Whole Woman's Health All. v. United States Food & Drug Admin.

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WHOLE WOMAN'S HEALTH ALLIANCE, et al., Plaintiffs, v. UNITED STATES FOOD AND DRUG ADMINISTRATION, et al., Defendants.

Civil Action No. 3:23-cv-00019

United States District Court, W.D. Virginia, Charlottesville Division

August 22, 2023

MEMORANDUM OPINION

Hon Robert S. Ballou United States District Judge.

In 2000, the United States Food and Drug Administration (“FDA”) approved mifepristone as a safe and effective drug used as part of a two-drug regimen to terminate early pregnancy. In every review of mifepristone since then, FDA has reached the same conclusions about the drug's safety and effectiveness, but FDA has attached several restrictions, commonly known as REMS, which affect the prescribing and dispensing of the drug. This case challenges those restrictions and asks me to order FDA to remove all REMS on the drug. In the wake of Dobbs v Jackson Women's Health Org., 142 S.Ct. 2228 (2022) which held that the Constitution does not provide a right to abortion and returned the authority to regulate abortion to the people's elected representatives, several states have restricted or effectively eliminated access to abortion.^[1] Plaintiffs are abortion providers in Virginia, Kansas, and Montana where mifepristone remains an available FDA-approved drug for early termination of pregnancy.

Plaintiffs fear, however, that in a post-Dobbs climate, mifepristone soon might not be available for their patients. Plaintiffs ask me to issue a preliminary injunction to enjoin Defendants from “altering the status quo” as it relates to access to mifepristone, due to the current legal uncertainty surrounding access to the drug and abortion in general.^[2] Plaintiffs' request underscores the importance of maintaining access to mifepristone, a drug deemed safe and effective by FDA for over 20 years, in those states where it can be prescribed consistent with current laws regarding abortion. However, a preliminary injunction is an extraordinary remedy with clear requirements that Plaintiffs do not currently meet. In each state in this action, mifepristone remains available to prescribe, and FDA has made no indication that it intends to limit access to mifepristone. The uncertainty at the heart of Plaintiffs' preliminary injunction request comes from circumstances unrelated to any party in this case and not because of FDA action or impending action.

I. Background

A. Statutory Background

In September 2000, FDA approved mifepristone under the brand name Mifeprex for use in medication-induced abortions. Dkt. 1 at 11. FDA specifically approved mifepristone as part of a two-drug regimen with the already approved drug misoprostol.^[3] Id. FDA concluded that mifepristone was effective and safe “for the medical termination of intrauterine pregnancy through 49 days' pregnancy.” Dkt. 1, Ex. A at 2. Subpart H of the FDA regulations authorized FDA to require that approved medications be prescribed with certain conditions “needed to assure safe use.” Final Rule, 57 Fed.Reg. 58,942, 58,958 (Dec. 11, 1992) (codified at 21 C.F.R. § 314.520). The imposed conditions in 2000 on the prescription of mifepristone required: (1) inperson dispensing of mifepristone only in a clinic, medical office, or hospital by or under the supervision of a certified provider, who could only be a physician, (2) a certification by clinicians who prescribe mifepristone attesting to their clinical abilities on a signed form kept on file by the manufacturer, and agreeing with reporting and other requirements, and (3) an agreement between the prescriber and patient which contains information about the mifepristone regimen and its risks, and which requires the prescriber to provide a copy to the patient and to place a copy in the patient's medical record. Dkt. 1 at 23-24.

The Food and Drug Administration Amendments Act of 2007 removed Subpart H but gave FDA the authority to require a Risk Evaluation and Mitigation Strategy (“REMS”) when “necessary to ensure that the benefits of the drug outweigh the risks of the drug.” 21 U.S.C. 355-1(a)(1). The 2007 statute also authorized FDA to require that any REMS included as part of a drug authorization include “elements to assure safe use” (“ETASU”) if medically necessary due to a drug's “inherent toxicity or potential harmfulness[.]” Id. at 355-1(f)(1). For a drug to have ETASU, the Secretary of the FDA must determine that the drug is associated with “a serious adverse drug experience,” which includes death, immediate risk of death, and inpatient hospitalization. Id. at 355-1(f)(1)(A), (b)(4). The ETASU must “not be unduly burdensome on patient access to the drug” and must “minimize the burden on the health care delivery system[.]” Id. at 355-1(f)(2). All drugs approved with restrictions under Subpart H, like mifepristone, were deemed to have a REMS in effect, with the Subpart H restrictions serving as ETASU. Pub. L. No. 110-85, tit. IX, § 909(b). Thus, the original restrictions attached to mifepristone under Subpart H became REMS affecting the prescribing and dispensing of the drug. FDA may also require an applicant to submit proposed modifications for existing REMS if the agency “determines that 1 or more goals or elements should be added, modified, or removed” from the current REMS to “ensure the benefits of the drug outweigh the risks of the drug” or to “minimize the burden on the health care delivery system of complying with the strategy.” 21 U.S.C. § 355-1(g)(4)(B).

B. REMS Placed on Mifepristone

Since 2007, FDA has reevaluated the mifepristone REMS, including in 2016, 2019, 2021, and 2023. Dkt. 1 at 24. “During FDA's 2016 review of the REMS, dozens of medical experts and their organizations asked FDA to eliminate the REMS because of the harms it imposed on patients and providers without any medical benefits.”^[4] Id. Thirty organizations submitted a letter to FDA during the 2016 review asking that it lift the REMS and extend the gestational age indicated on mifepristone's labeling from 49 to 70 days. Dkt. 1, Ex. K, at 1-2. They argued that “[e]xtensive scientific and clinical evidence of mifepristone's safety and efficacy, and the everincreasing burden on patient access to abortion care, clearly demonstrate that mifepristone's REMS program is not needed to protect patients.” Id. at 6. The organizations asked FDA to consider this burden “[i]n light of the FDA's statutory mandate from Congress to consider the burden caused to patients by REMS, and the agency's own stated commitment to ensuring that drug restrictions do not unduly burden patient access.” Id.

The conclusions from FDA in its 2016 review included (1) that Mifeprix “has been increasingly used as its efficacy and safety have become well-established by both research and experience, and serious complications have proven to be extremely rare;” (2) that “[g]iven that the numbers of . . . adverse events appear to be stable or decreased over time, it is likely that . . . serious adverse events will remain acceptably low[,]” and (3) that the risk of death from mifepristone is 0.00000232%.^[5] Dkt. 1, Ex. E at 14, 49; see also Dkt. 1, Ex. I; Dkt. 1 at 14. FDA updated the mifepristone REMS to allow a broader set of healthcare providers other than physicians to prescribe mifepristone and increased the indicated gestational age limit from 49 to 70 days. Dkt. 1 at 15; Dkt. 1, Ex. F at 10.

FDA received a citizen petition^[6] in 2020 from 21 state attorneys general asking that because of the COVID-19 pandemic, FDA remove the REMS which are “unnecessary, undue burdens in accessing safe and time-sensitive, essential medical care.” Dkt. 1, Ex. Q at 4. In the alternative, the attorneys general asked FDA to allow certified prescribers to use telehealth to prescribe mifepristone. Id. In July 2020, the District of Maryland temporarily enjoined FDA from enforcing the in-person dispensation requirements under the REMS during the COVID-19 pandemic. Am. Coll. of Obstetricians & Gynecologists v. U.S. Food and Drug Admin., 472 F.Supp.3d 183, 233 (D. Md. 2020). In April 2021, FDA found that safety concerns regarding the use of mifepristone had not increased after the court enjoined in-person prescription requirements. FDA then suspended the in-person dispensing requirement during the COVID-19 public health emergency, Dkt. 1, Ex. J at 1-2, and in January 2023, amended the REMS to remove the in-person dispensing requirement permanently, but it imposed a pharmacy certification requirement in its place. Dkt. 1 at 16, 27.

In 2022, a citizen petition consisting of 49 organizations requested that FDA “ask Danco Laboratories, LLC (“Danco”) - the holder of the approved new drug application for Mifeprex (mifepristone) - to submit a Supplemental New Drug Application (sNDA) that seeks to add miscarriage management as an indication to the drug's label and to eliminate or modify mifepristone's [REMS] . . . so that it is not unduly burdensome for that use.” Dkt. 1, Ex. O at 1. FDA denied the citizen petition and noted that FDA could not order Danco to submit a sNDA but that if Danco submitted a sNDA, FDA “will review such application consistent with the [Food, Drug, and Cosmetic Act], FDA regulations, and [the] standard process for sNDAs.” Dkt. 1, Ex. P at 3. FDA also denied the citizen petition's request for review of mifepristone's REMS and noted that because it had not approved mifepristone for miscarriage management, reviewing the burdens of the REMS Program for that purpose would be premature. Id. at 3.

C. Legal Challenges to Mifepristone Use

Legal challenges to FDA's approval and regulation of mifepristone are ongoing since the Supreme Court's decision in Dobbs v. Jackson Women's Health Org., 142 S.Ct. 2228 (2022), which held that the Constitution does not provide a right to abortion and returned...