Abortion decision blow to science-based regulation, legal experts, biopharma leaders say
Concerns raised about Texas ruling’s implications for drug regulation
Texas District Judge Matthew Kacsmaryk issued a ruling Friday that aims to bar access to mifepristone, but his opinion could have effects that go far beyond the abortion drug, according to biopharma executives and some attorneys who specialize in FDA law. Because it strikes at the fundamental principles underpinning FDA’s regulation of medical products, it could undermine the agency and harm patients and drug developers that rely on science-based regulation of drugs, former senior attorneys at the agency told BioCentury.
Lawyers at FDA were expecting a negative decision, but they were surprised by Kacsmaryk’s lack of deference to the agency’s scientific and medical expertise, individuals who have spoken with staff in FDA’s Office of Chief Counsel told BioCentury.
If it is upheld, the ruling has the potential to inject ideology and politics into drug regulation, and to create opportunities for drug companies to use the courts as weapons to cripple competitors, according to Joshua Sharfstein, vice dean for public health practice and community engagement at the Johns Hopkins Bloomberg School of Health. “Ideological polarization, reflected in the Texas decision’s embrace of extreme language about abortion and health, poses new risks to the FDA’s integrity,” Sharfstein, a former FDA principal deputy commissioner, wrote in a commentary published in The New York Times.
More than 400 biopharma leaders have signed a letter condemning the decision, warning of negative consequences for the industry and patients, and calling for its reversal. “The decision,” the letter states, “ignores decades of scientific evidence and legal precedent.” It asserts that Kacsmaryk has “set a precedent for diminishing FDA’s authority over drug approvals, and in so doing, creates uncertainty for the entire biopharma industry.”
“This is about abortion and nothing else.”
While biopharma industry leaders and a number of former FDA attorneys contend that Kacsmaryk’s ruling could have broad implications for drug regulation, some attorneys with deep experience at FDA and in the biopharma industry disagree.
Daniel Troy, a former FDA chief counsel, believes its impact is far more limited. It is a “one-off” ruling that “is not a precedent for anything other than mifepristone,” Troy told BioCentury.
Troy said that FDA’s treatment of abortion drugs has been unique, so the issues raised in the Texas case are not applicable to other kinds of medical products. In addition, the argument at the core of the case about whether the Comstock Act makes distribution of mifepristone illegal, is specific to abortion drugs, he said. Kacsmaryk ruled that the Comstock Act of 1873, which prohibited the mailing of drugs that can be used in an abortion, applies to mifepristone, while the Department of Justice has stated that the law doesn’t apply to drugs like mifepristone that are used legally.
“This is about abortion and nothing else,” Troy, who served as general counsel at GSK plc (LSE:GSK; NYSE:GSK) in 2008-18, said. Regardless of the ultimate outcome, the case is highly unlikely to have a broad impact on FDA’s ability to regulate drugs and should not impact companies that are not marketing or developing abortion drugs.
FDA, the Biden administration and drug manufacturers have a variety of options for side-stepping Kacsmaryk’s ruling to ensure continued access to abortion drugs, including by encouraging a sponsor to resubmit an NDA. They also could seek to overturn the ruling by convincing a higher court that the physicians who brought the case lack standing to bring the suit, or by arguing that a district court lacks authority to issue a nationwide injunction, attorneys told BioCentury.
The path to repairing the damage to the basic tenets of drug regulation inflicted by the sole judge in the Amarillo division of the U.S. District Court for the Northern District of Texas is narrower, attorneys who believe his ruling could destabilize drug regulation, said.
Monday, the Justice Department asked the U.S. Fifth Circuit Court of Appeals to block Kacsmaryk’s ruling to give the government time to appeal. The appeal stated that the Biden administration is prepared to take the case to the Supreme Court. Danco Laboratories, which distributes mifepristone, made a similar request.
The full impact of Kacsmaryk’s ruling will not become clear until the Fifth Circuit rules on the Biden administration’s appeal, or possibly until the Supreme Court rules on the case.
“It is hard to know the broader ramifications largely because we don’t know what the Fifth Circuit or the Justice Department will do and how FDA will interpret the decision,” Eva Temkin, a partner at King & Spalding, told BioCentury. Prior to joining the firm, she served in policy and legal positions at FDA, including as associate chief counsel from 2013-17.
Unless specific sections of the Texas ruling are repudiated by higher courts, individuals and organizations with religious or commercial motives could be empowered to challenge regulatory decisions and judges could have the power to substitute their views on safety and efficacy for FDA’s expertise, seven lawyers who served in senior roles at FDA in Republican and Democratic administrations told BioCentury.
‘Arbitrary and capricious’
By echoing and amplifying the language of groups that oppose abortion for ideological and philosophical reasons, “Kacsmaryk said the quiet part out loud: religion and policy issues drove the decision,” a former FDA attorney told BioCentury. The attorney did not want to be identified because he is advising parties involved in the litigation.
Kacsmaryk peppered his opinion with words and expressions that reflect the views of the religious anti-abortion movement and that antagonize abortion rights advocates, but for FDA lawyers the most vexing expression he used was “arbitrary and capricious.”
“Judge Kacsmaryk asserted that FDA’s decision to modify adverse event reporting requirements for mifepristone was ‘arbitrary and capricious,’ and therefore violates the Administrative Procedures Act which is the foundation for judicial oversight of administrative decisions,” a former senior FDA attorney told BioCentury.
“The judge substituted his personal analysis of cherry-picked safety data to overrule the FDA’s scientific analysis.”
The attorney, who did not want to be identified, said that this contention “opens every FDA drug decision to oversight and second-guessing by every court in the land.”
He added that while this approach has been proposed previously, experienced FDA lawyers “have scoffed because we presumed no court would ever invoke the APA in this manner, as it would require the court to elevate its judgment on scientific matters above FDA’s scientific expertise.”
This is precisely what Kacsmaryk did, Temkin noted. “The judge substituted his personal analysis of cherry-picked safety data to overrule the FDA’s scientific analysis.”
In addition to ignoring the judiciary’s tradition of deference to FDA’s scientific expertise, Kacsmaryk has taken on a drug that has been subject to an extraordinary amount of scrutiny since it was first approved 23 yeas ago. Decades of data demonstrate that it is “safer than Tylenol, nearly all antibiotics and insulin,” according to the letter from biopharma industry leaders.
“In determining whether the agency has been ‘arbitrary and capricious,’ the standard of review, courts have long respected the judgments of the FDA’s experts, especially those that are in line with expert advice and the consensus of leading medical organizations,” Sharfstein noted in The Times. He added that courts have intervened to overturn FDA decisions in rare instances “when inappropriate political interference has disrupted the agency’s normal processes.”
At odds with precedent
The Texas decision is at odds both with FDA’s interpretation of the Food, Drug, and Cosmetic Act (FDCA), and with the ways drugs are developed and deployed.
For example, Kacsmaryk stated that FDA’s approval of mifepristone was “arbitrary and capricious” because the label approved by the agency did not precisely match the parameters of the clinical studies that supported the approval.
Studies, however, are not intended to perfectly mimic the clinical settings in which a drug will be used. To ensure the safety of participants, and to learn as much as possible about a drug’s characteristics, data are often collected, including through invasive tests, that would not be conducted in routine medical practice. And inclusion criteria are set to minimize confounding data, for example by precluding participation by individuals with specific medical conditions or those who are being treated with certain medicines.
If Kacsmaryk’s contention is not repudiated by a higher court, the lack of concordance between parameters of clinical trials and FDA-approved labels could be cited in litigation against almost any drug.
“This decision has ramifications that extend well beyond this case, setting a dangerous precedent for undermining the FDA.”
“I can’t think of a single drug label that exactly matches the conditions of use in the clinical studies” that supported approval, Temkin told BioCentury.
The Department of Justice made this argument in its request for the Fifth Circuit to delay implementation of the order overturning the approval of mifepristone. “The court criticized FDA for relying on studies with somewhat different protocols than the conditions of use approved by the agency,” the department stated, “but an obligation to approve drugs only with conditions of use identical to the study protocols in supporting clinical trials finds no support in the FDCA.”
Temkin cited two other ways the Texas ruling conflicts with the FDCA. “The opinion suggests that head-to-head studies are necessary to demonstrate therapeutic benefit, but that is not what the law requires.”
The opinion also asserts that for FDA to approve a supplemental indication, “the sponsor would have to do studies that perfectly compare pre- and post-change conditions. That’s not what the FDCA requires,” Temkin said.
If it is not completely reversed, the Texas ruling could add an element of uncertainty to every drug approval, former FDA leaders, biopharma CEOs, and attorneys specializing in FDA law said.
Rachel King, interim CEO of BIO, said the ruling is an “assault on science and the FDA’s long-standing role as the authority to make decisions on the safety and efficacy of medicines.”
She added: “This decision has ramifications that extend well beyond this case, setting a dangerous precedent for undermining the FDA and creating regulatory uncertainty that will impede the development of important new treatments and therapies.”
By giving judges power to second-guess approval decisions, the Texas decision runs counter to decades of bipartisan efforts to bolster FDA’s authority and independence, Mark McClellan, director of the Duke-Margolis Center for Health Policy, told BioCentury.
Across the political spectrum “there’s support for FDA’s authority, even though people differ on what states should do with respect to access to abortion drugs,” McClellan, who served as FDA commissioner in the George W. Bush administration, said.
He expressed concern that if the ruling stands, “you could see extensions of the decision in areas like contraceptive drugs, or even for drugs for cancer or heart disease that have often been approved with some kind of accelerated pathway and with less than ideal evidence.” McClellan serves on the boards of Johnson & Johnson (NYSE:JNJ), Cigna Corp. (NYSE:CI) and other healthcare companies.
FDA’s citizen petition docket is filled with examples of the disputes that could end up in the courts if the mifepristone case is not reversed.
Groups opposed to vaccination could try to have vaccine approvals invalidated. Scientologists, who have filed citizen petitions and lawsuits trying to ban approvals and use of psychiatric drugs, could use the strategy. And drug companies would also be tempted to ask courts to prevent FDA from approving or force the removal of competing products.