Last year, on September 28, 2000, after almost two decades of political, ethical, and legal controversy, the U.S. Food and Drug Administration (FDA) finally approved the oral antiprogestin mifepristone--the so-called French abortion pill--for sale in the United States. In part one of this three-part series, we'll review some facts about abortion in the U.S. and the tortuous path of mifepristone, from discovery to U.S. market.

Where's the need?
Do women in the U.S. need another form of abortion? Moral and ethical arguments aside, these facts remain: 

• It's estimated 43% of women in the U.S. will have at least one abortion by the time they are 45 years old.
• Almost one half (49%) of the 5.4 million pregnancies that occur in the U.S. each year are unintended; and 54% of those unintended pregnancies (roughly 1.4 million) end in abortion.
• Abortion is the most frequently performed surgical procedure in this country and the patient's risk of death from surgical abortion is miniscule miniscule, about 0.3 per 100,000. The risk of major complications is less than 1%. By these measures, legally induced abortion is in fact safer than continuing a pregnancy to term. 
• Fifty-four percent of abortions are performed before 9 weeks (63 days), i.e., inside the window of opportunity for the non-surgical type of abortion performed with mifepristone, known as medical abortion.
• Between 1992 and 1996 (the most recent period for which reliable statistics are available), the U.S. abortion rate for women aged 15 to 45 years declined, from 26 to 23 per 1,000 women.  
• From 1992 to 1996, the number of abortion providers in this country declined by 14%. Today 86% of all U.S. counties have no abortion provider, and 32% of U.S women live in counties with no provider.

  Mifepristone has the potential to increase women's access to abortion by increasing the number of providers. In a 1998 Kaiser Family Foundation survey of obstetricians and gynecologists (OB-GYNs), 50% said they were likely to offer mifepristone if and when it were approved. Nearly half of OB-GYNs who did not perform surgical abortions said they would provide medical abortions.

  Medical abortions can be carried out in a doctor's' office, as opposed to established abortion clinics, whose patrons and providers may be subject to harassment and/or physical endangerment. Other arguments for medical abortion turn on the ideas of greater privacy, greater freedom of choice, and greater sense of personal control for the woman who has decided to end an early pregnancy.

  Mifepristone: a timeline 

The following timeline highlights the major events leading up to the approval of mifepristone for sale in the U.S.: 

1980 -- Mifepristone first synthesized by the French pharmaceutical firm Roussel Uclaf. 

1982 -- Roussel Uclaf reports the first successful trial of mifepristone as a component of medical abortion. 

1983 -- Population Council obtains FDA approval for the first U.S. studies. 

1985 -- National Institutes of Health support research on other potential uses for mifepristone. 

1988 -- Mifepristone-prostaglandin combination approved for medical abortion in France, but after months of protests by antiabortion groups, Roussel Uclaf announces it will suspend the sale of mifepristone. The French Minister of Health responds by ordering the drug back on the market, declaring it "the moral property of women." 

1989 -- The Bush administration bans importation of mifepristone to the U.S. for personal use. 

1991 -- Mifepristone approved in Sweden. 

1992 -- Mifepristone approved in the U.K. 

1993 -- January: President Clinton directs the Department of Health and Human Services to "promote the testing, licensing, and manufacturing in the U.S. of mifepristone and other antiprogestins. April: Roussel Uclaf agrees to license mifepristone to the Population Council to conduct clinical trials and apply for FDA approval. September: Institute of Medicine report suggests mifepristone may be effective for a number of diseases and conditions, including endometriosis, uterine fibroids, emergency contraception, breast cancer, and at least one form of brain cancer. 

1994 -- May: Roussel Uclaf announces that instead of licensing mifepristone, it will donate all U.S. rights for all identified medical uses of the drug to the Population Council. October: Clinical trials of mifepristone for medical abortion begin under the sponsorship of the Council. 

1995 -- U.S. clinical trials, enrolling a total of 2,121 women at 17 sites, end. 

1996 -- March: The Population Council submits an application for FDA approval of mifepristone. September: FDA issues a letter saying mifepristone is "approvable," but also requests additional information related to labeling and manufacture. 

1997 -- Manufacturer who had agreed to produce mifepristone for the U.S. market backs out. 

1998 -- U.S. Representative Tom Coburn (R-OK) attempts to block approval of mifepristone with an amendment to a spending bill that would prohibit FDA from spending any money to test, develop, or approve any drug for medical abortion. The measure was approved by the House, but was dropped from the final spending bill. (Coburn reintroduced the amendment in 1999; it passed the House, but got no further. A similar amendment was re-introduced in 2000 but was rejected by the House.) 

1999 -- Mifepristone approved in Austria, Belgium, Denmark, Finland, Germany, Greece, Israel, Luxembourg, the Netherlands, Spain, and Switzerland. (In Europe, more than 620,000 women have used a mifepristone-prostaglandin combination for medical abortion.) The Population Council and a new manufacturer, Danco Laboratories, submit labeling and manufacturing information requested by FDA in 1996. 

2000 -- Mifepristone approved in Norway, Russia, and Ukraine. September: FDA approves mifepristone for marketing in the U.S. 

In part two of this series we will look at the basic pharmacology of mifepristone and review its performance in the major clinical trials.