of mifepristone, the thoroughness of FDA's
review, and warn of the potential unraveling of a rigorous
regulatory framework for the approval of all drugs.
Mifepristone
FDA first approved mifepristone, branded as Mifeprex, for use with misoprostol (a previously approved drug) in September 2000 for medical termination of pregnancy through seven weeks gestation. In 2016, FDA approved a labeling change that extended the indication to 10 weeks gestation based on safety and effectiveness data submitted to FDA in a supplement to the original approved new drug application. FDA approved a generic version of Mifeprex in April 2019 based on a finding that the generic is therapeutically equivalent to Mifeprex and can be safely substituted for it.
When FDA approved the original new drug application for Mifeprex in 2000, it concluded that certain restrictions were necessary to ensure the safe use of the drug. A change in the law subsumed these restrictions under a "risk evaluation and mitigation strategy" (REMS) program for mifepristone in 2011. The Mifepristone REMS Program applies to the generic version of the drug as well. On March 29, 2016, FDA approved a supplemental new drug application submitted by Danco to modify Mifeprex's indication, labeling, and REMS. Specifically, FDA's approval increased the gestational age limit from seven weeks to 10 weeks based on safety and efficacy data from multiple studies and reduced the number of in-person clinic visits required to one, finding that at-home administration of the drug was safe because of "exceedingly low rates of serious adverse events." FDA also found no significant difference in outcomes based on whether patients had follow-up appointments via phone call or in-person. Finally, FDA allowed other healthcare providers, not only physicians, who meet the REMS certification requirements to prescribe mifepristone, finding no serious health concerns associated with such prescribing.
In March 2019, the plaintiffs filed a citizen petition with FDA requesting that the agency "restore and strengthen elements of the Mifeprex regimen and prescriber requirements approved in 2000," retain the Mifeprex REMS, and continue limiting the dispensing of Mifeprex so that it could only be dispensed to patients in certain healthcare settings by or under the supervision of a certified prescriber. FDA responded to this petition in December 2021 by denying the request to restore and strengthen the regimen and prescriber requirements and granting in part and denying in part the request to retain the mifepristone REMS. Specifically, FDA found that certain elements of the REMS program (such as the healthcare provider certification) continued to be necessary to ensure safe use but that the REMS must be modified to remove the requirement that mifepristone be dispensed in person only in certain healthcare settings. FDA had already announced in April 2021 that it intended to exercise enforcement discretion and not enforce the in-person dispensing requirement during the COVID-19 public health emergency.
In January 2023, FDA approved the sponsor's request to
change the Mifepristone REMS Program to permanently remove the
in-person dispensing requirement and permit certified pharmacies as
well as certified healthcare providers to dispense the drug. The
Mifepristone REMS Program continues to require patients to sign a
Patient Agreement Form before receiving the
drug. The current Mifepristone REMS documents can be found here.
The Plaintiffs' Claims
In the pending lawsuit, the plaintiffs have asked the court in their motion for preliminary injunction, among other things, to overturn:
- FDA's 2000 approval of mifepristone in part because FDA allegedly failed to properly evaluate the safety and effectiveness data supporting mifepristone's approval;
- FDA's 2016 and 2021 approvals of changes to the drug labeling because FDA allegedly had insufficient information to determine whether the drug was safe and effective;
- FDA's 2019 approval of the generic version of Mifeprex;
- FDA's changes to the Mifepristone REMS Program
- FDA's approvals of misoprostol drug products.
The plaintiffs have also asked the court to prohibit FDA from approving any marketing application "that fails to limit distribution of chemical abortion drugs" under a federal law referred to as the Comstock Act, which prohibits sending any articles designed, adapted, or intended for producing abortion through the U.S. mail. As we explain here, this action would be contrary to an opinion taken by the U.S. Justice Department's Office of Legal Counsel in December 2022, which concluded that the Comstock Act does not prohibit the mailing of mifepristone or misoprostol where the sender lacks the intent that the recipient will use them unlawfully.
Standard for Preliminary Injunction
A preliminary injunction is considered an "extraordinary remedy" and requires the plaintiffs to meet four criteria: (1) a substantial likelihood of success on the merits; (2) a substantial threat of irreparable injury if the injunction is not granted; (3) the threatened injury will outweigh any harm that will result if the injunction is granted; and (4) the injunction is in the public interest.
The Defendants' Response
The defendants filed an opposition to the plaintiffs' motion for preliminary injunction on January 13, 2023, arguing among other things that (1) plaintiffs have no legal standing or interest allowing them to challenge FDA's approvals and related actions; (2) most if not all of plaintiffs' claims are barred by the statute of limitations; (3) the only possibly actionable challenge is to FDA's 2019 denial of plaintiffs' citizen petition, in which they only asked FDA to revert the 2016 REMS restrictions for mifepristone to the original restrictions established in 2000; and (4) plaintiffs have suffered no harm, much less any imminent or irreparable harm, to justify a preliminary injunction.
Potential Impact of Court's Decision
If the court grants the plaintiffs' request for a preliminary injunction, the approvals to manufacture and distribute mifepristone and misoprostol, which are held by the sponsors of the marketing applications for each drug, could potentially be withdrawn or suspended pursuant to the court's order. The defendants would likely appeal such a decision promptly and ask the federal appellate court for the 5th Circuit to stay the order. A stay by the 5th Circuit may be needed for the sponsors to continue to manufacture and distribute the drugs lawfully pending a review by the appellate court. The further impact on individual healthcare providers, pharmacies, and patients may depend on state law as well as the actions of the federal government.
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