Abortion: Termination of Early Pregnancy with RU-486 (Mifepristone)

Congressional research reportFeb 23, 2001

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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)

Summary

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.

Contents

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)

Background

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.

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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

Roussel.

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,

1989.

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.

p. 26-27.

Rovner, J. RU-486: tiny pill with big impact. Congressional Quarterly, Feb. 24, 1990. p.

598.

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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

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].

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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.

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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

granted.

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,

2000. A1.

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.

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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.

p. A10.

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:

[www.feminist.org/rrights/abrights_links.html#violence].

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.

At: [www.nccbuscc.org/prolife/publicat/lifeissues/09152000.htm

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

(continued...)

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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

(...continued)

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.

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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,

1998.

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.

Ibid.

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.

Ibid.

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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

30, 2000.49

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.

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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

United States.56

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].

Ibid.

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.

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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.

p. 101.

Christin-Maitre, Medical termination of pregnancy, p. 951.

Kaufman, FDA approves abortion pill, p. A1, A18.

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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

heavy smokers.

The Mifeprex labeling warns that it should not be used in women with the

following conditions:

! 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

Misoprostol. [www.popcouncil.org/faqs/abortion.html]

Ibid.

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.

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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,

Ibid.

Abortion drug will be imported from Chinese government factory that plays key role in

population-control program, Oct. 12, 2000.

At: [www.nrlc.org/press_releases_arc/Release101200.html].

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.

A1.

Ibid.

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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.

Ibid.

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.

CRS-15

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

holds.”85

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:

[www.nccbuscc.org/comm/archives/2000/00-243.htm].

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.

Ibid.

CRS-16

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.

[www.gallup.com/poll/indicators/indabortion.asp]

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.

Ibid.

CRS-17

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.

[www.pediatrics.org/cgi/content/full/101/5/e4]

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.

100

Kaufman, Abortion pill deliveries begin soon, p. A2.

101

Kolata, G. Wary doctors spurn new abortion pill. New York Times, Nov. 14, 2000. p. F1.

102

Ibid.

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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

103

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.

104

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.

105

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.

106

Claiborne, W. Abortion foes want states to curb RU-486. Washington Post, Oct. 5, 2000.

p. A1.

107

Christin-Maitre, Medical termination of pregnancy, p. 954.

108

Ibid.

109

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.

CRS-19

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

110

Kolata, Wary doctors spurn new abortion pill, p. F1.

111

Ibid.

112

Ibid.

113

Ibid.

114

Ibid.

115

Kaufman, M. For one woman, drug was the right choice. Washington Post, Sept. 29,

2000. p. A18.

116

Talbot, The little white bombshell, p. 61.

117

Population Council, Frequently Asked Questions.

[www.popcouncil.org/faqs/abortion.html].

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! 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

of conception.

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

118

Stovall, T.G., et al. Single-dose methotrexate for treatment of ectopic pregnancy.

Obstetrics and Gynecology, v. 77, 1991. p. 754-757.

119

Creinin, M.D., and Darney, P.D. Methotrexate and misoprostol for early abortion.

Contraception, v. 48, 1993. p. 339-348.

120

Dr. Richard U. Hausknecht is currently the medical director for Danco Laboratories.

121

Tierney, J. A lone doctor adopts drug for abortion. New York Times, Oct. 10, 1994. p.

A1, B12.

122

Hausknecht, R.U. Methotrexate and misoprostol to terminate early pregnancy. New

England Journal of Medicine, v. 333, Aug. 31, 1995. p. 537-540.

123

Joffe, Medical abortion in social context, p. S11.

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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

124

Hausknecht, Methotrexate and misoprostol to terminate early pregnancy, p. 537.

125

Joffe, Medical abortion in social context, p. S11.

126

Brooke, J. Ulcer drug tied to numerous abortions in Brazil. New York Times, May 19,

1993. p. C13.

127

Goldberg, A.B., et al. Misoprostol and pregnancy. New England Journal of Medicine, v.

344, Jan. 4, 2001. p. 38-47.

128

Hale, R.W., and S. Zinberg. Use of misoprostol in pregnancy. New England Journal of

Medicine, v. 344, Jan. 4, 2001. p. 59-60.

129

Goldberg, Misoprostol and pregnancy, p. 45.

130

Ibid., p. 38.

131

Searle Cytotec pregnancy reminder issued as RU-486 action nears. Pink Sheet, Aug. 28,

2000. p. 14.

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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,

132

Hale and Zinberg, Use of misoprostol in pregnancy, p. 59-60.

133

Friedman, M.A. Manufacturer’s warning regarding unapproved uses of misoprostol. New

England Journal of Medicine, v. 344, Jan. 4, 2001. p. 61.

134

Pharmacia Cytotec use for labor induction reaffirmed by ACOG. Pink Sheet, Oct. 16,

2000. p. 23.

135

Zimmerman, R. Drug maker tries to slip out of RU-486 controversy. Wall Street Journal,

Oct. 24, 2000. p. D1.

136

Goldberg, J.R., et al. Mifepristone (RU-486): current knowledge and future prospects.

Archives of Family Medicine, May/June 1998. p. 219-222.

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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

pregnancies.

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.

Congressional Actions

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

unnecessary.

137

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.

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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.

This is a copy of a public record, reproduced as it was published. It is not legal advice, and it may not be the version a court would rely on. Check the official source before you cite it.