“Mifepristone was approved by the US Food and Drug Administration (FDA) in 2000. In its 23 years on the market, it has been established as a common, safe, and effective method for the termination of pregnancy. Although mifepristone was approved with safety restrictions (now called a Risk Evaluation and Management Strategy, or REMS, program), the FDA greatly reduced these restrictions in 2016 and 2021 because it determined they were unwarranted and unnecessarily restricted access.
But in 2021, a group of antiabortion physicians filed a lawsuit in Texas challenging the 2000 FDA approval and the 2016 and 2021 REMS changes that broadened access to mifepristone. On April 7, 2023, US District Judge Matthew Kacsmaryk in Amarillo, Texas, issued a stay on mifepristone’s FDA approval. Judge Kacsmaryk’s opinion signaled that courts should feel empowered to second-guess the scientific evidence behind FDA approvals. He argued that he could upend FDA’s approval and subsequent REMS because FDA used “plainly unsound reasoning and studies that did not support its conclusions” (Alliance for Hippocratic Medicine v US Food and Drug Administration, 2:22-CV-223-Z [ND Tex 2023]). Although a lawsuit requires a showing of concrete harm to the person suing—often called standing—the judge instead emphasized the potential harm to physicians who are forced to treat patients with complications from mifepristone. It is this peculiar formulation of harm that allowed the case to proceed. Highlighting the unusual nature of this decision, an amicus brief filed by 19 FDA scholars stated they were “not aware of any case in which a court has removed a drug from the market over FDA’s objection.”
Within minutes of the Texas decision, US District Judge Thomas Rice in Spokane, Washington, issued a contradictory injunction blocking the FDA from “altering the status quo and rights as it relates to the availability of [m]ifepristone” in 17 states and Washington, DC. In keeping with the more traditional role of judicial review of agency decisions, Judge Rice declined “to review the scientific evidence and decide whether mifepristone’s benefits outweigh its risks without REMS” because “[t]hat is precisely FDA’s role.” But he concluded that the FDA failed to consider whether mifepristone even qualifies for REMS, given that the FDA itself acknowledged that serious adverse events are “exceedingly rare” (State of Washington v US Food and Drug Administration, 1:23-CV-3026-TOR [ED Wa 2023]).
[..] This conflict set the stage for a potential resolution by the US Supreme Court. Federal judges are supposed to defer to agency findings and conclusions unless they are “arbitrary and capricious”—lacking any basis in reason. Under existing authority, Judge Kacsmaryk’s failure to defer to the FDA’s nonarbitrary scientific findings could have been labeled ultra vires (beyond his authority).
The Appeal
The FDA appealed Judge Kacsmaryk’s decision to the Fifth Circuit Court of Appeals, emphasizing the harm of “blocking the distribution of a drug that has been found safe and effective by FDA and available to millions of patients for more than two decades” (Alliance for Hippocratic Medicine v US Food and Drug Administration, No. 23-10362 [5th Cir 2023]). Numerous amicus briefs were filed, including one from a coalition of biotechnology and pharmaceutical companies that accused Judge Kacsmaryk of casting aside “voluminous scientific evidence FDA considered,” instead relying on “personal stories told by plaintiffs” and cherry-picked studies.
On April 12, a 3-judge panel on the Fifth Circuit found that the challenge to the 2000 FDA approval of mifepristone was likely time-barred—meaning that mifepristone would remain approved by the FDA (Alliance for Hippocratic Medicine v US Food and Drug Administration [5th Cir 2023]). But the court did not question Judge Kacsmaryk’s lack of deference to the FDA, instead surprising many by finding that the FDA failed to prove that its actions were not “arbitrary and capricious.” The panel agreed with Judge Kacsmaryk that the FDA did not examine the relevant data in 2016 when it eliminated REMS safeguards—even though the FDA made this decision based on studies that evaluated those very safeguards. The Fifth Circuit decision would have restored the pre-2016 REMS program, meaning that 3 in-person visits would be required prior to mifepristone access—except in the 18 jurisdictions covered by the Washington injunction. Long-time FDA official Janet Woodcock, MD, expressed in a court document that returning to pre-2016 rules on mifepristone would create “significant chaos.” The reversion would also increase the approved dosage from 200 mg (contained in the 2016 label changes) to 600 mg (the original labeling), which seems internally inconsistent with the stated goals of reducing risk from mifepristone.
The Fifth Circuit also criticized the FDA for ending collection of nonfatal adverse event data in 2016—what the court called the “ostrich’s-head-in-the-sand approach.” But the FDA had deemed this data collection unnecessary based on “15 years of adverse event reports” prior to 2016. And for the 2021 removal of the in-person dispensing requirement, the FDA relied on compliance data, applicant-submitted data, its own postmarket data (albeit limited), and an “extensive review of the published literature.” That any court believes it could approximate the FDA’s considerable scientific expertise and scrutiny in 3 days of court consideration does more than express judicial hubris: it undermines the value and purpose of the FDA’s regulation of pharmaceuticals.
[..] on April 21, the Supreme Court weighed in to block the Texas injunction while the case proceeds through the appeals process. In the meantime, the Fifth Circuit has expedited the case for review, with oral arguments scheduled for May 17, 2023, and a full opinion coming soon thereafter. Despite the Supreme Court’s temporary intervention, mifepristone’s approval may still be in question.
Consequences of the Decisions
Together, these decisions portend a larger role for the judiciary in the FDA’s regulation of drugs. If Judge Kacsmaryk’s reweighing of the safety and effectiveness of mifepristone and its REMS is ultimately upheld, the finality of and deference to FDA approvals may come under question. Challenges to other politicized drugs, such as vaccines, contraceptives, medication for opioid use disorder, and HIV preexposure prophylaxis, could follow. This could threaten access to drugs that primarily benefit LGBTQ people, women, and people with substance use disorders. The ripple effect could extend to any patient who depends on the regular administration of drugs.
This series of decisions also generates significant uncertainty in the US pharmaceutical market. Judges and state attorneys general could further politicize a process meant to be guided by scientific experts. The prospect of unpredictable litigation over drug approvals could disrupt an industry that favors stability and reliable returns on investment. Pharmaceutical companies may shy away from commercializing new products, especially those that benefit marginalized groups. And this second-guessing through lawsuits will not stop at pharmaceuticals. The Texas court’s lack of deference to scientific findings could be applied to question the FDA’s scientific decisions pertaining to tobacco, medical devices, food safety, and more. Of note, judicial skepticism of science is not new, but these cases build on a growing trend of courts deciding they are better equipped than public health agencies to answer scientific questions.
Given Judge Kacsmaryk’s novel take on the proper scope of standing and judicial review, there is a significant possibility this case returns to the Supreme Court. The FDA has generally avoided appearing before the Supreme Court—in part because recent decisions have sapped agency authority and reversed agency decisions. Although undercutting the FDA’s drug approval process would be unprecedented, the current Supreme Court has recently shown its willingness to discard its own long-standing precedents to engage in abortion exceptionalism.
FDA’s Approach and Possible Solutions
The Supreme Court’s ruling means that access to mifepristone will not be disrupted—for now. But the Supreme Court’s emergency decision did not criticize or fully reverse the lower court decisions. Therefore, Congress, the FDA, and the public should plan to preserve access to a drug integral for reproductive health care while protecting the FDA’s scientific decisions from court intrusion.
Some have suggested FDA use enforcement discretion to circumvent the court rulings and ensure continued access to mifepristone. Enforcement discretion is a limited power afforded federal agencies to decide when and how to enforce the law. The FDA has sometimes used enforcement discretion to avoid enforcing the removal of illegal products it believes are helpful, or at least not a public health threat.
An exercise of enforcement discretion could allow manufacturers and pharmacies to continue selling mifepristone, even if it becomes unapproved or subject to older REMS limitations. But enforcement discretion is a short-term solution that does not repair courts’ intrusion into scientific decisions. Enforcement discretion can lead to unchecked behavior on the part of the FDA, which can result in the marketing of products without FDA clearance. Products subject to enforcement discretion have at times caused grave harm, including e-cigarettes and certain diagnostic tests. Moreover, there are doubts as to whether enforcement discretion is workable for mifepristone. While one administration may decline to enforce an order, the next may begin enforcement immediately on taking office. We need enduring solutions that respect, rather than flout, the regulatory process.
To reduce the uncertainty that these courts have created, Congress could explicitly give the FDA the final say in approving abortion drugs—or drugs more generally. This change would formally restrict courts’ ability to second-guess the FDA’s scientific decisions. With leadership in Congress split between the parties, social mobilization may be needed to drive the passage of such legislation.
Importantly, the mifepristone decisions come at a time in which pharmaceutical companies and other FDA-regulated entities have engaged in a decades-long campaign to disempower the FDA. Although they enjoy the legitimacy and market monopolies that flow from the gold stamp of FDA approval, they have sought to limit FDA funding while bringing an array of court challenges to FDA’s public health efforts. Pharmaceutical companies have donated lavishly to conservative politicians, who in turn have installed antiregulatory, antiabortion judges onto US courts. [..] Regulated industry has perhaps created its own monster by failing to empower the FDA, thereby fueling the very antiscience trends it now decries.
Conclusions
The uncertainty generated by these court decisions for the FDA, pharmaceutical regulation and development, and the US health care system suggests that courts are ill-equipped to conduct measured reviews of agency expert decisions. Significant reform is needed to protect the FDA’s scientific process and the very foundations of evidence-based medicine.”
Full article, DG Aaron, TR Brown and MS Sinha, JAMA 2023.4.26