Order Code RL30866
CRS Report for Congress
Received through the CRS Web
Abortion: Termination of Early Pregnancy
with RU-486 (Mifepristone)
February 23, 2001
Judith A. Johnson
Specialist in Life Sciences
Domestic Social Policy Division
Congressional Research Service ˜ The Library of Congress
Abortion: Termination of Early Pregnancy
with RU-486 (Mifepristone)
On September 28, 2000, the Food and Drug Administration (FDA) approved the
drug mifepristone, also known as RU-486, for the termination of early pregnancy. In
1988, France became the first country to approve the drug. China and the United
Kingdom approved RU-486 in 1991, Sweden in 1992, and the following countries in
1999: Russia, Austria, Belgium, Denmark, Finland, Germany, Greece, Israel, the
Netherlands, Spain, and Switzerland. Since 1988, more than 620,000 European
women have used the drug to terminate pregnancy. Ten million abortions are
performed annually in China, and about half are carried out with RU-486.
Because RU-486 is an abortion agent, the process of moving it out of the lab and
into mainstream medicine has been fraught with controversy. Since its discovery, the
pro-life movement has been adamantly against the use of this drug for abortion. In
the United States, the drug’s long journey to FDA approval began in 1983, when the
agency agreed to clinical trials of RU-486 sponsored by the Population Council.
After many difficulties in finding a manufacturer and distributor for the drug, final
FDA approval was granted and the first U.S. orders for RU-486 were shipped on
November 20, 2000.
The drug will not be available to women by prescription in pharmacies; instead
women will receive it directly in a physician’s office. Each woman must be given a
Medication Guide which explains how to take the drug, who should avoid taking it
and what complications may occur. A patient agreement similar to an informed
consent document in a clinical trial must be signed. In contrast with surgical abortion,
which is completed in minutes, drug induced abortion is more time consuming and
uncomfortable. Treatment with RU-486 requires that the patient make three office
visits over a 2-week period. Short-term risks associated with the drug are limited:
about 1% of women require surgery to stop heavy bleeding and only 0.1% of women
in clinical trials required a blood transfusion. To date, there is little evidence of any
long term health effects due to use of RU-486.
Nevertheless, legislation introduced in the 107th Congress adds requirements for
doctors dispensing RU-486 which, the sponsors state, would provide additional
protection for women taking the drug. The bill stipulates that physicians prescribing
the drug must meet the following requirements: (1) qualified to handle complications
resulting from an incomplete abortion or tubal pregnancy; (2) trained to perform
surgical abortions and met all applicable legal requirements to perform such abortions;
(3) certified for ultrasound dating of pregnancy and detecting tubal pregnancy; (4)
completed a program regarding the prescribing of such drug that uses a curriculum
approved by the Secretary of the Department of Health and Human Services (HHS);
and (5) have admitting privileges at a hospital located 1 hour or less away from the
physician’s medical office. In the opinion of pro-choice groups, this legislation
represents an unprecedented intrusion into the jurisdiction of FDA and the practice
of medicine. They point out that FDA reviewed all the scientific data reflecting the
experiences of thousands of women and the agency rejected most of these
requirements as medically unnecessary.
Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
FDA Approval of RU-486 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Potential Impact of RU-486 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
Other Methods of Medical Abortion . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Other Uses of RU-486 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Congressional Actions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Abortion: Termination of Early Pregnancy
with RU-486 (Mifepristone)
The drug mifepristone, commonly known as RU-486, is a medical or druginduced alternative to surgical abortion for use in early pregnancy. It was discovered
in 1980 by researchers at Roussel Uclaf, a pharmaceutical company jointly owned by
the French government and the German company, Hoechst AG. RU-486 belongs to
a class of drugs known as antiprogestins. These drugs can prevent or interrupt a
pregnancy by blocking the action of progesterone, a naturally occurring hormone.
Progesterone allows for the implantation of the embryo and aids in maintaining
pregnancy by inhibiting uterine contractions. In early studies, the efficacy of RU-486
as an abortifacient ranged from 60% to 80% when used during the first 7 weeks of
pregnancy.1 Such a rate is too low to be clinically acceptable. However, interest in
the drug was greatly increased by a 1985 report which found that efficacy is raised to
nearly 100% if administration of RU-486 is followed a few days later by a second type
of drug called a prostaglandin, which stimulates uterine contractions.
On September 23, 1988, France became the first country to license RU-486 in
combination with a prostaglandin for early abortion. Approval in China and the
United Kingdom occurred in 1991, in Sweden in 1992, and in the following countries
from 1999: Austria, Belgium, Denmark, Finland, Georgia, Germany, Greece, Israel,
Luxembourg, the Netherlands, Norway, Russia, Spain, Switzerland, Taiwan, Tunisia,
and Ukraine.2 According to FDA, since 1988, more than 620,000 European women
have used the drug combination to terminate pregnancy. About 5 million abortions
annually are carried out in China with RU-486.3 On September 28, 2000, FDA
announced the approval of RU-486 and the prostaglandin misoprostal for use in the
United States as an abortifacient in pregnancies of 49 days or less.
The process of moving RU-486 out of the lab and onto the market has been
fraught with controversy. In France, Roussel Uclaf suspended distribution of RU-486
on October 26, 1988, in response to threats of boycott and violence from groups
opposed to abortion. However, following protests from the public and the medical
The start of pregnancy is marked from the first day of the last menstrual period (LMP).
However, because there are about 2 weeks between when a menstrual period starts and
ovulation occurs, 7 weeks pregnant, or 49 days LMP, actually means a 35 day-old embryo.
Christin-Maitre, S., P. Bouchard, and I. M. Spitz. Medical termination of pregnancy. New
England Journal of Medicine, v. 342, Mar. 30, 2000. p. 946-956; and, personal
communication with Sandra Waldman of the Population Council, Feb. 9, 2001.
Pan, P.P. Chinese to make RU-486 for U.S. Washington Post, Oct. 12, 2000. p. A1, A18.
community, 2 days later on October 28, 1988, the French Minister of Health Claude
Evin ordered RU-486 back on the market, stating that “from the moment
governmental approval for the drug was granted, RU-486 became the moral property
of women, not just the property of the drug company.”4 At that time, the French
government owned 36% of Roussel’s stock and therefore was able to exert some
influence over company decisions. Also, a 1968 French law gave the health minister
the authority to withdraw a company’s license to market a drug and award the license
to another firm if the company refused to make a drug available.
In the United States, the drug’s long journey to FDA approval began in 1983,
when the agency agreed to clinical trials of RU-486 conducted at the University of
Southern California (USC), under the auspices of the Population Council.5 More than
300 women received the drug from 1984 until February 1990, when USC researchers
exhausted their supply of the drug.6 USC was unable to obtain more because in 1989
Roussel had made a policy decision not to provide RU-486 for abortion research in
the United States. This decision resulted in the drug being used here only in very
limited research settings (that did not involve abortion) through arrangements with
The Roussel decision was influenced by and came shortly after the June 1989
FDA announcement during the former Bush Administration which placed RU-486 on
the import alert list. Import Alert 66-47 (Automatic Detention of Abortifacient
Drugs) prohibited the importation of RU-486 into the United States for personal use.7
The alert was imposed by FDA because of concerns over the drug's possible health
risks and use without physician supervision. In general, FDA has the power to
prevent the importation of unapproved drugs, and has exercised its authority in a
discretionary manner. In 1988 FDA relaxed its rules on importing unapproved drugs
for the personal use of those suffering from fatal illnesses like AIDS and cancer.
In July 1992, Leona Benten, a 29-year old pregnant woman, tried to challenge
the import ban by bringing into the United States enough RU-486 for her own use.
The drug was confiscated on July 1, 1992, by U.S. Customs at New York’s JFK
airport. Benten filed suit against the FDA and the U.S. Customs Bureau for their
enforcement of the import ban. U.S. District Court Judge Charles Sifton heard the
case and ruled in her favor on July 14, 1992, finding the FDA policy illegal. Judge
Klitsch, M. RU-486: The Science and the Politics. New York, Alan Guttmacher Institute,
The Population Council is an international, non-profit research organization established in
1952 by John D. Rockefeller, III to search for a better understanding of problems related to
population. The Council conducts research on three fronts: biomedical, social science, and
public health. Its mission is to improve the well-being and reproductive health of current and
future generations and to help achieve a humane, equitable, and sustainable balance between
people and resources. More information at: [http://www.popcouncil.org].
Stephens, T. RU-486 mired in abortion debate. Journal of NIH Research, v. 2, Sept. 1990.
Rovner, J. RU-486: tiny pill with big impact. Congressional Quarterly, Feb. 24, 1990. p.
Sifton concluded “the decision to ban the drug was based not from any bona fide
concern for the safety of users of the drug, but on political considerations having no
place in FDA decisions on health and safety.”8 The decision was stayed hours later
by the U.S. Court of Appeals for the Second Circuit. The U.S. Supreme Court
agreed to consider an appeal filed by Benten and her attorney, but ultimately the
confiscation was upheld by a 7-2 decision on July 17, 1992. The woman subsequently
had a surgical abortion.
On January 22, 1993, 2 days after taking office, President Clinton directed
Department of Health and Human Services (HHS) Secretary Donna Shalala to: (1)
rescind the personal use import ban, barring sufficient evidence to warrant it; and, (2)
“assess initiatives” for the promotion of testing, licensing, and manufacturing
RU-486.9 In response to the President’s directive, Secretary Shalala published in the
Federal Register actions to be taken regarding the status of RU-486.10 The Secretary
directed FDA to initiate an immediate and thorough review of the health and safety
implications of the potential import of RU-486 for personal use. The findings of the
review were to be reported to the Secretary. If there was not enough evidence to
limit RU-486 from qualifying as a drug that could be imported for personal use, the
import alert would be rescinded.11 The Secretary also directed FDA to assess
promptly initiatives to promote the testing, licensing and manufacturing of RU-486
or other antiprogestins in the United States, and report on options to the Assistant
Secretary for Health and the Secretary of HHS.
The change in the Administration’s policy on RU-486 generated an increased
commercial interest in the drug. According to Roussel, 10 American companies
contacted the French firm about manufacturing the drug in the United States.
Hurtado, P., and P. Moses. Pill’s new life: ok by judge but appeals court says no. Newsday,
July 15, 1992. p. 3.
Presidential Documents. Memorandum of Jan. 22, 1993. Importation of RU-486. Federal
Register, v. 58, no. 23, Feb. 5, 1993. p. 7459.
Department of Health and Human Services. Office of the Secretary. Federal Register, v.
58, no. 23, Feb. 5, 1993. p. 7468.
Import alert 66-47 was cancelled on Sept. 28, 2000, (the day RU-486 received final
approval from FDA) and the following paragraph was added to the end of Import Alert 66-41:
FDA has determined that unapproved versions of mifepristone manufactured
outside the U.S. are being promoted in this country for use to end pregnancy. Due
to the risks to the safety of the user in inadequately controlled settings,
mifepristone should be considered inappropriate for release under the Personal
Import Guidance. Districts encountering entries of mifepristone should determine
whether the importer of record for the article being entered is Danco Laboratories,
LLC, New York, New York (distributor of the U.S. approved product) or whether
the article is being entered under an IND that is in effect. In such circumstances
(when the article is being imported by the distributor of the U.S. approved product
or under an IND that is in effect), the article is outside the scope of this guidance.
FDA. Congressional Liaison Office. Personal communication with Joy Stevens. Full text
of Import Alert 66-41 can be found at: [www.fda.gov/ora/fiars/ora_import_ia6641.html].
Although it would have preferred enlisting a large pharmaceutical company for U.S.
production, only smaller companies and nonprofit agencies came “forward for
consideration because of their relative immunity to boycotts on the part of abortion
opponents.”12 In April 1993 the Population Council and Roussel announced they had
reached a preliminary agreement whereby the company would license the rights for
the drug’s production to the Council which would conduct a U.S. clinical trial and
find a U.S. manufacturer.13 Roussel agreed to supply RU-486 for the clinical trials.
However, the Population Council put its efforts on hold in the fall of 1993 because
the two parties were unable to come to a final agreement and sign a contract.14
In September 1993, the Institute of Medicine (IOM) released its report, Clinical
Applications of Mifepristone RU-486 and Other Antiprogestins, funded by the Henry
J. Kaiser Family Foundation. Because the drug had been tested extensively in Europe,
the IOM panel recommended immediate submission of previous clinical trial data
directly to FDA, in lieu of US trials, to determine whether they met U.S. regulatory
requirements.15 The report also recommended aggressive pursuit of research on RU486 in the treatment of a variety of pregnancy-related conditions and other hormonelinked diseases, such as endometriosis, uterine fibroid tumors, breast cancer, and
certain types of brain tumors.16 However, a citizen petition filed by a pro-life group
and signed by several Members of Congress called on the FDA to “strictly review any
foreign data submitted for U.S. approval of RU-486.”17
Following discussions between HHS, the Population Council, and Roussel, on
May 16, 1994, the Clinton Administration announced that the company would donate
U.S. patent rights for RU-486 to the Population Council.18 The company agreed to
give up potential American profits from sales of the drug reportedly “because of its
stated reluctance to market RU-486 in the highly charged U.S. political climate
surrounding the issue of abortion.”19 At a congressional hearing, company
representative Lester Hyman stated that Roussel originally decided not to seek U.S.
approval of the drug because “then-President Bush spoke stridently against any
procedure that would result in early pregnancy termination. ... It was only when
RU-486 distribution plan, physician training would be key elements of U.S. phase III clinical
trial. Blue Sheet, Mar. 24, 1993. p. 6-7.
Schwartz, J. U.S. group to get rights to produce abortion pill. Washington Post, Apr. 21,
1993. p. A1, A5.
RU-486 U.S. status will be reviewed by Rep. Wyden’s House Regulations Subcommittee
May 16. Blue Sheet, Apr. 27, 1994. p. 9-10.
Schwartz, J. Science panel urges FDA to evaluate use of RU-486 abortion pill. Washington
Post, Sept. 9, 1993. p. A12.
Usdin, S. NAS backs aggressive research on controversial RU-486 drug. Pharmaceutical
Daily, v. 1, Sept. 8, 1993. p. 1, 4.
Conlan, M. Congressional logic. Drug Topics, Mar. 20, 1995. p. 74.
U.S. Congress. House. Committee on Small Business. RU-486, status report on the U.S.
commercialization project, transfer of antiprogestin technology to the United States. 103rd
Cong., 2nd Sess., May 16, 1994. 48pgs.
Ibid., p. A1.
President Clinton changed the governmental policy and specifically asked Roussel to
make the procedure available here, that [Roussel], out of respect for the President of
the United States, agreed to make every effort to comply with his request.”20
From October 1994 to September 1995 the Population Council conducted a U.S.
trial of RU-486 involving 2,121 women.21 The Population Council raised $16 million
from other organizations, such as the Open Society and the Kaiser Family Foundation,
in order to conduct the trial and prepare the documentation necessary to receive FDA
approval.22 A New Drug Application (NDA) was submitted to FDA on March 18,
1996 by the Population Council seeking approval for RU-486 in combination with the
prostaglandin misoprostol. The NDA was based on safety and efficacy data derived
primarily from two French trials involving 2,480 women and preliminary data from
the U.S. trial. The NDA was classified as a “priority” by FDA because RU-486 was
the first drug submitted to the agency for medical abortion.23
FDA’s Reproductive Health Drugs Advisory Committee evaluated RU-486 and
concluded on July 19, 1996, in a 6 to 0 vote (with 2 abstentions) that it is safe and
effective as an abortifacient when used under close medical supervision.24 Although
the advisory committee’s recommendations are not binding on the agency, FDA
generally follows its advice. On September 18, 1996, the FDA issued an approvable
letter to the Population Council for RU-486 with misoprostol pending additional
information on the manufacturer and the labeling of the drug.25 An approvable letter
is frequently used by FDA to indicate that safety and efficacy data have passed agency
review, but additional information needs to be submitted before final approval is
House Committee on Small Business, RU-486, status report, p. 16.
After the Population Council trial of RU-486 was completed in September 1995, the drug
was not available in the United States again until 1997 when a small pro-choice group,
Abortion Rights Mobilization (ARM) began conducting their own research trial. ARM
developed its own version of the drug and gained FDA approval for its trials in 1996; the
manufacturer was a closely guarded secret. ARM made up to 10,000 doses of mifepristone
available for research purposes and conducted trials at 15 different sites. Lewin, T. Group
is intensifying its campaign to distribute abortion pill. New York Times, July 2, 1997. p.
A21; and, Joffe, C. Medical abortion and the potential for new abortion providers: a
cautionary tale. Journal of the American Medical Women’s Association, v. 55, supplement
2000. p. 151-154.
Bernstein, S. Persistence brought the abortion pill to U.S. Los Angeles Times, Nov. 5,
Under the Prescription Drug User Fee Act of 1992, P.L. 102-571, priority drugs such as
RU-486 have a 6-month goal for initial agency action. FDA Talk Paper, Sept. 18, 1996.
The overall vote for benefits exceeding risk was 6-yes, 0-no, and 2-abstentions. The
Committee voted 6-yes and 2-no for data supporting efficacy, and 7-yes and 1-abstention for
data supporting safety. FDA memorandum to the Population Council, Sept. 28, 2000.
Bachorik, L. FDA issued approvable letter for mifepristone. FDA Talk Paper, Sept. 18,
1996. For more information on the approvable letter, see 21 CFR 314.110.
Some predicted that RU-486 would become generally available in the United
States by mid-1997.26 However, the Population Council “had a number of difficulties
in finding an appropriate manufacturer and distributor for the drug, in part because
of the reluctance of established pharmaceutical firms to enter into such a controversial
and potentially violent arena.”27 28 Because of continued fear on the part of investors
and manufacturers of being targeted by pro-life groups, the Population Council
apparently found it necessary “to set up elaborate consortiums and front groups to
protect participants, to the point of using cumbrous and ultimately unworkable
arrangements.”29 A Hungarian company, Gedeon Richter, agreed to produce the drug
for the Population Council in 1995, but backed out of the agreement in February
1997; the dispute ended in a breach of contract lawsuit.30 Although fear of boycotts
and violence may have deterred some manufacturers from becoming involved in
manufacturing RU-486, others speculate, including some pro-life groups, that the
companies also feared the costs of potential product liability litigation.31
In April 1996, 1 month after filing the RU-486 NDA with FDA, the Population
Council granted to Advances in Health Technology (AHT) exclusive legal rights to
arrange for and coordinate U.S. manufacture and distribution of RU-486. AHT was
a nonprofit organization formed by the Population Council in late 1995.32 Almost a
RU-486 decision a milestone in abortion rights effort. Los Angeles Times, Sept. 20, 1996.
Joffe, C. Medical abortion in social context. American Journal of Obstetrics and
Gynecology, v. 183, Aug. 2000 supplement. p. S10-S15.
The National Abortion Federation tracks clinic violence statistics by year and maintains a
chronological history of murder/shootings and arson/bombings that have occurred at abortion
clinics. Click on Clinic Violence at: [www.prochoice.org/]. In addition, the Feminist
Majority Foundation provides information on clinic violence at:
Safe drug, no sales. Washington Post, May 18, 1998. p. A16.
Murphy, C. Abortion pill’s U.S. sponsor suing Hungarian drug firm. Washington Post,
June 12, 1997. p. A3.
Wills, S.E. RU-486: Coming to America? National Conference of Catholic Bishops. Life
Issues Forum, Sept. 15, 2000.
While the approval process for RU-486 has been complicated by the opposition of pro-life
groups, the Population Council also experienced another unrelated delay. Between the end
of 1996 and early 1997, the Population Council was distracted by a court case involving a
lawyer/investor named Joseph D. Pike. On November 4, 1996, the Population Council and
AHT filed a complaint in New York Superior Court against Mr. Pike, a lawyer selected by
the Population Council in 1995 to raise funds needed to market, manufacture and distribute
RU-486. Media reported that the complaint charged Pike with fraud for withholding
information on his 1993 disbarment and a May 1996 conviction, both of which stemmed from
1985 real estate deal in North Carolina. The Population Council and AHT sought to remove
Pike from control of the license to market RU-486 and appoint a court-ordered receiver with
authority to sell all stock owned by Pike to acceptable third parties. By 1996, Pike was said
to have raised more than $27 million for the RU-486 project, including $6 million of his own
year later, AHT’s functions were merged into Advances for Choice, and the new
company was to be responsible for marketing and distributing RU-486 for the
termination of early pregnancy as well as development of the drug for other medical
conditions. However, the company name changed several times from Advances for
Choice to Advances/Neogen, and then finally to Danco Laboratories LLC, with some
management and investor switches along the way.33 Danco currently is the Population
Council’s sublicensee responsible for marketing RU-486 in the United States. Danco
and the Population Council received financial assistance, in the form of grants and
loans, from foundations set up by investor George Soros (the Open Society), investor
Warren Buffet (the Buffet Foundation), and co-founder of Hewlett-Packard, David
Packard (the David and Lucille Packard Foundation).34
Meanwhile, the prospects for RU-486 remaining an abortion option for women
in Europe also began to look uncertain. On April 8, 1997, the German company,
Hoechst announced that it would cease production of RU-486.35 The decision was
influenced by a pro-life group boycott of the company’s new (and potentially far more
lucrative) allergy drug, Allegra. Roussel, now fully owned by Hoechst, was directed
to transfer the patent rights and the remaining stockpile of RU-486 to a new company
headed by Roussel’s former chief executive, Dr. Edouard Sakiz. Dr. Sakiz was also
on the team of scientists that had originally developed the drug. The new company,
Exelgyn, would continue to provide RU-486 in Europe; however, without a
manufacturing facility, the stockpile was predicted to run out by the end of 1998.
Strict guidelines developed by Roussel had effectively limited the drug to France, the
UK and Sweden and legal requirements confined abortion services to residents of
those three countries. Attempts to expand the drug’s distribution to other countries
had been hampered by Roussel’s highly unusual demand that “a government must
issue a formal request...and secure means of distribution and quality follow-up care
must be provided.”36 Exelgyn planned to introduce RU-486 in several more European
countries and make it available to researchers examining other uses of the drug.
However, like Danco, Exelgyn had great difficulty finding a manufacturer; several
large companies refused, due to concern over potential violence from groups opposed
funds. Although a trial was scheduled for March 31, 1997, the Population Council announced
on February 12, 1997 that the litigation had been settled and that Pike had sold a “substantial
portion” of his equity to a new company, Advances for Choice. Murphy, C., and K. Day.
Abortion pill’s U.S. debut snagged by business dispute. Washington Post, Jan. 12, 1997.
p. A1, A18, A19; Lewin, T. Lawsuits’ settlement brings hope for abortion pill. New York
Times, Nov. 13, 1997. p. A14; Bernstein, S. Persistence brought the abortion pill to U.S.
Los Angeles Times, Nov. 5, 2000. p. A1; and, Murphy, C. Abortion pill accord clears way
for sales. Washington Post, Feb. 13, 1997. p. A1, A15.
RU-486 action date is Sept. 30; Allen named Reproductive Division Director. Pink Sheet,
June 12, 2000. p. 14.
Zimmerman, R. Choice allies: awaiting green light, abortion-pill venture keeps to the
shadows. Wall Street Journal, Sept. 5, 2000. p. A1.
Schuman, J. Firm gives up rights to RU-486. Washington Post, Apr. 9, 1997. p. C12.
Medical and health news: Roussel-Uclaf to transfer RU-486 rights. Reproductive Freedom
News, v. 6, Apr. 18, 1997. p. 8.
to abortion. By early 1998, Exelgyn had found manufacturing partners but refused
to identify them publicly.37 RU-486 was approved for use by a number of other
European countries in 1999.38
In early June 2000, the FDA offered in a letter to the Population Council and
Danco a proposal for allowing the drug to be marketed so long as the following
conditions were met: (1) a national registry of all physicians prescribing RU-486
would be established by Danco; (2) all physicians on the registry would have
admitting privileges at a hospital within 1 hour of their offices; (3) only physicians
trained in providing surgical abortions would be allowed to prescribe RU-486; (4)
physicians would have to be trained in using RU-486; (5) physicians would have to
be trained in reading ultrasound scans; and, (6) a follow up study of all women who
have had medical abortions would be conducted by the Population Council.39 A
spokesperson for the Population Council indicated that the FDA proposal was “more
restricted than we had expected.”40 41 Pro-life groups believed that the agency’s
proposal was prudent, and should be strengthened even further.42
Pro-choice advocates were alarmed at the FDA proposal, particularly with the
national registry which might cause physicians prescribing RU-486 to become a target
for violence by groups opposed to abortion. In a Washington Post article, Gloria
Feldt, president of the Planned Parenthood Federation of America, stated that the
FDA proposal “would so violate physicians’ privacy and security concerns that [RU486] could be approved by the agency but never really be on the market.”43 In the
same article, Paul Blumenthal, medical director of Planned Parenthood of Maryland,
stated that FDA was making unprecedented demands on physicians prescribing RU486. According to Blumenthal, “what they have recommended in terms of the kind
of certification and licensing of providers before they can provide the drug is beyond
what they do with any other drug. ... [It] certainly seems that a different standard is
being used for [RU-486].”44 Generally, FDA either approves or does not approve a
drug, and only rarely does the agency place restrictions on how a drug can be used
by doctors. Lars Noah, a University of Florida law professor who specializes in FDA
Scientist has maker for RU-486 but says issue still sensitive. Associated Press, Feb. 13,
See footnote 2.
Kaufman, M. Abortion drug proposal criticized. Washington Post, June 7, 2000. p. A1,
A8; and, Stolberg, S.G. FDA adds hurdles in approval of abortion pill. New York Times,
June 7, 2000. p. A21.
However, at the time of the July 1996 advisory committee review of RU-486, the Population
Council stated it planned to distribute the pregnancy termination pill only to physicians trained
in surgical abortion, and AHT stated it would offer training in surgical abortion to facilitate
availability of the product. Pink Sheet, June 12, 2000. p. 14.
Zimmerman, R. Abortion-rights leaders fight FDA limits on RU-486. Wall Street Journal,
June 13, 2000. p. B6.
Kaufman, Abortion drug proposal criticized, p. A8.
issues, could only identify two cases in which severe restrictions were placed on the
use of a drug, Acutane (acne drug) and thalidomide (AIDS and leprosy treatment),
both because of the risk of birth defects.45
Abortion rights advocates were also concerned about requiring that only
physicians trained in providing surgical abortions be allowed to prescribe RU-486.
The number of physicians trained in performing surgical abortion has been steadily
declining.46 Many attribute the decline to terrorism from groups opposed to abortion.
Pro-choice advocates, on the other hand, agreed with FDA that “providers need
specific training in how to administer the drug, counsel patients on its use and provide
surgical backup in case there are complications or the drug fails to work, which
happens in 5% of cases.”47
A second approvable letter had been issued by FDA to Danco on February 18,
2000, that addressed labeling, manufacturing, chemistry and distribution issues.
Danco had responded to the second letter at the end of March 2000.48 Because
RU-486 is a Class 2 submission requiring substantial review work, according to
guidelines in the Prescription Drug User Fee Act, a response must be made by FDA
within 6 months. This requirement resulted in an agency action deadline of September
FDA Approval of RU-486
Two days before its deadline (see above), on September 28, 2000, FDA
announced the approval of RU-486 in combination with misoprostol for the
termination of early pregnancy, which was defined as 49 days or less counting from
the beginning of the last menstrual period.50 Mifeprex is the trademark of Danco
Laboratories; company literature also refers to the drug as “The Early Option Pill.”51
The cost of the Mifeprex is expected to be around $300, about the same as a surgical
abortion. The drug will not be dispensed to women by prescription in pharmacies.
Instead women will receive Mifeprex directly in a physician’s office, and it must be
administered in the presence of a health professional. The physician must be able to
determine accurately the duration of the pregnancy from (menstrual history and
clinical examination) and must be able to diagnose an ectopic (tubal) pregnancy. Each
woman receiving the drug must be given a Medication Guide which explains how to
Marbella, J. FDA fuels abortion pill debate. Baltimore Sun, June 12, 2000. p. 1A.
Abortion providers decrease 14% between 1992 and 1996. News Release, Alan Guttmacher
Institute, Dec. 11, 1998.
Mann, J. We need the abortion pill now. Washington Post, June 23, 2000. p. C9.
Searle Cytotec pregnancy reminder issued as RU-486 action nears. Pink Sheet, Aug. 28,
2000, p. 14.
RU-486 action date is Sept. 30,Pink Sheet, p. 14.
For more information, including the FDA Press Release, mifepristone label, and approval
letter, see the FDA website [www.fda.gov/cder/drug/infopage/mifepristone/].
Danco has opened a toll-free telephone number at 1-877-4-Early Option (1-877-432-7596)
and a website [www.earlyoptionpill.com] to provide information about mifepristone.
take the drug, who should avoid taking it, and what complications may occur. The
physician and the patient must sign a patient agreement similar to an informed consent
document in a clinical trial.
Most of the restrictions proposed by FDA in the June 2000 letter to Danco were
not included as part of the final approval. There will be no registry of doctors
prescribing the drug or special certification program. Prescribing doctors will not be
required to be trained in performing surgical abortions, nor be required to have
admitting privileges at a hospital within 1 hour of their offices. However, prescribing
doctors must be prepared to refer the patient to another trained individual in case of
incomplete abortion. Although the FDA Label states that ultrasound should be used
if the duration of pregnancy is uncertain or if a ectopic pregnancy is suspected, the
physician need not be trained in ultrasound and may refer the patient elsewhere if an
ultrasound scan is needed in his medical judgement.
Randall K. O’Bannon, Ph.D., Director of Education and Research at the
National Right to Life Committee (NRLC), believes that FDA “modified or set aside
many of the patient protections” contained in the June 2000 FDA letter “under
pressure from pro-abortion groups and many of their sympathizers in the medical
establishment.”52 O’Bannon is of the opinion that “giving a woman RU-486 without
giving her an ultrasound thus invites futility, if not outright disaster, if a doctor
miscalculates the length of a woman’s pregnancy or fails to eliminate the possibility
of a tubal pregnancy.”53 According to CDC data, 2% of pregnancies in the United
States are ectopic.54 However, “the reported rate of ectopic pregnancy among
women who seek early abortion is much lower” for unknown reasons.55
The post-marketing studies mentioned in the June 2000 FDA letter will be
conducted by the Population Council. These will include: (1) a comparison of patient
outcomes among physicians who refer their patients needing surgical intervention to
those who perform the procedure themselves; (2) an audit of prescribers that will
examine whether doctors and patients are signing the patient agreement form and
filing it in the patient’s medical record as required; and, (3) a system for surveillance,
reporting and tracking rare ongoing pregnancies after treatment with RU-486 in the
If a significant degree of adverse events or problems are found in the
post-marketing studies, individual doctors could lose their prescribing rights for this
drug and the overall approval could be reexamined. The media has speculated that
this requirement “could make the drug more easily withdrawn under a new
O’Bannon, R.K. Proposed bill would reinstate safeguards for women taking RU-486, Feb.
8, 2001. At: [www.nrlc.org/RU486/safegardbill.html].
Ectopic pregnancy – United States, 1990-1992. MMWR, v. 44, Jan. 27, 1995. p. 46-48.
Kruse, B., et al. Management of side effects and complications in medical abortion.
American Journal of Obstetrics and Gynecology, v. 183, Aug. 2000 supplement. p. S65-75.
FDA approves RU-486 with several risk management measures. FDA Week, Sept. 29,
2000. p. 7-8.
administration. ... Republican leaders have made clear they want to overturn the
decision, and House Republican Conference Chairman J.C. Watts said that ‘a new
administration, I am certain, with moral leadership and a commitment to the family
will reverse this Clinton-Gore decision.’”57
In contrast with surgical abortion, which is completed in minutes, medical
abortion is more time consuming, somewhat like a natural miscarriage. Treatment
with Mifeprex and misoprostal requires that the patient make three office visits over
a 2-week period. On day 1, the patient reads the Medication Guide, reads and signs
the patient agreement, and then swallows three tablets of Mifeprex in the presence
of a health professional. Some women do not experience any physical discomfort
after taking the drug while others experience light uterine bleeding. The side effects
of Mifeprex are similar to “morning sickness” of a normal pregnancy: nausea,
headache, weakness and fatigue.
On day 3, the patient returns to the office and is examined to determine if she is
still pregnant.58 If pregnant, she will be given two tablets of misoprostol. Side effects
are more commonly experienced after taking misoprostol, including nausea, vomiting
and diarrhea. Abdominal cramps are a normal and expected part of the abortion
process. In the U.S. trials, 96% of women experienced cramping; in the French trials,
83% of women experienced cramping. The pain can be severe and last for several
hours. Bleeding and spotting will occur for an average of 9-16 days. According to
the FDA and the Population Council, in about 1 out of 100 women, surgery is
required to stop heavy bleeding. Serious bleeding requiring blood transfusion can
occur but is very rare; only 38 women received transfusions of a total of 25,907
(0.1%) in clinical trials of mifepristone with misoprostol.59
On day 14, the patient has a follow-up visit to confirm the pregnancy has been
terminated and assess the level of bleeding. Although researchers have been
experimenting with different dosages and reduced doctor visits since the approval of
September 18, 1996, FDA “will not allow divergences from the approved protocol
and doctors who use different protocols could lose their ability to order the drug.”60
According to FDA, since 1988 more than 620,000 women in Europe have taken
RU-486. RU-486 is given up to the 49th day of pregnancy in most countries; in
Sweden and the UK, RU-486 is given up to the 63rd day in combination with
gemeprost, a prostaglandin in vaginal suppository form. RU-486 is less effective later
in pregnancy because the placenta begins to produce progesterone in larger amounts
by the 10th week of pregnancy, and therefore antiprogestins like RU-486 are unable
to compete with the natural hormone. In France, both injectable and suppository
forms of prostaglandins were used initially. However, since May 1992 oral
prostaglandin has been used in France instead of the injectable form because there
Kaufman, M. FDA approves abortion pill. Washington Post, Sept. 29, 2000. p. A1, A18.
Only 2% to 5% of patients abort with mifepristone alone. Medical Letter, Oct. 30, 2000.
Christin-Maitre, Medical termination of pregnancy, p. 951.
Kaufman, FDA approves abortion pill, p. A1, A18.
were a few serious cardiovascular complications (including one fatal heart attack in
1991) during medical abortions following the use of the injectable prostaglandin
(suprostone).61 The complications were most often associated with patients who were
The Mifeprex labeling warns that it should not be used in women with the
! ectopic (tubal) pregnancy;
! intrauterine device in place;
! chronic failure of adrenal glands;
! current long-term therapy with corticosteroids (anti-inflammatory);
! allergy to RU-486, misoprostal or other prostaglandins; and
! bleeding disorders or current anticoagulant (blood-thinning) therapy.
According to the Population Council, there is little evidence of any long-term
health effects due to use of RU-486.62 Risk is very small because the drug causes very
few side effects, exposure is brief, dosage is small, and most of the drug is eliminated
from the body within 2 to 3 days. The oral prostaglandin misoprostol has been used
safely for gastric ulcers for many years, and the small dosage taken following the use
of RU-486 is much less than the daily dose taken by those who use the drug for
ulcers. There are no indications that treatment with RU-486 and misoprostol will
cause fetal deformities.63 Nor is there evidence that the treatment will affect a
woman’s future fertility. However, pro-life groups claim that the use of RU-486
carries risks and doctors and women need to be made aware of the risks. American
Life League President Judith Brown states that “grass-roots people have to be
encouraged to identify who these physicians are who are going to distribute this drug,
and then try to educate them about the problems.”64
Reportedly, due to fears of potential violence by abortion opponents, FDA, for
the first time, did not publish the names of the experts who reviewed RU-486 for the
agency, nor did it publish the name or location of the company that will manufacture
the drug.65 An article in the Washington Post identified the manufacturer as Hua Lian
Pharmaceuticals located near Shanghai.66 RU-486 will be shipped in bulk amounts
in powder form to another factory, possibly in the U.S., in order to be formulated into
Population Council. Frequently Asked Questions, Medical Abortion, Mifepristone and
In Europe, of 71cases studied of continuing pregnancy (woman changes her mind after
starting treatment or doctor fails to follow up), eight malformations were reported. Five were
discovered in pregnancy and led to therapeutic abortion, and three were found at birth. All
cases of malformation occurred with mifepristone alone (one case) or with the prostaglandin
gemeprost (seven cases). No cases of malformation were associated with use of mifepristone
and misoprostol. Sirruk-Ware, R., et al. Fetal malformation and failed medical termination
of pregnancy. Lancet, v. 352, July 25, 1998. p. 323.
Toner, R. A tactical challenge. New York Times, Sept. 29, 2000. p. 10.
Kaufman, FDA approves abortion pill, p. A1, A18.
Pan, Chinese to make RU-486 for U.S., A18.
200mg pills. Hua Lian has been making the drug for 9 years, one of three Chinese
companies that has been manufacturing RU-486 under different brand names for use
in China. The Washington Post article said that 10 million abortions are performed
annually in China, and about half are carried out with RU-486 citing the director of
the Shanghai Institute of Planned Parenthood Research.67 Hua Lian “has been working
for three years to upgrade its equipment and retrain its staff to meet international
standards in order to be permitted to export the drug.”68 The company received
assistance from the Rockefeller Foundation and the Bangkok-based Concept
Foundation in this effort to upgrade its factory.69
In a press release dated October 12, 2000, NRLC legislative director Douglas
Johnson expressed concern over the importation of RU-486 from Hua Lian. “It is a
public health issue because China is a major source of impure drugs – and the FDA
cannot possibly monitor a Chinese factory effectively. It is a human rights issue
because Hua Lian Pharmaceutical is a major component of the Chinese government’s
population control program, which relies heavily on compulsory abortion.”70 The
NRLC’s Randall O’Bannon believes the Chinese manufacturer of RU-486 is
“problematic” for two reasons. “First, the Chinese developed their version of the
abortion pill in the 1980s after copying the pill produced by the French. Whether this
has the same chemical formula, whether it has the same level of safety and
effectiveness as the French pill, whether it has the same risks and provokes the same
side effects, or worse, is not clear. Second, another huge challenge would be the
ability of Danco and FDA to monitor the production process in a distant, totalitarian
country, with a notorious human rights record, particularly when it comes to
state-mandated abortions and sterilizations.”71
The House Commerce Committee raised questions about Hua Lian in a letter to
FDA concerning the company previously being “cited by federal regulators for
bringing mislabeled and impure drugs into the United States.”72 According to an FDA
spokesperson, “As with all drugs the FDA approves, in the case of mifepristone, the
FDA throughly inspected its manufacturer and the facility passed. It fully met the
FDA’s standards.”73 According to an FDA memorandum to the Population Council,
Abortion drug will be imported from Chinese government factory that plays key role in
population-control program, Oct. 12, 2000.
O’Bannon, R.K. Made in China? At: [www.nrlc.org/RU486/china/html].
Zitner, A. RU-486 firm linked to drug impurities. Los Angeles Times, Oct. 20, 2000. p.
that inspection took place on July 24-28, 2000; “Deficiencies were cited and the
manufacturer corrected these. These corrections were found acceptable.”74
Although the FDA Commissioner who presided over the approval of RU-486,
Dr. Jane E. Henney, indicated her interest in staying on with the agency, her
resignation was accepted by the incoming Administration.75 76 At his Senate
confirmation hearing, then Wisconsin Governor Tommy G. Thompson, the Bush
appointee for Secretary of HHS, indicated that “he would conduct a new review of
the safety of the abortion drug RU-486.”77 Mr. Thompson stated that the approval
of the drug “was contentious, was controversial,” however, he also stated that he did
“not intend to roll back anything unless it is proven to be unsafe. ... I don’t know the
specifics, people have told me there are some safety concerns. If there are, we want
to review them.”78
Potential Impact of RU-486
Danco began shipping the first orders for RU-486 on November 20, 2000.79
Planned Parenthood, a family planning group that supports abortion rights, stated that
about 60 of its clinics would begin offering the drug that same week.80 Activists on
both sides of the abortion debate have recognized that RU-486 could fundamentally
change the struggle by allowing women to obtain “abortions in many more doctors’
offices and clinics, making the procedure much more widely available and private.”81
Gloria Feldt, president of Planned Parenthood Federation of America, has stated that
the approval “is an historic moment, comparable to the arrival of the birth control pill
40 years ago.”82 According to Judith Brown, president of the American Life League,
“Mifepristone will absolutely make our battle harder to fight and harder to win.”83
Pro-life groups are concerned about the approval of RU-486 because of their
larger concerns over abortion and the sanctity of life. In response to the FDA
approval, the National Conference of Catholic Bishops commented that “approving
chemical abortion will further numb our consciences to the violence of abortion and
U.S. Department of Health and Human Services. Public Health Service. Food and Drug
Administration. Center for Drug Evaluation and Research. Memorandum to NDA 20-687
MIFEPREX (mifepristone) Population Council. September 28, 2000.
Henney calls FDA commissioner “best job;” low-key bid to stay is long shot. Pink Sheet,
Dec. 18, 2000. p. 26.
Pear, R. Thompson says he will order a new review of abortion drug. New York Times,
Jan. 20, 2001. p. A11.
Associated Press. RU-486 is shipped to clinics, doctors. Newsday, Nov. 21, 2000. p. A44.
First shipments of RU-486 head to doctors. St. Louis Post-Dispatch, Nov. 21, 2000. p. A5.
Kaufman, M. Abortion pill deliveries begin soon. Washington Post, Nov. 16, 2000. p. A2.
Kaufman, FDA approves abortion pill, p. A1.
Pill alters abortion debate. Christian Century, Jan. 26, 2000. p. 84-85.
the taking of innocent human life.”84 Although pro-life groups have some specific
concerns about the safety of the drug for women, their more general concern is that
RU-486 is another abortion procedure that will be used to end the life of the unborn.
In the opinion of the NRLC, “chemical abortions, like RU-486, give supporters of
abortion a chance to change the image of abortion, making it seem as simple as taking
a pill and concentrating on smaller, less developed babies whose destruction seems an
easier political sell. That the reality is far different – that these abortions offer a whole
new set of significant risks, that the objective is still the destruction of a unique human
life – is of little consequence to abortion’s promoters as long as their false perception
Furthermore, pro-life groups are concerned that RU-486 will increase the
number of abortions performed in this country. In response to the FDA approval,
then Texas Governor George W. Bush reportedly stated his concern that RU-486
would make abortions “more and more common rather than more and more rare.”86
However, other observers have concluded that “the availability of medical abortion
in France, England and Sweden has not increased the number of abortions overall in
those countries.”87 According to pro-choice advocates, the impact of RU-486 in the
United States is expected to be the same as in Europe, and a decline in abortions in
the United States is expected to continue.
According to the Centers for Disease Control and Prevention (CDC) the annual
number of abortions in the United States has been falling for a variety of reasons,
including the demographics of the U.S. female population (aging baby boomers), the
passage of abortion laws affecting adolescents (requiring parental consent) and
increased use by adolescents of condoms and long-acting hormonal contraceptives.88
From 1990 (the year in which the number of abortions was highest) through 1995, the
annual number of abortions in the United States decreased by 15%. From 1995 to
1996, the number of abortions increased slightly by 0.9%, and in 1997, the number
of abortions declined again by 3%. The number of abortions reported to CDC for
1997 was 1,186,039, the lowest recorded number since 1978.89
Proponents of RU-486 also argue that it could help shift abortions to an earlier
stage within the first trimester, the first 12 weeks of pregnancy. Polling data indicate
United States Catholic Conference. National Conference of Catholic Bishops. Bishops
conference official comments on approval of abortion pill. Sept. 28, 2000. At:
RU-486: the pill, the process, the problems. At: [www.nrlc.org/RU486/ru486all.html].
Kaufman, FDA approves abortion pill, p. A18.
Talbot, M. The little white bombshell. New York Times Magazine, July 11, 1999. p. 3943, 48, 61-63.
Centers for Disease Control and Prevention. CDC Surveillance Summaries, Dec. 8, 2000.
MMWR 2000, v. 49. 44 p.
that early abortions are “more politically tenable.”90 A March 30-April 2, 2000,
Gallup poll found that 65% of Americans think abortion should be legal in the first 3
months of pregnancy, and 50% favor the FDA decision to make RU-486 available in
the United States.91 According to CDC data, in 1997, 88% of abortions were
performed before 13 weeks; 55% were performed at 8 weeks or earlier.92 With the
increased use of at-home pregnancy tests, women are requesting abortion services as
early as the fourth week. Some clinicians have been reluctant to perform a surgical
abortion before the eighth week because the size of the embryo is so small, it could
be missed during the abortion procedure which uses a suction tube device to remove
the embryo from the uterus. It is standard procedure for the doctor to inspect the
tissue removed during an abortion in order to confirm that the pregnancy has been
terminated. Identification of the gestational sac, which contains the embryo, can be
more difficult at the very early stages of pregnancy. However, a combination of
increased use by doctors of: (1) medical abortion via RU-486; and (2) newer surgical
techniques used with ultrasound to confirm early pregnancy termination, may shift the
timing of when many abortions are performed to between the fourth and the seventh
week of pregnancy.
Pro-choice groups hope that RU-486 will improve access to abortion services
by reversing the steady decline in the number of physicians and clinics offering such
services. According to research conducted by the Alan Guttmacher Institute (AGI),
the number of abortion providers in the United States began to declined in the 1980s.
In its most recent survey, AGI found that between 1992 and 1996, the number of
providers fell 14%.93 In 1996, 86% of U.S. counties lacked abortion services and
32% of women of reproductive age lived in counties with no provider.94 The Institute
found that many nonmetropolitan areas particularly lack such services; “95% of such
counties had no abortion services and 87% of nonmetropolitan women lived in
unserved counties.”95 Members of the pro-choice movement attribute the continued
decline in abortion providers to ongoing harassment and violence from groups
opposed to abortion. Pro-choice leaders believe that if more physicians quietly began
offering RU-486 in their private offices, this may reduce the potential for violence
associated with abortion provision by greatly increasing the number of sites where
such services are available and by making these sites more dispersed and less publicly
identified with abortion.
Surveys examining the intentions of doctors from various specialties to provide
medical abortion using RU-486 have found that many are considering offering the
Talbot, The little white bombshell, p. 41.
Gallup Organization. Abortion Issues.
Centers for Disease Control and Prevention; MMWR 2000.
Henshaw, S. Abortion incidence and services in the United States, 1995-1996. Family
Planning Perspectives, v. 30, Nov./Dec. 1998. p. 263-270.
drug to their patients.96 97 A survey conducted by the Henry J. Kaiser Family
Foundation from January 19-April 27, 2000, found that 44% of gynecologists and
31% of family practice physicians were very or somewhat likely to prescribe
RU-486.98 According to the Kaiser survey, those most likely to offer RU-486 are the
26% of gynecologists who routinely or occasionally perform abortions: 79% of these
doctors said they would offer the drug. “Of particular note are those providers who
have never or not within the last five years performed a surgical abortion: 31% of
gynecologists who fall in this group (72% of all gynecologists) say they are at least
somewhat likely to prescribe mifepristone, as are 31% of family practice physicians,
the large majority of whom (98%) do not perform abortions.”99 However, of those
interested in providing RU-486, major deterrents would be the need for: (1)
additional malpractice insurance; and (2) completion of certified training program and
requirement that FDA labeling be followed exactly.
In 2000, the National Abortion Federation reportedly trained over 2,000 doctors
and health care professionals on how to use RU-486; 25% of those trained were not
currently providing abortion services.100 If orders received by Danco for RU-486 are
any indication, however, interest in prescribing by doctors not currently providing
abortion has not yet materialized. According to a Danco spokesperson, “most of the
orders are from Planned Parenthood or independent abortion clinics.”101 A recent
New York Times article stated that “while in theory, at least, any licensed doctor could
offer mifepristone, many say now that they have no intention of doing so and others
say they will try to avoid providing the drug.”102
Some doctors will decide against dispensing RU-486 because they have moral
objections to providing any form of abortion. Additional reasons for the doctors’
position on the drug include: the risk of being picketed or shunned by the community;
the prolonged amount of time it takes to provide a mifepristone abortion; and, the
A 1996 survey of doctors belonging to the Society for Adolescent Medicine found that 42%
would prescribe legal medical abortion; only 2% were offering surgical abortion at the time
of the survey. Miller, N., et al. Attitudes of the physician membership of the Society for
Adolescent Medicine toward medical abortion for adolescents. Pediatrics, v. 101, May 1998.
A 1994 survey of doctors practicing in small communities in Idaho found that 26% would
definitely prescribe RU-486 and 35% were uncertain. Although a majority of the doctors in
the study refused to perform a surgical abortion, almost half said they currently are
prescribing the morning after pill. The study was funded by the U.S. Public Health Service.
Rosenblatt, R., et al. Abortion in rural Idaho: physicians’ attitudes and practices. American
Journal of Public Health, v. 85, Oct. 1995. p. 1423-1425.
Henry J. Kaiser Family Foundation. Views of Women’s Health Care Providers on
Abortion: An Update on Mifepristone, and What Happens after FDA Approval. Menlo
Park, CA, June 2000. 19 p. A total of 767 physicians were surveyed.
Ibid., p. 2-3.
Kaufman, Abortion pill deliveries begin soon, p. A2.
Kolata, G. Wary doctors spurn new abortion pill. New York Times, Nov. 14, 2000. p. F1.
expensive ($27,000) ultrasound equipment needed to check on the status of early
pregnancy.103 Other potential constraints are the numerous state laws regulating
doctors who perform abortions. Proponents of these state laws believe they provide
useful protection for women undergoing abortion while opponents feel that many of
the laws are a thinly veiled attempt to restrict and discourage access to abortion.
These state laws cover such topics as: reporting requirements; informed consent and
waiting periods; drug dispensing authority; parental notification or consent; and,
examination and disposal of fetal tissue.104 One legal analysis found that although
some of “these laws ... make little sense in the context of medical abortion, ... most
abortion restrictions are broadly written and could be interpreted by state officials as
applying to medical abortion.”105 These same authors point out that because some
state abortion laws impose an undue burden on access when applied to medical
abortion, they may be vulnerable to legal challenge. Some state legislatures are
considering bills that would limit access to RU-486.106
European countries where RU-486 is approved have shown a pattern of gradual
increase in use of the drug for early abortion. In France, RU-486 was used in 15%
of women undergoing abortions in 1994, 21% in 1996 and 26% in 1998.107 The drug
began being used in Edinburgh, Scotland, in 1991, and by “1994, 57% of women
there who were less than 9 weeks pregnant and wanted to terminate the pregnancy
requested medical termination.”108 In Sweden, following approval of RU-486 in
1992, educational courses for physicians on medical abortion were arranged around
the country by the drug company and the Swedish Society of Obstetrics and
Gynecology. Use of the medical method grew fairly slowly “from 7% in 1993 to 32%
in 1998 and more than 40% in 1999. Several reasons may explain the slow increase.
The most important seems to be physician reluctance to use a treatment associated
with more pain and bleeding than vacuum aspiration.”109
For additional perspective on the reluctance of doctors to provide medical abortion, see:
Joffe, C. Medical abortion and the potential for new abortion providers: a cautionary tale.
Journal of the American Medical Women’s Association, v. 55, supplement 2000. p. 151154; and, Kolata, G. Doctors looking at abortion pill are often unaware of obstacles. New
York Times, Sept. 30, 2000.
Borgmann, C.E., and B. Scott Jones. Legal issues in the provision of medical abortion.
American Journal of Obstetrics and Gynecology, v. 183, Aug. 2000 supplement. p. S84S94.
Jones, B., and S. Heller. Providing medical abortion: legal issues of relevance to providers.
Journal of the American Medical Women’s Association, v. 55, supplement 2000. p. 145-150.
Claiborne, W. Abortion foes want states to curb RU-486. Washington Post, Oct. 5, 2000.
Christin-Maitre, Medical termination of pregnancy, p. 954.
Bygdeman, M., et al. Medical termination of early pregnancy: the Swedish experience.
Journal of the American Medical Women’s Association, v. 55, supplement 2000. p. 195197.
Some believe the driving force that will bring mifepristone to private doctors’
offices will be the women who demand it, and many women in the general public do
seem to be very interested in the drug. The National Abortion Federation reports
receiving 3,000 calls per month, and the calls are increasing in number.110 Planned
Parenthood Association of America indicates it has “been deluged with calls. We’re
taking tens of thousands of calls here.”111 “Doctors at abortion clinics also say they
have been inundated with calls from women who are interested in mifepristone.
[However,] most of the women are confused about what the drug does.”112 A
common misconception in the lay public (and even some physicians) is that RU-486
is “a nice, easy way to get rid of a pregnancy.”113 Abortion providers inform women
that although the drug is an option, “surgery is faster and less painful and requires one
visit to the clinic rather than three.”114
Large scale surveys of women who have taken RU-486 in clinical trials indicate
a high level of patient satisfaction with the drug. The Population Council trial which
ended in 1995 found that 88% of the 2,121 women thought that RU-486 was “very
to moderately satisfactory,” and 96% of those surveyed would recommend it to
friends or relatives.115 Even when the method failed, 70% said they would try it again.
However, “women who prefer the method would be loathe to call it easy. Medical
abortion requires stamina, patience and tolerance for bleeding. ...It can cause nausea
and diarrhea, and it always causes cramps. [In contrast to the surgical method, in
which] you lie there and it’s done.”116 Many women consider medical abortion to be
safer than surgical abortion which poses the risks of anesthesia, infection and damage
to the uterus and cervix. Medical abortion is less convenient than surgical abortion;
expulsion of the fetus can occur any time, any place after the first pills are swallowed.
According to the Population Council, a woman might choose a medical abortion
over a surgical abortion because:117
! it can be used in the earliest weeks following fertilization;
! it requires no invasive procedure or surgery;
! it requires no anesthesia;
! side effects tend to be moderate;
! it does not have the risk of uterine perforation or injury to the cervix;
! it has the potential for greater privacy; and
Kolata, Wary doctors spurn new abortion pill, p. F1.
Kaufman, M. For one woman, drug was the right choice. Washington Post, Sept. 29,
2000. p. A18.
Talbot, The little white bombshell, p. 61.
Population Council, Frequently Asked Questions.
! some women feel they have greater control over their own bodies; when they
use the medical abortion procedure.
A woman might choose a surgical abortion over a medical abortion because:
! it requires fewer office visits and is over quickly;
! it is slightly more effective than medical abortion; and
! the woman notices less blood loss and is unaware of the passing of the product
Other Methods of Medical Abortion
Following the 1989 decision by Roussel to stop providing RU-486 for abortion
research in the United States, researchers here began searching for other substances
to provide medical abortion. A paper published in 1991 on the use of methotrexate
in treating ectopic pregnancies caused researchers to turn to this drug as a possible
alternative to RU-486.118 In 1993, investigators at University of California published
a preliminary study combining methotrexate with misoprostal for early abortion.119
The method received attention in the press and in the medical community in 1994
when Dr. Richard Hausknecht,120 a gynecologist and long-time abortion rights activist
with a private practice in New York City, announced that he had administered this
drug combination to 126 women: 121 of the women had a successful abortion, and
five required surgery to complete the procedure.121 He subsequently reported in the
medical literature a 96% success rate among 178 women who received methotrexate
followed by misoprostol.122
Although efficacy is similar to the RU-486 and misoprostol combination, the
various methotrexate regimens do not act as quickly and predictably. Methotrexate
terminates pregnancy by blocking the action of folic acid and interfering with DNA
synthesis so that fetal cells cannot divide. “Because methotrexate has already been
approved by FDA for other purposes, U.S. physicians can legally use this medication
for the “off label” purpose of abortion induction.”123 It has been used for a long time
as a treatment for cancer, psoriasis, rheumatoid arthritis, and more recently to treat
Stovall, T.G., et al. Single-dose methotrexate for treatment of ectopic pregnancy.
Obstetrics and Gynecology, v. 77, 1991. p. 754-757.
Creinin, M.D., and Darney, P.D. Methotrexate and misoprostol for early abortion.
Contraception, v. 48, 1993. p. 339-348.
Dr. Richard U. Hausknecht is currently the medical director for Danco Laboratories.
Tierney, J. A lone doctor adopts drug for abortion. New York Times, Oct. 10, 1994. p.
Hausknecht, R.U. Methotrexate and misoprostol to terminate early pregnancy. New
England Journal of Medicine, v. 333, Aug. 31, 1995. p. 537-540.
Joffe, Medical abortion in social context, p. S11.
ectopic pregnancies.124 As of April 2000, the National Abortion Federation listed 116
providers of medical abortion who use methotrexate.125
Prostaglandins began to be examined in research protocols during the 1970s as
a possible medical abortion agent. However, the most effective dosages had
unacceptably high rates of side effects, such as nausea, vomiting, diarrhea, fever,
chills, dizziness, rashes, and severe abdominal pain. The prostaglandin misoprostol,
which was originally approved by FDA for the treatment of gastric ulcers, has also
been investigated by itself as an abortion drug. So far in clinical trials, it too has been
found to have unacceptably high rates of side effects. Misoprostol is relatively
inexpensive, and unlike other prostaglandins, is stable at room temperature. In
countries where abortion is illegal, such as Brazil, misoprostol (often referred to as
the star pill because of its shape) has been used by poor women to initiate the
abortion process.126 The woman would then report to a health clinic as if she were
undergoing a spontaneous abortion which required surgical attention.
Misoprostol has a number of other uses at various stages of pregnancy, such as
induction of labor and treatment of postpartum hemorrhage.127 In fact, misoprostol
has been used so frequently and effectively that it has become the treatment of choice
in the induction of labor, and has been recognized as such by the American College
of Obstetricians and Gynecologists.128 “Misoprostol is one of the most important
medications in obstetrical practice, yet its use in pregnant women remains unapproved
by the FDA.”129 “Current product labeling includes a warning that misoprostol is
contraindicated during pregnancy because of its abortifacient properties. However,
FDA recognizes that, in certain circumstances, off-label uses of approved products
are appropriate, rational, and accepted medical practice. Prescribing a medication for
an off-label indication is common in the treatment of pregnant women and is not
considered experimental if based on sound scientific evidence.”130
On August 23, 2000, Searle, the manufacturer of the prostaglandin misoprostol
(trade name Cytotec), sent a letter to physicians reminding them that their drug is
contraindicated for use in pregnant women.131 The letter provoked “a response from
many hospital attorneys, administrators, and pharmacies – an automatic refusal to
allow misoprostol to be dispensed or used. ...The timing of the letter, just 2 weeks
Hausknecht, Methotrexate and misoprostol to terminate early pregnancy, p. 537.
Joffe, Medical abortion in social context, p. S11.
Brooke, J. Ulcer drug tied to numerous abortions in Brazil. New York Times, May 19,
1993. p. C13.
Goldberg, A.B., et al. Misoprostol and pregnancy. New England Journal of Medicine, v.
344, Jan. 4, 2001. p. 38-47.
Hale, R.W., and S. Zinberg. Use of misoprostol in pregnancy. New England Journal of
Medicine, v. 344, Jan. 4, 2001. p. 59-60.
Goldberg, Misoprostol and pregnancy, p. 45.
Ibid., p. 38.
Searle Cytotec pregnancy reminder issued as RU-486 action nears. Pink Sheet, Aug. 28,
2000. p. 14.
before the FDA announced its approval of mifepristone, left many people wondering
whether there were other motivations for Searle’s actions.”132 The company states
that its letter “resulted from lengthy discussions between Searle and FDA after reports
were received of uterine rupture in connection with off-label use of Cytotec in
pregnant women. ...The fact that [the letter] was distributed just over a month before
the FDA approval of mifepristone was entirely coincidental.”133 Searle is currently
working with the FDA to revise the labeling of misoprostol.134 At the present time,
Searle, a unit of Monsanto, is the only U.S. manufacturer of misoprostol; Monsanto
merged with Pharmacia in 2000.135
Other Uses of RU-486
Mifepristone was originally designed by the scientists at Roussel as a
antiglucocorticoid. These drugs interfere with certain adrenal gland hormones, such
as cortisol, involved in the regulation of tissues throughout the body. It was only
inadvertently discovered to have the antiprogesterone effects which make it useful as
an abortion agent. Potential applications that take advantage of the drug’s
antiglucocorticoid effects include the treatment of glaucoma and Cushing’s syndrome,
a condition in which dangerously high levels of cortisol are produced by the body.
Mifepristone has also been investigated as a post-coital contraceptive, or
morning after pill. In this case, the drug would be used within a few hours or days
of intercourse in order to prevent pregnancy, certainly before a woman even knows
if she is pregnant. Currently, there are several highly effective post-coital
contraceptives available on the market, including high-dose estrogen and estrogenprogesterone combinations. However, these treatments are effective only before
implantation occurs, and therefore are most effective within 72 hours of unprotected
intercourse. In contrast, “mifepristone is effective regardless of implantation and can
be administered up to 12 to 17 days after intercourse. In repeated studies, a single
600 mg. dose of mifepristone alone has been shown to be 94% to 100% effective for
preventing pregnancy when administered almost anytime before the expected date of
menses.”136 When compared with other post-coital contraceptives, mifepristone was
as effective and produced fewer side effects. Because of these findings, mifepristone
is also being investigated as a monthly birth control treatment.
Other potential uses of mifepristone include menstrual regulation and a treatment
for fibroid tumors, a condition that can cause pain and heavy bleeding that sometimes
leads to a hysterectomy. It is also being investigated as a treatment for endometriosis,
Hale and Zinberg, Use of misoprostol in pregnancy, p. 59-60.
Friedman, M.A. Manufacturer’s warning regarding unapproved uses of misoprostol. New
England Journal of Medicine, v. 344, Jan. 4, 2001. p. 61.
Pharmacia Cytotec use for labor induction reaffirmed by ACOG. Pink Sheet, Oct. 16,
2000. p. 23.
Zimmerman, R. Drug maker tries to slip out of RU-486 controversy. Wall Street Journal,
Oct. 24, 2000. p. D1.
Goldberg, J.R., et al. Mifepristone (RU-486): current knowledge and future prospects.
Archives of Family Medicine, May/June 1998. p. 219-222.
a condition in which tissue resembling the uterine lining grows in other locations. It
is thought to be a leading cause of female infertility. Small clinical trials of the drug
have shown that mifepristone can reduce pain in women with endometriosis, but it is
unclear whether the amount of tissue outside the uterus actually decreases. The drug
that helps some women end unwanted pregnancies may eventually help others have
children. Mifepristone has been shown to be effective for labor induction in postdate
Finally, mifepristone has been used to treat meningioma, a type of benign tumor
that arises from the tissue covering the brain or spinal cord. When the tumor cannot
be surgically removed, treatment with mifepristone has been tried because the tumor’s
growth is often stimulated by progesterone, and the drug blocks the action of this
hormone. For similar reasons, mifepristone is being looked at as a potential treatment
for breast cancer and prostate cancer.
The 107th Congress will likely consider legislation on RU-486. Prior to the FDA
approval, three times (for FY1999, FY2000, FY2001) the House considered attaching
an amendment to the agriculture appropriation bill that would “prohibit any funds to
be used by the FDA for the testing, development, or approval (including approval of
production, manufacturing or distribution) of any drug for the chemical inducement
of abortion.” The final version of the bill in all three cases, however, did not contain
the amendment language. The FDA approved RU-486 for termination of early
pregnancy on September 28, 2000.
On February 6, 2001, the RU-486 Patient Health and Safety Act was introduced
by Representative David Vitter in the House (H.R. 482) and Senator Tim Hutchinson
in the Senate (S. 251). The legislation would reinstate restrictions FDA had listed in
its June 2000 letter to the Population Council and Danco. The same bill language was
introduced in the second session of the 106th Congress by Representative Tom Coburn
(H.R. 5385) and Senator Hutchinson (S. 3157). The bill stipulates that physicians
prescribing the drug must meet the following requirements: (1) qualified to handle
complications resulting from an incomplete abortion or ectopic pregnancy; (2) trained
to perform surgical abortions and met all applicable legal requirements to perform
such abortions; (3) certified for ultrasound dating of pregnancy and detecting ectopic
pregnancy; (4) completed a program regarding the prescribing of such drug that uses
a curriculum approved by the Secretary of HHS; and (5) have admitting privileges at
a hospital located 1 hour or less away from the physician’s medical office.
In the opinion of the National Abortion Federation, this legislation represents an
unprecedented intrusion into the jurisdiction of FDA and the practice of medicine.137
They point out that FDA reviewed all the scientific data reflecting the experiences of
thousands of women and the agency rejected most of these requirements as medically
S. 251/H.R. 482 would impose restrictions on RU-486 (mifepristone) already rejected as
medically unnecessary by the FDA. National Abortion Federation Fact Sheet, Feb. 2001.
Apart from issues related to approval or conditions for use by physicians,
RU-486 also raises issues related to federal funding for health programs that might
provide access to the drug for women seeking an abortion. The Hyde Amendment
has attached to annual appropriation bills for many years a prohibition on the use of
federal funds for abortion except in the case of rape, incest or if the life of the woman
is in danger. Because RU-486 is used in an abortion procedure, its use under these
federal health programs would also be prohibited and the same exceptions would
apply. Women relying on such programs as Medicaid, Community Health Centers,
and clinics funded by Maternal and Child Health Block Grants will not have access
to federal support for their use of RU-486.