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

Supreme Court briefOct 12, 2023

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NOS. 23-235, 23-236

IN THE

Supreme Court of the United States

ALLIANCE FOR HIPPOCRATIC MEDICINE, ET AL.,

Cross-Petitioners,

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

Cross-Respondents.

and

ALLIANCE FOR HIPPOCRATIC MEDICINE, ET AL.,

Cross-Petitioners,

DANCO LABORATORIES, L.L.C.,

Cross-Respondent.

On Petitions for Writ of Certiorari to the

United States Court of Appeals for the Fifth Circuit

CONDITIONAL CROSS-PETITION FOR A

WRIT OF CERTIORARI

JAMES A. CAMPBELL

CODY S. BARNETT

ALLIANCE DEFENDING

FREEDOM

44180 Riverside Pkwy

Lansdowne, VA 20176

(571) 707-4655

ERIN M. HAWLEY

Counsel of Record

JOHN J. BURSCH

MATTHEW S. BOWMAN

ERIK C. BAPTIST

ALLIANCE DEFENDING FREEDOM

440 First Street NW, Suite 600

Washington, DC 20001

(202) 393-8690

ehawley@adflegal.org

Counsel for Cross-Petitioners/Respondents

QUESTIONS PRESENTED

In 2000, the U.S. Food and Drug Administration

(FDA) approved the drug mifepristone to cause

abortions. Central to FDA’s controversial approval

was its conclusion that in-person doctor visits and

dispensing requirements, gestational limits, and

adverse event reporting were crucial to protect

women. Beginning in 2016, FDA stripped away those

safety measures in violation of the Administrative

Procedure Act (APA).

The Fifth Circuit rightly held that FDA acted

unlawfully in removing those safety measures, and

Cross-Petitioners—pro-life healthcare organizations

and doctors harmed by FDA’s actions—oppose FDA’s

and Danco Laboratories’ interlocutory petitions in

Case Nos. 23-235 and 23-236. As set forth in the Brief

in Opposition, the Court should deny those petitions.

But if the Court grants review, it should also

grant this conditional cross-petition and review FDA’s

approval of mifepristone. As Judge Ho explained in

dissent, the “challenge to the 2000 approval is timely,”

FDA.Pet.App.84a, and “the 2000 approval [is]

unlawful,”

FDA.Pet.App.89a.

The

questions

presented in this conditional cross-petition are:

1. Whether Cross-Petitioners’ challenge to FDA’s

2000 mifepristone approval is timely.

2. Whether FDA’s 2000 approval of mifepristone

under Subpart H, which applies only to drugs

that “treat[ ] serious or life-threatening

illnesses,” 21 C.F.R. 314.500, and FDA’s

subsequent approval of generic mifepristone

were unlawful.

PARTIES TO THE PROCEEDING AND

CORPORATE DISCLOSURE STATEMENT

Cross-Petitioners were plaintiffs-appellees below.

They are 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.; and George

Delgado, M.D.

Cross-Respondents were defendants-appellants

and an intervenor-appellant below. The defendantsappellants are the U.S. Food and Drug Administration (FDA); Robert M. Califf, M.D., in his official

capacity as FDA’s Commissioner of Food and Drugs;

Janet Woodcock, M.D., in her official capacity as

Principal Deputy Commissioner of FDA; Patrizia

Cavazzoni, M.D., in her official capacity as Director of

FDA’s Center for Drug Evaluation and Research; the

U.S. Department of Health and Human Services

(HHS), and Xavier Becerra, in his official capacity as

Secretary of HHS. The intervenor-appellant is Danco

Laboratories, L.L.C.

Pursuant to Rule 29.6, Alliance for Hippocratic

Medicine, American Association of Pro-Life

Obstetricians & Gynecologists, American College of

Pediatricians, and Christian Medical & Dental

Associations have no parent corporations, and no

publicly held corporation owns 10% or more of the

stock of any of them.

iii

RELATED PROCEEDINGS

Supreme Court of the United States (U.S.):

Danco Laboratories, LLC v. Alliance for

Hippocratic Medicine, et al., No. 22A901

(Apr. 21, 2023) (granting application for stay)

U.S. Food & Drug Administration, et al. v.

Alliance for Hippocratic Medicine, et al., No.

22A902 (Apr. 21, 2023) (granting application

for stay)

United States Court of Appeals (5th Cir.):

Alliance for Hippocratic Medicine, et al. v.

U.S. Food & Drug Administration, et al., No.

23-10362 (Aug. 16, 2023) (partially affirming

and partially reversing district court order)

Alliance for Hippocratic Medicine, et al. v.

U.S. Food & Drug Administration, et al., No.

23-10362 (Apr. 12, 2023) (partially granting

and partially denying stay pending appeal)

United States District Court (N.D. Tex.):

Alliance for Hippocratic Medicine, et al. v.

U.S. Food & Drug Administration, et al., No.

2:22-cv-223 (Apr. 7, 2023) (staying the

challenged agency actions)

TABLE OF CONTENTS

QUESTIONS PRESENTED ....................................... i

PARTIES TO THE PROCEEDING AND

CORPORATE DISCLOSURE STATEMENT ...... ii

RELATED PROCEEDINGS ..................................... iii

APPENDIX TABLE OF CONTENTS ...................... vi

TABLE OF AUTHORITIES .................................... vii

DECISIONS BELOW................................................. 1

STATEMENT OF JURISDICTION .......................... 1

PERTINENT CONSTITUTIONAL PROVISIONS

AND STATUTES .................................................. 1

INTRODUCTION ...................................................... 2

STATEMENT OF THE CASE ................................... 4

A. FDA’s approval of mifepristone ...................... 4

B. FDA’s removal of critical safeguards .............. 7

C. Proceedings below ........................................... 9

REASONS FOR GRANTING THE

CONDITIONAL WRIT ....................................... 11

I. The Court should review the entire Fifth

Circuit decision if it grants FDA’s or Danco’s

petitions............................................................... 11

A. FDA disregarded law, science, and safety

in pursuit of a political end. .......................... 11

B. The questions presented in this crosspetition are part and parcel of those

presented in FDA’s and Danco’s petitions.... 15

II. The Fifth Circuit erred in rejecting the

challenges to FDA’s approvals of chemical

abortion drugs. .................................................... 16

A. FDA reopened its 2000 Approval when it

overhauled the mifepristone regimen in

2016 and authorized mail-order abortion in

2021. ............................................................... 16

1. FDA expressly reopened the 2000

Approval. .................................................. 18

2. FDA constructively reopened the 2000

Approval. .................................................. 21

B. FDA violated its own regulations and

federal laws when it approved mifepristone

in 2000. .......................................................... 24

1. FDA impermissibly invoked Subpart

H by classifying pregnancy as an

“illness.” .................................................... 24

a. Pregnancy is not a serious or

life-threatening illness. ..................... 25

b. Chemical abortion does not

provide a meaningful

therapeutic benefit over existing

options. ............................................... 26

2. The 2000 Approval also violated the

APA and FDCA. ....................................... 28

C. Because FDA’s 2000 Approval and 2016

Major Changes were unlawful, FDA’s

2019 Generic Approval was also

unlawful. ........................................................ 31

CONCLUSION ......................................................... 36

APPENDIX TABLE OF CONTENTS

18 U.S.C. 1461 .......................................................... 1a

18 U.S.C. 1462 .......................................................... 3a

21 U.S.C. 355 ............................................................ 5a

21 U.S.C. 355-1..................................................... 117a

21 C.F.R. 10.30 ..................................................... 147a

21 C.F.R. 10.45 ..................................................... 156a

21 C.F.R. 312.300(a)............................................. 162a

21 C.F.R. 314.50 ................................................... 163a

21 C.F.R. 314.94 ................................................... 194a

21 C.F.R. 314.105(c) ............................................. 214a

21 C.F.R. 314.151 ................................................. 215a

21 C.F.R. 314.430(b)............................................. 218a

21 C.F.R. 314.500 ................................................. 219a

21 C.F.R. 314.520 ................................................. 219a

vii

TABLE OF AUTHORITIES

Cases

Alaska v. United States Department of

Agriculture,

772 F.3d 899 (D.C. Cir. 2014) ............................ 17

Baltimore Contractors, Inc. v. Bodinger,

348 U.S. 176 (1955)............................................ 16

Baltimore Gas & Electric Company v. Natural

Resources Defense Council, Inc.,

462 U.S. 87 (1983).............................................. 29

City of Waukesha v. EPA,

320 F.3d 228 (D.C. Cir. 2003) ............................ 34

Cuomo v. Clearing House Association,

557 U.S. 519 (2009)............................................ 26

Department of Commerce v. New York,

139 S. Ct. 2551 (2019)........................................ 33

Duke Power Company v. Carolina

Environmental Study Group, Inc.,

438 U.S. 59 (1978).............................................. 34

Environmental Defense v. EPA,

467 F.3d 1329 (D.C. Cir. 2006) .................... 21, 23

FCC v. Fox Television Stations, Inc.,

556 U.S. 502 (2009)............................................ 21

Fort Stewart Schools v. Federal Labor Relations

Authority,

495 U.S. 641 (1990)............................................ 24

viii

Friends of the Earth, Inc. v. Gaston Copper

Recycling Corp.,

204 F.3d 149 (4th Cir. 2000) ............................. 34

Growth Energy v. EPA,

5 F.4th 1 (D.C. Cir. 2021) .................................. 20

Hammoud v. Equifax Information Services, LLC,

52 F.4th 669 (6th Cir. 2022) .............................. 35

Kennecott Utah Copper Corp. v. United States

Department of Interior,

88 F.3d 1191 (D.C. Cir. 1996) .............3, 17–18, 23

Kisor v. Wilkie,

139 S. Ct. 2400 (2019)........................................ 26

Lamie v. United States Trustee,

540 U.S. 526 (2004)............................................ 26

Motor Vehicle Manufacturers Association of

United States, Inc. v. State Farm Mutual

Automobile Insurance Company,

463 U.S. 29 (1983).................................... 2, 29, 31

National Biodiesel Board v. EPA,

843 F.3d 1010 (D.C. Cir. 2016) .................... 17, 21

National Family Farm Coalition v. EPA,

966 F.3d 893 (9th Cir. 2020) ............................. 34

National Mining Association v. United States

Department of Interior,

70 F.3d 1345 (D.C. Cir. 1995) ............................ 19

Natural Resources Defense Council v. EPA,

571 F.3d 1245 (D.C. Cir. 2009) ................ 3, 15, 21

Natural Resources Defense Council v. Watkins,

954 F.2d 974 (4th Cir. 1992) ............................. 34

Ohio v. EPA,

838 F.2d 1325 (D.C. Cir. 1988) .................... 17, 21

Public Citizen v. Nuclear Regulatory

Commission,

901 F.2d 147 (D.C. Cir. 1990) ...................... 20–21

Public Interest Research Group of New Jersey,

Inc. v. Powell Duffryn Terminals Inc.,

913 F.2d 64 (3d Cir. 1990) ........................... 33–34

Sierra Club v. EPA,

551 F.3d 1019 (D.C. Cir.

2008) ........................................3, 10, 17–18, 22–23

Switzerland Cheese Association v. E. Horne’s

Market, Inc.,

385 U.S. 23 (1966).............................................. 16

Washington Alliance of Technology Workers

v. DHS,

892 F.3d 332 (D.C. Cir. 2018) ............................ 21

Statutes

18 U.S.C. 1461 ................................................. vi, 8, 13

18 U.S.C. 1462 ................................................. vi, 8, 13

21 U.S.C. 321 .............................................................. 4

21 U.S.C. 355 ....................................vi, 4, 8, 13, 29–32

21 U.S.C. 355-1.......................................... vi, 7, 19–20

5 U.S.C. 706 .............................................................. 29

Food and Drug Administration Amendments Act

of 2007, Pub. L. No. 110-85, tit. IX

§ 909(b)(1), 121 Stat. 823........................... 6–7, 18

Other Authorities

Allysia Finley, DayQuil, Covid

Vaccine Boosters and FDA Science, Wall

St. J. (Sept. 17, 2023, 2:44 P.M.) ....................... 14

Andrew Kolodny, How FDA Failures

Contributed to the Opioid Crisis, 22 AMA

J. of Ethics 743 (2020) ....................................... 14

Caroline Chen, FDA Increasingly Approves

Drugs Without Conclusive Proof They

Work, PBS News Hour (June 26, 2018,

2:31 P.M.) ..................................................... 14–15

Celine Castronuovo, OxyContin Decision

Involved FDA ‘Miscalculation,’ Woodcock

Says, Bloomberg Law (June 15, 2022,

11:31 A.M.) ......................................................... 14

FDA Approval Mem. to Population Council

(Sept. 28, 2000) .................................................... 6

Irving M. Spitz, et al., Early Pregnancy

Termination with Mifepristone and

Misoprostol in the United States, New

England J. of Med. (Apr. 30, 1998) ................... 31

Population Council Letter to FDA (Sep. 6, 2000) ..... 5

Therapeutic, Merriam Webster ............................... 27

Regulations

21 C.F.R. 10.30 ................................................ vi, 7, 13

21 C.F.R. 312.300 ................................................ vi, 26

21 C.F.R. 314 subpt. H ............................................... 5

21 C.F.R. 314.105 .................................................. vi, 4

21 C.F.R. 314.151 ................................................ vi, 32

21 C.F.R. 314.430 ................................................ vi, 23

21 C.F.R. 314.50 .................................................... vi, 4

21 C.F.R. 314.500 ................... i, vi, 2, 5, 11–12, 25, 28

21 C.F.R. 314.520 .................................... vi, 12, 18, 24

21 C.F.R. 314.94 .................................................. vi, 32

57 Fed. Reg. 58,942 (Dec. 11, 1992)........................... 5

DECISIONS BELOW

The opinion of the court of appeals is reported at

78 F.4th 210 and reprinted at FDA.Pet.App.1a. The

opinion and order of the district court is not reported

but is available at 2023 WL 2825871 and reprinted at

FDA.Pet.App.111a. This Court’s order granting a stay

is reported at 143 S. Ct. 1075 and reprinted at

FDA.Pet.App.245a. The court of appeals order

granting a stay in part is not reported but is available

at 2023 WL 2913725 and reprinted at

FDA.Pet.App.196a.

STATEMENT OF JURISDICTION

The court of appeals’ interlocutory opinion was

entered on August 16, 2023. This Court has

jurisdiction under 28 U.S.C. 1254(1).

PERTINENT CONSTITUTIONAL

PROVISIONS AND STATUTES

Pertinent statutory and regulatory provisions are

reproduced

FDA’s

petition

appendix,

FDA.Pet.App.249a–54a, Danco’s petition appendix,

Danco.Pet.App.250a–51a, and the appendix to this

cross-petition, Cross.Pet.App.1a–219a.

INTRODUCTION

As set forth in Cross-Petitioners’ Brief in Opposition in Case Nos. 23-235 and 23-236, there is no

compelling reason for this Court to grant interlocutory review of the Fifth Circuit’s decision. That opinion merely reinstated safety standards that governed

the use of mifepristone for 16 years. Applying

straightforward administrative law principles, the

unanimous court of appeals held that FDA failed to

adequately explain its decisions to remove these

safeguards. Far from “unprecedented,” FDA.Pet.3,

the Fifth Circuit applied the well-established principle that an agency violates the APA when it “fail[s] to

consider an important aspect of the problem” before

it. Motor Vehicle Mfrs. Ass’n of U.S., Inc. v. State

Farm Mut. Auto. Ins. Co., 463 U.S. 29, 43 (1983).

Nor is this Court’s immediate review necessary.

Reinstating safety conditions under which millions of

women have previously taken mifepristone will not

make that drug inaccessible. Ensuring that women

see a doctor before receiving dangerous drugs is good

medicine and common practice—not cause for this

Court to intervene mid-litigation. And Danco has had

months to reproduce its pre-2016 labels to continue its

ongoing sale of the abortion drug.

That said, if the Court grants interlocutory review

now, it should also grant this cross-petition and

review the Fifth Circuit’s entire decision. FDA

approved mifepristone in 2000 under Subpart H,

which authorizes the agency to approve only drugs

that “treat[ ] serious or life-threatening illnesses.” 21

C.F.R. 314.500. But as Judge Ho explained in his

dissent below, “pregnancy is plainly not an illness.”

FDA.Pet.App.92a (cleaned up).

This challenge to FDA’s 2000 Approval is timely

under the reopening doctrine. Nat. Res. Def. Council

v. EPA, 571 F.3d 1245, 1266 (D.C. Cir. 2009) (NRDC)

(per curiam). That rule restarts the clock for an APA

claim where an agency revises a prior action so that

it “significantly alters the stakes of judicial review.”

Sierra Club v. EPA, 551 F.3d 1019, 1025 (D.C. Cir.

2008) (quoting Kennecott Utah Copper Corp. v. U.S.

Dep’t of Interior, 88 F.3d 1191, 1227 (D.C. Cir. 1996)).

“That standard is easily met here,” as Judge Ho

concluded. FDA.Pet.App.84a. “It seems obvious that

the 2016 and 2021 revisions”—the subject of FDA’s

and Danco’s petitions—“significantly altered the

regulatory landscape.” Ibid. “Indeed, the FDA recently told [this] Court that setting aside those revisions

would ‘upend the regulatory regime for mifepristone.’” Ibid. (quoting App. to Stay, 2023 WL 3127519,

at *2–3, FDA v. All. for Hippocratic Med., 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.” Ibid.

Simply put, the issues presented by Petitioners

and those presented in this cross-petition should be

considered together. If the Court believes review is

warranted now, it should also grant this crosspetition.

STATEMENT OF THE CASE

A. FDA’s approval of mifepristone

Congress delegated to FDA the responsibility to

make sure that “new drug[s]” are both “safe and

effective.” 21 U.S.C. 321(p), 355. FDA’s approval

determinations evaluate whether a new drug

application (NDA) includes scientific evidence

demonstrating that the drug is safe and effective for

its intended uses. Id. 355(d); 21 C.F.R. 314.50,

314.105(c).

In 2000, FDA approved a chemical abortion

regimen that requires two drugs: mifepristone—also

known as “RU-486” and “Mifeprex”—and misoprostol.

C.A.Add.90. Mifepristone is a synthetic steroid that

blocks nutrition to the unborn baby. Ibid. Misoprostol

induces contractions to expel the unborn child from

the mother’s womb. C.A.Add.90–91. This approval

was politically charged from the beginning.

During the early 1990s, the Clinton Administration asked Roussel Uclaf, the French firm that

manufactured RU-486, to make its drug available in

the U.S. C.A.Add.106. Roussel initially declined but

continued to face intense pressure from the administration. Ibid. Political appointees, including the HHS

secretary and the FDA commissioner, lobbied Roussel

to donate its U.S. patent rights for mifepristone.

C.A.Add.107.

Roussel ultimately agreed, donating those patent

rights to the Population Council—a nonprofit that

John Rockefeller III founded to address supposed

world “overpopulation.” Ibid. The Clinton Administration then boasted about bringing mifepristone

stateside. Ibid.

In 1996, the Population Council applied to FDA

for mifepristone’s approval but needed Danco—a

Cayman Islands-based company with no other

pharmaceutical product—to distribute the drugs in

the U.S. market. C.A.Add.115. So the Population

Council granted to Danco an exclusive license to

manufacture, market, and distribute mifepristone in

the U.S. Ibid. Six months later, FDA approved the

drug under an accelerated approval process known as

“Subpart H.” 21 C.F.R. 314 subpt. H.

Subpart H was primarily “designed to expedite

investigational HIV medications during the AIDS

epidemic.” FDA.Pet.App.113a–14a & n.3. It applies

only to drugs that “treat[ ] serious or life-threatening

illnesses.” 21 C.F.R. 314.500. FDA must “‘determine[ ]

that [the] drug, effective [to] the treatment of a

disease, can be used safely only if distribution or use

is modified or restricted.’” FDA.Pet.App.5a (quoting

57 Fed. Reg. 58,942, 58,942 (Dec. 11, 1992) (emphasis

added)). Before 2000, FDA had approved fewer than

40 drugs under Subpart H—including 20 “for the

treatment of HIV and HIV-related diseases,” nine “for

the treatment of various cancers,” four “for severe

bacterial infections,” one for hypertension, and one for

leprosy. FDA.Pet.App.163a.

Recognizing mifepristone’s dangers to women,

FDA resorted to Subpart H because the drug “could

not be administered safely without imposing certain

use restrictions.” FDA.Pet.App.7a. But Subpart H

was not a good fit. As the Population Council

explained in 2000, “[n]either pregnancy nor unwanted

pregnancy is an illness, and subpart H is therefore

inapplicable for that reason alone.” FDA.Pet.App.77a

(quoting Population Council Ltr. to FDA at 1–2 (Sep.

6, 2000)).

Ignoring that warning, FDA charged ahead,

declaring that mifepristone treated a “serious or lifethreatening illness.” FDA.Pet.App.91a (citing FDA

Approval Mem. to Population Council at 6 (Sept. 28,

2000)). The agency did this even though pregnancy is

a “natural process” that many women experience.

FDA.Pet.App.161a.

To mitigate mifepristone’s acknowledged risks,

FDA’s 2000 Approval included numerous safety

requirements, such as a seven-week gestational limit,

confining prescribing authority to physicians, and

mandating three in-person office visits: (1) the Day 1

in-person administration of mifepristone; (2) the

Day 3 in-person administration of misoprostol; and

(3) the Day 14 office visit to confirm no fetal parts or

tissue remain in the uterus. C.A.Add.591–98. FDA

also required abortion providers to report all adverse

events. C.A.Add.596.

Cross-Petitioners American Association of ProLife Obstetricians & Gynecologists (AAPLOG) and

Christian Medical & Dental Associations (CMDA)

timely filed a citizen petition with FDA challenging

that approval (2002 Citizen Petition). C.A.Add.353–

448.

While that petition was pending before FDA,

Congress amended the Food, Drug, and Cosmetic Act

(FDCA) by codifying Subpart H through the Food and

Drug Administration Amendments Act (FDAAA).

Food and Drug Administration Amendments Act of

2007, Pub. L. No. 110-85, tit. IX § 909(b)(1), 121 Stat.

823, 950. These changes require FDA to obtain a risk

evaluation and mitigation strategy (REMS) whenever

the agency determines that a REMS is “necessary to

assure safe use of the drug, because of its inherent

toxicity or potential harmfulness” and its association

“with a serious adverse drug experience.” 21 U.S.C.

355-1(f)(1).

The FDAAA further specified that a previously

approved drug is “deemed to have in effect an

approved [REMS] … if there are in effect on the

effective date of this Act elements to assure safe use

[pursuant to Subpart H].” §909(b)(1), 121 Stat. at 950.

This stop-gap measure said nothing about any specific

drug approval or post-marketing restrictions. The

FDAAA required drug sponsors to submit proposed

REMS to FDA. Ibid. Danco’s supplemental new drug

application implementing the REMS was approved in

2011. C.A.Add.672.

Though FDA had “180 days” to respond to the

2002 Citizen Petition, 21 C.F.R. 10.30(e)(2), approximately 14 years elapsed before FDA rejected it in 2016

(2016 Petition Denial). C.A.Add.123.

B. FDA’s removal of critical safeguards

The same day FDA denied the 2002 Citizen

Petition in 2016, the agency approved “major

changes” to the regimen that eviscerated many

crucial

safeguards

(2016

Major

Changes).

FDA.Pet.App.10a, 200a. Among other things, the

agency (1) eliminated the requirement for an inperson follow-up examination, (2) allowed non-doctors

to prescribe and administer the drug, (3) increased

the maximum gestational age from seven to ten

weeks, (4) removed the in-person administration

requirement for misoprostol, and (5) eliminated nonfatal adverse event reporting. C.A.Add.697–725.

In 2019, Cross-Petitioners AAPLOG and

American College of Pediatricians (ACPeds) timely

filed a citizen petition challenging the 2016 Major

Changes (2019 Citizen Petition). C.A.Add.740–66.

One month later, FDA approved GenBioPro, Inc.’s

abbreviated new drug application (ANDA) for a generic version of mifepristone (2019 Generic Approval).

C.A.Add.767–73. Relying on the safety data for

Danco’s name-brand version, FDA determined the

generic version “to be bioequivalent and, therefore,

therapeutically equivalent” to Danco’s version.

C.A.Add.768; see 21 U.S.C. 355(j)(2) (requiring

generic version to have the same active ingredients,

route of administration, dosage form, strength,

bioequivalence, and labeling as the brand version).

In April 2021, FDA stated that it would “exercise

enforcement discretion” and allow “dispensing of

mifepristone through the mail … or through a mailorder pharmacy” during the COVID pandemic (2021

Non-Enforcement Decision). FDA.Pet.App.11a. FDA

took this action even though the Comstock Act

expressly prohibits distribution of chemical abortion

drugs by mail, express company, or common carrier.

18 U.S.C. 1461–62.

Then, in December 2021—nearly three years

after the filing of the 2019 Citizen Petition—FDA

denied almost all of that petition (2021 Petition

Denial). C.A.Add.141–42. FDA simultaneously announced that the agency had decided it would

permanently allow chemical abortion by mail—

requiring only that the sponsors of mifepristone

submit updated REMS. C.A.Add.140–41. This

effectively federalized abortion by allowing abortion

drugs to be mailed into states where the citizens have

determined to prohibit such drugs.

C. Proceedings below

In November 2022, Cross-Petitioners filed this

lawsuit alleging that the 2000 Approval, 2016

Petition Denial, 2016 Major Changes, 2019 Generic

Approval, 2021 Non-Enforcement Decision, and 2021

Petition Denial all violated the APA. Danco

intervened. C.A.Add.74–186.

Cross-Petitioners filed a motion for a preliminary

injunction that the district court granted in part.

FDA.Pet.App.111a. Rather than issue an injunction,

the court used its power under 5 U.S.C. 705 to stay

the effective date for each of FDA’s challenged

actions. FDA.Pet.App.193a–95a. The district court

noted that it would have imposed a preliminary

injunction in the alternative. FDA.Pet.App.195a.

FDA and Danco appealed and moved to stay the

district court’s order pending appeal. A Fifth Circuit

motions panel stayed the district court’s ruling as it

applied to the 2000 Approval but did not disturb the

rest of the order. FDA.Pet.App.196a. After FDA and

Danco appealed, this Court stayed the order through

the ruling on any petition for certiorari.

FDA.Pet.App.245a.

After full briefing and argument, the Fifth Circuit

affirmed in part and reversed in part the district

court’s stay. FDA.Pet.App.3a. Exercising wellestablished principles of judicial review over agency

actions, the court of appeals held that the 2016 Major

Changes, the 2021 Non-Enforcement Decision, and

2021

Petition

Denial

violated

the

APA.

FDA.Pet.App.51a–56a, 56a–63a. The court explained

that, contrary to congressional command, FDA did

not adequately explain its 2016 and 2021 decisions.

Ibid. FDA’s and Danco’s petitions for certiorari

challenge that portion of the ruling.

In contrast, the court of appeals reversed the

district court’s ruling on the 2000 Approval—the

subject of this cross-petition. FDA.Pet.App.46a–51a.

It held that Cross-Petitioners’ challenge to the 2000

Approval was not timely filed. Ibid.

Judge Ho dissented. He concluded that CrossPetitioners timely challenged the 2000 Approval and

that FDA acted unlawfully when it approved

mifepristone under Subpart H. FDA.Pet.App.84a,

89a–90a.

Judge Ho observed that the reopening doctrine

restarts the timeline for challenging agency actions in

two instances: “(1) if the agency opened the issue up

anew, and then reexamined and reaffirmed its prior

decision, or (2) if the revision of accompanying regulations significantly alters the stakes of judicial

review as the result of a change that could not have

been reasonably anticipated.” FDA.Pet.App.85a

(cleaned up). He then concluded that the second type

of reopening—“constructive reopening”—applies

here. FDA.Pet.App.85a. As he put it, “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.’” FDA.Pet.App.86a. (quoting Sierra

Club, 551 F.3d at 1026).

Turning to the merits of the 2000 Approval, Judge

Ho found it unlawful. FDA.Pet.App.89a. “It’s a longstanding principle that agencies must follow their

own regulations.” Ibid. (cleaned up). And the “FDA

violated that principle when it approved mifepristone

under Subpart H—as even the drug’s sponsor, the

Population Council, admitted in 2000.” FDA.Pet.App.

90a. That’s because “[p]regnancy is not an illness” and

“Subpart H authorizes the FDA to approve only those

drugs that treat ‘serious or life-threatening

illnesses.’” Ibid. (quoting 21 C.F.R. 314.500).

REASONS FOR GRANTING

THE CONDITIONAL WRIT

The Court should review the entire Fifth

Circuit decision if it grants FDA’s or

Danco’s petitions.

A. FDA disregarded law, science, and safety

in pursuit of a political end.

FDA’s actions concerning mifepristone—spanning

from the 2000 Approval to its most recent removal of

safeguards—have consistently elevated politics above

law, science, and safety. If this Court grants FDA’s

and Danco’s interlocutory petitions, it should grant

this cross-petition, review the Fifth Circuit’s entire

decision, and assess the full range of FDA’s misdeeds.

FDA’s early actions in approving mifepristone are

inextricably intertwined with its more recent

decisions to remove critical safeguards surrounding

its use. To review one without the other is like reading

a novel starting in the middle.

From the beginning, political actors have

orchestrated mifepristone’s approval and deregulation. In 1993 and 1994, the Clinton Administration

negotiated for the Population Council—a nonprofit

that John Rockefeller III founded to address supposed

world “overpopulation”—to obtain the U.S. patent

rights to mifepristone from its French manufacturer.

C.A.Add.106–07.

Subpart H is tailored to dangerous drugs that

“can be safely used only if distribution or use is

restricted.” 21 C.F.R. 314.520(a). Given the dangers of

mifepristone, Subpart H was the only regulatory

pathway for FDA to approve mifepristone.

C.A.Add.587, 605–06. But Subpart H applies only to

drugs that “treat[ ] serious or life-threatening

illnesses.” 21 C.F.R. 314.500. Despite the Population

Council warning FDA that the agency lacked

authority to approve mifepristone under Subpart H,

FDA did so anyway, violating its own regulations.

C.A.Add.600.

Worse yet, FDA greenlit mifepristone despite the

agency’s reservations about the drug’s safety.

FDA.Pet.App.181a. In February 2000, FDA

determined that it lacked “adequate information” to

demonstrate the safety and effectiveness of

mifepristone. C.A.Add.108. And in June 2000, FDA

told Danco that prescribing physicians would be

required to assess gestational age via ultrasound and

that other requirements would be necessary to treat

post-abortion complications. C.A.Add.405. But when

that information was leaked to the public, FDA faced

significant political backlash from Capitol Hill and

pro-abortion groups. C.A.Add.406–407. Caving to this

pressure, FDA approved mifepristone only three

months later without any ultrasound requirement or

any of its recommended safeguards against postabortion complications. C.A.Add.406–08. As the

district court concluded here, “FDA acquiesced on its

legitimate safety concerns—in violation of its

statutory duty.” FDA.Pet.App.182a.

As if that wasn’t enough, FDA’s 2000 Approval

relied on one U.S. trial and two French studies that

all included safeguards not incorporated into the

approved labeling. C.A.Add.591. FDA failed to offer

any evidence, testing, or information—each required

by the law governing new drug approvals, 21 U.S.C.

355(d)—to show the safety and effectiveness of

mifepristone without these safeguards. This violated

the APA’s most basic tenets. 21 U.S.C. 355(d);

C.A.Add.4356, 4362.

And the political gamesmanship did not stop with

that approval. Following the filing of the 2002 Citizen

Petition challenging the 2000 Approval, FDA took 14

years—until 2016—to reject it, simultaneously

issuing “major changes” to the regimen that

eviscerated crucial safeguards for women and girls.

C.A.Add.634–67, 688–96. FDA’s own regulations

require tentative or final responses to citizen

petitions within 180 days. 21 C.F.R. 10.30(e)(2). By

delaying, FDA was able to forestall a lawsuit until it

was ready to implement its major changes, forcing

Cross-Petitioners to play a game of whack-a-mole.

Then, on April 12, 2021, in the early days of the

Biden Administration, FDA stated that it would

“exercise enforcement discretion” and allow

“dispensing of mifepristone through the mail … or

through a mail-order pharmacy” during the COVID

pandemic. C.A.Add.788. FDA did so even though the

Comstock Act expressly bans the sending of abortion

drugs by mail, express company, or common carrier.

18 U.S.C. 1461–62 (prohibiting the mailing or

delivery of “[e]very article or thing designed, adapted,

or intended for producing abortion.”). In rejecting the

2019 Citizen Petition in December 2021, FDA

announced that it would permanently allow abortion

by mail, C.A.Add.808, an ongoing violation of federal

law.

It is these unlawful and arbitrary actions that

FDA deems its “scientific judgment,” FDA.Pet.30,

expressing indignation that a federal court of appeals

would dare question that judgment in a legal

proceeding. But as Judge Ho explained, it is hardly

“unprecedented” for FDA’s judgment to be wrong.

FDA.Pet.App.104a–09a.

Consider the opioid crisis. This epidemic comes in

part because FDA “failed to adequately predict the

harms associated with” opioids. Celine Castronuovo,

OxyContin Decision Involved FDA ‘Miscalculation,’

Woodcock Says, Bloomberg Law (June 15, 2022, 2:31

P.M.), https://perma.cc/WJY3-7LVE. Even today,

ignoring criticism from the National Academy of

Sciences, senators, and former commissioners, FDA

has not changed its opioid policies but instead has

“adopted a defensive posture and sought to shift

blame.” Andrew Kolodny, How FDA Failures

Contributed to the Opioid Crisis, 22 AMA J. of Ethics

743, 747 (2020); accord Allysia Finley, DayQuil, Covid

Vaccine Boosters and FDA Science, Wall St. J. (Sept.

17, 2023, 2:44 P.M.), https://perma.cc/QNU6-2VLN.

FDA’s accelerated approvals are also emblematic

of the agency’s penchant to subordinate patient safety

to politics. Starting in 1992, advocacy groups started

“contribut[ing] to the salaries of the agency’s drug

reviewers in exchange for time limits on reviews.”

Caroline Chen, FDA Increasingly Approves Drugs

Without Conclusive Proof They Work, PBS News Hour

(June 26, 2018, 11:31 A.M.), https://perma.cc/3V3XAK3V. This, despite FDA’s own admission that

“accelerated approval has greater uncertainty.” Ibid.

As a result, “[t]he FDA is increasingly green-lighting

expensive drugs despite dangerous or little-known

side effects and inconclusive evidence that they curb

or cure disease.” Ibid. The lower courts’ opinions

recognize that’s what FDA did here, too.

B. The questions presented in this crosspetition are part and parcel of those

presented in FDA’s and Danco’s petitions.

FDA’s and Danco’s petitions ask the Court to

examine the 2016 Major Changes, 2021 Non-Enforcement Decision, and 2021 Petition Denial. But the

Court will have an incomplete view of those issues

unless it also considers the FDA’s approval of mifepristone. Indeed, FDA’s decisions to remove safety

restrictions that the agency found indispensable in

granting mifepristone’s approval are central to issues

raised in this cross petition.

A clear overlap exists between FDA’s defense of

its decisions to eliminate mifepristone’s safety

measures and Cross-Petitioners’ arguments that

their challenge to the 2000 Approval is timely. If

FDA’s actions to remove those safety requirements in

2016 and 2021 changed “the basic regulatory

scheme,” NRDC, 571 F.3d at 1266, the Fifth Circuit

was wrong to reject Cross-Petitioners’ reopening

argument. Yet FDA previously “told [this] Court that

setting aside those revisions would ‘upend the

regulatory regime for mifepristone’ and ‘unleash[ ]

regulatory chaos.’” FDA.Pet.App.84a (Ho, J.,

concurring and dissenting in part (quoting App. to

Stay, 2023 WL 3127519, at *2–3, FDA v. All. for

Hippocratic Med., 143 S. Ct. 1075 (2023))).

Meanwhile, FDA insists that the reopening doctrine

does not apply because the 2016 and 2021 changes did

not alter the basic regulatory scheme. C.A.Add.2114.

FDA can’t have it both ways. Accordingly, it would not

only be inefficient but unjust to Cross-Petitioners if

the Court were to review FDA’s arguments without

also considering those arguments’ impact on CrossPetitioners’ challenge to the 2000 Approval.

Unlike some state courts, “federal law expresses

the policy against piecemeal appeals.” Switzerland

Cheese Ass’n v. E. Horne’s Market, Inc., 385 U.S. 23,

24 (1966) (citing Baltimore Contractors, Inc. v.

Bodinger, 348 U.S. 176 (1955)). And this case shows

why that is so. It makes no sense that this Court

would grant the petitions and resolve only part of the

case, especially where the 2000 Approval involves

interrelated questions and provides the background

for the 2016 Major Changes, the 2021 NonEnforcement Decision, and 2021 Petition Denial.

Thus, if the Court believes interlocutory review is

warranted, it should consider all those issues at once.

II. The Fifth Circuit erred in rejecting the

challenges to FDA’s approvals of chemical

abortion drugs.

A. FDA reopened its 2000 Approval when it

overhauled the mifepristone regimen in

2016 and authorized mail-order abortion

in 2021.

Cross-Petitioners’ challenge to FDA’s 2000

Approval is timely. The Fifth Circuit erred in

concluding otherwise. The reopening doctrine “allows

an otherwise untimely challenge to proceed where an

agency has—either explicitly or implicitly—

undertaken to reexamine its former choice.” Nat’l

Biodiesel Bd. v. EPA, 843 F.3d 1010, 1017 (D.C. Cir.

2016) (cleaned up); cf. Alaska v. U.S. Dep’t of Agric.,

772 F.3d 899, 900 (D.C. Cir. 2014) (Kavanaugh, J.)

(“[R]eopening … giv[es] rise to a new right of action

even though the regulation challenged is no

different.”) (cleaned up). As Judge Sentelle explained,

“without weakening [the] general and appropriate

rule” that a jurisdictional statute of limitations “may

not be enlarged or altered by the courts,” the “period

for seeking judicial review may be made to run anew

when the agency in question by some new

promulgation” reopens an agency action. Ohio v. EPA,

838 F.2d 1325, 1328 (D.C. Cir. 1988).

Express reopening occurs where an agency

“reexamine[s] its former choice.” Nat’l Biodiesel Bd.,

843 F.3d at 1017 (cleaned up). Constructive reopening

exists where the agency alters the “basic regulatory

scheme” by, among other things, removing necessary

safeguards. Ibid. Both express and constructive

reopening occurred here because FDA re-examined its

approval of mifepristone and altered the basic

regulatory scheme by removing safeguards it

previously found indispensable to the drug’s safe use.

The reopening doctrine is a necessary backstop to

agency gamesmanship. As the D.C. Circuit recognizes, the doctrine prevents an agency from evading

review by “creat[ing] a different regulatory

construct.” Sierra Club, 551 F.3d at 1025. Reopening

applies when “the revision of [ ] underlying regulations significantly alters the stakes of judicial review”

because the underlying regulations “may not have

been worth challenging” initially, but the subsequent

“[r]egulations gave them new significance.”

Kennecott, 88 F.3d at 122627. In other words,

reopening arises from the regulatory bait-and-switch

that occurs when an agency fundamentally alters the

“package deal that [it] devised and sold to the public

as adequate protection.” Sierra Club, 551 F.3d at

1026. Just as “new and potentially more onerous”

regulations can change the stakes for judicial review,

Kennecott, 88 F.3d at 1227, so can a new and more

dangerous drug regimen.

The application of the reopening doctrine here

takes on greater importance in light of the Court’s

grant of certiorari in Corner Post, Inc. v. Board of

Governors of the Federal Reserve System, No. 22-1008.

Federal agencies should not be able to avoid judicial

review by pulling a regulatory bait-and-switch. But

whether they can also avoid accountability when their

actions injure parties who could not have filed a

challenge within the six-year limitations period

impacts this case, too. At least one Cross-Petitioner

was first harmed by mifepristone just last year.

C.A.Add.959. This Cross-Petitioner could not have

sued until now.

1. FDA expressly

Approval.

reopened

the

2000

Under Subpart H, FDA approved mifepristone

contingent on certain safeguards. Indeed, the 2000

Approval relied on Subpart H because it was the only

way FDA could require post-marketing restrictions

“needed to assure safe use” of mifepristone. 21 C.F.R.

314.520(a).

The 2007 FDAAA then codified Subpart H’s postmarketing restrictions, renaming them REMS.

§909(b)(1), 121 Stat. at 950. In a section entitled

“initial approval,” the FDAAA (like Subpart H)

requires FDA to impose a REMS when it “determines

that a risk evaluation and mitigation strategy is

necessary to ensure that the benefits of the drug

outweigh the risks of the drug.” 21 U.S.C. 355-1(a)(1)

(emphasis added). Echoing Subpart H, REMS that

contain “elements [ ] necessary to assure safe use”

“[p]rovid[e] safe access for patients to drugs with

known serious risks that would otherwise be

unavailable.” Id. 355-1(f) (emphasis added). Because

FDA found mifepristone to be “associated with a

serious adverse drug experience,” the agency

concluded that mifepristone could “be approved only

if, or would be withdrawn unless, such elements are

required” as part of a REMS. See id. 355-1(f)(1)(A).

The 2000 Approval’s safeguards—initially under

Subpart H and subsequently pursuant to a REMS—

were necessary to allow mifepristone into the market.

Without these safeguards, FDA would not have

issued its 2000 Approval. Neither FDA nor Danco has

ever disputed this. But the 2016 Major Changes and

the 2021 Petition Denial removed the very safeguards

indispensable to the 2000 Approval. In fact, FDA

issued the 2016 Major Changes in response to Danco’s

request to reopen, reconsider, and remove crucial

elements assuring safe use required for the 2000

Approval. C.A.Add.700–01. This literal reopening was

“a serious, substantive reconsideration” of the 2000

Approval. Nat’l Mining Ass’n v. U.S. Dep’t of Interior,

70 F.3d 1345, 1352 (D.C. Cir. 1995).

Simply put, FDA’s 2016 and 2021 actions

necessarily reconsidered and revised the 2000

Approval by re-evaluating and changing the

safeguards essential to that original approval. Those

express re-examinations reopened that initial

decision and restarted the clock to challenge it.

Two members of the panel below believed that

FDA had taken the 2000 Approval “as a given, and

considered only whether the REMS amendments

were safe.” FDA.Pet.App.47a. But this view overlooks

that the removed safety requirements were preconditions to FDA’s approval of chemical abortion. Erasing

them necessarily reopened the question whether

mifepristone was safe without them—the very

question FDA considered in 2000.

The context of the 2016 Major Changes confirms

that FDA reopened its 2000 Approval. Pub. Citizen v.

Nuclear Regul. Comm’n, 901 F.2d 147, 150 (D.C. Cir.

1990) (reviewing court “must look to the entire

context … to determine whether an issue was in fact

reopened”). FDA denied the 2002 Citizen Petition’s

request for reconsideration of the 2000 Approval—a

petition it had “carefully considered” for 14 years—on

the same day it issued the 2016 Major Changes.

C.A.Add.635. Those same-day decisions reinforce that

the 2016 Major Changes reconsidered the 2000

Approval. See Growth Energy v. EPA, 5 F.4th 1, 21

(D.C. Cir. 2021).

The context of the 2021 Petition Denial is also

probative. There, FDA explicitly stated that it “undertook a full review of the Mifepristone REMS Program.” C.A.Add.808 (emphasis added). A “full review”

of a REMS for a drug that requires safeguards to

obtain and retain approval necessarily reconsiders

whether the initial approval was inappropriate and

thus the drug should “otherwise be unavailable.” 21

U.S.C. 355-1(f).

In these unique circumstances, reopening simply

reflects the commonsense proposition that the

entirety of a final agency action is reviewable under

the APA. The 2016 and 2021 removal of safeguards

that FDA determined to be essential for mifepristone’s initial approval necessarily considered

whether

mifepristone

meets

the

statutory

requirements for approval without those safeguards.

Just as “an official interpretation of a regulation may

trigger a reopening,” Env’t Def. v. EPA, 467 F.3d 1329,

1334 (D.C. Cir. 2006) (citing Pub. Citizen, 901 F.2d at

151), so too does FDA’s removal of statutorily required

preconditions to approval. See FCC v. Fox Television

Stations, Inc., 556 U.S. 502, 515–16 (2009) (agencies

must provide courts with “a reasoned explanation …

for disregarding facts and circumstances that

underlay or were engendered by [a] prior policy”);

Wash. All. of Tech. Workers v. DHS, 892 F.3d 332,

345–46 (D.C. Cir. 2018); Ohio, 838 F.2d at 1328

(applying reopening doctrine and allowing challenge

to entire regulatory regime to proceed).

2. FDA constructively reopened the 2000

Approval.

The 2016 Major Changes, 2021 Non-Enforcement

Decision, and 2021 Petition Denial also constructively

reopened the 2000 Approval. Removing in-person

doctor visits and dispensing requirements and

expanding the gestational age of the unborn infants

enacted a “sea change” in the chemical abortion

regimen, NRDC, 571 F.3d at 1266, dramatically

altering the “basic regulatory scheme” by removing

necessary safeguards, Nat’l Biodiesel Bd., 843 F.3d at

1017.

FDA effectively admits this. It says that reinstating mifepristone’s pre-2016 safeguards would be

“destabilizing,” FDA.Pet.29, “upend[ing] the regulatory regime for mifepristone” and “unleashing regulatory chaos,” FDA.Stay.App.2–3. FDA also asserts that

“the substantially more restrictive pre-2016

conditions of use” differ from the post-2016 conditions

so much that to return to them would “unnecessarily

impair or even eliminate access to mifepristone.”

FDA.Pet.28. As Judge Ho explained below, “[i]f

switching from the 2016/2021 regime to the 2000-era

regime significantly alters the basic regulatory

scheme, then surely the reverse does, too.”

FDA.Pet.App.84a (cleaned up). Constructive reopening thus applies here.

This case is on all fours with Sierra Club. There,

EPA adopted a 1994 rule that exempted major

sources from the Clean Air Act’s emission standards

during startups, shutdowns, and malfunctions (the

SSM exemption). Sierra Club, 551 F.3d at 1022. The

rule required these sources to develop a publicly

available SSM plan detailing efforts “to maintain

compliance with the standards, even during SSMs.”

Ibid. (cleaned up). In a series of rulemakings, EPA:

(1) stopped making plans publicly available;

(2) removed the requirement that a permit

incorporate the SSM plan; and (3) took away the

requirement that major sources implement the SSM

plans during SSM periods. Id. at 1023.

The Sierra Club filed suit in 2007, challenging the

legality of the 1994 SSM exemption. Id. at 1024. The

D.C. Circuit correctly held the challenge timely. The

Court recognized that EPA had constructively

reopened that decision “by stripping out virtually all

of the SSM plan requirements that it created to

contain that exemption.” Id. at 1025 (quotation

omitted). By abandoning “necessary safeguards,”

EPA had “changed the calculus for petitioners in

seeking judicial review and thereby constructively

reopened consideration of the [initial] exemption.” Id.

at 1025–26 (cleaned up).

So too here. By stripping out virtually all the

restrictions accompanying the 2000 Approval, and by

abandoning necessary safeguards, FDA constructively reopened the 2000 Approval. In fact, every

panel member below acknowledged that the 2016 and

2021 changes “meaningfully altered” the drug

regimen. FDA.Pet.App.47a.

Despite this, two judges below believed the

reopening doctrine did not apply because the 2016

and 2021 changes could “have been reasonably

anticipated.” FDA.Pet.App.48a (quoting Env’t Def.,

467 F.3d at 1334). Not so. Danco’s supplemental

petition requesting that nine safeguards be removed

was confidential. 21 C.F.R. 314.430(b) (stating that

“FDA will not publicly disclose the existence of an

application or abbreviated application before an

approval letter is sent to the applicant”). Nor did FDA

disclose before December 2021 its self-initiated

decision to permanently remove the in-person

dispensing requirement. It is simply untrue that

Cross-Petitioners “had adequate notice of a

forthcoming change that might alter their incentive

to seek judicial review.” Kennecott, 88 F.3d at 1214.

Further, the in-person dispensing requirement

served as “the cornerstone” for pre-2021 REMS,

alleviating “concerns about provider qualifications,

improper use, illicit distribution, and the detection of

adverse events.” FDA.Pet.App.229a. Eliminating that

cornerstone requirement worked a sea change in the

basic regulatory structure. Cross-Petitioners could

not reasonably anticipate the removal of safeguards

that FDA had said were necessary preconditions to

mifepristone’s approval.

B. FDA violated its own regulations and

federal laws when it approved mifepristone in 2000.

Once it is clear that Cross-Petitioners timely filed

their challenge to the 2000 Approval, the merits

analysis of that claim is straightforward. The 2000

Approval violated the APA because it conflicted with

FDA’s own regulations and federal law.

1. FDA impermissibly invoked Subpart H

by classifying pregnancy as an “illness.”

“It is a familiar rule of administrative law that an

agency must abide by its own regulations.” Fort

Stewart Schs. v. Fed. Labor Rels. Auth., 495 U.S. 641,

654 (1990) (citations omitted). FDA violated this rule

when it used Subpart H to approve mifepristone in

2000.

Subpart H was the only source of authority that

would have allowed FDA to approve chemical

abortion drugs in 2000. C.A.Add.596. FDA

determined that chemical abortion drugs could not be

safely approved without post-marketing restrictions.

C.A.Add.111. Restrictions were “needed to assure safe

use of this product.” C.A.Add.587. And Subpart H was

the only approval mechanism that provided for such

restrictions. 21 C.F.R. 314.520(a).

Yet Subpart H was never a good fit for mifepristone. That provision provides for the accelerated

approval of certain high-need drugs. It applies to new

drugs “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 (e.g., the

ability to treat patients unresponsive to, or intolerant

of, available therapy, or improved patient response

over available therapy).” 21 C.F.R 314.500 (emphasis

added). Like a square peg in the proverbial round

hole, chemical abortion meets none of Subpart H’s

requirements. Pregnancy is not an illness, much less

a serious or life-threatening one. Nor does chemical

abortion provide a therapeutic benefit over existing

treatments. Indeed, FDA put forward no evidence on

the administrative record produced to date that it

found any such benefit.

Pregnancy is not a serious or lifethreatening illness.

FDA has repeatedly conceded that pregnancy is

not an illness. C.A.Add.638, 4217. Defined as when a

woman is “with child,” FDA.Pet.App.90a (Ho, J.,

concurring and dissenting), pregnancy is a normal

physiological state that many females experience one

or more times during their lifetimes, C.A.Add.88. An

“illness,” by contrast, is “a disease, ailment, sickness,

[or] malady.” FDA.Pet.App.90a (Ho, J., concurring

and dissenting) (quoting Oxford English Dictionary

(2nd ed. 1989)) (cleaned up). The only “‘reasonable

construction’ of the word ‘illness’ … doesn’t include

pregnancy.” FDA.Pet.App.91a (cleaned up).

Even mifepristone’s champion—the Population

Counsel—agreed with this analysis. Just three weeks

before the 2000 Approval, the Population Council

wrote to FDA stating that “[n]either pregnancy nor

unwanted pregnancy is an illness, and Subpart H is

therefore inapplicable for that reason alone.”

C.A.Add.109. Well said.

Seeking to avoid that obvious conclusion, FDA

invokes the preamble to the final rule for Subpart H.

The agency says that the preamble somehow expands

the text of Subpart H to encompass “serious or lifethreatening conditions, as well as … illnesses or

diseases.” C.A.Add.638 (emphasis added). But

preamble language that contradicts the operative

regulatory text is entitled to no weight. See Cuomo v.

Clearing House Ass’n, 557 U.S. 519, 533 (2009)

(invalidating an agency’s interpretation of a regulation inconsistent with the regulation’s text and the

statute).

FDA’s expansive interpretation of Subpart H is

unreasonable. If FDA wanted to include “conditions”

in Subpart H, the agency knew how to draft such

language. E.g., 21 C.F.R. 312.300(a) (including

“disease or condition” within the scope of FDA’s

“Subpart I” regulations for certain investigational

drugs). To read “condition” into Subpart H would

violate the well-established omitted-case canon of

construction. See Lamie v. U.S. Tr., 540 U.S. 526, 538

(2004) (refusing to “read an absent word into the

statute”). Because FDA’s interpretation defies the

plain text of Subpart H, it is entitled to no deference.

See Kisor v. Wilkie, 139 S. Ct. 2400, 2415 (2019) (“If

uncertainty does not exist, there is no plausible

reason for deference.”).

Chemical abortion does not provide

a meaningful therapeutic benefit

over existing options.

FDA’s 2000 Approval violates Subpart H twiceover because chemical abortion drugs do not provide

a “meaningful therapeutic benefit” over existing

options, including surgical abortion. FDA’s politically

motivated approval of chemical abortion glossed over

two glaring flaws: (1) chemical abortion is not

“therapeutic”; and (2) chemical abortion does not

provide a meaningful benefit over surgical abortion.

C.A.Add.377.

1. Mifepristone is not “therapeutic” for at least

three reasons. First, the term “therapeutic” relates to

the treatment or curing of a disease or disorder.

Therapeutic,

Merriam

Webster,

https://perma.cc/6KL5-NFKP. But as explained

above, pregnancy is not an illness requiring

therapeutic treatment. Second, FDA approved these

drugs for use in healthy pregnant women who lack a

serious or life-threatening illness to treat.

C.A.Add.373. Third, these drugs do not treat

pregnancy-related complications, such as lifethreatening ectopic pregnancies. C.A.Add.413. In

fact, “if a woman who has an ectopic pregnancy

undergoes a [chemical] abortion, she is at risk for

tubal rupture and subsequent hemorrhage due to

delay in diagnosis and delay in treatment.” Ibid.

That’s because the symptoms of an ectopic

pregnancy—vaginal bleeding, pelvic pain, and

cramping—are confusingly similar to certain side

effects of chemical abortion drugs. Ibid. FDA

acknowledges this danger. C.A.Add.2366 (warning

that “some of the expected symptoms experienced

with a medical abortion (abdominal pain, uterine

bleeding) may be similar to those of a ruptured ectopic

pregnancy”).

2. Chemical abortion does not provide a “meaningful” benefit over existing options. These drugs are not

an alternative “therapy” for patients “unresponsive

to, or intolerant of,” surgical abortion—indeed,

surgical intervention is often required after an

incomplete or failed chemical abortion. See 21 C.F.R.

314.500. Nor do these drugs provide an “improved

patient response” over surgical abortions. See ibid. In

fact, chemical abortion drugs pose a higher risk of

serious and life-threatening adverse effects on women

and girls. For example, “[c]hemical abortions are over

fifty percent (50%) more likely than surgical abortions

to result in an emergency department visit within

thirty days.” C.A.Add.92 (citation omitted). And “[t]he

number of chemical abortion-related emergency room

visits increased by over five hundred percent (500%)

between 2002 and 2015. Ibid. (citation omitted).

Tellingly, FDA’s cited clinical trials did not compare

chemical abortion with surgical abortion to assess

whether a benefit existed. C.A.Add.377.

FDA offered only one “meaningful therapeutic

benefit” of chemical abortion: “the avoidance of a

surgical procedure.” C.A.Add.596. But “[b]y defining

the ‘therapeutic benefit’ solely as the avoidance of the

current standard of care’s delivery mechanism, FDA

effectively guarantees that a drug will satisfy this

second prong of Subpart H.” C.A.Add.374. Such

circularity cannot itself be the requisite “benefit.”

FDA’s 2000 Approval thus failed to satisfy the

requirements of Subpart H.

2. The 2000 Approval also violated the

APA and FDCA.

FDA’s 2000 Approval also failed to satisfy the

requirements of the APA and the FDCA.

The APA forbids “arbitrary” and “capricious”

agency actions. 5 U.S.C. 706(2)(A). Regulatory action

is arbitrary and capricious when the agency ignores

“the relevant data” and fails to “articulate a

satisfactory explanation for its action[s].” State Farm,

463 U.S. at 43. A court must “consider whether the

decision was based on a consideration of the relevant

factors and whether there has been a clear error of

judgment.” Ibid. (cleaned up). The agency misses the

mark if it “entirely failed to consider an important

aspect of the problem, offered 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.” Ibid.

The APA also requires courts “to determine

whether the agency [action] conformed with controlling statutes.” Balt. Gas & Elec. Co. v. Nat. Res. Def.

Council, Inc., 462 U.S. 87, 97 (1983). The FDCA

requires companies seeking to market any new drug

in the U.S. to obtain FDA’s approval by filing an NDA.

21 U.S.C. 355(a), (b). The NDA must contain scientific

data showing the safety and effectiveness of the drug

under real-world conditions. Id. 355(d).

The FDCA requires FDA to reject the NDA if the

clinical investigations “do not include adequate tests

… to show whether or not such drug is safe for use

under the conditions prescribed, recommended, or

suggested in the proposed labeling thereof.” Ibid. FDA

must also reject the NDA if “the results of such tests

… do not show that such drug is safe for use under

such conditions.” Ibid. Similarly, FDA must deny the

NDA if the agency “has insufficient information to

determine whether such drug is safe for use under

such conditions.” Ibid. Finally, FDA must deny the

NDA 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 of use

prescribed, recommended, or suggested in the

proposed labeling thereof.” Ibid. In short, numerous

provisions require that FDA evaluate a new drug

under the conditions for use.

Yet none of the studies cited by FDA evaluated

mifepristone under the prescribed conditions for use

in 2000. After obtaining the U.S. patent rights to

mifepristone, the Population Council conducted a

U.S. clinical trial of the drug. C.A.Add.107. But this

clinical trial failed to evaluate the conditions of use

under the proposed labeling. For example, the trial

included two safeguards: (1) each woman received an

ultrasound to confirm gestational age and to exclude

an ectopic pregnancy; and (2) the women needed to be

monitored over the course of four hours to check for

adverse

events

after

taking

misoprostol.

C.A.Add.428–29. And the two previous French

clinical trials included two similar safeguards:

(1) each woman received an ultrasound, if available;

and (2) the women remained under observation for

three to five hours after taking misoprostol.

C.A.Add.378–79.

But FDA included none of these requirements in

the 2000 Approval. FDA.Pet.App.173a. Though the

trials included ultrasounds to diagnose life-threatening ectopic pregnancies, FDA was silent—in evidence

and explanation—on how a doctor could do that

without an ultrasound. C.A.Add.595. And while FDA

asserted that a doctor could use “other clinical

methods” to diagnose gestational age, ibid., those

other clinical methods are not equal to ultrasounds in

their accuracy and reliability. Indeed, an ultrasound

is the most accurate method to determine gestational

age. C.A.Add.410–414. FDA has never denied this

fact. And accuracy in gestational age is crucial

because there is a “significant increase in failures and

complications”

C.A.Add.411.

the

pregnancy

progresses.

FDA also excluded the clinical trials’ safeguard

that women remain under the doctor’s observation for

at least three to five hours after ingesting

misoprostol. In doing so, it ignored the U.S. trial’s

finding that “many adverse events, including those

rated as severe, occurred during this period, as did

almost half the expulsions, and some women may

prefer to be in the clinic during these events.” Irving

M. Spitz, et al., Early Pregnancy Termination with

Mifepristone and Misoprostol in the United States,

New England J. of Med. (Apr. 30, 1998).

The 2000 Approval thus lacked the adequate

testing, sufficient information, and substantial evidence required to show the safety and effectiveness of

chemical abortion drugs under the approved conditions. See 21 U.S.C. 355(d). What’s more, FDA

entirely disregarded important aspects of the

identified problems, ignored the relevant data, and

failed to articulate satisfactory explanations for its

action. State Farm, 463 U.S. at 43. These failures

violate the basic tenets of the APA and the FDCA.

C. Because FDA’s 2000 Approval and 2016

Major Changes were unlawful, FDA’s 2019

Generic Approval was also unlawful.

FDA also violated the FDCA and the APA when

approving a generic version of mifepristone in 2019.

The FDCA allows a generic drug manufacturer to

submit an ANDA for premarket review and approval.

21 U.S.C. 355(j); 21 C.F.R. 314.94. The generic

company must show that (1) the conditions of use

prescribed, recommended, or suggested in the

labeling proposed for the new drug have been

previously approved for a drug listed, and (2) the drug

product is chemically the same as the already

approved drug, allowing it to rely on FDA’s previous

finding of safety and effectiveness for the approved

drug. Ibid. The route of administration, dosage form,

and strength must also be the same. Ibid. Based on

GenBioPro’s application for its generic version, FDA

determined that the 2019 ANDA “demonstrate[d]

that the drug is safe and effective … in the submitted

labeling” because it is “bioequivalent and, therefore,

therapeutically equivalent” to Danco’s version.

C.A.Add.768.

If the listed drug—on which the ANDA-approved

generic drug is based—is withdrawn, the FDCA and

FDA’s implementing regulations generally require

FDA to withdraw the generic drug as well. 21 U.S.C.

355(j)(6); 21 C.F.R. 314.151.

The 2019 Generic Approval violated the FDCA

because FDA relied on the unlawful 2000 Approval

and 2016 Major Changes to approve GenBioPro’s

generic chemical abortion drug. C.A.Add.179–80,

1061–62. Because the 2000 Approval must be

withdrawn and the Fifth Circuit has already upheld

the stay of the 2016 Major Changes, the 2019 Generic

Approval must meet the same fate. Unable to rely on

the unlawful 2000 Approval and 2016 Major Changes,

the 2019 Generic Approval violated the FDCA

because it lacked its own clinical investigations,

adequate testing, sufficient information, and

substantial evidence to show the generic drug’s safety

and effectiveness under the proposed labeling. 1

The Fifth Circuit faulted Cross-Petitioners for

failing to show traceability—i.e., that the 2019

Generic Approval caused them the same harms as

name-brand mifepristone. FDA.Pet.App.47a. But

“Article III requires no more than de facto causality.”

Dep’t of Com. v. New York, 139 S. Ct. 2551, 2566

(2019) (cleaned up). Traceability is satisfied where

plaintiffs show that an action “causes or contributes

to the kinds of injuries alleged by the plaintiffs.” Pub.

Int. Rsch. Grp. of N.J., Inc. v. Powell Duffryn

Terminals Inc., 913 F.2d 64, 72 (3d Cir. 1990). That is

undeniably true here.

As GenBioPro admits, its sales of generic

mifepristone represent roughly two-thirds of chemical

abortions annually. GenBioPro.Stay.Amicus.Br.2.

And since the 2019 Generic Approval, chemical

abortions have skyrocketed. C.A.Add.2435 (showing

dramatic increase—39% in 2017 to 53% in 2020—in

chemical abortions among all abortions). The

availability of generic chemical abortion drugs

through the mail and without a single in-person

doctor’s visit harms Cross-Petitioners. See City of

Waukesha v. EPA, 320 F.3d 228, 235 (D.C. Cir. 2003)

(per curiam) (reviewing courts must assume claims

are meritorious for Article III inquiry). Under these

circumstances, traceability is easily satisfied.

Cross-Respondents did not respond to the merits of CrossPetitioners’ challenge to the 2019 Generic Approval in the

district court proceedings and thus waived any objection.

C.A.Add.3354–55, 2026.

It is no answer to say that name-brand mifepristone also causes harm to Cross-Petitioners. The

“fairly traceable” standard is “not equivalent to a

requirement of tort causation.” Friends of the Earth,

Inc. v. Gaston Copper Recycling Corp., 204 F.3d 149,

161–62 (4th Cir. 2000) (cleaned up). It is satisfied by

a “substantial likelihood” that the challenged action

caused the alleged injury. Duke Power Co. v. Carolina

Env’t Study Grp., Inc., 438 U.S. 59, 75 n.20 (1978).

Plaintiffs need not “show to a scientific certainty” that

a particular product alone caused their harm. Powell

Duffryn Terminals, 913 F.2d at 72. Rather than

“pinpointing the origins of particular molecules,” as

with environmental challenges—or a particular drug

manufacturer, as here—a plaintiff “must merely

show” that the defendant’s actions “causes or

contributes to the kinds of injuries alleged.” Gaston

Copper, 204 F.3d at 161 (citing Nat. Res. Def. Council

v. Watkins, 954 F.2d 974, 980 (4th Cir. 1992)).

That’s why an environmental plaintiff “need not

sue every discharger in one action.” Powell Duffryn

Terminals, 913 F.2d at 72 n.8. (“the pollution of any

one may be shown to cause some part of the injury

suffered”) (emphasis omitted). It’s why an organization can challenge EPA’s approval of a particular

pesticide registration when other versions exist in the

market. Nat’l Fam. Farm Coal. v. EPA, 966 F.3d 893,

910 (9th Cir. 2020) (cleaned up) (“[t]he causation

requirement is satisfied by showing a reasonable

probability of the challenged action’s threat to

[petitioner’s] concrete interest”). And it’s why a

consumer can sue only one of the credit-reporting

agencies. Hammoud v. Equifax Info. Servs., LLC, 52

F.4th 669, 679 (6th Cir. 2022) (Nalbandian, J.,

concurring) (traceability satisfied where plaintiff

showed a “substantial likelihood” that “Experian, as

opposed to Equifax, provided the faulty credit

information”).

Here, there is no dispute that the 2019 generic

has the same chemical makeup as name-brand

mifepristone and will cause the same harms. Indeed,

Cross-Petitioners will continue to be harmed by both

the generic and name-brand drug. Moreover, it’s

substantially likely that approving a generic

version—which increases the amount of the drug

available on the market, and at a lower price—will

increase the incidents of those harms. This is

confirmed by data demonstrating that chemical

abortions have surged since the 2019 General

Approval. C.A.Add.2435 (FDA’s expert showing that

the percentage of chemical rather than surgical

abortions “has grown especially rapidly in recent

years”). These facts satisfy Article III.

CONCLUSION

The petitions for a writ of certiorari in Case Nos.

23-236 and 23-236 should be denied. But if those

petitions are granted, this conditional cross-petition

for a writ of certiorari should also be granted.

Respectfully submitted,

JAMES A. CAMPBELL

CODY S. BARNETT

ALLIANCE DEFENDING

FREEDOM

44180 Riverside Pkwy

Lansdowne, VA 20176

(571) 707-4655

OCTOBER 2023

ERIN M. HAWLEY

Counsel of Record

JOHN J. BURSCH

MATTHEW S. BOWMAN

ERIK C. BAPTIST

ALLIANCE DEFENDING

FREEDOM

440 First Street NW

Suite 600

Washington, DC 20001

(202) 393-8690

ehawley@ADFlegal.org

APPENDIX