Petition for Writ of Certiorari — Food and Drug Administration, et al., Petitioners v. Alliance for Hippocratic Medicine, et al.

No. XX-XX

In the Supreme Court of the United States

U.S. FOOD AND DRUG ADMINISTRATION, ET AL.,

PETITIONERS

v.

ALLIANCE FOR HIPPOCRATIC MEDICINE, ET AL.

ON PETITION FOR A WRIT OF CERTIORARI

TO THE UNITED STATES COURT OF APPEALS

FOR THE FIFTH CIRCUIT

APPENDIX TO THE

PETITION FOR A WRIT OF CERTIORARI

ELIZABETH B. PRELOGAR

Solicitor General

Counsel of Record

BRIAN M. BOYNTON

Principal Deputy Assistant

Attorney General

BRIAN H. FLETCHER

EDWIN S. KNEEDLER

Deputy Solicitors General

SARAH E. HARRINGTON

Deputy Assistant Attorney

General

ERICA L. ROSS

CHARLES L. MCCLOUD

Assistants to the Solicitor

General

MICHAEL S. RAAB

CYNTHIA A. BARMORE

Attorneys

Department of Justice

Washington, D.C. 20530-0001

SupremeCtBriefs@usdoj.gov

(202) 514-2217

APPENDIX

TABLE OF CONTENTS

Page

Appendix A

—

Appendix B

—

Appendix C

—

Appendix D

—

Appendix E —

Court of appeals opinion

(Aug. 16, 2023) ................................. 1a

District court memorandum

opinion and order

(Apr. 7, 2023) ................................ 111a

Court of appeals unpublished

order (Apr. 12, 2023) .................... 196a

Supreme Court opinion

(Apr. 21, 2023) .............................. 245a

Statutory provisions:

5 U.S.C. 705................................... 249a

21 U.S.C. 355 ................................. 249a

21 U.S.C. 355-1.............................. 251a

APPENDIX A

UNITED STATES COURT OF APPEALS

FOR THE FIFTH CIRCUIT

No. 23-10362

ALLIANCE FOR HIPPOCRATIC MEDICINE; AMERICAN

ASSOCIATION OF PRO-LIFE OBSTETRICIANS &

GYNECOLOGISTS; AMERICAN COLLEGE OF

PEDIATRICIANS; CHRISTIAN MEDICAL & DENTAL

ASSOCIATIONS; SHAUN JESTER, D.O.; REGINA

FROST-CLARK, M.D.; TYLER JOHNSON, D.O.;

GEORGE DELGADO, M.D., PLAINTIFFS-APPELLEES

v.

U.S. FOOD & DRUG ADMINISTRATION; ROBERT M.

CALIFF, COMMISSIONER OF FOOD AND DRUGS; JANET

WOODCOCK, M.D., IN HER OFFICIAL CAPACITY AS

PRINCIPAL DEPUTY COMMISSIONER, U.S. FOOD AND

DRUG ADMINISTRATION; PATRIZIA CAVAZZONI, M.D.,

IN HER OFFICIAL CAPACITY AS DIRECTOR, CENTER

FOR DRUG EVALUATION AND RESEARCH, U.S. FOOD

AND DRUG ADMINISTRATION; UNITED STATES

DEPARTMENT OF HEALTH AND HUMAN SERVICES;

XAVIER BECERRA, SECRETARY, U.S. DEPARTMENT OF

HEALTH AND HUMAN SERVICES,

DEFENDANTS-APPELLANTS

v.

DANCO LABORATORIES, L.L.C.,

INTERVENOR-APPELLANT

Filed:

Aug. 16, 2023

(1a)

2a

Appeal from the United States District Court

for the Northern District of Texas

USDC No. 2:22-CV-223

Before ELROD, HO, and WILSON, Circuit Judges.

JENNIFER WALKER E LROD, Circuit Judge:

This complicated administrative law appeal concerns

the regulation of mifepristone, a drug used to cause

abortion. The United States Food and Drug Administration approved mifepristone for use in 2000 under

the brand name Mifeprex. At the same time, FDA imposed a number of conditions designed to prevent the

drug from causing serious medical side effects. FDA

amended those conditions in 2016, generally lightening

the prior protections. It then approved a generic version in 2019. And in 2021, FDA announced that it

would not enforce an agency regulation requiring mifepristone to be prescribed and dispensed in person.

The agency ultimately removed that requirement from

mifepristone’s conditions for use.

The subject of this appeal is those four actions: the

2000 Approval, 2016 Amendments, 2019 Generic Approval, and 2021 Non-Enforcement Decision. They are

challenged by the Alliance for Hippocratic Medicine—

an association of doctors who research, teach, and advocate for ethical medical practices—several similar organizations, and several individual doctors. At bottom,

the Medical Organizations and Doctors contend that

FDA overlooked important safety risks in approving

mifepristone and amending its restrictions. They assert that FDA’s actions were unlawful under the Administrative Procedure Act.

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The Organizations seek relief on behalf of their members, many of whom are OB/Gyns or emergency-room

doctors. Many women face severe complications as a

result of taking mifepristone. The Doctors allege that

they are harmed when they treat those kinds of patients.

According to the Doctors, when they treat women

who are experiencing complications after taking mifepristone, they are required to perform or complete an

abortion, or otherwise required to participate in a process that facilitates abortion. They maintain that personally conducting those procedures violates their sincerely held moral beliefs. The Doctors also contend

that treatment of mifepristone patients diverts time and

resources away from their ordinary patients, causes

substantial mental and emotional distress, and exposes

them to heightened malpractice risk and increased insurance costs.

Seeking to prevent those alleged injuries, the Medical Organizations and Doctors moved for preliminary injunctive relief. The district court granted the motion,

but rather than entering a traditional injunction, the

court stayed the effective date of each of the challenged

actions under 5 U.S.C. § 705. FDA appealed, as did Intervenor Danco Laboratories, LLC, the pharmaceutical

company that distributes Mifeprex.

After extensive briefing and oral argument, we hold

that the district court’s stay order should be VACATED

in part and AFFIRMED in part. We conclude that the

Medical Organizations and Doctors’ claim as to the 2000

Approval is likely barred by the statute of limitations.

Accordingly, that component of the district court’s order

must be VACATED. This means that, until final judg-

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ment, Mifeprex will remain available to the public under

the conditions for use that existed in 2016.

We also VACATE the portion of the order relating to

the 2019 Generic Approval because the Medical Organizations and Doctors have not shown that they are injured by that particular action. The generic version of

mifepristone will also be available under the same conditions as Mifeprex.

We AFFIRM the components of the stay order that

concern the 2016 Amendments and the 2021 Non-Enforcement Decision.

Those agency actions—which

generally loosen the protections and regulations relating to the use of mifepristone—will be stayed during the

pendency of this litigation.

Finally, we note that our holding is subject to the

prior order of the Supreme Court, which stayed the district court’s order pending resolution of this appeal and

disposition of any petition for writ of certiorari. Danco

Lab’ys, LLC v. All. for Hippocratic Med., 143 S. Ct. 1075

(2023) (mem.).

I.

Background

This case arises under the Federal Food, Drug, and

Cosmetic Act and related amendments. 21 U.S.C. ch.

9. The Department of Health and Human Services is

charged with responsibility for implementing that law,

and has delegated that obligation to FDA, its subagency. Id. § 393. The relevant events center on the

particular duty of approving new drugs.

The approval process begins with a new drug application. Id. § 355(a). At this stage, it is the applicant’s

burden to prove that the proposed drug is safe and effective. The Act directs FDA to deny a new drug ap-

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plication if, among other reasons, the applicant fails to

include tests and data that show that the drug “is safe

for use under the conditions prescribed, recommended,

or suggested in the proposed labeling”; if “any other information” before FDA tends to show that the drug is

not safe; or if “there is a lack of substantial evidence that

the drug will have the effect it purports or is represented to have under the conditions for use prescribed,

recommended, or suggested in the proposed labeling

thereof.” Id. § 355(d); see 21 C.F.R. § 314.125 (regulations expanding on those requirements).

Certain new drug applications may be designated for

“accelerated approval.” 21 C.F.R. § 314 subpt. H.

This category applies to drugs treating “serious or lifethreatening illnesses” and that “provide meaningful

therapeutic benefit to patients over existing treatments.” Id. § 314.500. The regulations also require

FDA to impose “postmarketing restrictions” where necessary to ensure the drug is used safely. Id. § 314.520(a).

Relevant here, the agency may mandate that the drug

be administered at “certain facilities or [by] physicians

with special training or experience,” or that “specified

medical procedures” be used.

Id. § 314.520(a)(1),

(a)(2).

FDA has explained that it will consider accelerated

approval in two situations: where the agency can reliably estimate effectiveness using a “surrogate endpoint”;

and where FDA “determines that a drug, effective to the

treatment of a disease, can be used safely only if distribution or use is modified or restricted.” 57 Fed. Reg.

58942, 58942 (Dec. 11, 1992). The agency has understood approval under Subpart H as also satisfying the

general approval conditions provided by the Food, Drug,

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and Cosmetic Act. See id. (“Drugs or biological products

approved under these procedures will have met the requisite standards for safety and effectiveness under the

[Act] . . . and, thus, will have full approval for marketing.”).

In March of 1996, an entity known as the Population

Council applied for FDA to approve mifepristone as a

new drug, as part of a two-drug regimen designed to

cause abortion.1 The regimen works like this: First,

a pregnant woman takes mifepristone, which suppresses

the production of the hormone progesterone. Progesterone is needed for the pregnancy to continue; it prepares

and maintains the uterine lining and stimulates the production of nutrients. After taking mifepristone, a patient takes misoprostol, which causes the uterus to

cramp and expel its contents.

As part of the new drug application, the Population

Council relied on three clinical studies, one conducted in

the United States and two conducted in France. The

studies purported to show that mifepristone was effective in the majority of cases, under the conditions imposed in each study. Those conditions included: an ultrasound to verify gestational age and diagnose ectopic

pregnancies; that prescribing physicians have experience performing surgical abortions and have admitting

privileges at a nearby hospital; that the testing facilities

The Population Council is a non-profit organization. Roussel

Uclaf—the French pharmaceutical company that originally developed mifepristone—donated the American patent rights to the Population Council in 1994. The Population Council then granted

Danco an exclusive license to manufacture and distribute Mifeprex

in the United States.

1

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be located close to a local hospital; and a four-hour monitoring period after taking misoprostol.

Although mifepristone was effective for most patients, the studies showed a trend of adverse events for

some women. According to FDA, “surgical intervention” was required in 7.9% of the subjects in the American trial and 4.5% of subjects in the French trials. The

reasons for surgery included heavy bleeding, infection,

incomplete abortion, and ongoing pregnancy—meaning

that the embryo or fetus continued to grow and develop.

FDA approved the new drug application in September 2000. The letters that the agency sent to the Population Council explained that the approval was “under

Subpart H.” FDA Approval Memorandum to Population

Council at 6 (Sept. 28, 2000). This was for two reasons.

First, FDA understood Mifeprex to be a drug that

treated a serious or life threatening illness.

Id.

(“FDA has determined that the termination of an unwanted pregnancy is a serious condition within the scope

of Subpart H. The meaningful therapeutic benefit over

existing surgical abortion is the avoidance of a surgical

procedure.”). And second, Subpart H was required because Mifeprex could not be administered safely without

imposing certain use restrictions. Id. (“Subpart H

applies when FDA concludes that a drug product shown

to be effective can be safely used only if distribution or

use is restricted. . . . ”).

In order to address the safety risks discussed above,

FDA imposed several safeguards. First, it required

the following black-box warning:

If Mifeprex results in incomplete abortion, surgical

intervention may be necessary. Prescribers should

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determine in advance whether they will provide such

care themselves or through other providers. Prescribers should also give patients clear instructions

of whom to call and what to do in the event of an

emergency following administration of Mifeprex.

Approval Memorandum at 2. FDA also set the following controls on the use and prescription of Mifeprex:

•

Only women whose pregnancies have a gestational age of forty-nine days or less are eligible;

•

Only physicians can prescribe Mifeprex;

•

All prescribing physicians must be able to assess gestational age, diagnose ectopic pregnancies, and “provide surgical intervention in cases

of incomplete abortion or severe bleeding” or

have arranged for another physician to provide

such care;

•

Prescription must occur in person; and

•

Prescribers must report any “hospitalization,

transfusion, or other serious event[] to the sponsor.”

Id. at 1, 6. Finally, FDA required three doctor’s-office

visits, which are summarized as follows. The patient

first takes mifepristone at the doctor’s office. Three

days later, she returns to the office to take misoprostol.

Finally, the patient visits the doctor for a follow-up appointment, to determine whether the drug has successfully terminated the pregnancy and to screen for any

adverse effects.

In August of 2002, the American Association of ProLife Obstetricians and Gynecologists (a party to the instant case) and several other similar organizations filed

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a citizen petition, asking FDA to revoke its approval of

mifepristone. See 21 C.F.R. § 10.30. The petition argued that mifepristone was not safe to use under the

approved conditions. FDA reviewed the petition over

the next fourteen years, ultimately denying it in 2016.

Two significant developments occurred in the meantime. First, in 2007, Congress amended the Food,

Drug, and Cosmetic Act. See Food and Drug Administration Amendments Act of 2007, Pub. L. No. 110-85,

tit. IX, § 901, 121 Stat. 823, 922-43. The amendment

authorizes FDA to require a “risk evaluation and mitigation strategy” (REMS) if it determines that such a

strategy is “necessary to ensure that the benefits of the

drug outweigh the risks of the drug.” 21 U.S.C. § 3551(a)(1). The Act further allowed FDA to impose use

restrictions via the REMS, like physician qualifications

or reporting requirements. Id. § 355-1(f ). The law

also regarded all drugs approved before the Act as having an approved REMS. See Amendments Act § 909(b),

121 Stat. at 950 (“A drug that was approved before the

effective date of this Act is . . . deemed to have in

effect an approved risk evaluation and mitigation strategy under section 505-1 of the [Act].”).

Then in 2011, FDA approved a REMS for mifepristone, imposing essentially the same restrictions as

those FDA required when it approved Mifeprex in 2000.

The REMS included four essential parts: a general

summary, medication guide, prescriber agreement, and

patient agreement. The medication guide explains

how to use mifepristone and the risks associated with

doing so. Mifepristone REMS at 4-6 (June 8, 2011).

The prescriber agreement requires prescribers to

promise to follow FDA’s restrictions. Id. at 7-8. And

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the patient agreement is a form that women must sign

prior to using mifepristone; it obliges a patient to confirm that she meets the conditions for using mifepristone and acknowledge the risk of adverse events. Id.

at 9-10. The mifepristone REMS was later amended

in several respects. But its general form—the summary,

medical guide, prescriber’s agreement, and patient

agreement—remains the same.

In 2016, FDA addressed Mifeprex in two respects.

First, it denied the 2002 citizen petition, defending Mifeprex’s safety and effectiveness as approved in 2000.

Second, FDA approved a supplemental new drug application by Danco. That application requested a number

of amendments to Mifeprex’s REMS that FDA described as “major” and “interrelated.” FDA Summary

Review of 2016 Amendments at 5 (Mar. 29, 2016).

Those changes included:

•

Increasing the maximum gestational age from

forty-nine days to seventy days;

•

Allowing non-physicians to prescribe mifepristone;

•

Removing the requirement that the administration of misoprostol and the subsequent followup appointment be conducted in person;

•

Eliminating prescribers’ obligation to report

non-fatal adverse events;

•

Switching the method of administration for

misoprostol from oral to buccal; and

•

Changing the dose of mifepristone (600 mg to

200 mg) and misoprostol (400 mcg to 800 mcg).

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Id. at 2, 26. FDA also pointed to a number of studies as

evidence that Mifeprex would be safe and effective despite the amendments. Id. at 5-17.

Several years later, in 2019, the American Association of Pro-Life Obstetricians and Gynecologists and

American College of Pediatricians filed a citizen petition challenging the 2016 Amendments. The petition

generally requested that FDA restore the restrictions

it imposed in 2000. Separately, in April of 2019, FDA

approved an “abbreviated new drug application” by

GenBioPro, Inc. for a generic version of mifepristone.

To assess whether the drug was safe, the agency relied

on the same data that it had relied upon for the 2000

Approval and 2016 Amendments regarding Mifeprex.

FDA then took several notable steps in 2021. In

April, it announced that, in connection with the COVID19 pandemic, the agency would not enforce the in-person dispensing requirement. Effectively, this allowed

mifepristone to be prescribed remotely and sent via

mail.

[FDA] intends to exercise enforcement discretion

during the COVID-19 [pandemic] with respect to the

in-person dispensing requirement of the Mifepristone REMS Program, including any in-person requirements that may be related to the Patient

Agreement Form. Further . . . [FDA] intends

to exercise enforcement discretion during the COVID19 [pandemic] with respect to the dispensing of mifepristone through the mail either by or under the

supervision of a certified prescriber, or through a

mail-order pharmacy when such dispensing is done

under the supervision of a certified prescriber.

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FDA Letter to American College of Obstetricians and

Gynecologists at 2 (Apr. 12, 2021). Later that year,

FDA stated that it would adopt the change on a permanent basis. It then amended mifepristone’s REMS

(which applies to Mifeprex and the generic version) in

January of 2023 to formalize the removal of the in-person dispensing requirement. FDA Br. at 11.

Finally, in December of 2021, FDA denied the 2019

citizen petition. According to FDA, the agency “undertook a full review of the Mifepristone REMS Program”

and ultimately concluded that the drug was safe to use

as amended. FDA Denial Letter to American College

of Obstetricians and Gynecologists at 6 (Dec. 16, 2021).

FDA specifically addressed its reasons for removing

the in-person dispensing requirement. Id. at 25-36.

* * *

Against this background, the Medical Organizations

and Doctors filed the instant complaint in district court.

As relevant here, they alleged that each FDA action—

the 2000 Approval, 2016 Amendments, 2019 Generic Approval, and 2021 Non-Enforcement Decision—violates

the Administrative Procedure Act. Danco intervened to

represent its interest as the manufacturer and distributor of Mifeprex in the United States. GenBioPro

filed an amicus brief before this court but did not intervene or otherwise participate in the litigation, either in

the district court or on appeal.

The Medical Organizations and Doctors filed a motion for a preliminary injunction. The district court held

a hearing on the matter and granted the motion in part.

All. for Hippocratic Med. v. FDA, __ F. Supp. 3d __,

2023 WL 2825871 (N.D. Tex. Apr. 7, 2023). For relief,

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the court “stayed” the “effective date” of FDA’s actions

under 5 U.S.C. § 705.

FDA and Danco appealed and moved to stay the district court’s order pending appeal. A motions panel of

this court stayed the district court’s order in part. All.

for Hippocratic Med. v. FDA, No. 23-10362, 2023 WL

2913725 (5th Cir. Apr. 12, 2023). The panel stayed the

portion of the district court’s order relating to the 2000

Approval but did not disturb the other components of

the order—regarding the 2016 Amendments, 2019 Generic Approval, and 2021 Non-Enforcement Decision.

FDA and Danco then applied to the Supreme Court for

a full stay of the district court’s order, which was

granted. Danco Lab’ys, LLC v. All. for Hippocratic

Med., 143 S. Ct. 1075 (2023) (mem.). The Court further provided that its stay of the district court’s order

would extend through the request for a petition for certiorari, if any:

The April 7, 2023 order of the United States District

Court for the Northern District of Texas, case No.

2:22-cv-223, is stayed pending disposition of the appeal in the United States Court of Appeals for the

Fifth Circuit and disposition of a petition for a writ

of certiorari, if such a writ is timely sought. Should

certiorari be denied, this stay shall terminate automatically. In the event certiorari is granted, the

stay shall terminate upon the sending down of the

judgment of this Court.

Id. at 1075. The parties then fully briefed the ultimate

question of whether the district court erred in issuing

the stay order. Over thirty amici filed separate briefs

on various topics. Oral argument was held on May 17,

2023, in which each side was allowed forty minutes to

14a

present its argument, double the ordinary allotted time.

We now consider the merits of the appeal.

II.

Standing

Before considering the Medical Organizations and

Doctors’ claims, we must determine whether they have

standing to assert them; an injunction is always improper if the district court lacked jurisdiction. Cruz v.

Abbott, 849 F.3d 594, 598-99 (5th Cir. 2017). At this

stage, it is the plaintiffs’ burden to “make a ‘clear showing’ that they have standing to maintain the preliminary

injunction.” Barber v. Bryant, 860 F.3d 345, 352 (5th

Cir. 2017) (quoting Winter v. Nat. Res. Def. Council,

Inc., 555 U.S. 7, 22 (2008)). And so the Medical Organizations and Doctors must satisfy the three basic elements of standing: injury, traceability, and redressability. Lujan v. Defs. of Wildlife, 504 U.S. 555, 560 (1992).

Standing in this appeal turns principally on the “injury” prong. The Medical Organizations and Doctors

seek prospective relief, so they must establish future injury. To do that, they must show that “the threatened

injury is ‘certainly impending,’ or there is a ‘substantial

risk’ that the harm will occur.” Susan B. Anthony List

v. Driehaus, 573 U.S. 149, 158 (2014) (quoting Clapper v.

Amnesty Int’l USA, 568 U.S. 398, 414 n.5 (2013)). As

those standards indicate, the plaintiffs must show that

the threat of future injury is sufficiently likely. The

Supreme Court has thus rejected standing theories that

rely “on a highly attenuated chain of possibilities” or

that “require guesswork as to how independent decisionmakers will exercise their judgment.” Clapper,

568 U.S. at 410, 413.

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Even so, a “substantial risk” does not require that

the threatened injury be “literally certain.” Id. at 414

n.5; see Lujan, 504 U.S. at 564 n.2 (acknowledging that

imminence “is concededly a somewhat elastic concept”);

Babbitt v. United Farm Workers Nat’l Union, 442 U.S.

289, 298 (1979) (requiring that the plaintiff “demonstrate a realistic danger of sustaining a direct injury”);

Kolender v. Lawson, 461 U.S. 352, 355 n.3 (1983) (“a

credible threat”); Frame v. City of Arlington, 657 F.3d

215, 235 (5th Cir. 2011) (“a sufficiently high degree of

likelihood”). Instead, a plaintiff seeking prospective

relief need only show that future injury is “fairly likely.”

Crawford v. Hinds Cnty. Bd. of Supervisors, 1 F.4th

371, 376 (5th Cir. 2021); accord Arcia v. Fla. Sec’y of

State, 772 F.3d 1335, 1341 (11th Cir. 2014) (“a realistic

probability”).

In assessing whether the threatened injury is fairly

likely to occur, evidence of prior injury is especially probative. See Crawford, 1 F.4th at 376 (citing Los Angeles v. Lyons, 461 U.S. 95, 102 (1983)). Said another way,

it “is not unduly conjectural” to use the “predictable effect” of the defendant’s prior actions as a method to predict what will happen in the future. Apple Inc. v. Vidal, 63 F.4th 1, 17 (Fed. Cir. 2023) (quoting Dep’t of

Com. v. New York, 139 S. Ct. 2551, 2566 (2019)). Injuries that are “one-off ” instances or “episodic” in nature

do not move the needle much. Crawford, 1 F.4th at 376.

But where the causes that produced the first injury remain in place, past-injury evidence bears strongly “on

whether there is a real and immediate threat of repeated injury.” O’Shea v. Littleton, 414 U.S. 488, 496

(1974); see Crawford, 1 F.4th at 376; accord In re Navy

Chaplaincy, 697 F.3d 1171, 1176-77 (D.C. Cir. 2012)

(“The prospect of future injury becomes significantly

16a

less speculative where, as here, plaintiffs have identified concrete and consistently-implemented policies

claimed to produce such injury.”).

Finally, a group of plaintiffs need not show that

more than one of them is likely to be injured. “If at least

one plaintiff has standing, the suit may proceed.” Biden

v. Nebraska, 143 S. Ct. 2355, 2365 (2023) (citing

Rumsfeld v. F. for Acad. and Institutional Rts., Inc.,

547 U.S. 47, 52 n.2 (2006)).

A.

Associational Standing

1.

Factual Predicate

The Medical Organizations and Doctors chiefly rely

on associational standing. That is, the organizations

contend that they have standing because their members

are likely to sustain injuries as a result of FDA’s actions. See Hunt v. Wash. State Apple Adv. Comm’n,

432 U.S. 333, 343 (1977). We conclude that the Medical

Organizations and Doctors have made a “clear showing”

that their members face injury with sufficient likelihood

to support entering a preliminary injunction. Barber,

860 F.3d at 352.

The standing theory forwarded here rests on several

basic premises, which are recited as follows. Mifepristone causes adverse effects for a certain percentage

of the women who take it. Those adverse events are

traceable to FDA because it approved the drug. And

hundreds of the Medical Organizations’ members are

OB/Gyns or emergency-room doctors who treat women

who experience severe adverse effects.

The Doctors are allegedly injured when they treat

mifepristone patients. They offer four reasons why

that is so. First, when a doctor treats a woman suffer-

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ing from a mifepristone complication, he or she will often be required to perform or complete an abortion.

And even if not, the doctor must participate in the medical treatment that facilitates an abortion. The Doctors allege that being made to provide this treatment

conflicts with their sincerely held moral beliefs and violates their rights of conscience.

Second, treating mifepristone patients imposes

mental and emotional strain above what is ordinarily

experienced in an emergency-room setting. Third,

providing emergency treatment forces the Doctors to

divert time and resources away from their ordinary patients, hampering their normal practice. And fourth,

the Doctors allege that mifepristone patients involve

more risk of complication than the average patient, and

so expose the Doctors to heightened risk of liability and

increased insurance costs.

The Organizations reason that, given the millions of

women who take mifepristone, the number of women

who experience complications from taking the drug, and

the high number of the Organizations’ members who

treat such women, their members are likely to continue

to treat women suffering complications as a result of

mifepristone. For the reasons listed above, providing

that treatment will injure the Doctors. Thus, the Medical Organizations (via their members) are likely to be

injured by FDA’s actions. We first examine the evidence supporting those contentions.

a.

Adverse Effects

FDA and Danco do not dispute that a significant

percentage of women who take mifepristone experience

adverse effects. From Mifeprex’s initial approval to

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subsequent amendments to the REMS, FDA has acknowledged that a certain fraction of patients would require surgery due to miscellaneous complications. Approval Memorandum at 1; see also 2011 Mifepristone

REMS at 5 (“[A]bout 5-8 out of 100 women taking Mifeprex will need a surgical procedure to end the pregnancy or to stop too much bleeding.”). Similarly, as

explained by the motions panel, the required patient

agreement discloses that “the treatment will not work”

in “about 2 to 7 out of 100 women” who use mifepristone.

All. for Hippocratic Med., 2023 WL 2913725, at * 5.

To be sure, not every woman who experiences complications will present to the emergency room or require surgery and/or some other form of urgent care.

But many will. According to the most updated REMS

medication guide, in studies conducted in the United

States, between 2.9% and 4.6% of women visited the

emergency room after taking mifepristone. Mifeprex

Prescribing Information at 8 tbl.2 (Jan. 2023). Some

women experience especially severe conditions, such as

sepsis (.02%) or hospitalization relating to abortion

(.04% to .06%), and some women require a blood transfusion because of heavy bleeding (.03% to .05%). Id.2

The data FDA cited in its 2000 approval memo is

similar. For the American clinical trial, surgical intervention was required for 7.9% of women (4.5% for the

French studies). Approval Memorandum at 1. Of that

To be clear, we do not understand the Medical Organizations and

Doctors’ standing theory as applying only to women who present to

the emergency room with severe complications such as those listed

above. Rather, they also contend that they are injured by treating

women who experience less urgent medical side-effects because such

treatment forces the doctor to participate in the abortion process.

2

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percentage, 1.2% of women required surgery due to

heavy bleeding (.3% for France) and .12% required a

blood transfusion (.11% for France). Id. FDA and

Danco agree that over five million women have taken

Mifeprex since it was first approved. These figures

show that thousands of women, and as many as hundreds of thousands, have experienced serious adverse

effects as a result of taking the drug, and required surgery or emergency care to treat those effects.

The Medical Organizations contend that their members treat women who suffer serious complications after taking mifepristone. These doctors submitted declarations testifying to their experience giving this sort

of emergency care. For example, Dr. Christina Francis recounted an instance where a patient took mifepristone at approximately ten weeks gestation.

The

woman experienced serious complications and the doctor was forced to perform a surgical abortion because

the drug failed to terminate the pregnancy:

[T]he patient presented back at our emergency

room with heavy vaginal bleeding and unstable vital

signs as a result of taking chemical abortion drugs.

One of my partners was able to detect a fetal heartbeat. Due to the amount of bleeding that she was

experiencing and evidence of hemodynamic instability, however, my partner had no choice but to perform an emergency D&C. The patient needed to

be hospitalized overnight for close observation after

the D&C.

Not only did my partner need to provide several

hours of critical care for this patient, but my partner

also needed to call in a back-up physician to care for

another critically ill patient. And because the pre-

20a

born baby still had a heartbeat when the patient presented, my partner felt as though she was forced to

participate in something that she did not want to be

a part of—completing the abortion.

Dr. Francis Declaration ¶ 13. Dr. Francis also testified to another example where a woman had developed

an infection as a result of using mifepristone:

After taking the chemical abortion drugs, [the patient] began having very heavy bleeding followed by

significant abdominal pain and a fever. When I saw

her in the emergency room, she had evidence of retained pregnancy tissue along with endometritis, an

infection of the uterine lining. She also had acute

kidney injury, with elevated creatinine. She required a dilation and curettage (D&C) surgery to finish evacuating her uterus of the remaining pregnancy tissue and hospitalization for intravenous (IV)

antibiotics, IV hydration, and a blood transfusion.

Id. ¶ 12.3 Dr. Ingrid Skop also testified to caring for

many women experiencing severe complications due to

mifepristone:

In my practice, I have cared for at least a dozen

women who have required surgery to remove retained pregnancy tissue after a chemical abortion.

Sometimes this includes the embryo or fetus, and

At oral argument, Defendants discounted the relevance of this

instance because the patient obtained mifepristone from outside of

the country. Mifeprex is only marketed and distributed in the

United States, so the incident almost certainly did not involve FDA

approved Mifeprex. We agree that the evidence is not as probative

as other examples—discussed below—that involve brand name mifepristone. But the incident still supports the proposition that mifepristone sometimes causes severe adverse events.

3

21a

sometimes it is placental tissue that has not been

completely expelled.

I have cared for approximately five women who, after a chemical abortion,

have required admission for a blood transfusion or

intravenous antibiotics or both.

For example, in one month while covering the emergency room, my group practice admitted three

women to the hospital. Of the three women admitted in one month due to chemical abortion complications, one required admission to the intensive care

unit for sepsis and intravenous antibiotics, one required a blood transfusion for hemorrhage, and one

required surgical completion for the retained products of conception (i.e., the doctors had to surgically

finish the abortion with a suction aspiration procedure).

Dr. Skop Declaration ¶¶ 17-18, 22. She also described

one occurrence where a woman’s mifepristone prescriber

did not offer surgical care in response to heavy bleeding. That, in turn, required Dr. Skop to perform the

follow-up surgical procedure:

In my office, I treated one young woman who had

been bleeding for six weeks after she took the chemical abortion drugs given to her by a doctor at a

Planned Parenthood clinic. After two follow-ups at

Planned Parenthood, during which she was given additional misoprostol but not offered surgical completion, she presented to me for help. I performed a

sonogram, identified a significant amount of pregnancy tissue remaining in her uterus, and performed

a suction aspiration procedure to resolve her complication.

22a

Id. ¶ 23. Dr. Nancy Wozniak also described a serious

complication in detail, in which the patient was at risk

of bleeding to death:

One of my patients, who was about nine weeks pregnant, had previously been treated by hospital staff for

a pulmonary embolism with anti-coagulants. She was

advised that she could not seek a chemical abortion because it was contraindicated due to the medications; yet

the woman left the hospital and sought an abortion at

Planned Parenthood of Indiana.

The woman was given mifepristone by the doctor at

Planned Parenthood and took the drug.

The

woman called an Uber for a ride home from Planned

Parenthood.

The woman began to experience

bleeding and other adverse side effects from the mifepristone. The woman’s Uber driver did not take

her home because she was so ill and instead brought

her to the hospital’s emergency department.

At the hospital, the woman came under my care.

The woman had not yet taken the second abortion

drug, misoprostol. I treated the patient for the adverse effects she suffered and told her not to take the

misoprostol given to her by Planned Parenthood because of the grave risk that she could bleed out and

die.

The woman had a subsequent ultrasound,

which showed that her unborn child was still alive.

I advised the internists treating this patient to avoid

administering certain medications that could harm

the patient and her unborn child.

Dr. Wozniak Declaration ¶ 24. The risk of complications, the Medical Organizations say, is only heightened

in the case of ectopic pregnancy. Dr. Skop testified

23a

about the dangers of taking mifepristone under that

condition:

[A]pproximately 2% of pregnancies are ectopic pregnancies, implanted outside of the uterine cavity.

Chemical abortion drugs will not effectually end an ectopic pregnancy because they exert their effects on the

uterus, which leaves women at risk of severe harm from

hemorrhage due to tubal rupture, in need of emergent

surgery or potentially at risk of death. Failure to perform an ultrasound prior to prescribing abortion drugs

will cause some women to remain undiagnosed and at

high risk for these adverse outcomes.

Dr. Skop Declaration ¶ 29; see also Dr. Barrows Declaration ¶ 18.

According to the Medical Organizations and Doctors, these are examples of medical cases that occur

across the county. The occurrences extend not just to

the declarants, they say, but to all of the Organizations’

members who are doctors. The Organizations offered

testimony from representatives of the American College of Pediatricians, American Association of Pro-Life

Obstetricians and Gynecologists, Christian Medical and

Dental Associations, and Catholic Medical Association

—each of whom explained that their membership includes thousands of doctors and hundreds of OB/Gyns

and emergency-room doctors. See Dickerson Declaration ¶¶ 3, 13; Dr. Harrison Declaration ¶ 8; Dr. Barrows

Declaration ¶ 5; Dr. Van Meter Declaration ¶ 8. Given

the large number of women who experience serious medical complications due to mifepristone, and the large number of association members who are emergency-room

doctors, the Medical Organizations argue, it is highly

likely that one or more of their members will be re-

24a

quired to provide emergency care to a mifepristone patient in the near future.

b.

Doctors’ Injuries

The Medical Organizations and Doctors present evidence of four ways they are injured by providing emergency care to women who used mifepristone. First,

that treatment violates their conscience rights, putting

them in a position where they must perform or complete

an abortion even though doing so is contrary to their

moral beliefs. As described by one doctor:

The FDA’s expansion of chemical abortion . . .

harms my conscience rights because it could force

me to have to surgically finish an incomplete elective

chemical abortion. I object to abortion because it

ends a human life. My moral and ethical obligation

to my patients is to promote human life and health.

But the FDA’s actions may force me to end the life of

a human being in the womb for no medical reason.

Dr. Skop Declaration ¶ 34. And multiple doctors testified that others they knew have been required to complete a failed chemical abortion against their consciences,

or to provide related care. Dr. Francis Declaration ¶ 13;

cf. Dr. Barrows Declaration ¶ 26.

Second, treating mifepristone patients imposes considerable mental and emotional stress on emergencyroom doctors. This is due to the unique nature of chemical abortions, which, according to the plaintiff-doctors,

frequently cause “regret” or “trauma” for the patients

and, by extension, the physicians. Alliance Br. at 18.

Dr. George Delgado testified that his work with such

patients is “some of the most emotionally taxing work I

have done in my career.” Dr. Delgado Declaration

25a

¶ 14; see also Dickerson Declaration ¶ 14; Dr. Skop Declaration ¶ 33; Dr. Wozniak Declaration ¶ 17.

Third, the Doctors are injured because they must divert time and resources away from their ordinary practice to treat mifepristone patients. In particular, the

Doctors describe this treatment as often requiring extended physician attention, blood for transfusions, and

other hospital resources. As one doctor testified:

When I must perform surgery [for] complications

from chemical abortions, this takes attention away

from my other patients. As a hospitalist, I am often

supervising multiple laboring patients on labor and

delivery. When I am called to the operating room

to address an emergency resulting from chemical

abortion, this necessarily means I may not be immediately available if an emergency should occur with

one of my laboring patients.

Dr. Skop Declaration ¶ 32; see also Dr. Francis Declaration ¶ 12 (“I spent several hours with [my patient] the

day of her surgery/hospital admission, keeping me from

my primary patient responsibilities in the labor and delivery unit and requiring me to call in an additional physician to help cover those responsibilities.”); Dr. Harrison Declaration ¶ 30 (“Patients who suffer complications from chemical abortions require significantly

more time and attention from providers than the typical

OB/Gyn patient requires.”).

This diversion of resources, the Doctors say, directly harms their medical

practices. See Dr. Harrison Declaration ¶¶ 27-30.

Fourth, such patients involve more risk than the average emergency room patient, which exposes the Doctors to greater malpractice liability and increased in-

26a

surance costs. See Dr. Barrows Declaration ¶ 23 (testifying that providing emergency treatment to women

suffering complications because of taking mifepristone

puts doctors in “riskier, emergent medical situations”);

Dr. Jester Declaration ¶ 20 (“These situations are naturally higher risk for both the patient and for the physician providing care.”). The more mifepristone patients the Doctors treat, the higher their liability and

greater their injury. See Dr. Barrows Declaration

¶¶ 21-24; Dr. Jester Declaration ¶¶ 20-21; Dr. Johnson

Declaration ¶ 15. Having examined the factual basis

for the Medical Organizations and Doctors’ claims, we

now answer the question of whether they have associational standing to assert those claims.

2.

a.

Analysis

Imminent Injury

We conclude that the Medical Organizations and

Doctors have made a “clear showing” of associational

standing. Barber, 860 F.3d at 352. To begin, it is “fairly

likely” that the Doctors—both those who testified and

those who are members of the Medical Organizations

but did not testify—will continue treating women who experience severe complications after taking mifepristone. Crawford, 1 F.4th at 376. FDA’s own data shows

that a definite percentage of women who take mifepristone will require emergency-room care, be it a blood

transfusion, a surgery to complete a failed abortion or

ongoing pregnancy, or some other complication. The

data further shows that millions of women take mifepristone. And the Medical Organizations testified that

hundreds of their members are OB/Gyns and emergency-room doctors who care for women in these circumstances. The Medical Organizations and Doctors

27a

therefore face a “substantial risk” of future injury.

Susan B. Anthony List, 573 U.S. at 158.

That risk is supported by the fact that many Doctors

have already been required to treat patients experiencing complications due to mifepristone. Lyons, 461

U.S. at 102. These are not merely “one-off ” instances.

Crawford, 1 F.4th at 376. On the contrary, FDA’s data

and the Doctors’ testimony show that women will continue to present to the emergency room after taking

mifepristone, requiring urgent treatment. That trend

is not speculative—it is “predictable” and “consistent[].”

Vidal, 63 F.4th at 17; In re Navy Chaplaincy, 697 F.3d

at 1176. And it does not matter that the foundation of

the Doctors’ standing rests, in part, on “choices made

by independent actors.”

Lujan, 504 U.S. at 562.

That concern is alleviated where, as here, “third parties

will likely act in predictable ways.” Dep’t of Com., 139

S. Ct. at 2566.

It is worth repeating that the Medical Organizations

and Doctors are not required to show that it is “literally

certain” that they will be injured. Clapper, 568 U.S. at

414 n.5. They need only show a “substantial risk” that

injury will occur. Susan B. Anthony List, 573 U.S. at

158; see also United Farm Workers, 442 U.S. at 298 (“a

realistic danger”); Kolender, 461 U.S. at 356 n.3 (“a

credible threat”); Arcia, 772 F.3d at 1341 (“a realistic

probability”). At this preliminary-injunction stage,

they have carried their burden. All. for Hippocratic

Med., 2023 WL 2913725, at *8.

FDA and Danco’s primary objection to the Medical

Organizations and Doctors’ standing theory is that it is

speculative and inconsistent with the Supreme Court’s

decision in Summers v. Earth Island Institute, 555 U.S.

28a

488 (2009). We disagree. For one thing, testimony

was offered from multiple doctors who have personally

given emergency care to women suffering complications

from mifepristone. Dr. Francis Declaration ¶¶ 12-13;

Dr. Skop Declaration ¶¶ 17-18, 22; Dr. Jester ¶ 17.

Given those prior instances, and given mifepristone’s

continued availability, the Medical Organizations reason that these members are reasonably likely to be injured again. The record amply supports that claim.

Moreover, it is not speculative to base standing on

the likelihood that some members of a discrete group,

but not all, will be injured. To be sure, the record must

be specific enough to establish that a group of members

who claim future injury are really at risk. But the evidence before us meets that standard. The Medical

Organizations and Doctors have proven up each link in

the chain of causation—that a percentage of women who

take mifepristone will suffer serious medical complications; that hundreds of the Medical Organizations’ members are physicians who treat patients in those circumstances; that many of the Doctors have in fact treated

such patients; and that providing such treatment causes

the Doctors to violate their rights of conscience, sustain

mental and emotional distress, divert time and resources away from their ordinary practice, and incur additional liability and insurance costs. Contrary to

what FDA and Danco argue, the conclusion the Doctors

draw from that data is not speculative.

And the Medical Organizations’ standing argument

does not conflict with Summers. The problem in that

case was not that plaintiffs’ standing theory was invalid.

It was that the organizational plaintiffs failed to prove

that their members would be injured.

29a

Summers concerned parks administered by the federal Forest Service. The Forest Service issued a regulation allowing it to sell burned timber and conduct

fire-remediation activities on certain low-acreage lots

without the ordinary notice and comment procedures.

Various environmental organizations sued on behalf of

their members, asserting recreational injury based on

their members’ professed intent to visit one of the hundreds of parks that might be affected by the new Service regulation. 555 U.S. at 490-92. Their primary

evidence was an affidavit executed by one member who

had visited a park already subject to fire-remediation

activities, and who intended to visit the park again.

The Service conceded that this plaintiff had standing,

but the parties settled the dispute as to the particular

park, and so it was “not at issue” once the case was before the Supreme Court. Id. at 491 (quoting Earth Island Inst. v. Pengilly, 376 F. Supp. 2d 994, 999 (E.D.

Cal. 2005)).

The plaintiffs attempted to continue their challenge

to the regulation, asserting that their other members

were statistically likely to travel to one of the many

parks that would likely be affected by the regulation.

To be sure, the majority expressed skepticism with that

theory. See id. at 497 (criticizing the dissent’s “hitherto unheard-of test for organizational standing: whether . . . there is a statistical probability that some of

[the plaintiffs’] members are threatened with concrete

injury”). But its bigger concern was that plaintiffs

failed to prove their claims: they lacked evidence of the

number of association members who intended to visit

the parks, and when:

30a

A major problem with the dissent’s approach is that

it accepts the organizations’ self-descriptions of their

membership, on the simple ground that “no one denies” them. But it is well established that the court

has an independent obligation to assure that standing exists, regardless of whether it is challenged by

any of the parties.

Id. at 499. A primary reason for the lack of evidence

was the majority’s decision to not consider several affidavits offered after the district court entered judgment

—affidavits that would have made the required showing. See id. at 495 n.* (declining to consider the affidavits); cf. id. at 508-09 (Breyer, J., dissenting) (arguing

that the Court should consider them). Without those

affidavits, the majority understood itself as not having

evidence of any other member’s injury:

In part because of the difficulty of verifying the facts

upon which such probabilistic standing depends, the

Court has required plaintiffs claiming an organizational standing to identify members who have suffered the requisite harm—surely not a difficult task

here, when so many thousands are alleged to have

been harmed.

Id. at 499. This understanding of Summers is reinforced by the Court’s recent decision in Department of

Education v. Brown, 143 S. Ct. 2343 (2023). There,

the Court reiterated its view that no plaintiff had shown

that he or she actively planned to visit the sites at issue.

See id. at 2354 n.3 (“[N]o plaintiff in Summers had

standing because none had alleged specific plans to observe nature in one of the areas at issue. . . . ”).

Summers does not stand for the proposition that

courts must categorically reject standing when a plain-

31a

tiff alleges that a defendant’s action puts hundreds of

association members at risk of future injury. It stands

for the proposition that courts must treat such assertions with caution.

The standard for making this

showing is high, but the Medical Organizations and

Doctors have met it. They have provided multiple examples of organization members who sustained the exact harm they say will recur. They have explained that

the conditions producing that harm remain in place.

And they have testified to having hundreds of members

who are reasonably likely to be harmed. At this stage,

that is enough.

b.

Cognizable Injury

In addition to being sufficiently imminent, threatened injuries must also be legally cognizable. TransUnion LLC v. Ramirez, 141 S. Ct. 2190, 2204-07 (2021);

Lujan, 504 U.S. at 562. The injuries here are. To begin,

economic harm—like damage to one’s business interest

—is a quintessential Article III injury. TransUnion,

142 S. Ct. at 2204; see, e.g., Greater Phila. Chamber of

Com. v. City of Philadelphia, 949 F.3d 116, 131 (3d Cir.

2020) (recognizing that businesses had standing to challenge local ordinance, which would hamper hiring and

salary decisions). The Doctors therefore sustain a concrete injury when they are forced to divert time and resources away from their regular patients. Dr. Skop

Declaration ¶ 32; Dr. Francis Declaration ¶ 12; Dr. Harrison Declaration ¶¶ 27-30; see also All. for Hippocratic

Med., 2023 WL 2913725, at *6-7. And by the same token, the Doctors sustain a concrete injury when mifepristone patients expose them to greater liability and

increased insurance costs. Dr. Barrows Declaration

32a

¶¶ 21-24; Dr. Jester Declaration ¶¶ 20-21; Dr. Johnson

Declaration ¶ 15.

The Medical Organizations and Doctors also face a

concrete injury when they are forced to choose between

following their conscience and providing care to a

woman experiencing complications as a result of taking

mifepristone. As recounted above, evidence was offered of a doctor who personally gave care in these circumstances. Dr. Skop Declaration ¶ 17 (“In my practice, I have cared for at least a dozen women who have

required surgery to remove retained pregnancy tissue

after a chemical abortion. Sometimes this includes the

embryo or fetus, and sometimes it is placental tissue

that has not been completely expelled.”). Another

doctor testified about her partner, who experienced the

same thing. Dr. Francis Declaration ¶ 13 (“Due to the

amount of bleeding . . . my partner had no choice

but to perform an emergency D&C. . . . And because the preborn baby still had a heartbeat when the

patient presented, my partner felt as though she was

forced to participate in something that she did not want

to be a part of—completing the abortion.”). And other

doctors testified of fear that they or fellow physicians

will be forced into similar situations. Dr. Barrows

Declaration ¶ 26; Dr. Skop Declaration ¶ 34; cf. Dickerson Declaration ¶ 16.

FDA and Danco do not dispute that the Medical Organizations and Doctors’ conscience injury is cognizable. But they defend FDA’s actions on the ground that

federal law would allow the Doctors to refuse care

based on a conscientious objection. FDA Br. at 26;

Danco Br. at 21 (citing 42 U.S.C. §§ 238n, 300a-7(c), (d)).

The Medical Organizations and Doctors respond by

33a

pointing out that the federal government has recently

taken a contrary position. That is, in July 2022, the

Department of Health and Human Services issued a

guidance document that interprets the Emergency

Medical Treatment and Active Labor Act to require

hospitals to provide care to, among others, a woman

with an “incomplete medical abortion,” irrespective of

objections of conscience. Reinforcement of EMTALA

Obligations Specific to Patients Who Are Pregnant or

Are Experiencing Pregnancy Loss, at 6, Centers for

Medicare & Medicaid Services (July 11, 2022). A district court has enjoined that guidance, and an appeal is

proceeding before this court. Texas v. Becerra, 623

F. Supp. 3d 696 (N.D. Tex. 2022) (entering preliminary

injunction); Texas v. Becerra, No. 5:22-CV-185, 2023

WL 2467217 (N.D. Tex. Jan. 10, 2023) (final judgment

and permanent injunction).

At oral argument, counsel for FDA disputed that

EMTALA binds individual doctors, arguing instead

that the obligation to provide abortion-related care runs

to hospitals. That is, individual doctors may assert

conscience objections so long as one doctor at the hospital can provide the required care. This raises the

question of what would happen if no other doctor were

available—a situation that seems particularly likely in

smaller clinics. But setting that issue to the side,

counsel’s argument appears to conflict with the Government’s position on appeal in the Texas case. See Br.

for Appellants at 25, Texas v. Becerra (5th Cir. May 1,

2023) (No. 23-10246) (“EMTALA requires doctors to offer abortion care when that care is the necessary stabilizing treatment for an emergency medical condition.”)

(emphasis added); id. at 27 (“[W]hen pregnant women

come to a Medicare-funded hospital with an emergency

34a

medical condition, EMTALA obligates the treating

physician to provide stabilizing treatment, including

abortion care.”) (quoting United States v. Idaho, 623

F. Supp. 3d 1096, 1109 (D. Idaho 2022)).

We conclude that the federal laws Defendants cite

do not alleviate the Doctors’ conscience injury, at least

for purposes of this preliminary posture. The inconsistencies between the Government’s position in Texas

v. Becerra and FDA’s position here tend to rebut the

notion that Doctors are free to refuse treatment to mifepristone patients.

We next address the Doctors’ argument that they

will suffer an independent injury by way of the “enormous stress and pressure” that is involved with treating

women suffering complications from taking mifepristone. Dr. Wozniak Declaration ¶ 17. They maintain

that FDA’s actions cause women to present at the emergency room with complications that involve a unique

level of trauma and distress, due to the high amount of

emotional and physical strain often associated with the

experience. Dr. Delgado Declaration ¶ 14; Dickerson

Declaration ¶ 14; Dr. Skop Declaration ¶ 33.

It is true that the Supreme Court has interpreted

Article III to recognize injuries that “significantly affect[]” a plaintiff ’s “quality of life.” Sierra Club v.

Morton, 405 U.S. 727, 734-35 (1972). And several of our

sister circuits acknowledge standing that is predicated

on “emotional or psychological harm.” Maddox v.

Bank of N.Y. Mellon Tr. Co., 19 F.4th 58, 65 (2d Cir.

2021) (quoting TransUnion, 141 S. Ct. at 2211 n.7); see

also Clemens v. ExecuPharm Inc., 48 F.4th 146, 155 (3d

Cir. 2022) (same). However, the mental and emotional

stress shown here is best understood as additional to

35a

the Doctors’ conscience injuries, not independent from

them. The threat of being forced to violate a sincerely

held moral belief is cognizable at least in part because

the event would involve acute emotional and psychological harm. Maddox, 19 F.4th at 65; Clemens, 48 F.4th

at 155. The emotional and mental strain of which the

Doctors testify is of the same nature, albeit of an arguably lesser magnitude. In this way, the “enormous

stress and pressure” that the Medical Organizations

and Doctors cite augment the Doctors’ conscience injuries, but does not provide a separate basis for Article

III standing.4

Danco argues that the Medical Organizations and

Doctors’ standing argument is “limitless,” and worries

that its logic would allow doctors to challenge firearm

laws based on the stress involved with treating gunshot

victims. Danco Br. at 22-23 (citing E.T. v. Paxton, 41

F.4th 709, 721 (5th Cir. 2022)). But we see several limits. Foremost is the rigorous evidence needed to

prove traceability and redressability. The plaintiffs in

Danco’s hypothetical would lack standing unless they

could prove that a particular law caused there to be

more gunshot victims, and that enjoining enforcement

of the law would cause there to be fewer. That is a tall

order, to say the least. Equally significant is the requirement that a plaintiff be threatened with injury

akin to being forced to violate his or her sincerely held

conscience beliefs. That sort of injury will be absent

except in the most exceptional cases. We do not think

We understand the Doctors’ conscience injuries as being supported by longstanding precedent of the Supreme Court and this

court. We thus do not discuss our colleague’s thoughtful comments

on other types of injuries that may be cognizable. Post at 67-70.

4

36a

that our holding will open the floodgates to the litigation

Danco describes.

c.

Traceability

Standing to challenge mifepristone’s approval does

not necessarily include standing to challenge FDA’s

subsequent actions. That is so because “standing is

not dispensed in gross; rather, plaintiffs must demonstrate standing for each claim that they press and for

each form of relief that they seek.” TransUnion, 141

S. Ct. at 2208. As we have said many times, standing

proceeds claim by claim. E.g., In re Gee, 941 F.3d 153,

170-71 (5th Cir. 2019); Friends of St. Frances Xavier v.

FEMA, 658 F.3d 460, 466 (5th Cir. 2011). The Medical

Organizations and Doctors are correct, then, to acknowledge that they must show “harms to the plaintiff doctors and associations [that] flow from each of the relevant FDA actions.” Alliance Br. at 22.

i.

2016 Amendments

The Medical Organizations and Doctors contend

that the 2016 Amendments will increase the number of

women who suffer complications as a result of taking

mifepristone. That is so for three reasons, they say.

First, the risk of complication increases with gestational age, and the Amendments increase the maximum

permissible age from forty-nine days to seventy days.

See Dr. Skop Declaration ¶ 28 (asserting that taking

mifepristone at later stages of gestation increases the

chance of “complications due to the increased amount of

tissue, leading to hemorrhage, infection and/or the need

for surgeries or other emergency care”); see also Dr.

Barrows Declaration ¶ 22; Dr. Wozniak Declaration

¶ 10.

37a

Second, the percentage of women who experience

complications that present to the emergency room (as

opposed to their mifepristone provider) will increase

because the Amendments remove the requirement for a

second and third in-person visit. One doctor explained

this phenomenon:

Under the current practice by those who prescribe

and dispense chemical abortion drugs like mifepristone and misoprostol, there is no follow-up or additional care provided to patients. Instead, with no

established relationship with a physician, patients

are simply left to report to the emergency room

when they experience adverse events.

Dr. Foley Declaration ¶ 11; see also Dr. Harrison Declaration ¶ 44 (testifying that eliminating in-person evaluations and follow-up care “places our member doctors

at increased risk of being forced to violate their conscience rights”); Dr. Frost-Clark Declaration ¶ 21 (similar).

Third, and relatedly, the percentage of women who

present to the emergency room will increase because

the Amendments allow non-physicians to prescribe mifepristone. As the motions panel explained, women

who receive the drug from someone other than a doctor

“cannot possibly go back to their non-doctor-prescribers for surgical abortions.” All. for Hippocratic Med.,

2023 WL 2913725, at *5. And multiple doctors testified that they have seen or expect to see more women

with serious complications resulting from mifepristone.

Dr. Harrison Declaration ¶ 26; Dr. Skop Declaration

¶¶ 20- 21; Dr. Wozniak Declaration ¶¶ 18, 29; Dr. Johnson Declaration ¶ 18; Dr. Frost-Clark Declaration ¶ 18;

Dr. Jester Declaration ¶ 13. Given the already sub-

38a

stantial risk of harm, the evidence of increased risk is

sufficient to confer standing to challenge the 2016

Amendments. See Nat. Res. Def. Council, Inc. v.

EPA, 464 F.3d 1, 6-7 (D.C. Cir. 2006) (holding that plaintiffs had standing based on “increased risk” of developing skin cancer); Sutton v. St. Jude Med. S.C., Inc., 419

F.3d 568, 570-75 (6th Cir. 2005) (holding that plaintiffs

had standing based on an “increased risk” of harm from

a medical device).

ii.

2021 Non-Enforcement Decision

The Medical Organizations and Doctors have also

shown that the 2021 Non-Enforcement Decision contributes to their injury. That decision effectively removes the in-person dispensing requirement, allowing

women to request and take mifepristone without ever

going to the doctor’s office. Evidence was introduced

that this change will cause additional severe complications. Among other things, several doctors testified

that supervision is necessary to ensure patients’ safety:

The FDA’s actions harm women, including my patients, because clinics and physicians prescribing or

dispensing chemical abortion drugs, or websites that

provide these drugs through mail order delivery

without any physician involvement, often underprepare women for the severity and risks of chemical

abortion, and they often provide insufficient or no

follow-up care to those women.

Dr. Skop Declaration ¶ 27; see also Dr. Harrison Declaration ¶ 25 (“Mifepristone and misoprostol are serious

drugs that should not be administered without medical

supervision. The FDA’s actions to eliminate the necessary supervision of these drugs harms women and ob-

39a

stetrics professionals. . . . ”); cf. Dickerson Declaration ¶ 12 (“[Mifepristone] can now be administered

and dispensed with no in-person examination or oversight by a physician.”).

Doctors also testified that, without in-person examination, the prescriber is less likely to accurately determine gestational age:

Mifepristone and misoprostol are dangerous drugs

that can potentially harm women. Relaxing the required medical supervision and oversight for patients taking these drugs puts women’s health at

risk.

By eliminating the in-person dispensing requirement and the requirement for a post-abortion follow-up, the FDA has exposed women to a higher

likelihood of undetected serious complications. Specifically, the expanded use of telemedicine for chemical abortions means that some women who are beyond 70 days’ gestation because they are mistaken

or wrong about the gestational age of their unborn

child will take these drugs outside of the appropriate

window.

Dr. Barrows Declaration ¶¶ 16-17; see also Dr. Skop

Declaration ¶ 28 (“Unsupervised chemical abortion

. . . harms women because they may have underestimated the gestational age of their unborn child.”).

And the Doctors say that the need for in-person supervision is even greater in cases of ectopic pregnancy.

Dr. Skop Declaration ¶¶ 27, 29.

Finally, many doctors offered testimony that, as a

result of the 2021 Non-Enforcement Decision, more

women will suffer serious adverse events. Dr. Woz-

40a

niak Declaration ¶ 14 (“The increasing number of chemical abortions through mail-order or telemedicine methods means that more women will suffer complications

from unsupervised use of mifepristone and misoprostol.”); Dr. Frost-Clark Declaration ¶ 12 (“The FDA’s

suspension of the in-person dispensing requirement of

mifepristone and misoprostol harms women and doctors because it has resulted in an increase in complications.”); see also Dr. Skop Declaration ¶¶ 20-21; Dr.

Johnson Declaration ¶ 18; Dr. Jester Declaration ¶ 13.

One doctor personally witnessed an increase in complications after a district court temporarily enjoined the

in-person dispensing requirement in the midst of the

COVID-19 pandemic. Dr. Francis Declaration ¶ 11

(“The frequency of these complications has increased

since a federal district court first enjoined and set aside

the FDA’s in-person dispensing requirement of mifepristone in 2020.”); see generally Am. Coll. of Obstetricians & Gynecologists v. FDA, 472 F. Supp. 3d 183 (D.

Md. 2020) (district court opinion enjoining the in-person

requirements).5

Based on that evidence, the Medical Organizations

and Doctors have made a clear showing that the 2021

Non-Enforcement Decision causes an increased risk of

injury. FDA and Danco resist this conclusion, arguing

that any increase to the Medical Organizations and Doctors injury is speculative because the number of women

who experience ectopic pregnancies is so small. FDA

FDA initially appealed that ruling, but the parties dismissed the

appeal after FDA announced that it would decline to enforce the inperson dispensing and prescription requirements. See Am. Coll. of

Obstetricians & Gynecologists v. Indiana, No. 20-1784, 2021 WL

3276054 (4th Cir. May 19, 2021).

5

41a

Reply Br. at 24; Danco Reply Br. at 11-12. But that

understates the bases of the alleged injury. The Medical Organizations and Doctors argue that ectopic pregnancy (and the possible failure to diagnose it) is one of

the reasons why removing the in-person dispensing requirement will lead to more complications—not the only

reason. As explained above, the declarants offer several other grounds for their contention, including the

need for in-person supervision when a patient takes

mifepristone, the need to accurately assess gestational

age, and the need for in-person follow-up. We conclude that the Medical Organizations and Doctors have

shown a substantial risk of injury due to the 2021 NonEnforcement Decision. As such, they have associational standing to challenge this action.

* * *

Because we hold that the Medical Organizations and

Doctors have associational standing, we need not consider whether they also have organizational or thirdparty standing. See generally ACORN v. Fowler, 178

F.3d 350, 356-57 (5th Cir. 1999); see also All. for Hippocratic Med., 2023 WL 2913725, at *4 n.4. However, to

the extent that it were necessary to consider thirdparty standing, it is likely that emergency-room doctors

have a sufficiently “close relationship” with mifepristone patients. Kowalski v. Tesmer, 543 U.S. 125, 130

(2004); cf. June Med. Servs. LLC v. Russo, 140 S. Ct.

2103, 2118-19 (2020), overruled on other grounds, Dobbs

v. Jackson Women’s Health Org., 142 S. Ct. 2228 (2022).

Indeed, the Court has “long permitted abortion providers to invoke the rights of their actual or potential patients.” June Med. Servs., 140 S. Ct. at 2118. We fail

to see how this case is materially different.

42a

FDA and Danco deny that third-party standing applies, saying that the Doctors have a “diametrically opposed” or “antagonistic” relationship with women experiencing severe complications as a result of taking mifepristone. FDA Br. at 33; Danco Br. at 32. That is

so, Defendants contend, because the relief the Doctors

seek would reimpose certain conditions of using mifepristone. That dubious proposition misunderstands

the nature of the would-be representation. The Doctors pursue third-party standing to represent their patients’ interest in avoiding or limiting the dangerous

side effects that sometimes occur when a woman takes

mifepristone.

Although we do not fulsomely consider the issue

here, we suspect that the Doctors—who have provided

firsthand care to dozens of mifepristone patients experiencing acute physical and emotional distress in an

emergency setting—have a relationship with their patients that is more than adequate to support third-party

standing. In many respects, such a relationship may

be closer than those previously recognized by the Supreme Court. June Med. Servs., 140 S. Ct. at 2118-19;

Whole Women’s Health v. Hellerstedt, 136 S. Ct. 2292,

2314 (2016); Gonzales v. Carhart, 550 U.S. 124, 133

(2007).

B.

2019 Generic Approval

Unlike FDA’s other actions, the Medical Organizations and Doctors did not introduce evidence showing

that they are likely to be injured by the 2019 Generic

Approval. They point to the 2000 Approval, arguing

that the two actions impose the same injuries. Alliance Br. at 23 n.4 (“The generic drug comes with all the

same harms as does the name brand—so the district

43a

court’s harm analysis applies fully to the 2019 ANDA

approval.”). That may be true, but the Medical Organizations and Doctors cannot carry their burden of proof

with legal argument. There is nothing in the record

tending to show that the 2019 Generic Approval contributes to the risk of harm—no evidence that the women

the Doctors have treated took the generic version of

mifepristone, and no evidence that the number of

women experiencing medical complications after taking

mifepristone has risen as a result of the generic.

Indeed, the preliminary-injunction exhibits do not

mention generic mifepristone at all. Separate from associational standing, there is no evidence that the 2019

Generic Approval contributed to any organizational injury sustained by the Medical Organizations or any individual injury sustained by a third-party patient. In

short, the Medical Organizations and Doctors did not

prove that the 2019 Generic Approval affects their risk

of future harm. Accordingly, we must vacate the component the district court’s order staying the effective

date of FDA’s approval of the generic version of mifepristone.

This holding means that generic mifepristone, like

the brand version, will remain available for use under

the conditions provided by the relevant mifepristone

REMS. FDA amended that REMS in 2016 and 2021, but

for the reasons explained below, we affirm the portion

of the district court’s order that stays the effective

dates of those amendments. And so pending trial on

the merits, the current REMS will be the version that

was in effect prior to the 2016 Amendments. Of course,

the mifepristone REMS does not distinguish between

branded and generic mifepristone.

FDA Br. at 9

44a

(“The same REMS covers both versions of mifepristone.”). As such, the generic version will be available

under the same conditions as Mifeprex.

III.

Merits

Having concluded that the Medical Organizations

and Doctors have standing except as to the 2019 Generic Approval, we now turn to the merits of the district

court’s stay order. That inquiry involves the traditional four-factor test for a preliminary injunction. To

merit relief, a movant must show: (1) a substantial

likelihood of success on the merits, (2) a substantial

threat of irreparable harm, (3) that the threat of injury

outweighs any harm that an injunction would cause, and

(4) that the public interest is not disserved by an injunction. Garcia v. Jones, 910 F.3d 188, 190 (5th Cir.

2018).

In reviewing those factors, we review legal conclusions de novo and findings of fact for clear error.

Jones v. Tex. Dep’t of Crim. Just., 880 F.3d 756, 759 (5th

Cir. 2018). The parties agree that these preliminaryinjunction factors apply even though the district court

entered a stay under 5 U.S.C. § 705. That is so because a stay has the practical effect of an injunction. 28

U.S.C. § 1292(a); see All. for Hippocratic Med., 2023

WL 2913725, at *3 n.3; accord Colorado v. EPA, 989

F.3d 874, 883 (10th Cir. 2021) (“These four factors also

determine when a court should grant a stay of agency

action under section 705 of the APA.”).

The first question is whether the Medical Organizations and Doctors have shown a substantial likelihood of

success on the merits. At the outset, we note that “substantial” does not mean “certain.” Byrne v. Roemer,

45a

847 F.2d 1130, 1133 (5th Cir. 1988) (explaining that “the

movant need not always show a probability of success

on the merits”) (quoting Celestine v. Butler, 823 F.2d

74, 77 (5th Cir. 1987)); see Jefferson Cmty. Health Care

Ctrs., Inc. v. Jefferson Parish, 849 F.3d 615, 626 (5th

Cir. 2017) (“Though there is no particular degree of

likelihood of success that is required in every case, the

party seeking a preliminary injunction must establish

at least some likelihood of success on the merits before

the court may proceed to assess the remaining requirements.”). A plaintiff need not prove “its entitlement to

summary judgment in order to establish a substantial

likelihood of success on the merits.” Byrum v. Landreth, 566 F.3d 442, 446 (5th Cir. 2009) (internal quotation marks omitted). But at a minimum, it must “present a substantial case on the merits.” Bryne, 847

F.2d at 1133 (quoting Celestine, 823 F.2d at 77).

A.

2000 Approval

As explained above, the Medical Organizations and

Doctors have standing to challenge the 2000 Approval,

the 2016 Amendments, and the 2021 Non-Enforcement

Decision. Before addressing the merits of the challenge as to the 2000 Approval, we must consider a threshold issue: whether that claim was timely asserted.

The Medical Organizations and Doctors admit that

they did not raise a claim as to FDA’s denial of their

2002 citizen petition within six years, as required for

civil actions filed against the United States. 28 U.S.C.

§ 2401. They present two independent arguments for

why their claim as to the 2000 Approval is nonetheless

timely. The motions panel rejected both arguments.

All. for Hippocratic Med., 2023 WL 2913725, at *13-15.

We do the same.

46a

1.

Reopening Doctrine

First, the Medical Organizations and Doctors point

to a judge-made exception to the statute of limitations

called the “reopening doctrine.” Essentially, this doctrine allows a plaintiff to challenge an agency action

past the ordinary timeline if the agency substantively

reconsiders the original action in a subsequent decision.

See Nat’l Biodiesel Bd. v. EPA, 843 F.3d 1010, 1017

(D.C. Cir. 2016); Sierra Club v. EPA, 551 F.3d 1019,

1024 (D.C. Cir. 2008). The Medical Organizations and

Doctors maintain that the 2016 Amendments and 2021

Petition Denial each trigger reopening. We disagree.6

a.

2016 Amendments

The Medical Organizations and Doctors point both

to FDA’s denial of their 2002 citizen petition and to the

agency’s approval of the amendments to mifepristone’s

conditions for use. They argue that, when FDA denied

the citizen petition, it denied their request to rescind

approval of mifepristone. And when FDA approved

the 2016 Amendments, it altered the regime by which

mifepristone is prescribed and used. Taken together,

they say, these actions show that FDA substantively reconsidered the 2000 Approval.

The Supreme Court has cast some doubt on whether the reopening doctrine is a legitimate exception to a statute of limitations. See

Biden v. Texas, 142 S. Ct. 2528, 2545 n.8 (2022) (“[T]his Court has

never adopted [the reopening doctrine], and [it] appears to be inapposite to the question of final agency action.”). But the parties both

assume that the doctrine is good law in this circuit. And in any

event, we need not address that threshold question because we ultimately conclude that the doctrine does not apply here.

6

47a

To begin, the 2016 petition denial does not inform

the 2016 Amendments. They are plainly different in

nature; the former reaffirms FDA’s conclusion that the

agency properly approved mifepristone for use in 2000

and the latter considers relaxed conditions for the

drug’s use. The Medical Organizations and Doctors

likely could have challenged the 2000 Approval if they

had timely filed suit in response to the petition denial.

But they did not. The argument that the two decisions

must be considered in tandem is really just an end-run

around the fact that the Medical Organizations and

Doctors were too late to challenge FDA’s denial of their

citizen petition.

Accordingly, we consider only whether the 2016

Amendments themselves give rise to the reopening doctrine. They do not. Nothing in FDA’s approval of the

amendments shows that it undertook a “serious, substantive reconsideration” of the 2000 Approval. Texas

v. Biden, 20 F.4th 928, 951-52 (5th Cir. 2021), rev’d on

other grounds, 142 S. Ct. 2528 (2022). Actually, the opposite is true. FDA took the restrictions imposed in

2000 as a given, and considered only whether the REMS

amendments were safe and effective. As explained by

the motions panel: “FDA’s 2016 decision to relax

many of the REMS was issued in response to Danco’s

supplemental application requesting as much.” All.

for Hippocratic Med., 2023 WL 2913725, at *13.

The Medical Organizations and Doctors respond

that the 2016 Amendments were so significant as to constitute a change to the “basic regulatory scheme,” Nat’l

Biodiesel Bd., 843 F.3d at 1017, thereby constructively

reopening the 2000 Approval. It is certainly true that

the amendments meaningfully altered the conditions

48a

under which mifepristone is prescribed and taken.

But a regulatory amendment, even a major one, is insufficient to satisfy the reopening doctrine. Nat. Res.

Def. Council, Inc. v. EPA, 571 F.3d 1245, 1265-66 (D.C.

Cir. 2009); see also Nat’l Ass’n of Reversionary Prop.

Owners v. Surface Transp. Bd., 158 F.3d 135, 144-46

(D.C. Cir. 1998); United Transp. Union-Ill. Legis. Bd.

v. Surface Transp. Bd., 132 F.3d 71, 76 (D.C. Cir. 1998)

(Ginsburg, J.). To meet this high bar and trigger the

reopening doctrine, the amendment must fundamentally alter the nature of the regulation such that it

“could not have been reasonably anticipated.” Env’t

Def. v. EPA, 467 F.3d 1329, 1334 (D.C. Cir. 2006).

The 2016 Amendments do not clear that bar. They

do not alter FDA’s basic assumption that mifepristone

is safe and effective, subject to certain conditions for

use. To be sure, the amendments put the public on notice of a significant change in the degree of mifepristone’s availability and restriction. Disagreement with

that decision would support challenging the new

amendments—and that is exactly what the Medical Organizations did. But as to mifepristone’s approval per

se, the 2016 Amendments tell the public nothing they

did not already know. As before, FDA approved a

drug that chemically induces abortion, with the knowledge that the drug causes medical complications in a

definite percentage of women. We cannot say that the

amendments “significantly alter[ed] the stakes of judicial review” so as to allow the Medical Organizations

and Doctors to challenge the 2000 Approval sixteen

years after the fact. Sierra Club, 551 F.3d at 1025.

49a

b.

2019 Citizen Petition

The Medical Organizations and Doctors also contend that FDA reopened the 2000 Approval when it denied their 2019 citizen petition. They emphasize the

agency’s use of the phrase “full review,” and argue that

FDA actively questioned whether mifepristone was

safe.

The record does not bear out that claim. To start,

the citizen petition did not actually ask FDA to reconsider its approval of mifepristone; it requested that

FDA “restore” previous restrictions and “retain” others currently in place. 2019 Citizen Petition at 1, 2.

So FDA had no reason to reevaluate mifepristone from

the ground up. Turning to the denial itself, FDA did

not reexamine its prior approval. It certainly described its action as “a full review of the Mifepristone

REMS Program,” 2021 Denial Letter at 6, but the letter’s context shows that the agency reviewed the conditions for use that the citizen petition had put at issue—

not mifepristone’s underlying approval.

Nor did FDA constructively reopen the 2000 Approval by adopting a significant amendment to the mifepristone REMS. As with the 2016 Amendments, removing the in-person dispensing requirement does not

change the basic concept of allowing women to use mifepristone. Nat’l Biodiesel Bd., 843 F.3d at 1017. Between an “incremental adjustment[]” to the 2000 Approval and a “substantive reconsideration” of it, the decision to allow remote prescription and dispensing of

mifepristone looks more like the former. Texas, 20

F.4th at 953, 952 (citations omitted). And so if the reopening doctrine is a valid exception to the statute of

limitations, and we are not sure that it is, that doctrine

50a

does not apply here because neither the 2016 Amendments nor the 2021 Petition Denial reevaluated FDA’s

decision in 2000 to approve mifepristone. The reopening

doctrine therefore does not permit the Medical Organizations and Doctors to challenge the 2000 Approval after the prescribed limitations period.

2.

Equitable Tolling

The Medical Organizations and Doctors also point to

equitable tolling as a justification for considering the

2000 Approval claim even though it is untimely. But that

is a very narrow exception. See Jones v. Lumpkin, 22

F.4th 486, 490 (5th Cir. 2022) (reiterating that equitable

tolling “is warranted in only ‘rare and exceptional circumstances’ ”) (quoting Davis v. Johnson, 158 F.3d 806,

811 (5th Cir. 1998)). It applies only if the plaintiff satisfies two conditions: “(1) that he has been pursuing his

rights diligently, and (2) that some extraordinary circumstance stood in his way and prevented timely filing.” Menominee Indian Tribe of Wis. v. United

States, 577 U.S. 250, 255 (2016) (citation omitted).

Supposing that the Medical Organizations and Doctors could meet the first condition, they cannot meet the

second. This court has stressed that equitable tolling

does not apply if the party seeking its benefit could have

complied with the relevant deadline. Jones, 22 F.4th at

490 (“[A] petitioner’s failure to satisfy the statute of limitations must result from external factors beyond his

control; delays of the petitioner’s own making do not

qualify.”) (quoting In re Wilson, 442 F.3d 872, 875 (5th

Cir. 2006)). Here, the Medical Organizations and Doctors offer no reason why they could not have filed their

lawsuit within the six-year limitations period. See All.

for Hippocratic Med., 2023 WL 2913725, at *15 (ex-

51a

plaining that FDA’s delay in ruling on the 2002 Citizen

Petition “had no impact on the length of the statute-oflimitations period or plaintiffs’ capacity to challenge the

2016 Petition Denial”). Their failure to do so forecloses

any possibility of relief.

* * *

For the reasons stated above, we conclude that the

claim as to the 2000 Approval is untimely. Consequently, the Medical Organizations and Doctors are not

likely to succeed on that claim. And that means that we

must vacate the component of the district court’s order

that stays the 2000 Approval. Willey v. Harris Cnty.

Dist. Att’y, 27 F.4th 1125, 1129 (5th Cir. 2022).

B.

2016 Amendments

In addition to the 2000 Approval claim, which is not

likely to succeed, the Medical Organizations and Doctors challenge two other actions taken by FDA: the

2016 Amendments to the mifepristone REMS and the

2021 decision to not enforce regulations requiring in-person prescription. The parties agree that the claims as

to the 2016 Amendments and the 2021 Non-Enforcement

decision are timely, so we proceed to the merits.

The Medical Organizations and Doctors ground

their claims in the Administrative Procedure Act.

That law requires federal courts to “hold unlawful and

set aside agency action, findings, and conclusions found

to be arbitrary, capricious, an abuse of discretion, or

otherwise not in accordance with the law.” 5 U.S.C.

§ 706(2)(A). The Supreme Court has explained that

the “arbitrary-and-capricious standard requires that

agency action be reasonable and reasonably explained.”

FCC v. Prometheus Radio Project, 141 S. Ct. 1150, 1158

52a

(2021). That standard of review is “deferential,” id.,

but “not toothless.” Sw. Elec. Power Co. v. EPA, 920

F.3d 999, 1013 (5th Cir. 2019).

On the contrary, our review is “searching and careful.” Univ. of Texas M.D. Anderson Cancer Ctr. v.

U.S. Dep’t of Health and Hum. Servs., 985 F.3d 472, 475

(5th Cir. 2021) (quoting Marsh v. Or. Nat. Res. Council,

490 U.S. 360, 378 (1989)). Above all, an agency must

“examine the relevant data and articulate a satisfactory

explanation for its action including a ‘rational connection between the facts found and the choice made.’ ”

Motor Vehicle Mfrs. Ass’n v. State Farm Mut. Auto.

Ins. Co., 463 U.S. 29, 43 (1983) (quoting Burlington

Truck Lines v. United States, 371 U.S. 156, 168 (1962)).

An agency violates these rules where it “entirely fail[s]

to consider an important aspect of the problem,” or offers “an explanation for its decision that runs counter

to the evidence before the agency, or is so implausible

that it could not be ascribed to a difference in view or

the product of agency expertise.” Id.; see also Michigan v. EPA, 576 U.S. 743, 752 (2015); Mexican Gulf

Fishing Co. v. U.S. Dep’t of Com., 60 F.4th 956, 971 (5th

Cir. 2023); Sw. Elec. Power Co., 920 F.3d at 1018-19 (explaining that courts must set aside agency action where

there are “shortcomings in the agency’s explanations”).

With those standards in mind, we first address the

2016 Amendments and hold that the Medical Organizations and Doctors are substantially likely to succeed on

the merits of that claim. Byrne, 847 F.3d at 1133.

That is so for two instances of the same defect: failing

to consider an important aspect of the problem. Michigan, 576 U.S. at 752; State Farm, 463 U.S. at 43.

53a

First, FDA did not consider the cumulative effect of

the 2016 Amendments. Those changes include: increasing the maximum gestational age from forty-nine

days to seventy days; allowing non-physicians to prescribe mifepristone; removing the requirement that the

administration of misoprostol and the subsequent follow-up appointment be conducted in person; eliminating prescribers’ obligation to report non-fatal adverse

events; switching the method of administration for

misoprostol from oral to buccal; and changing the dose

of mifepristone (600 mg to 200 mg) and misoprostol (400

mcg to 800 mcg). FDA Summary Review of 2016

Amendments at 2.

FDA admits that none of the studies it relied on examined the effect of implementing all of those changes

together. It studied the amendments individually.

FDA Medical Review of 2016 Amendments at 32-38

(Mar. 29, 2016) (gestational age); id. at 38-41 (in-person

appointments); id. at 43-44 (prescription by non-physician). And some clinical trials considered “multiple

changes.” FDA Summary Review of 2016 Amendments at 5-9. But FDA neither considered the effects

as a whole, nor explained why it declined to do so. The

cumulative effect of the 2016 Amendments is unquestionably an important aspect of the problem; indeed,

that was the whole point of FDA’s action. Because

FDA failed to seek data on the cumulative effect, and

failed to explain why it did not, its decision to approve

the amendments was likely arbitrary and capricious.

Michigan, 576 U.S. at 752; State Farm, 463 U.S. at 43;

Sw. Elec. Power Co., 920 F.3d at 1019.

FDA and Danco defend the 2016 Amendments, asserting that FDA is not required to conduct a study that

54a

perfectly mirrors the conditions under which the drug

will be used. That is true, so far as it goes. Indeed,

the APA gives agencies discretion “in determining

whether a study is adequate and well controlled.”

FDA Br. at 43 (quoting Weinberger v. Hynson, Westcott

& Dunning, Inc., 412 U.S. 609, 621 n.17 (1973)).

But Defendants attack a rule that is not at issue.

The problem is not that FDA failed to conduct a clinical

trial that included each of the proposed changes as a

control. It is that FDA failed to address the cumulative effect at all. At a minimum, the agency needed to

acknowledge the question, determine if the evidence before it adequately satisfied the concern, and explain its

reasoning. See All. for Hippocratic Med., 2023 WL

2913725, at *17 (“[FDA] relied on zero studies that evaluated the safety-and-effectiveness consequences of the

2016 Major REMS Changes as a whole. This deficiency shows that FDA failed to consider ‘an important

aspect of the problem’ when it made the 2016 Major

REMS Changes.”) (quoting Michigan, 576 U.S. at 752).

FDA did not do those things, and so likely violated the

APA.

The second important aspect that FDA failed to consider is whether it needed to continue to collect data of

non-fatal adverse events in light of the “major” changes

to the mifepristone REMS. When considering the

data-collection question, FDA reasoned that non-fatal

adverse events did not have to be recorded because the

risks associated with mifepristone were well known.

FDA Summary Review of 2016 Amendments at 26

(“[A]fter 15 years of reporting serious adverse events, the

safety profile for Mifeprex is essentially unchanged.”).

55a

But FDA failed to account for the fact that it was

about to significantly loosen mifepristone’s conditions

for use. At no point during the decision did the agency

acknowledge that the 2016 Amendments might alter the

risk profile. And when FDA addressed this subject in

its response to the 2019 citizen petition, it just referred

back to its statement that the risks were minimal under

the 2011 REMS. See 2021 Denial Letter at 20. We

conclude that FDA ignored “an important aspect of the

problem,” Michigan, 576 U.S. at 752 (quoting State

Farm, 463 U.S. at 43), and that its explanation of the

basis for the change contains significant “shortcomings.” Sw. Elec. Power Co., 920 F.3d at 1018-19. This

also likely violates the APA.

Defendants respond that the change is insignificant

because Danco remains obligated to report serious adverse events to FDA. See FDA Br. at 53; Danco Br.

47 (citing 21 C.F.R. §§ 314.80, 314.98). True, Danco is

still subject to some reporting requirements, but these

are significantly different than the ones that were removed. Before, prescribers were required to report

certain adverse events directly to FDA. Given that

prescribers interact with the women taking mifepristone, they are well placed to know if a patient actually

experiences an adverse event. By contrast, Danco has

no direct relationship with Mifeprex patients and little

ability to track events. Like any member of the public,

Danco can access the FDA Adverse Event Reporting

System (FAERS), a voluntary reporting website. But

prescribers are not required to log non-fatal adverse

events. Indeed, no one is required to report anything

on FAERS. Nor are prescribers required to report to

Danco. The end result is that the removal of the

adverse-event reporting requirement significantly di-

56a

minishes FDA’s ability to collect this data. Danco’s

residual reporting requirements do not cure this APA

violation.

C.

2021 Non-Enforcement Decision

We now assess whether the Medical Organizations

and Doctors are likely to succeed on their claim regarding the 2021 Non-Enforcement Decision. That decision essentially involves three parts. First, in April

2021, FDA announced that it would temporarily suspend enforcement of the in-person dispensing requirement in light of the COVID-19 pandemic. Next, in December of that year, FDA stated its intent to eliminate

the requirement permanently. See 2021 Denial Letter

at 25 (“[W]e believe that the Mifepristone REMS Program must be modified to remove the requirement that

mifepristone be dispensed only in certain healthcare

settings . . . because this requirement is no longer

necessary to ensure that the benefits of the drug outweigh the risks.”). And then in January 2023, FDA

amended mifepristone’s REMS, for Mifeprex and the

generic, formalizing the change.

FDA supported its decision by pointing to two sources

of information. First, the agency examined adverseevents data collected during the period of time when the

in-person dispensing requirement was enjoined. FDA

obtained this data from FAERS—the voluntary reporting website. 2021 Denial Letter at 26. Danco also submitted its records of adverse events during the relevant

interval, but its data set was the same as the one obtained via FAERS. Id. at 27 (“The information provided by the Applicants included the same cases identi-

57a

fied in FAERS. . . . ”). Five events 7 were reported during that time, but FDA concluded that there

did not “appear to be a difference in adverse events

when in-person dispensing was and was not enforced.”

Id.

Second, FDA considered published literature relating to remote prescription of mifepristone. It determined that those studies were “not inconsistent with

our conclusion that . . . mifepristone will remain

safe and efficacy will be maintained if the in-person dispensing requirement is removed from the Mifepristone

REMS Program.” Id. at 28. Based on these sources,

FDA concluded that “mifepristone will remain safe and

effective if the in-person dispensing requirement is removed.” Id. at 35.

1.

Mootness

Defendants first raise a threshold question: whether

the Medical Organizations and Doctors’ challenge to the

2021 non-enforcement policy is moot. They contend

that the 2023 modification of mifepristone’s REMS supersedes the 2021 policy, and also that the prior policy

was tied to the Government’s COVID-19 public health

emergency, which has since expired. For these reasons, FDA and Danco say, there is no longer a live dispute as to the 2021 Non-Enforcement Decision.

Neither reason is availing. First, FDA is incorrect

to say that it tied its December 2021 decision not to enforce the in-person dispensing requirement to the

According to FDA, the causes of those events are as follows: ongoing pregnancy, drug intoxication and death, death (unknown cause),

sepsis and death, and pulmonary embolism. 2021 Denial Letter at

26.

7

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COVID-19 pandemic. True, FDA cited the pandemic

as a justification for taking the initial action. FDA Letter of April 2021 at 2 (“[FDA] intends to exercise enforcement discretion during the COVID-19 [pandemic] with respect to the in-person dispensing requirement of the

Mifepristone REMS Program. . . . ”). But when

FDA “directed mifepristone’s sponsors to submit a proposed REMS modification,” several months later, it did

so without regard to pandemic conditions. FDA Br. at

11; see 2021 Denial Letter at 6, 25-26. FDA simply did

not tether its action in December of 2021 to the continued existence of the public health emergency.

Second, FDA’s formalization of the policy it announced in 2021 does not render this claim moot. At

bottom, the mootness doctrine asks whether the court

faces a live dispute. Freedom from Religion Found.,

Inc. v. Abbott, 58 F.4th 824, 831 (5th Cir. 2023). That is,

a case is moot if “the parties lack a legally cognizable

interest in the outcome.” Id. (quoting Already, LLC

v. Nike, Inc., 568 U.S. 85, 91, (2013)).

A live dispute exists as to the 2021 Non-Enforcement Decision. The decision that FDA made in 2021—

to permanently not enforce in-person prescription and

dispensing requirements—remains in force.

FDA

may have formalized that policy by modifying the mifepristone REMS. But the effect is the same, as is FDA’s

ultimate judgment that mifepristone can be safely used

without in-person prescription and dispensing.

Moreover, the Supreme Court has recognized that

the government does not moot a controversy when it introduces the final form of a previous, identical policy.

Biden v. Texas, 142 S. Ct. 2528, 2544-45 (2022) (considering a prior agency action even after it was formalized

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by a later, similar action); see All. for Hippocratic Med.,

2023 WL 2913725, at *2 n.2. That type of action is different in kind than the repeal or modification of a government policy. Freedom from Religion Found., 58

F.4th at 832. Unlike a repealed policy, FDA’s policy

remains unchanged and on the books (albeit in a permanent form). We see no jurisdictional obstacle to reviewing the claim as to the 2021 Non-Enforcement Decision.

2.

Merits

Because the 2021 Non-Enforcement claim is not

moot, we must proceed to the question of whether that

action was arbitrary and capricious. For two reasons,

we hold that it likely was. First, FDA gave dispositive

weight to adverse-event data in FAERS—despite the

uncontested limitations of doing so. Recall that, because of the 2016 Amendments, FDA no longer had access to perhaps the best source of data: the prescribers. The agency is responsible for its own inability to

obtain probative data; it cannot then cite its lack of information as an argument in favor of removing further

safeguards. As the motions panel aptly put it: “It’s unreasonable for an agency to eliminate a reporting requirement for a thing and then use the resulting absence of data to support its decision.” All. for Hippocratic Med., 2023 WL 2913725, at *17.

Moreover, considerable evidence shows that FAERS

data is insufficient to draw general conclusions about

adverse events. Indeed, in describing the database,

FDA itself recognizes that “FAERS data cannot be

used to calculate the incidence of an adverse event or

medication error in the U.S. population.” FDA admits

that FAERS reporting is purely voluntary, FDA Br. at

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53; consequently, many adverse events will go unreported.

For example, one doctor testified that she obtained

adverse-event data from one provider (Planned

Parenthood) and compared it to FAERS data for the

same time period. For 2010, the provider reported 1,530

adverse events, whereas FAERS reported only 664

events for all providers nationwide.

Dr. Harrison

Declaration ¶ 17; see also id. (“These discrepancies render FAERS inadequate to evaluate the safety of mifepristone abortions.”).

In addition, the Doctors introduced evidence that

many physicians do not use FAERS, either because

they are not aware of the system or because they believe that using the system is difficult, and takes time

away from their ordinary medical practice:

Many doctors likely do not know about the need to

report adverse events related to chemical abortion

to the FDA. Similarly, many doctors likely do not

know how to report adverse events. . . . I personally know of practitioners

. . .

who have

tried to report adverse events related to chemical

abortion drugs to the FDA. The process is complicated, cumbersome, and time-consuming. The adverse event reporting requirements and the FAERS

submission process harm medical practices by taking away significant time from a doctor to treat and

meet with patients.

Dr. Harrison Declaration ¶¶ 33-34; see also Dr. FrostClark Declaration ¶ 23 (“I have not reported adverse

events that I have witnessed as a result of chemical

abortions because the process is so cumbersome.”).

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One doctor testified that it can take hours to report an

adverse event to FAERS:

[T]he process of reporting to [FAERS] is also cumbersome. The actual form to be filled out is not

easy to find online—requiring several steps to get it.

It once took me two hours to get the website to accept submission of the form, taking me away from

the care of my other patients. The minimum amount

of time I have spent reporting a mifepristone complication to the FAERS is thirty minutes—valuable

time that should be spent in patient care.

Dr. Francis Declaration ¶ 18. FDA’s decision to rely

so heavily on data from FAERS “runs counter to” the

critical limitations associated with that data. State

Farm, 463 U.S. at 43; Sw. Elec. Power Co., 920 F.3d at

1018-19.

FDA responds that it also considered adverse-event

data submitted by Danco, but Danco’s data was exactly

the same as the data FDA obtained from FAERS. FDA

acknowledged as much in its letter denying the 2019 citizen petition. 2021 Denial Letter at 27. (“The information provided by the Applicants included the same

cases identified in FAERS. . . . ”). If anything,

the fact that Danco submitted identical data tends to

confirm the assertion that FDA lacked sufficient information; it shows that neither FDA nor Danco had the

means to collect data directly from prescribers.

The second defect in the Non-Enforcement Decision

is that it relied on various literature relating to remote

prescription of mifepristone—despite FDA’s admission

that the literature did not affirmatively support its position. Danco insists that the studies “all . . . sup-

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ported the conclusion that mifepristone would still be

safe and effective even with a relaxed in-person dispensing requirement,” Danco Br. at 48, but that is not

what FDA said in 2021. On the contrary, FDA candidly acknowledged that the literature was only “not inconsistent with [its] conclusion.” 2021 Denial Letter

at 28. In other words, the studies neither confirmed

nor rejected the idea that mifepristone would be safe if

the in-person dispensing requirement were removed.

In discussing the various studies, FDA recognized

many significant limitations:

We note that the ability to generalize the results of

these studies to the United States population is hampered by differences between the studies with regard to pre-abortion care (e.g., telemedicine versus

in-person). In addition, the usefulness of the studies is limited in some instances by small sample sizes

and lack of follow-up information on outcomes with

regard to both safety and efficacy.

There are also factors which complicate the analysis

of the dispensing element alone. Some of these factors are: (1) only a few studies have evaluated alternatives for in-person dispensing of mifepristone

in isolation (for example, most studies on mail dispensing of mifepristone also include telemedicine

consultation); and (2) because most serious adverse

events with medical abortion are infrequent, further

evaluation of changes in dispensing would require

studies with larger numbers of participants. We

did not find any large clinical studies that were designed to collect safety outcomes in healthcare systems similar to the United States.

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Id. Given those limitations, FDA concluded that the

studies were “not adequate on their own to establish the

safety of the model of dispensing mifepristone by mail.”

Id. at 35.

Especially in light of the unreliability of the adverseevent data, it was not reasonable for FDA to depend on

the published literature to support its decision. Courts

must set aside agency action where there are “shortcomings in the agency’s explanations” or where “[n]o

record evidence affirmatively makes” the agency’s case.

Sw. Elec. Power Co., 920 F.3d at 1018-19; see also State

Farm, 463 U.S. at 56 (“While [an] agency is entitled to

change its view . . . it is obligated to explain its reasons for doing so.”). That is the case here.

In the face of concededly limited data, and lacking

more probative information from prescribers, FDA fell

back on studies that were merely “not inconsistent”

with its intended conclusion. It did not refer to any literature that affirmatively supported the notion that

mifepristone would remain safe and effective even without the in-person dispensing requirement. We conclude that the Medical Organizations and Doctors are

likely to succeed in showing that this action violated the

APA.8

IV.

Irreparable Harm and Balance of the Equities

We now proceed to the remaining steps of the preliminary-injunction analysis. First, we ask if the Medical Organizations and Doctors are likely to sustain irreparable harm absent an injunction. Garcia, 910

Given this holding, we do not consider the Medical Organizations

and Doctors’ independent argument that the 2021 Non-Enforcement

Decision violates the Comstock Act of 1873.

8

64a

F.3d at 190. If so, we then balance the equities and

consider whether an injunction serves the public interest. Winter, 555 U.S. at 20. And where the government appeals an injunction, its interests “merge” with

the public interest. Tex. Democratic Party v. Abbott,

961 F.3d 389, 412 (5th Cir. 2020) (quoting Veasey v. Abbott, 870 F.3d 387, 391 (5th Cir. 2017)).

We have already concluded that the Medical Organizations and Doctors are likely to sustain injury; now we

need only determine whether the threatened injuries

are irreparable. They are. An irreparable harm is one

“for which there is no adequate remedy at law.” Louisiana v. Biden, 55 F.4th 1017, 1033-34 (5th Cir. 2022)

(quoting Daniels Health Scis., LLC v. Vascular Health

Scis., LLC, 710 F.3d 579, 585 (5th Cir. 2013)). No legal

remedy can adequately redress the Doctors’ conscience

and mental-distress injuries. And the economic injuries

—the potential damage to their medical practice, heightened exposure to malpractice liability, and increased

insurance costs—are irreparable too. Monetary harm

cannot be remedied where, as here, the defendant is entitled to sovereign immunity. See Wages & White Lion

Invs., LLC v. FDA, 16 F.4th 1130, 1142 (5th Cir. 2021).

This risk of irreparable harm must be weighed

against any injury FDA and Danco would sustain as a

result of the stay order, as well as against the public

interest. Starting with FDA, we recognize that anytime the Government is enjoined from enforcing its

statutes or regulations, “it suffers a form of irreparable

injury.” Maryland v. King, 567 U.S. 1301, 1303 (2012)

(Roberts, C.J., in chambers); accord Valentine v. Collier, 956 F.3d 797, 803 (5th Cir. 2020). But on the other

hand, neither FDA nor the public has any interest in

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enforcing a regulation that violates federal law. Louisiana, 55 F.4th at 1035 (“There is generally no public

interest in the perpetuation of unlawful agency action.”)

(citations omitted).

In this regard, the government/public-interest analysis collapses with the merits. See Sierra Club v. U.S.

Army Corps of Eng’rs, 990 F. Supp. 2d 9, 43 (D.D.C.

2013) (Jackson, J.) (explaining that “public interest arguments” are “derivative of . . . merits arguments

and depend in large part on the vitality of the latter”)

(citing Serono Lab’ys, Inc. v. Shalala, 158 F.3d 1313,

1326 (D.C. Cir. 1998)); see also Louisiana, 55 F.4th at

1035; League of Women Voters of U.S. v. Newby, 838

F.3d 1, 12 (D.C. Cir. 2016). The Medical Organizations

and Doctors are likely to succeed on their claims as to

the 2016 Amendments and 2021 Non-Enforcement Decision. It follows that FDA and the public will not be

injured by an order staying those likely unlawful actions.

FDA also points to the “disruptive practical effects”

of a stay, FDA Br. at 66-67, arguing that it will incur

substantial costs if it complies with the stay order, only

for the order to be reversed later. As a preliminary

matter, this argument is also highly duplicative of the

merits. FDA’s injury only comes into play if the stay

order is vacated—that is, if the Medical Organizations

and Doctors are not likely to succeed on the merits.

After careful consideration, we have concluded that

these claims are likely to succeed. Accordingly, we do

not consider the costs that might be incurred if the stay

order goes into effect and is later vacated. Moreover,

we doubt whether an agency’s interim compliance costs

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could outweigh a threat of irreparable harm. See Al

Otro Lado v. Wolf, 952 F.3d 999, 1008 (9th Cir. 2020).

Turning to Danco’s interest, we acknowledge that

the district court’s stay order would impose significant

injury. See Texas v. EPA, 829 F.3d 405, 434 (5th Cir.

2016) (explaining that financial harm may be irreparable “where the loss threatens the very existence of the

[party’s] business”) (quoting Wis. Gas Co. v. FERC, 758

F.2d 669, 674 (D.C. Cir. 1985)). That threat, however,

is substantially lessened because we vacate the component of the stay order that would pause FDA’s initial

approval of mifepristone in 2000.

What remains is any injury that Danco will face as a

result of the stay order as amended. The Medical Organizations and Doctors point out that Danco already

has drug labels and documentation that comply with the

mifepristone REMS as of 2011. Danco does not deny

this, but responds that “[r]equiring a return to a prior

and outdated REMS and label would also create

months-long loss of access, while FDA and Danco work

through the sNDA process.” Danco Br. at 61 (citing

Declaration of Dr. Janet Woodcock ¶ 14). But this potential injury is greatly diminished by the fact that the

Supreme Court’s stay of the district court’s order will

remain in effect pending disposition of any petition for

certiorari.

It is a well-established maxim that “equity regards

substance rather than form.” Dobbs, 1 Law of Remedies 83 (2d ed. 1993). This means, among other things,

that courts exercising equitable power should account

for the real, boots-on-the-ground circumstances, not

those supposed or theorized by the parties. As Pomeroy has explained:

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Equity always attempts to get at the substance of

things, and to ascertain, uphold, and enforce rights

and duties which spring from the real relations of

parties. It will never suffer the mere appearance and

external form to conceal the true purposes, objects,

and consequences of a transaction.

Pomeroy, II Equity Jurisprudence § 378 (5th ed. 1941);

see, e.g., Freedom from Religion Found., 58 F.4th at

837. Applying this principle, we must take into consideration the fact that the district court’s stay order will

likely not go into effect for several months, if not more

than a year.

The Supreme Court’s stay alleviates (or at least

greatly reduces) any possible harm to Danco because it

establishes a substantial window to prepare to comply

with the district court’s stay order, as modified by this

court. The soonest the district court’s stay order

could go into effect would be if neither party filed a petition for certiorari, and the deadline to do so is ninety

days after the entry of this court’s judgment. Sup. Ct.

R. 13. Alternatively, if either of the Defendants seek

certiorari, the stay will remain in effect at least until the

denial of that petition, should it be denied. But even

that would likely require a minimum of six months for

briefing by the parties and disposition by the Supreme

Court. And if the Court grants the writ, that would

extend the stay for upwards of another year. Either

way, Danco will have “months” of time needed to arrange for mifepristone to be distributed under the 2011

REMS and prevent any “loss of access.”

Other public-interest considerations merit discussion. Various amici assert that eliminating access to

mifepristone, even temporarily, may pose health risks

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to certain women, including those who use the drug to

manage miscarriage. Br. of American College of Obstetricians and Gynecologists et al. at 21-26; Br. of Physicians for Reproductive Health at 18-27; Br. of Over

200 Reproductive Health, Rights, and Justice Organizations at 14-25; Br. of Doctors for America et al. at 1423; Br. of Advocates for Survivors of Intimate Partner

Violence at 18-26. Other amici argue that “disrupting

access to mifepristone” would burden state and local

health-care systems. Br. of New York et al. at 4; see

also Br. of Local Governments at 24-26; Br. of the City

of New York et al. at 8-31; Br. of Medical Students for

Choice at 3-22. And still other amici say that staying

FDA’s approval of mifepristone would destabilize the

pharmaceutical industry, especially research-and-development sections. Br. of Pharmaceutical Companies, Executives, and Investors at 3-4; Br. of Pharmaceutical Research and Manufacturers of America et al.

at 22-26; Br. of Patient and Provider Advocacy Organizations at 9-20.

These concerns are not insignificant. But they apply primarily (if not wholly) to the challenge to the 2000

Approval—a claim that we have concluded is not likely

to succeed.

All. for Hippocratic Med., 2023 WL

2913725, at *20 (“[T]hese concerns center on the district

court’s removal of mifepristone from the market. [Defendants] make no arguments as to why the 2016 Major

REMS Changes, the 2019 Generic Approval, or the 2021

and 2023 Mail Order Decisions are similarly critical

to the public. . . . ”). Insofar as these concerns

translate to the 2016 Amendments and 2021 NonEnforcement Decision, they are lessened by the fact

that mifepristone would remain available under the

2011 REMS, as would options for surgical abortion.

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And of course, the public interest is disserved by a

drug that does not afford adequate protections to its users. See Deerfield Med. Ctr. v. City of Deerfield

Beach, 661 F.2d 328, 338 (5th Cir. 1981); Hill Dermaceuticals, Inc. v. FDA, 524 F. Supp. 2d 5, 12 (D.D.C.

2007) (“[T]he public interest weighs strongly in favor of

preventing unsafe drugs from entering the market.”).

To be clear, the evidence does not show that mifepristone is unsafe in all applications. But on this record

and at this preliminary stage, the Medical Organizations and Doctors have made a substantial showing that

the 2016 Amendments and 2021 Non-Enforcement Decision were taken without sufficient consideration of the

effects those changes would have on patients.

Weighing all of these considerations, we conclude

that the balance of the equities favors the Medical Organizations and Doctors. They face a substantial risk

of irreparable harm to their medical practice, mental

and emotional health, and conscience. The limited relief affirmed by our judgment threatens neither FDA

nor Danco with substantial harm. Nor does it offend

the public interest. The Medical Organizations and

Doctors therefore satisfy the remaining preliminary-injunction factors. Winter, 555 U.S. at 20.

V.

Form of Relief

Finally, FDA and Danco challenge the form of the

relief entered by the district court—a stay of the actions’ effective dates. FDA argues that the Medical

Organizations and Doctors were required to first seek

an administrative stay, but failed to do so. See 21

C.F.R. § 10.45(c) (“A request that administrative action

be stayed must first be the subject of an administrative

decision based upon a petition for stay of action . . .

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before a request is made that a court stay the action.”).

It also contends that § 705 authorizes only requests

made at the same time the challenged action is enacted.

Here, by contrast, the Medical Organizations and Doctors seek a stay years after the relevant policies took

effect. And Danco maintains that injunctive relief is

categorically unavailable, reasoning that if the Medical

Organizations and Doctors prevailed, they would only

be entitled to remand without vacatur.

We hold that the district court entered an appropriate form of relief. To begin, consider the nature of a

“stay” under § 705. In the same way that a preliminary injunction is the temporary form of a permanent

injunction, a stay is the temporary form of vacatur.

Between vacatur and an injunction, the former is the

“less drastic remedy.” Monsanto Co. v. Geertson Seed

Farms, 561 U.S. 139, 165 (2010). That is so because

vacatur does not order the defendant to do anything; it

only removes the source of the defendant’s authority.

See Nken v. Holder, 556 U.S. 418, 428-29 (2009) (“[A]

stay achieves this result by temporarily suspending the

source of authority to act—the order or judgment in

question—not by directing an actor’s conduct.”); see

also Texas v. United States, 40 F.4th 205, 220 (5th Cir.

2022) (“Apart from the constitutional or statutory basis

on which the court invalidated an agency action, vacatur

neither compels nor restrains . . . agency decisionmaking.”).

Upon a successful APA claim, vacatur effectively rescinds the unlawful agency action. See Data Mktg.

P’ship, LP v. U.S. Dep’t of Lab., 45 F.4th 846, 859 (5th

Cir. 2022) (“Vacatur . . . retroactively undoes or expunges a past state action. . . . Unlike an injunc-

71a

tion, which merely blocks enforcement, vacatur unwinds the challenged agency action.”) (quoting Driftless

Area Land Conservancy v. Valcq, 16 F.4th 508, 522 (7th

Cir. 2021)). Keeping with the preliminary-permanent

injunction analogy, a stay temporarily voids the challenged authority.

Practically speaking, a stay means that—while the

order is in effect—Danco will have legal authority to

market and sell Mifeprex under the conditions that

were in effect before 2016. Likewise, GenBioPro will

have authority to market and sell the generic version of

mifepristone under those same conditions—that is,

those that appeared in the 2011 REMS. The in-person

dispensing requirements, and FDA’s obligation to enforce them, will continue to apply.

In terms of enforcement, unlike with a preliminary

injunction, a stay does not actively prohibit conduct,

and so does not carry the same threat of contempt.

Plaintiffs could move to enforce the stay in the unlikely

event that FDA or Danco took some action to violate it.

But of course, we have absolutely no reason to believe

that such a motion would be necessary. And we should

reiterate that the Supreme Court’s stay of the district

court’s order will remain in effect pending disposition

of any petition for certiorari.

Turning to Danco’s objection to a stay, we do not

agree that the Medical Organizations and Doctors will

be limited to remand without vacatur if they obtain a

favorable judgment. “[V]acatur of an agency action is

the default rule in this Circuit.” Cargill v. Garland, 57

F.4th 447, 472 (5th Cir. 2023) (en banc) (plurality op.);

Data Mktg. P’ship, 45 F.4th at 859; accord United Steel

v. Mine Safety & Health Admin., 925 F.3d 1279, 1287

72a

(D.C. Cir. 2019) (“The ordinary practice is to vacate unlawful agency action.”). Given that presumption, remand without vacatur is appropriate only if “there is at

least a serious possibility that the agency will be able to

substantiate its decision given an opportunity to do so.”

Texas v. United States, 50 F.4th 498, 529 (5th Cir. 2022)

(quoting Texas Assn. of Mfrs. v. U.S. Consumer Prod.

Safety Comm’n, 989 F.3d 368, 389-90 (5th Cir. 2021));

accord Radio-Television News Dirs. Ass’n v. FCC, 184

F.3d 872, 888 (D.C. Cir. 1999).

Remand without vacatur is likely not appropriate

because “it is far from certain” that FDA could cure its

mistakes with further consideration. Env’t Def. Fund

v. FERC, 2 F.4th 953, 976 (D.C. Cir. 2021). FDA erred

by failing to consider the cumulative effects of the 2016

Amendments on mifepristone’s safety and by disregarding the lack of recent data on adverse events when

removing the in-person dispensing requirement. The

record does not tend to show that FDA would have arrived at the same decision if it had considered those

things. See Oglala Sioux Tribe v. U.S. Nuclear Regul.

Comm’n, 896 F.3d 520, 536 (D.C. Cir. 2018) (declining

to remand without vacatur because of the “seriousness”

of the action’s “deficiency”); Pollinator Stewardship

Council v. EPA, 806 F.3d 520, 532 (9th Cir. 2015)

(same); cf. Sierra Club v. FERC, 68 F.4th 630, 652 (D.C.

Cir. 2023) (remanding without vacatur because it was

possible that FERC could “adequately explain its decision” if given another opportunity). If the Medical Organizations and Doctors succeed on the merits, it is

likely that the default remedy—vacatur—will be appropriate. And the temporary version of vacatur is a stay.

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We are also unpersuaded by FDA’s contentions.

First, FDA argues Medical Organizations and Doctors

cannot seek a stay before the district court because they

failed to seek one from the agency. But the record

shows that FDA would have denied any request for an

administrative stay. See Gulf Restoration Network v.

Salazar, 683 F.3d 158, 176 (5th Cir. 2012). FDA unequivocally denied the 2019 citizen petition, rejecting the

premise that 2016 Amendments made mifepristone less

safe. It discussed the 2021 Non-Enforcement Decision in the same document, and then formalized the policy in 2023. These pronouncements show that FDA

was committed to implementing these changes, and

foreclose any notion that the agency would have granted

an administrative stay. Tesoro Refin. & Mktg. Co. v.

FERC, 552 F.3d 868, 874 (D.C. Cir. 2009) (explaining

that the exhaustion requirement does not apply “when

resort to administrative remedies [would be] clearly

useless”) (citations omitted). That FDA denied a request to stay the 2000 Approval further aids this conclusion. See 2016 Denial Letter at 32 (“As described

above, we are denying your Petition. Therefore, your

request for a stay pending final action on your Petition

is moot.”).

Second, FDA provides no authority for its assertion

that § 705 of the APA limits stays to contemporaneous

agency actions. The text does not provide such a limitation. Instead, it empowers a reviewing court to “issue all necessary and appropriate process to postpone

the effective date of an agency action or to preserve status or rights pending conclusion of the review proceedings.” 5 U.S.C. § 705. Circuit courts have interpreted this statute as providing something akin to the

general stay power recognized by Rule 18 of the Fed-

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eral Rules of Appellate Procedure, see Ohio v. Nuclear

Regul. Comm’n, 812 F.2d 288, 290 (6th Cir. 1987); In re

GTE Serv. Corp., 762 F.2d 1024, 1026 (D.C. Cir. 1985),

which weighs against construing § 705 as requiring that

a stay be issued concurrently with an agency action.

We are disinclined to reach a definitive answer on this

question, given the cursory treatment by both parties.

But we strongly doubt that § 705 should be read to impose the limit urged by FDA. Nothing about this argument persuades us that the district court abused its discretion by entering this particular form of relief.

VI.

Conclusion

For the foregoing reasons, the stay order entered by

the district court is VACATED in part and AFFIRMED

in part. We vacate the component of the order that

stayed the effective date of the 2000 Approval and the

2019 Generic Approval. Mifeprex will remain available under the safety restrictions that were in effect

prior to 2016. Generic mifepristone will also remain

available under those same restrictions.

We affirm the portions of the stay order regarding

the 2016 Amendments and the 2021 Non-Enforcement

Decision. In loosening mifepristone’s safety restrictions, FDA failed to address several important concerns

about whether the drug would be safe for the women

who use it. It failed to consider the cumulative effect

of removing several important safeguards at the same

time. It failed to consider whether those “major” and

“interrelated” changes might alter the risk profile, such

that the agency should continue to mandate reporting

of non-fatal adverse events. And it failed to gather evidence that affirmatively showed that mifepristone

75a

could be used safely without being prescribed and dispensed in person.

At this preliminary stage, the Medical Organizations

and Doctors have made a substantial showing that the

2016 Amendments and the 2021 Non-Enforcement Decision violate the APA. Accordingly, those actions will

be stayed pending final judgment. But to repeat, all of

this relief is subject to the Supreme Court’s prior order,

which stays the district court’s order until the disposition of any petition for certiorari.

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JAMES C. HO, Circuit Judge, concurring in part and dissenting in part:

The Constitution vests “the authority to regulate

abortion” in “the people and their elected representatives.” Dobbs v. Jackson Women’s Health Org., 142

S. Ct. 2228, 2279 (2022). Congress has enacted a number of laws that affect the regulation of abortion, including the Administrative Procedure Act and the Comstock Act. Those laws dictate the outcome in this case.

Congress has conferred significant regulatory power

on administrative agencies such as the FDA. In exchange, Congress has enacted the APA to ensure that

agency action is subject to meaningful judicial review.

It requires courts to “hold unlawful and set aside

agency action” that we determine to be “arbitrary, capricious, an abuse of discretion, or otherwise not in accordance with law.” 5 U.S.C. § 706(2)(A).

That’s precisely what occurred here.

Plaintiffs

challenge the FDA’s approval of mifepristone in 2000,

as well as its 2016 and 2021 revisions to its mifepristone

regulations. I agree with the panel majority that the

FDA’s 2016 and 2021 revisions to its mifepristone regulations must be set aside as arbitrary and capricious

under the APA. I would add that the FDA’s initial approval of mifepristone in 2000 also violates the agency’s

own rules and thus must be set aside under the APA as

well.

The FDA approved mifepristone under its Subpart

H regulations. But Subpart H only authorizes the FDA

to approve drugs that “treat[] serious or life-threatening illnesses.” 21 C.F.R. § 314.500. And pregnancy

is plainly not an illness. So it was unlawful for the

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FDA to approve mifepristone under Subpart H. To

quote the Population Council, the entity that sought

FDA approval of mifepristone in 2000: “Neither pregnancy nor unwanted pregnancy is an illness, and Subpart H is therefore inapplicable for that reason alone.”

Population Council Letter to FDA at 1-2 (Sep. 6, 2000).

Perhaps the FDA could have approved mifepristone

through some other regulatory process. But established precedent requires us to review the FDA’s action

based on the path it took—not the path it might have

taken. See SEC v. Chenery Corp., 318 U.S. 80, 95

(1943); DHS v. Regents of the Univ. of Cal. 140 S. Ct.

1891, 1909 (2020) (“An agency must defend its actions

based on the reasons it gave when it acted.”).

The FDA’s 2021 revisions also violate the Comstock

Act. That Act makes it a federal crime to mail any “article or thing designed . . . or intended for producing abortion,” as well as any “drug, medicine, or thing

. . . advertised . . . in a manner calculated to lead

another to use . . . it for producing abortion.” 18

U.S.C. § 1461. It also makes it a crime to “use[] . . .

[an] express company” to ship a “drug, medicine, article, or thing designed . . . or intended for producing abortion.” 18 U.S.C. § 1462.

So I would affirm the district court.

concur in part and dissent in part.

Accordingly, I

I.

I agree with the thorough and well-reasoned panel

majority opinion that Plaintiffs have demonstrated Article III standing to challenge both the FDA’s 2000 approval of mifepristone and the 2016 and 2021 revisions.

I write separately to elaborate on the historical pedi-

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gree of Plaintiffs’ conscience injury, and to explore how

Plaintiffs suffer aesthetic injury as well.

A.

The Supreme Court has instructed that we look to

“history and tradition” as “a meaningful guide to the

types of cases that Article III empowers federal courts

to consider.” United States v. Texas, 143 S. Ct. 1964,

1970 (2023) (quoting Sprint Communications Co. v.

APCC Services, Inc., 554 U.S. 269, 274 (2008)). We ask

whether the “injury to the plaintiff has a ‘close relationship’ to a harm ‘traditionally’ recognized as providing a

basis for a lawsuit in American courts.” TransUnion

LLC v. Ramirez, 141 S. Ct. 2190, 2204 (2021) (quoting

Spokeo, Inc. v. Robins, 578 U.S. 330, 341 (2016)).

By the standards of history and tradition, the harm

to conscience that Plaintiffs suffer is a paradigmatically

cognizable injury. American law has recognized conscience rights from the start. See, e.g., N.H. CONST. of

1784, pt. I, art. IV (“Among the natural rights, some are

in their very nature unalienable, because no equivalent

can be given or received for them. Of this kind are the

rights of conscience.”); PA. CONST. of 1790, art. IX, § 3

(“[N]o human authority can, in any case whatever, control or interfere with the rights of conscience.”); KY.

CONST. of 1792, art. XII, § 3 (same); OHIO CONST. of

1803, art. VIII, § 3 (same); ALA. CONST. of 1819, art. I,

§ 4 (“No human authority ought, in any case whatever,

to control or interfere with the rights of conscience.”);

TENN. CONST. of 1835, art. I, § 3 (“[N]o human authority

can, in any case whatever, control or interfere with the

rights of conscience.”); MO. CONST. of 1820, art. XIII,

§ 4 (“[N]o human authority can control or interfere with

the rights of conscience.”); ARK. CONST. of 1836, art. II,

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§ 3 (“[N]o human authority can, in any case whatever,

interfere with the rights of conscience.”); WIS. CONST.

of 1848, art. I, § 18 (“Nor shall any control of, or interference with the rights of conscience be permitted.”);

MINN. CONST. of 1858, art. I, § 16 (same); KAN. CONST.

of 1859, Bill of Rights, § 7 (same).

Throughout the nineteenth century, American

courts granted relief to parties who challenged government action as injurious to conscience. See, e.g., White

v. McBride, 7 Ky. (4 Bibb) 61, 61 (1815) (suit brought

against sheriff by plaintiffs who “entertained conscientious scruples against bearing arms”); In re Dorsey, 7

Port. 293, 345, 365-69 (Ala. 1838) (attorney seeking conscience-based exemption from anti-dueling oath required for bar admission); State ex rel. Weiss v. Dist.

Bd. of Sch. Dist. No. 8 of City of Edgerton, 44 N.W. 967,

967-68, 976 (Wis. 1890) (writ of mandamus requested by

public school students who raised conscience-based objection to curriculum).

And even where parties were not ultimately granted

relief, courts entertained their suits alleging injuries to

conscience and reached the merits of their claims.

See, e.g., Donahoe v. Richards, 38 Me. 379, 413 (1854)

(public school student raised conscience-based objection to curriculum); Innis v. Bolton, 17 P. 264, 269 (Idaho

1888) (plaintiff brought conscience-based objection to

anti-polygamy oath required for voting).

Here, Plaintiffs have alleged conscience injuries

analogous to those historically recognized at law and in

equity. The FDA’s approval of mifepristone creates a

substantial risk that Plaintiffs will be forced to participate in the abortion process. See, e.g., Dr. Francis

Declaration ¶ 14 (“[M]ore physicians with ethical and

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medical objections to abortion will be forced to participate in completing unfinished elective chemical abortions, just as my partner was.”); Dr. Skop Declaration

¶ 34 (“The FDA’s expansion of chemical abortion . . .

harms my conscience rights because it could force me

to have to surgically finish an incomplete elective chemical abortion. I object to abortion because it ends a human life.”).

The Supreme Court has recognized that intangible

interests in free speech and free exercise are sufficiently concrete for Article III standing. See Spokeo,

578 U.S. at 340. So it’s not surprising that both the

FDA and intervenor Danco agree that conscience injuries can satisfy Article III. I agree with the panel majority that Plaintiffs have established Article III standing based on injury to conscience.

B.

In addition to the injuries analyzed by the majority,

Plaintiffs have demonstrated another basis for Article

III standing: the aesthetic injury they experience in

the course of their work. See, e.g., Sierra Club v. Morton, 405 U.S. 727, 734-35 (1972) (recognizing aesthetic

harm as “injury to a cognizable interest”); Lujan v.

Defs. of Wildlife, 504 U.S. 555, 562-63 (1992) (“[T]he desire to use or observe an animal species, even for purely

esthetic purposes, is undeniably a cognizable interest

for purpose of standing.”); id. at 566 (“[T]he person who

observes or works with a particular animal threatened

by a federal decision is facing perceptible harm.”).

It’s well established that, if a plaintiff has “concrete

plans” to visit an animal’s habitat and view that animal,

that plaintiff suffers aesthetic injury when an agency

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has approved a project that threatens the animal. See

Lujan, 504 U.S. at 564. See also Humane Soc’y v. Hodel, 840 F.2d 45, 52 (D.C. Cir. 1988) (standing where

agency expanded approval for hunting, “depleting the

supply of animals . . . that . . . [plaintiffs] seek to

view” and causing plaintiffs to witness “animal corpses”);

Am. Bottom Conservancy v. Army Corps of Engineers,

650 F.3d 652, 657 (7th Cir. 2011) (standing for birdwatchers to challenge agency permit that would allow

development and thus “diminish the wildlife population

visible to them”); Ctr. for Biological Diversity v. EPA,

861 F.3d 174, 183 (D.C. Cir. 2017) (standing where

agency authorization to use pesticide created “demonstrable risk” to beetles and butterflies that plaintiffs intended to view).

Unborn babies are a source of profound joy for those

who view them. Expectant parents eagerly share ultrasound photos with loved ones. Friends and family

cheer at the sight of an unborn child. Doctors delight

in working with their unborn patients—and experience

an aesthetic injury when they are aborted.

Plaintiffs’ declarations illustrate that they experience aesthetic injury from the destruction of unborn

life. Dr. Francis testified to working with an unborn

child who was subsequently killed by mifepristone:

[A] partner of mine and I cared for another patient

who also suffered complications from chemical abortion. I had taken care of her when she was hospitalized . . . at 9 weeks 5 days gestation. She

was discharged home in good condition after significant improvement with medications. During that

hospital stay, she had an ultrasound, which showed

a healthy pregnancy with no apparent complications

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and a strong fetal heart rate. . . . Approximately one week after her discharge, the patient

presented back at our emergency room with heavy

vaginal bleeding and unstable vital signs as a result

of taking chemical abortion drugs.

Dr. Francis Declaration ¶ 13.

Dr. Jester put Plaintiffs’ interest in unborn life this

way: “When my patients have chemical abortions, I

lose the opportunity . . . to care for the woman and

child through pregnancy and bring about a successful

delivery of new life.” Dr. Jester Declaration ¶ 19.

See Ctr. for Biological Diversity v. EPA, 937 F.3d 533,

541 (5th Cir. 2019) (recognizing judicially cognizable injury where plaintiff experiences aesthetic harm at work).

The Supreme Court has recognized that “the person

who observes or works with a particular animal threatened by a federal decision is facing perceptible harm,

since the very subject of his interest will no longer exist.” Lujan, 504 U.S. at 566. Every circuit, including

our own, has concluded that, when a federal agency authorizes third parties to harm flora or fauna that a

plaintiff intends to view or study, that satisfies all of the

requirements for Article III standing.

See, e.g.,

Housatonic River Initiative v. EPA, _ F.4th_, 2023 WL

4730222, *9 (1st Cir. July 25, 2023); NRDC v. FAA, 564

F.3d 549, 555 (2nd Cir. 2009); Sierra Club v. EPA, 972

F.3d 290, 298-99 (3rd Cir. 2020); Sierra Club v. Dep’t of

the Interior, 899 F.3d 260, 282-85 (4th Cir. 2018); Gulf

Restoration Network v. Salazar, 683 F.3d 158, 166-68

(5th Cir. 2012); Meister v. Dep’t of Agriculture, 623 F.3d

363, 369-70 (6th Cir. 2010); Am. Bottom Conservancy,

650 F.3d at 656-60; Sierra Club v. Army Corps of Engineers, 645 F.3d 978, 985-86 (8th Cir. 2011); Cottonwood

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Env’t Law Ctr. v. Forest Service, 789 F.3d 1075, 107983 (9th Cir. 2015); WildEarth Guardians v. EPA, 759

F.3d 1196, 1206-07 (10th Cir. 2014); Black Warrior

Riverkeeper, Inc. v. Army Corps of Engineers, 781 F.3d

1271, 1280-83 (11th Cir. 2015); Ctr. for Biological Diversity v. EPA, 56 F.4th 55, 66-69 (D.C. Cir. 2022).

In all of these cases, a federal agency approved some

action—such as developing land or using pesticides—

that threatens to destroy the animal or plant life that

plaintiffs wish to enjoy. This injury is redressable by

a court order holding unlawful and setting aside the

agency approval.

And so too here. The FDA has approved the use of

a drug that threatens to destroy the unborn children in

whom Plaintiffs have an interest. And this injury is

likewise redressable by a court order holding unlawful

and setting aside approval of that abortifacient drug.

I see no basis for allowing Article III standing based

on aesthetic injury when it comes to animals and plants

—but not unborn human life.

II.

I now turn specifically to Plaintiffs’ challenge to the

FDA’s 2000 approval of mifepristone. The FDA contends that the challenge is untimely. But it concedes

that “the well-established reopening doctrine” is binding precedent in this circuit. Texas v. Biden, 20 F.4th

928, 951 (5th Cir. 2021), rev’d on other grounds, 142

S. Ct. 2528 (2022). And it accepts that, under that doctrine, the clock for an APA claim restarts when an agency revises its regulations in a manner that “significantly

alters the stakes of judicial review.” Sierra Club v.

EPA, 551 F.3d 1019, 1025 (D.C. Cir. 2008). See also

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NRDC v. EPA, 571 F.3d 1245, 1266 (D.C. Cir. 2009)

(same).

That standard is easily met here. It seems obvious

that the 2016 and 2021 revisions significantly altered

the regulatory landscape. Indeed, the FDA recently

told the Supreme Court that setting aside those revisions would “upend the regulatory regime for mifepristone” and “unleash[] regulatory chaos.” Application

to Stay the Order Entered by the United States District

Court for the Northern District of Texas and for An Administrative Stay, 2023 WL 3127519, at *2-3, FDA v. Alliance for Hippocratic Medicine, 143 S. Ct. 1075 (2023).

If switching from the 2016/2021 regime to the 2000-era

regime significantly alters the “basic regulatory scheme,”

NRDC, 571 F.3d at 1266, then surely the reverse does,

too.

So the district court was correct that “FDA’s 2016

and 2021 Changes . . . significantly departed from

the agency’s original approval of the abortion regimen.

FDA . . . altered its original decision by removing

safeguards and changing the regulatory scheme for

chemical abortion drugs.” Alliance for Hippocratic

Medicine v. FDA, _ F. Supp. 3d _, 2023 WL 2825871, at

*11 (N.D. Tex. Apr. 7, 2023). As a result, the 2016 and

2021 revisions triggered the reopening doctrine.

Plaintiffs’ challenge to the 2000 approval is timely.

A.

Challenges to federal administrative action are subject to a six-year statute of limitations. See 28 U.S.C.

§ 2401(a). This six-year clock initially started ticking

in March 2016, when the FDA denied Plaintiffs’ 2002

petition objecting to the 2000 approval. See 21 C.F.R.

85a

§ 10.45(d). Absent reopening, Plaintiffs’ challenge to

the 2000 approval would be barred by this six-year statute of limitations, because Plaintiffs filed this suit after

March 2022.

But under the administrative reopening doctrine,

the agency can restart the clock in two ways: (1) if

“the agency opened the issue up anew, and then reexamined and reaffirmed its prior decision,” NRDC, 571

F.3d at 1265 (cleaned up), or (2) “if the revision of accompanying regulations ‘significantly alters the stakes

of judicial review’ as the result of a change that ‘could

have not been reasonably anticipated,’ ” id. at 1266

(quoting Sierra Club v. EPA, 551 F.3d 1019, 1025 (D.C.

Cir. 2008)).

This second type of reopening is called “constructive

reopening.” Id. I would hold that constructive reopening applies here, rendering Plaintiffs’ challenge to

the 2000 approval timely.

“A constructive reopening occurs if the revision of

. . . regulations ‘significantly alters the stakes of judicial review.’ ” Sierra Club, 551 F.3d at 1025 (quoting

Kennecott Utah Copper Corp. v. Dep’t of the Interior,

88 F.3d 1191, 1227 (D.C. Cir. 1996)). The paradigmatic

example of this is when the agency unexpectedly removes “necessary safeguards,” thus giving “new significance” to the original action. Id. at 1025-26.

In Sierra Club, the EPA’s initial 1994 rule exempted

pollutant-emitting plants from emission limits when the

plants were starting up, shutting down, or malfunctioning. See id. at 1022. To be eligible for the exemption,

a plant had to show it was doing its “reasonable best” to

stay under the emission limits. Id.

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But in the early 2000s, new EPA rules removed this

“reasonable best” requirement. To qualify for the exemption, plants no longer had to show they were doing

their best to limit emissions. See id. at 1023. This

elimination of safeguards “significantly altered the

stakes of judicial review” for the environmental plaintiffs, thereby triggering reopening.

Id. at 1025

(cleaned up).

The same is true here. Just as the EPA initially

authorized emissions under certain safeguards to minimize harm, the FDA initially authorized mifepristone

under certain safeguards to minimize harm. Remove

these safeguards, and you’ve significantly altered the

stakes of judicial review. The original scheme is now

much more “worth challenging.” Id. at 1026 (quotation omitted).

B.

Plaintiffs’ challenge to the 2000 approval easily satisfies the reopening doctrine. Both the 2016 and 2021

revisions made significant and unexpected alterations

to the basic regulatory scheme. They took away key

safeguards, significantly raising the stakes of judicial

review for the underlying approval.

When it approved mifepristone in 2000, the FDA included a number of “necessary safeguards” to minimize

harm from this dangerous drug. Sierra Club, 551 F.3d

at 1025. For example, the FDA required an in-person

follow-up appointment to protect the woman from sepsis, which occurs if the child’s remains are not removed

from her body after the abortion. See FDA Approval

Memorandum to Population Council at 3 (Sep. 28, 2000).

It also limited the use of mifepristone to the first seven

87a

weeks, ensuring that the abortion took place early in

pregnancy. See id. at 1. And it required a physician

to supervise the administration of mifepristone, in order to “date pregnancies and diagnose ectopic pregnancies.” Id. at 5. See also id. at 6 (same).

The 2016 amendments removed these key safeguards. By approving the abortifacient for use up to

ten weeks, by allowing non-physicians to prescribe and

administer the drug, and by removing the in-person follow-up requirement, the 2016 revisions significantly altered the stakes of judicial review. “These are not

mere ‘minor changes.’ ” Sierra Club, 551 F.3d at 1025.

By modifying its original restrictions, the FDA constructively reopened the drug’s approval.

The 2016 amendments became final in 2021, when

the FDA denied the 2019 Petition challenging them.

See 21 C.F.R. § 10.45(d). Plaintiffs’ challenge is therefore timely.

The 2021 Mail-Order Decision worked an even greater

“sea change” to the “basic regulatory scheme.” NRDC,

571 F.3d at 1266. From the getgo, the FDA’s approval

of mifepristone was explicitly premised on in-person

dispensing. The initial 2000 approval required “[p]rovision of [the] drug through a direct, confidential physician distribution system that ensures only qualified

physicians will receive the drug for patient dispensing.”

FDA Approval Memorandum to Population Council at

6. See also id. at 4 (“[T]he drug will be distributed directly to physicians. It will not be available from pharmacies.”). The agency viewed this as necessary to “address[] the issue of physical security of the drug.” Id.

88a

So “[t]he in-person dispensing requirement . . .

was critical to FDA’s initial approval of mifepristone in

2000, which relied on the in-person dispensing requirement to dismiss concerns about provider qualifications,

improper use, illicit distribution, and detection of adverse events.” Alliance for Hippocratic Medicine v.

FDA, 2023 WL 2913725, at *14 (5th Cir. Apr. 12, 2023).

“[T]he in-person dispensing requirement was FDA’s

primary tool for ensuring the safe distribution and use

of mifepristone.” Id. at *15.

“[T]his change eliminates a major safeguard against

complications and adverse effects arising from improper mifepristone use.” Id. It “significantly alters

the stakes of judicial review,” triggering reopening.

NRDC, 571 F.3d at 1266 (quoting Sierra Club, 551 F.3d

at 1025).

C.

The FDA counters that the 2016 and 2021 revisions

could not have significantly altered the stakes of judicial review or made the regulatory scheme worth challenging in a way it wasn’t before. After all, the FDA

says, Plaintiffs already challenged the original 2000 approval in their 2002 petition.

But not all of the Plaintiffs here participated in the

2002 petition. For those Plaintiffs, the FDA’s current

regime is clearly “worth challenging,” even if the ancien régime of 2000 “may not have been” on its own.

Kennecott Utah Copper Corp., 88 F.3d at 1227.

Indeed, the FDA itself has characterized the switch

from one regime to the other as a “sea change.” NRDC,

571 F.3d at 1266. Under the limited stay issued by a

previous panel of our court, the FDA was required to

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return to the regulatory regime that existed between

2000 and 2016. See Alliance, 2023 WL 2913725, at *1.

The FDA vigorously protested the substitution of the

2016 and 2021 regime with the original 2000 regulations. It urged the Supreme Court to restore the 2016

and 2021 regulations by granting a stay of the entire

district court order. Switching back to the 2000 restrictions, it argued, would “upend the regulatory regime for mifepristone, with sweeping consequences for

the pharmaceutical industry, women who need access to

the drug, and FDA’s ability to implement its statutory

authority.” FDA Stay Application, 2023 WL 3127519,

at *3. It would “unleash[] regulatory chaos” for “patients, prescribers, and the health care delivery system.” Id. at *2, *4.

In sum, the FDA insisted that switching from one

regime to the other would “change the basic regulatory

scheme.” NRDC, 571 F.3d at 1266. It claimed that

switching from the 2016/2021 scheme back to the 2000

scheme counts as a sweeping change with huge stakes.

The same must be true of switching from 2000 to 2016/

2021—that too “upend[ed] the regulatory regime for

mifepristone, with sweeping consequences.”

Plaintiffs’ challenge to the 2000 approval of mifepristone is timely.

III.

Turning to the merits, I would hold the 2000 approval unlawful. It’s a longstanding principle that

agencies must follow their own regulations. See Arizona Grocery Co. v. Atchison, Topeka & Santa Fe Ry.

Co., 284 U.S. 370, 386 (1932) (agency’s legislative rule

“has the force of a statute”); Fort Stewart Schools v.

90a

FLRA, 495 U.S. 641, 654 (1990) (“It is a familiar rule of

administrative law that an agency must abide by its own

regulations.”). The FDA violated that principle when

it approved mifepristone under Subpart H—as even the

drug’s sponsor, the Population Council, admitted in

2000.

A.

Subpart H authorizes the FDA to approve only

those drugs that treat “serious or life-threatening illnesses.” 21 C.F.R. § 314.500. See also 57 Fed. Reg.

58958 (Dec. 11, 1992) (Accelerated Approval of New

Drugs for Serious or Life-Threatening Illnesses). It

“applies to certain new drug products 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 (emphasis added).

Pregnancy is not an illness. An “illness” is a “[b]ad

or unhealthy condition of the body.” Oxford English

Dictionary (2nd ed. 1989), s.v. illness, sense 3. It’s a

“disease, ailment, sickness, malady.” Id. Pregnancy, by

contrast, is when a woman is “with child.” Oxford

English Dictionary, s.v. pregnancy, sense II.3.a.

Pregnancy is not a bad or unhealthy condition of the

body—it’s a natural consequence of a healthy and functioning reproductive system. See, e.g., Gudenkauf v.

Stauffer Communications, Inc., 922 F. Supp. 465, 473

(D. Kan. 1996) (“Being the natural consequence of a

properly functioning reproductive system, pregnancy

cannot be called an impairment.”); Lacount v. South

Lewis, 2017 WL 319217, at *3 (N.D. Okla. Jan. 20, 2017)

(same); Whitaker v. Bosch Braking Sys. Div. of Robert

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Bosch Corp., 180 F. Supp. 2d 922, 928 (W.D. Mich. 2001)

(pregnancy is “not a serious health condition”); Brennan v. National Telephone Directory Corp., 850 F. Supp.

331, 343 (E.D. Pa. 1994) (“it cannot be said that [a

woman’s] reproductive system is negatively affected”

by pregnancy).

To be sure, pregnancy can sometimes result in illness. Cf. Spees v. James Marine, Inc., 617 F.3d 380,

397 (6th Cir. 2010) (“Pregnancy-related conditions have

typically been found to be impairments where they are

not part of a ‘normal’ pregnancy.”). But that does not

make the pregnancy itself an illness. See Whitaker,

180 F. Supp. 2d at 929 (“pregnancy per se does not constitute a serious health condition”).

The same could be said about old age. Many people

become ill as they grow older. But growing older itself

is obviously not an illness. Like pregnancy, it’s the

“natural consequence” of a healthy and functioning

body. It’s entirely normal to celebrate pregnancies,

just as it’s normal to celebrate birthdays. We don’t

typically celebrate “bad or unhealthy conditions.”

So pregnancy does not qualify as a “serious or lifethreatening illness” within the meaning of 21 C.F.R.

§ 314.500. The FDA implausibly “determined” that it

does.

FDA Approval Memorandum to Population

Council at 6. Courts do not defer to agency interpretations of unambiguous regulations. See Kisor v. Wilkie,

139 S. Ct. 2400, 2415 (2019). There’s “only one reasonable construction” of the word “illness”—and it doesn’t

include pregnancy. Id.

There is accordingly no basis for deferring to the

agency. The FDA simply got it wrong. As even the

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sponsor of mifepristone, the Population Council, admitted, “[n]either pregnancy nor unwanted pregnancy is an

illness, and Subpart H is therefore inapplicable for that

reason alone.” Population Council Letter to FDA at 12. “The plain meaning of these terms does not comprehend normal, everyday occurrences such as pregnancy and unwanted pregnancy.” Id. at 2.

B.

The FDA does not even try to argue that pregnancy

is an “illness.” Instead, the FDA, along with intervenor

Danco, points out that the preamble to Subpart H uses

the terms “illness,” “disease,” and “condition” interchangeably. See, e.g., 57 Fed. Reg. 58942, 58948 (“The

drug in question must be for a serious or life-threatening condition.”). So they argue that Subpart H allows

the FDA to approve drugs that treat life-threating conditions, as well as life-threating illnesses. And although pregnancy is plainly not an “illness,” the argument goes, pregnancy is at least a “condition.”

There are two problems with this argument. First,

we do not use preambles to expand the meaning of clear

regulatory text. See District of Columbia v. Heller,

554 U.S. 570, 578 n.3 (2008) (“[I]n America ‘the settled

principle of law is that the preamble cannot control the

enacting part of the statute in cases where the enacting

part is expressed in clear, unambiguous terms.’ ”); ANTONIN SCALIA & BRYAN A. GARNER , READING LAW 218

(2012) (“[T]he prologue cannot give words and phrases

of the dispositive text a meaning that they cannot

bear.”).

Second, this argument—that the preamble broadens

“illness” to include “conditions”—equivocates between

93a

two distinct meanings of the word “condition.” As

used in the preamble, “condition” means a “defective

state of health.” MERRIAM-WEBSTER’S COLLEGIATE

DICTIONARY (11th ed. 2007), s.v. condition, sense 4c. In

this sense, “condition” is a synonym of “illness.” See

MERRIAM-WEBSTER’S COLLEGIATE THESAURUS (1988),

s.v. condition, sense 6 (listing “disease,” “aliment,” and

“sickness” as synonyms of “condition”).

Of course, “condition” can also mean “a state of being” more broadly. Merriam-Webster’s Collegiate Dictionary, s.v., condition, sense 4a. And pregnancy is certainly a “condition” in this broader sense.

But the fact that pregnancy is a “condition” in the

broad sense of “state of being” does not make it a “condition” in the narrow sense of “illness.” And Subpart

H plainly contemplates the narrow sense, because it

uses “condition” interchangeably with “illness.”

A

regulation about “cars” doesn’t cover bicycles just because its preamble sometimes mentions “vehicles.”

Likewise, a regulation about “illnesses” doesn’t address

pregnancy just because its preamble sometimes mentions “conditions.” 9

C.

Danco responds by citing a Government Accountability Office report, which observes that the FDA has used Subpart H to approve

drugs for treating “breakthrough cancer pain, specific symptoms of

narcolepsy, and severe acne.” GAO, Approval and Oversight of the

Drug Mifeprex at 10 (Aug. 2008). “Severe recalcitrant nodular

acne” may well be a serious illness. Id. at 44. But that has nothing

to do with whether pregnancy is a serious or life-threatening illness.

9

94a

The agency’s brief proclaims that “FDA Properly

Approved Mifepristone Under Subpart H.” Yet in the

very next paragraph, the FDA turns around and denies

that it used Subpart H to approve mifepristone—claiming that the approval was “based on FDA’s statutory

authority under 21 U.S.C. § 355, not Subpart H.”

As the panel majority opinion details, Subpart H encompasses two different paths. The first is entitled

“Approval based on a surrogate endpoint or on an effect

on a clinical endpoint other than survival or irreversible

morbidity.” 21 C.F.R. § 314.510 (emphasis omitted).

The second is entitled “Approval with restrictions to assure safe use.” 21 C.F.R. § 314.520 (emphasis omitted).

Mifepristone was approved under § 314.520 of Subpart H—approval with restrictions. But the FDA now

suggests that § 314.520 isn’t really a method of approval

at all—it’s just a method of adding restrictions on use.

This argument is belied by the regulations. The

header explicitly refers to this second path as a method

of “[a]pproval.” Id. § 314.520. More importantly, the

regulatory text repeatedly refers to § 314.520 as a

method of drug approval. See id. § 314.530(a) (“new

drugs approved under . . . 314.520”); id. § 314.530(b)

(“an application approved under . . . § 314.520”); id.

§ 314.560 (“drug products approved under § 314.520”).

The FDA’s argument contradicts not only the text,

but also its own statements over the past 23 years. See

Chenery, 318 U.S. at 95; Motor Vehicle Mfrs. Ass’n v.

State Farm, 463 U.S. 29, 50 (1983) (“[C]ourts may not

accept appellate counsel’s post hoc rationalizations for

agency action.”).

95a

In its original 2000 approval memo, the FDA expressly stated that “[t]his drug is being approved under

Subpart H.” FDA Approval Memorandum to Population Council at 8. And it has repeatedly reaffirmed

this view in the years since. See FDA Supplemental

Approval Letter to Danco Labs at 1 (June 6, 2011) (application “approved under the provisions of 21 CFR

314.520 (Subpart H)”); FDA Letter Denying 2002 Citizen Petition at 2 (Mar. 29, 2016) (“The application was

approved under 21 CFR part 314, subpart H.”); FDA

Letter Denying 2019 Citizen Petition at 2 (Dec. 16,

2021) (same).

The GAO report cited by both the FDA and Danco

likewise repeatedly describes mifepristone as having

been “approved” under Subpart H. GAO, Approval and

Oversight of the Drug Mifeprex at 1 (Aug. 2008) (“FDA

approved the drug under a provision of the agency’s

Subpart H regulations.”); id. at 5 (“FDA approved Mifeprex under the restricted distribution provision of its

Subpart H regulations.”); id. at 6 (FDA “approved the

Mifeprex [application] under Subpart H.”). See also

id. at 10, 14-15, 21-24, 32, 44 (same). The report also

notes that the FDA used Subpart H to “approve” other

drugs. See id. at 5 n.13, 25 n.46, 27 n.50, 29 n.53, 36 n.63.

And it explicitly refers to § 314.520 as an “approval provision.” Id. at 1 n.2.

The FDA notes that its statutory authority to approve drugs comes from 21 U.S.C. § 355. But that

doesn’t change the fact that the regulatory path it chose

was Subpart H. Section 355 gives the FDA the power

to approve drugs. And the agency exercised that

power when it promulgated Subpart H. The FDA did

96a

not have to adopt Subpart H in the first place. But once

it did, it was bound to follow it.

D.

As a final defense, the FDA contends that subsequent events cured any defects in its initial 2000 approval. Specifically, the FDA points to the 2007 Food

and Drug Administration Amendments Act and to the

agency’s 2011 Risk Evaluation and Mitigation Strategy.

It claims that both authorities render any faults with

the 2000 approval irrelevant.

First, the FDA argues that the 2007 Act “deemed”

mifepristone to be approved. But the statutory text

contradicts this argument. The Act makes clear that

“[a] drug that was approved before the effective date of

this Act is . . . deemed to have in effect an approved

risk evaluation and mitigation strategy . . . if there

are in effect on the effective date of this Act elements

to assure safe use . . . required under [21 C.F.R. §]

314.520.”

Food and Drug Administration Amendments Act of 2007, Pub. L. No. 110-85, tit. IX § 909(b)(1),

121 Stat. 823, 950 (emphasis added).

So the Act itself did not approve any drugs. It only

approved any risk evaluation and mitigation strategies

for those drugs that the FDA had already validly approved under § 314.520 of Subpart H. And as explained above, the FDA’s attempted approval was invalid because it failed to comply with Subpart H. The

FDA’s reliance on the 2007 Act is entirely circular—it

only works if you assume that the agency had already

validly approved mifepristone in the first place.

The FDA also points to its 2011 Risk Evaluation and

Mitigation Strategy, arguing that this too re-approved

97a

mifepristone and cured any defects in its 2000 approval.

It did not. To the contrary, the 2011 REMS letter

made clear that the agency continued to rely on Subpart

H for its approval of mifepristone—that it “is approved

under the provisions of 21 CFR 314.520 (Subpart H).”

FDA Supplemental Approval Letter to Danco Labs at

1. Moreover, the letter only approved the Risk Evaluation and Mitigation Strategy proposed in Danco’s

2008 Supplemental Application—it did not re-approve

the drug apart from Subpart H. In fact, the letter recognized the need for continued compliance with the conditions “required by” Subpart H. Id. at 2 (citing 21

C.F.R. § 314.550).

* * *

For these reasons, I would find that Plaintiffs are

likely to succeed on the merits of their challenge to the

2000 approval. Plaintiffs also satisfy the remaining

factors for equitable relief. The harm to Plaintiffs is

irreparable. No relief at law can adequately address

Plaintiffs’ conscience injuries.

See BST Holdings,

L.L.C. v. OSHA, 17 F.4th 604, 618 (5th Cir. 2021). Nor

can money damages remedy the destruction of life. Cf.

Amoco Production Co. v. Village of Gambell, 480 U.S.

531, 545 (1987). The balance of equities and public interest also favor Plaintiffs. Plaintiffs seek to vindicate

the “national policy of discountenancing abortion as inimical to the national life,” as reflected in Congressional

enactments including the Comstock Act. Bours v.

United States, 229 F. 960, 964 (7th Cir. 1915). See 18

U.S.C. § 1461; id. § 1462. Cf. 19 U.S.C. § 1305(a).

IV.

98a

With respect to the FDA’s 2016 and 2021 revisions,

I agree with the majority’s thoughtful analysis explaining how the FDA “entirely failed to consider an important aspect of the problem” in 2016 and “offered an

explanation for its decision that runs counter to the evidence before the agency” in 2021. State Farm, 463

U.S. at 43. The agency thus acted arbitrarily in violation of the APA.

I write separately to add that the 2021 revisions violate the Comstock Act, 18 U.S.C. §§ 1461-62, and ar

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