Decisions made by the Food and Drug Administration more than 20 years ago have come under heightened scrutiny thanks to a lawsuit calling for increased restrictions around the pregnancy-terminating drug mifepristone. The Alliance of Hippocratic Medicine, a recently formed umbrella organization composed of several anti-abortion groups, has argued the protocols first adopted to safeguard mifepristone are indicative of the drug’s danger. Yet these measures, according to those involved in the original FDA decision along with regulatory scholars, were originally put in place in an effort to be especially cautious, given the political controversy around the pill.
It was a “risky policy,” said Holly Fernandez Lynch, professor of medical ethics and law at University of Pennsylvania, who signed an amicus brief of food and drug law scholars submitted to the Supreme Court regarding the mifepristone case. Those initial protocols inadvertently implied heightened risk around mifepristone, she added: “That’s being leveraged by the Alliance of Hippocratic Medicine — in that way it seems to have backfired.”
Those tasked with reviewing the FDA application for approval of mifepristone were sensitive to the potential controversy around any abortion medication. Michael Greene, professor of obstetrics, gynecology, and reproductive biology at Harvard Medical School and chair of the reproductive drugs committee that advised the FDA on mifepristone approval in 2000, said members of the advisory committee were escorted to and from the first meeting venue under security, and the discussion took place in a windowless cinderblock room for fear of attack.
“Of course, you don’t live in a black box, you know that’s a controversial product,” said Jane Henney, commissioner of the FDA at the time mifepristone was approved. “What you’re asked to do is look at the evidence presented to you and make a decision.”
Throughout the lawsuit, the Alliance of Hippocratic Medicine has focused on Subpart H — the program through which the FDA approved mifepristone — as questionable, highlighting its use as an “accelerated approval” pathway. But although Subpart H could be used for accelerated approval, it was also a mechanism for installing additional safety measures at a time when the FDA had little other recourse. Mifepristone was approved in 2000, and, until the Risk Evaluation and Mitigation Strategy (REMS) program was introduced in 2007, the FDA didn’t have standard means of setting restrictions post approval, said Greer Donley, professor of law at the University of Pittsburgh School of Law, who was lead amici on an amicus brief of food and drug law scholars submitted to the Supreme Court regarding the mifepristone case.
And so Subpart H, said Greene, was used to make the mifepristone approval “more rigid” than for other drugs, rather than less. The entire evaluation and approval process was extremely diligent, he said, taking four years in total. In comparison, there were 27 new molecular drugs approved in 2000, including mifepristone, and the median approval process took 15.6 months.
When mifepristone was originally approved, it was under several conditions, including that three in-person visits to a physician were required, ensuring the patient took the drug under supervision and then returned to evaluate the effects. It was also only approved for use up until seven weeks of pregnancy.
“In retrospect, it was a bit more paternalistic than we needed to be, but that’s in retrospect,” said Henney. Population Council, the organization that originally applied for approval of mifepristone, cited evidence that mifepristone had been widely and safely used without such restrictions in Europe, but the FDA opted to be especially cautious. “It was always with the anticipation that, over time, the company could come back and either say we found these additional problems or evidence for a lessened safety profile,” said Henney.
The FDA ultimately changed many of the protocols, in both 2016 and 2021, including allowing mifepristone to be dispensed up until 10 weeks of pregnancy, and dispensed by mail for patients to take at home, rather than under medical supervision. In March, the Supreme Court will hear arguments that these revisions should be reversed, so mifepristone can once again only be dispensed under pre-2016 guidance.
Throughout the legal battle, those original protocols have been highlighted as signs that mifepristone is too risky for other means of rollout. An amicus brief submitted to the Supreme Court by the Alliance of Hippocratic Medicine reads: “Subpart H was the only path to mifepristone’s approval because the drug ‘could not be administered safely without imposing certain use restrictions.’”
And the original ruling last April by Texas Judge Matthew J. Kacsmaryk critiqued the defense that mifepristone has been on the market for more than 20 years. “This argument ignores that many restrictions and safeguards — which no longer exist — were in place for most of that time,” he wrote. “FDA’s 2016 and 2021 Changes thus significantly departed from the agency’s original approval of the abortion regimen. FDA repeatedly altered its original decision by removing safeguards and changing the regulatory scheme for chemical abortion drugs.”
In the intervening years, Beverly Winikoff, who was director of reproductive health at Population Council, said she studied the drug to the point of absurdity, including research on whether it was safe to take the pill at home, and on reducing the degree of clinical supervision, such as replacing a follow-up doctor’s visit with a phone call. “No one wants another doctor’s appointment to say, ‘Everything’s fine,’” she said. “The FDA wanted everything to be super cautious, politically and scientifically, everything had to be in a formal study. It’s probably one of the most studied pills to ever reach the market.”
People don’t go to hospital when they have a miscarriage, and so it seemed obvious to her that they wouldn’t need to simply because the termination was induced by a pill. But she studied it to create formal evidence. “This is the game we’ll play. We’ll do science, we’ll do tests,” she said. “We have to prove hot water is hotter than cold water.”
The evidence is not enough for the Alliance of Hippocratic Medicine, which argues that the shifts in regulation have all been tested individually, rather than collectively. “In 2016, FDA stripped away many safeguards, failing to explain why it was proper to eliminate them all without a study showing their cumulative safety,” reads an amicus brief submitted by the organization, which did not respond to requests for comment. It also argues the agency failed to properly collect data on non-fatal adverse events, and so could have missed risks.
Ultimately, Henney said the FDA made all decisions according to the usual safety and efficacy standards, and the notion that a court could overturn the decision puts “the whole industry” at risk. There were plenty of lawyers available to advise on appropriate parameters, she said, but legal knowledge isn’t sufficient. “You need panels of experts, not one person. Or even a panel all with law degrees making clinical judgements,” she said.
More than 20 years ago, Greene said the process was especially cautious in light of the climate. “It was a very hot political football,” he said. The specific arguments around mifepristone have shifted in the decades since, but its political controversy never faded.
This story is part of ongoing coverage of reproductive health care supported by a grant from the Commonwealth Fund.