Time-line: FDA 'exhaustively analyzed a massive body of evidence’ on mifepristone safety prior to regulation changes

PART IV: Mifepristone lawsuit

🔆 This is Part IV of an ongoing multi-part series examining the mifepristone lawsuit to be heard by the Supreme Court of the United States. Read the rest of the series here.

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✳️ A note from the author:

In 2017, I lost my nephew to a reaction to a synthetic antibiotic (Cipro). I do not pretend that the FDA is infallible. *However, the FDA’s regulations of mifepristone are unquestionably solid and supported by the best & most reputable evidence and data available. In sum, I wholeheartedly trust the FDA on the matter of mifepristone.

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The anti-abortion plaintiffs who sued the U.S. Food and Drug Administration (FDA) to eliminate/severely restrict access to mifepristone - one of the drugs used in a two-drug regimen for medication abortion - falsely insist that mifepristone is a dangerous drug, and that, “[b]y eliminating necessary safeguards for pregnant girls and women who undergo the dangerous mifepristone abortion drug regimen, the U.S. Food and Drug Administration failed to abide by its legal obligations to protect the health, safety, and welfare of girls and women.” [1] The FDA’s approval and subsequent regulation changes, the plaintiff’s say, were arbitrary and capricious. A review of the FDA’s actions, as well as the data the agency used to make its decisions, however, debunk the plaintiffs’ claims. The record clearly shows “the FDA exhaustively analyzed a massive body of evidence” on the safety of mifepristone, “establishing that [the agency’s regulation] changes were safe.” [17]

The following is a detailed time-line, from mifepristone's creation to the present day, including actions taken by the FDA. In-text links within the time-line below are included to provide you with detailed information regarding the particular actions by the FDA that the anti-abortion plaintiffs seek to void, as well as the research the FDA applied in regulating mifepristone.

🟩 1980

RU-486 (mifepristone) was developed in France for the termination of pregnancy. Endocrinologist Étienne-Émile Baulieu explained that he wanted to “give women a choice that, through a pill, respects their privacy and physical integrity and allows them to totally avoid the aggression of surgery.” [2] Thus, Baulieu “proposed creating a molecule that would block the hormone progesterone, without which the uterus can’t retain a fertilized egg.” [3]

🟩 1988 

France approved mifepristone for pregnancy termination in 1988. “The decision was met with protests, boycott threats and violence from antiabortion extremists, who at one point set fire to a Paris movie theater.” [4] 

🟩 1994 

Clinical trials of mifepristone began in the US in 1994. [5]

🟩 2000 

Twelve years after mifepristone was first approved in France, the U.S. Food and Drug Administration (FDA) approved the drug in 2000, as Mifeprex, under federal regulation Subpart H. [6] Subpart H “a set of regulations implemented to expedite the approval of “new drug products that have been studied for their safety and effectiveness in treating serious or life-threatening illnesses,” like those to used treat HIV. The FDA approval process for mifepristone, however, was not expedited, as it was approved more than four years after the original application was filed.” [7] Rather, Subpart H was “used to restrict the dispensing to prescribers who agreed to dispense it in certain health care settings, by or under the supervision of a qualified physician.” [8] Mifepristone was approved, in a single dose of 600 mg, for use up to 49 days of pregnancy (7 weeks), dating from the first day of the patient’s last menstrual period. [9]

🟩 2007

Congress passed the FDA Amendments Act of 2007 (FDAAA), which “added a new section (Section 505-1) to the Federal Food, Drug, and Cosmetic Act (FFDCA) authorizing the FDA to require a Risk Evaluation and Mitigation Strategy (REMS) for a drug if the FDA deems it is necessary to ensure that the drug’s benefits outweigh its risks; it also revises the terminology for eligibility for the drug from treating a ‘serious or life threatening illness’ to permitting the FDA to require a REMS for drugs intended to be used for a ‘disease or “condition.’” [10] Additionally, in Section 909 of the FDAAA, Congress “deemed all drugs with existing restricted-distribution programs,” which included mifepristone, “to require a REMS. Congress required sponsors of such ‘deemed’ drugs to submit a proposed REMS to the FDA — which mifepristone’s sponsor did.” [11] 

🟩 2011 

In 2011, the FDA approved the initial REMS for mifepristone. [12] It required “in-person dispensing by or under supervision of a certified physician.” [13] It also required misoprostol, the second drug used in the two-drug abortion regimen, to be dispensed at the provider’s office or clinic, as well as a follow-up visit 14 days later. [14] 

🟩 2016 

After 15 years of collecting and analyzing data on the safety and efficacy of mifepristone, the “FDA updated and approved a new evidence-based regimen and drug label.” [15] The dosage of mifepristone was decreased from 600 to 200 mg, and the approved usage window was increased from 49 to 70 days (10 weeks) of pregnancy, dating from the first day of the patient’s last menstrual period. (*It Is interesting, to say the least, that the anti-abortion plaintiffs claim mifepristone is a dangerous drug, yet want patients to return to pre-2016 regulations that would require patients to take triple the current dose.) Also in 2016, “the provider certification requirement was broadened from being limited to physicians only to include other advanced practice clinicians (e.g., nurse practitioners and physician assistants) who can meet the REMS requirements.” [16] Lastly, “the FDA decided to require that, going forward, prescribers report only fatal events. The approving official reasoned: ‘After 15 years of reporting serious adverse events, the safety profile of Mifeprex is essentially unchanged. Therefore, I agree that reporting of labeled serious adverse events other than deaths can be collected in the periodic safety update reports and annual reports to the Agency.’” [17] (See also Danco, pp. 40-41; U.S., pp. 34-43.)

🟩 2019

A generic version of Mifeprex (mifepristone) was approved in 2019. [18] At that time, the FDA issued a unified REMS for both the brand name and generic drug. [19] 

🟩 2021 

Due to the ongoing COVID pandemic, the FDA “decided that it would exercise its discretion not to enforce the in person requirement.” [20] Later that year, after an exhaustive review of data, the FDA concluded “that in-person dispensing ‘is no longer necessary to assure the safe use of mifepristone.’” [21] “The FDA then walked through that information in exhaustive detail. First, the FDA analyzed events in the FAERS. Second, the FDA noted that it required the applicants to provide a summary and analysis of certain additional adverse events, and analyzed the summary that was provided. Based on that analysis, the FDA concluded that ‘there does not appear to be a difference in adverse events when in-person dispensing was and was not enforced and that mifepristone may be safely used without in-person dispensing.’ However, the FDA did not stop there. It then conducted a detailed, lengthy analysis study of the published literature on this topic… [T]he FDA analyzed a total of 12 published studies: Aiken, Anger, Chong, Endler, Grossman, Hyland, Kerestes, Raymond, Reynolds-Wright, Rocca, Upadhyay, and Wiebe. After an exhaustive analysis of the findings and limitations of these studies, the FDA concluded that in-person dispensing is unnecessary.” [22] (See also U.S., pp. 34-43.)

🟩 2023 

The FDA updated the REMS in 2023, “approving the protocol for certification of pharmacies, allowing those that have been certified by the manufacturers to dispense mifepristone directly to patients (eliminating the requirement that it can only be dispensed directly to the patient by the certified provider).” [23]

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Citations:

[1] Biden admin defends FDA’s reckless betrayal of women, girls. ADFMedia.org. (2024, January 24). https://adfmedia.org/case/us-food-and-drug-administration-v-alliance-hippocratic-medicine#:~:text=Drug%20Administration%20v.-,Alliance%20for%20Hippocratic%20Medicine,welfare%20of%20girls%20and%20women 

[2] Hawkins, D. (2023, April 7). The controversial history of the abortion pill mifepristone - the ... Washington Post. https://www.washingtonpost.com/politics/2023/03/15/mifepristone-fda-approval-history/ 

[3] Ibid. 2

[4] Ibid. 2

[5] Ibid. 2

[6] Salganicoff, A., Sobel, L., & Felix, M. (2023, March 14). Legal challenges to the FDA approval of medication abortion pills. KFF. https://www.kff.org/womens-health-policy/issue-brief/legal-challenges-to-the-fda-approval-of-medication-abortion-pills/ 

[7] Ibid. 6

[8] Ibid. 6

[9] Ibid. 6

[10] Ibid. 6

[11] Ibid. 6

[12] Ibid. 6

[13] Ibid. 6

[14] Ibid. 6

[15] Ibid. 6

[16] Ibid. 6

[17] Unikowsky, A. (2023, April 16). Mifepristone and the rule of law, part IV. https://adamunikowsky.substack.com/p/mifepristone-and-the-rule-of-law-72e 

[18] Hawkins, D. (2023, April 7). The controversial history of the abortion pill mifepristone - the ... Washington Post. https://www.washingtonpost.com/politics/2023/03/15/mifepristone-fda-approval-history/ 

[19] Salganicoff, A., Sobel, L., & Felix, M. (2023, March 14). Legal challenges to the FDA approval of medication abortion pills. KFF. https://www.kff.org/womens-health-policy/issue-brief/legal-challenges-to-the-fda-approval-of-medication-abortion-pills/ 

[20] Unikowsky, A. (2023, April 16). Mifepristone and the rule of law, part IV. https://adamunikowsky.substack.com/p/mifepristone-and-the-rule-of-law-72e 

[21] Ibid. 20

[22] Ibid. 20

[23] Salganicoff, A., Sobel, L., & Felix, M. (2023, March 14). Legal challenges to the FDA approval of medication abortion pills. KFF. https://www.kff.org/womens-health-policy/issue-brief/legal-challenges-to-the-fda-approval-of-medication-abortion-pills/