Approval and Lingering Issues

What is the current status of RU486?

What are the conditions under which it may be prescribed?

What happened to the regulations the FDA was considering back in June 2000?

Who benefits from the FDA's adoption of looser restrictions on RU486?

Has the abortion industry always been satisfied with such low safety standards?

What is the possible impact of these looser restrictions on the health of women taking RU486/PG?

Was this a normal approval? What is a "Subpart H?" approval?

Was there anything suspicious about the timing of the approval?

Will the current regulations protect women's safety?

Do prescribers plan to follow FDA approved procedures?

What will women do if injured by the drugs? How will they collect if injured?

Is RU486 being manufactured by a foreign company?

What sort of problems does the drug's being manufactured in China create?

What sort of record does the Chinese manufacturer have when it comes to the safety and purity of exports?

Did the FDA find any sort of irregularities when inspecting the Chinese manufacturing plant for production of RU486?

What sort of confidence does the record of the Chinese manufacturing firm inspire?

Is the pill manufactured in China the same as the one made in France?

Will American women be told of any problems with the drug?

What is the status of the prostaglandin used in conjunction with RU486?

How has the drug been received?

Approval and Lingering Issues

What is the current status of RU486?

The U.S. Food and Drug Administration granted final marketing approval to RU486 on September 28, 2000.⁽¹⁾ It is now available from physicians who meet the FDA's requirements and order the pills from Danco Laboratories, the drug's U.S. distributor.⁽²⁾

What are the conditions under which it may be prescribed?

The FDA has mandated that the drug be made available to women who are no more than 49 days pregnant (7 weeks from their last menstrual period). Women taking the drug must sign a form indicating they are aware of the risks associated with the RU486/PG combination for them and their baby and promising to return for additional visits on day 3 (to take the prostaglandin) and about day 14 (to determine whether or not the abortion has taken place).⁽³⁾

Doctors prescribing RU486 are required to be able to date pregnancies and diagnose ectopics. They also must be able, the FDA says, to provide "surgical intervention" in situations where there are incomplete abortions or severe bleeding, or to have in place arrangements for patients to obtain such services from other physicians who can perform these sorts of surgical procedures. Furthermore, the prescriber must "assure patient access to medical facilities equipped to provide blood transfusion and resuscitation, if necessary."⁽⁴⁾

Physicians must also sign a form indicating they have read and understood the "prescribing information," a detailed description of the RU486's clinical pharmacology, the drug's indications and contraindications, and relevant warnings and precautions. Included on this form is the prescribed protocol and failure and complication rates from French and U.S. clinical trials of the drug.⁽⁵⁾

The "prescriber agreement" further mandates that any hospitalization, transfusion, or "other serious event" is to be reported to Danco Laboratories, the supplier.⁽⁶⁾

What happened to the regulations the FDA was considering back in June 2000?

Under pressure from pro-abortion groups⁽⁷⁾ and many of their sympathetic allies in the medical establishment,⁽⁸⁾ the FDA modified or set aside many of the patient protections it had considered just months before approval.⁽⁹⁾

While it kept in place measures mandating strict distribution and monitoring of pills and continued to call for some limited follow up studies,⁽¹⁰⁾ other regulations were scaled back or eliminated altogether.

Instead of special training in use of the drug, physicians now only have to certify that they have "read and understood the prescribing information" on RU486. While still being asked to date pregnancies and diagnose ectopic pregnancies, prescribers are no longer required to conduct or read ultrasounds to confirm their diagnoses.⁽¹¹⁾

While the original regulations would have limited prescription of the drug to physicians who had the surgical training to handle incomplete abortions or serious complications sometimes associated with the drug, current measures require only that a physician not having such skills make arrangements with some other physician with the appropriate surgical training.⁽¹²⁾

The rule that a doctor have admitting privileges at a hospital within an hour's drive of his practice was replaced by a much looser requirement that asked only that the physician assure that a woman had "access" to appropriate medical facilities.⁽¹³⁾

Though the FDA decided against dropping the second visit to the doctor to take the prostaglandin on day 3, it did drop the requirement, in place during American trials of the drug, that women stay at the clinic for four hours after taking that drug.⁽¹⁴⁾

Who benefits from the FDA's adoption of looser restrictions on RU486?

While none of the modifications appear to make things any safer for women or their babies, these less stringent rules do make things easier on the doctors and easier on their pocketbooks.

Because of the looser regulations, physicians considering prescription of RU486 no longer need to worry about getting special training, buying expensive medical equipment, or disrupting their medical practices. This opens up the pool of potential prescribers not only to long time abortionists presumed to have surgical skills and experience in dealing with abortion complications, but to ob-gyns, family practitioners, pediatricians, and others no matter what their medical specialty or surgical training.⁽¹⁵⁾

The dropping of the ultrasound requirement saves a doctor the expense of buying an ultrasound machine and undergoing special training or hiring new staff to conduct or read ultrasounds. Dropping the four hour wait that was once part of the second office visit in which the prostaglandin was given frees up office schedules, space, and bathrooms, making things more convenient for a doctor's staff and more comfortable for other patients who might be troubled by what they see aborting women going through.⁽¹⁶⁾

The FDA's decision to permit doctors to refer rather than treat patients for whom the method fails or causes problems doesn't make things easier on the woman, who must figure out how to get to yet another address, but does allow the doctor to make complications or late night trips to the emergency room somebody else's problem.

Has the abortion industry always been satisfied with such low safety standards?

Despite their current endorsement of the FDA's looser regulatory standards on RU486,⁽¹⁷⁾ the National Abortion Federation has, as recently as 1998, maintained that "all personnel performing abortions must receive training in the performance of abortions and in the prevention, recognition, and management of complications."⁽¹⁸⁾ Current FDA regulations require no special training in performing RU486/PG abortions or in preventing, recognizing, or managing complications that may arise from the method.⁽¹⁹⁾

What is the possible impact of these looser restrictions on the health of women taking RU486/PG?

There are real questions as to whether a doctor who has merely "read and understood"⁽²⁰⁾ prescribing instructions for RU486 really appreciates the medically complex, messy reality of chemical abortions.⁽²¹⁾ Even doctors who had abortion experience were surprised by the amount of blood lost in RU486/PG abortions in U.S. trials to the point that the sponsor of the trials offered this as a possible explanation of lower "success" rates in the U.S. than in France.⁽²²⁾

The RU486/PG method drops off significantly in effectiveness after the 7^th week of pregnancy⁽²³⁾ and is not an effective agent against ectopic pregnancies.⁽²⁴⁾ With ultrasound, the foremost diagnostic tool for dating and locating pregnancy, no longer required, errors in dating and diagnoses are more likely.⁽²⁵⁾ In the case of a missed date, an error could mean failure of the chemical method and the increased possibility of surgical intervention.⁽²⁶⁾ In the case of a missed tubal pregnancy, an error could mean a ruptured fallopian tube (which itself could be mistaken for an abortion) and tragedy for the mother as well as child.⁽²⁷⁾

The absence of a surgical training requirement means that a woman for whom the method fails or one who faces serious complications may have to rely upon the help of a stranger whose name and number lies on a crumpled piece of paper at the bottom of her purse. The removal of the four hour wait at her second visit means she may face the most painful and dangerous part of her abortion all alone, precisely when she could require the greatest help, support, and medical care.⁽²⁸⁾

Though the FDA still requires that a doctor assure "access" to appropriate medical services, the FDA's abandonment of the provision that a doctor practice within an hour of a hospital where he or she has admitting privileges means that even if the patient is able to get to an adequately equipped hospital in time, her doctor may not be there to get her in or to treat her. If an ER staff is unfamiliar with chemical abortions and doesn't recognize the danger a woman may be in, she could bleed to death.⁽²⁹⁾

Was this a normal approval? What is a "Subpart H?" approval?

The FDA approved RU486 under a special provision of the federal code governing drug approvals referred to as "Subpart H."⁽³⁰⁾

The U.S. Congress passed legislation creating the rules now reflected in "Subpart H" in 1992 as part of an effort to streamline the approval process for AIDS drugs that were being delayed from reaching the market by what many considered excessively lengthy and overly cautious safety analyses.⁽³¹⁾ Subpart H provides an accelerated review for drugs under consideration for the treatment of "serious or life-threatening illnesses" that offer "meaningful therapeutic benefit to patients over existing treatments."⁽³²⁾

Though the FDA has made repeated declarations of RU486's safety, its reclassification of "the termination of unwanted pregnancy" under Subpart H as a "serious condition"⁽³³⁾ allowing an accelerated approval, different standards of testing, higher levels of restrictions, and, if necessary, expedited withdrawal from the market for safety or other reasons,⁽³⁴⁾ has not received as much attention.

Was there anything suspicious about the timing of the approval?

Final government approval for RU486 came just over a month prior to the heavily contested 2000 U.S. presidential election, and close to the end of President Clinton's last term in office.⁽³⁵⁾

Bill Clinton initiated the process when on January 22, 1993, just three days into his first term of office, he signed an executive order directing the FDA and the Department of Health and Human Services to take steps to promote the testing, licensing, and manufacturing of the drug in the U.S.⁽³⁶⁾

Though compilation of U.S. trial data was still incomplete, the FDA accepted a marketing application for the drug and brought it up for a hearing in 1996, the year Clinton was running for a second term.⁽³⁷⁾ Though it did not grant final approval at the time, owing to then unresolved labeling and marketing issues, Clinton's FDA did declare RU486 "approvable" in September of 1996, in the closing months of the 1996 presidential campaign contest.⁽³⁸⁾

Will the current regulations protect women's safety?

While the current regulations and protocol may be better than nothing, women would have had more protection under the original protocol and the regulations proposed by the FDA in June of 2000.

Do prescribers plan to follow FDA approved procedures?

Even the modest limits and standards set by the FDA and agreed to by RU486's U.S. sponsor are too much for some members the abortion industry.

Representatives of Planned Parenthood and the National Abortion Federation told the Wall Street Journal that some abortionists in their organizations would be using different dosages and prescribing at later pregnancy dates than those specified in the FDA approved protocol.⁽³⁹⁾

While the efficacy and safety of these altered dosages have not been officially established, American trials did show a significant drop off in effectiveness when RU486 was used after the 49^th day of pregnancy.⁽⁴⁰⁾ Those failing to abort will either face the added risk of surgery or the risk of giving birth to a baby whose development may have been affected by the drugs.⁽⁴¹⁾

What will women do if injured by the drugs? How will they collect if injured?

Hopefully, they will get treatment early enough to avoid death or permanent injury. If, however, they are killed or injured, it is unclear who, if anyone, will compensate them or their families for losses.

The manufacturer of RU486 is a state-owned pharmaceutical firm in Communist China,⁽⁴²⁾ adding unique political and cultural difficulties on top of the challenges that would normally be involved in suing a foreign company.⁽⁴³⁾

The distributor and promoter of RU486 is a small single-product pharmaceutical firm started by a non-profit group and financed, in part, by large loans and foundation contributions. Total capital investment in Danco is only about $34.7 million to $36.7 million⁽⁴⁴⁾ and the market for the drug is relatively small,⁽⁴⁵⁾ leading one to wonder how many large awards could be sustained.

The manufacturer of the prostaglandin used in conjunction with RU486 has disavowed its use for abortion and has fought to keep its label from sanctioning such a use.⁽⁴⁶⁾ A recent letter to doctors by Searle warning against off label uses may make it easier for Searle to deny liability, leaving the doctor holding the bag.⁽⁴⁷⁾

Individual doctors signing the FDA and manufacturer mandated document saying they have "read and understood" the prescribing information⁽⁴⁸⁾ may have more difficulty avoiding responsibility, since their decision to prescribe the pills to a given patient presumably comes with full knowledge of both the patient's medical condition and the risks and contraindications associated with the drug.

Is RU486 being manufactured by a foreign company?

Yes. Press accounts have confirmed that the RU486 being sold in the United States is being made by the Hualian Pharmaceutical Company, a state-owned drug manufacturer located on the outskirts of Shanghai in Communist China.⁽⁴⁹⁾

What sort of problems does the drug's being manufactured in China create?

Members of the U.S. government have expressed special concerns about drug manufacturing in the Far East and the FDA's ability to monitor these manufacturers.⁽⁵⁰⁾ The political, cultural, and geographic distance presents problems, not just for inspectors monitoring the integrity of manufacturing, storage, and shipping practices, but for those seeking information for suits or compensation for injuries.⁽⁵¹⁾

What sort of record does the Chinese manufacturer have when it comes to the safety and purity of exports?

Not stellar. The Hualian pharmaceutical firm now manufacturing RU486 has been among those Chinese firms cited for various drug import violations in recent years. In 1998, a study by the California Department of Health Services found high levels of contaminants in an herbal medication made by Hualian's earlier incarnation, the Shanghai No. 12 Pharmacy Factory, known as composite tegafuri capsules, as well as high contamination levels in hundreds of similar products made at the same plant.⁽⁵²⁾

Another drug (betamethasone) produced by Hualian was detained by FDA officials in Cincinnati in July of 2000 because of false or misleading labeling. This was during a time when the Chinese plant was undergoing an FDA re-inspection associated with the production of RU486, though inspectors there were not informed of the problem with the betamethasone intercepted in Cincinnati.⁽⁵³⁾

Did the FDA find any sort of irregularities when inspecting the Chinese manufacturing plant for production of RU486?

Yes. FDA inspectors examining the RU486 manufacturing process encountered a number of irregularities during their visits of 1999 and 2000. In October of 1999, the inspector found that the methods and specifications section of the Chemistry and Manufacturing Controls report filed by Hualian "didn't correspond to methods and specifications used by the firm."⁽⁵⁴⁾

An interpreter explained to the FDA inspector that Hualian had simply "copied information from the Roussel NDA [the original French manufacturer's New Drug Application] in a number of sections rather than translate their own methods from Chinese to English."

The inspector also said Hualian had inserted numerous references to the United States Pharmacopeia (USP - the legally recognized compendium of standards for drugs in the United States) in its Chemistry and Manufacturing Controls report after Hualian's consultant told them the FDA wanted all raw materials to meet this standard, even though the references they inserted "have nothing to do with the testing they perform." The FDA inspector gave up after four days of waiting for translations that correctly reflected Hualian's testing practices.⁽⁵⁵⁾

The problems of October 1999 supposedly resolved, the FDA returned for another inspection in July of 2000. Even this inspection found several deficiencies, but, based on promises of corrective actions by Hualian, the FDA authorized moving forward on RU486.⁽⁵⁶⁾

What sort of confidence does the record of the Chinese manufacturing firm inspire?

Not much. Even if FDA inspectors attempted to act in charity and good faith, serious questions remain about the integrity of the manufacturing and testing processes at the Hualian factory. The factory has been identified as a source of tainted drugs shipped to the U.S. in the past and some question remains about Hualian's willingness to disclose deficiencies or possible problems, especially given some of their recent actions in regard to this drug (see above).

Is the pill manufactured in China the same as the one made in France?

It isn't clear whether the Chinese formula for RU486 is the same as the one tested and approved in the U.S.⁽⁵⁷⁾ If not, data from the U.S. trials of RU486, which used the French-made pill,⁽⁵⁸⁾ offer no reliable guide to the safety and efficacy of the Chinese product.

Will American women be told of any problems with the drug?

The FDA says that all "Adverse events, such as hospitalization, blood transfusion, ongoing pregnancy, or other major complications" are to be reported to Danco Laboratories, the U.S. distributor for the drug. Danco, in turn, is supposed to report data on "safety outcomes" and "ongoing pregnancies" to the FDA.⁽⁵⁹⁾

There is reason to be concerned about how forthcoming the abortion pill's promoters will be about problems with the drug.

In U.S. trials of the drug, those testing the RU486/PG method in Des Moines, Iowa told the press there had been no complications among the participants, even though at least one woman who had been a part of that study lost between half and two-thirds of her blood volume and nearly died.⁽⁶⁰⁾

The man now working as the medical director for Danco is the same man a September 12,1994 Chicago Tribune report referred to as "a self described maverick and longtime abortion rights activist" who had a run-in with the FDA over an earlier chemical abortion procedure. According to the Tribune, "contrary to accepted medical practice... without the permission of the Food and Drug Administration or sponsorship of a research institution," Manhattan Dr. Richard Hausknecht started using methotrexate, a powerful anti-cancer drug, that year to chemically abort women who answered his advertisement and paid to be part of his "study."

The Tribune said then that "other doctors find what he's doing unethical and potentially dangerous, and federal regulators, who learned about this experiment last week, have warned him that he might have violated the law." One fellow abortion researcher explicitly told the paper he considered what Hausknecht was doing "downright unethical." Even a representative of the Population Council, the non-profit which later created Danco, the company Hausknecht now works for, then called his work "extremely risky" and told the Tribune "I hope his malpractice insurance is paid up."

Even while admitting his "research" was "a little uncharted," the Tribune says Hausknecht initially resisted any oversight of his work, saying "D n it, I'm not going to wait!" The FDA finally told him to cease what he was doing unless he got the backing of some medical institution and submitted his data and procedures to the FDA for review. Only then, after having already performed his "experiment" on 126 women, does the paper indicate Hausknecht decided to comply with the FDA's wishes.⁽⁶¹⁾

A spokesperson for the National Abortion Federation claimed in February of 2001 that "hundreds" of women had used mifepristone (RU486) since distribution began in November of 2000 "without any serious complications."⁽⁶²⁾ Given the players involved and their history, it isn't clear how reliable these assurances are.

What is the status of the prostaglandin used in conjunction with RU486?

The FDA mandates that the prostaglandin misoprostol should be used in the second stage of of the RU486/PG chemical abortion,⁽⁶³⁾ even though this use contradicts instructions on misoprostol's FDA sanctioned label.

The prostaglandin misoprostol is sold by pharmaceutical maker R.G. Searle under the trade name Cytotec. Searle brought Cytotec to the market in 1988 as a special anti-ulcer medication for those, such as those suffering from arthritis, who take a lot of non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin. Searle's FDA approved label, from the beginning, has stated that the drug is contraindicated for, or not to be used by, pregnant women because of its capacity to induce miscarriage.⁽⁶⁴⁾

In a 1993 letter to the Wall Street Journal, Searle said directly that it did not want its product used with RU486 for abortion, a position it has never, as far as is known, publicly altered.⁽⁶⁵⁾

When the FDA approved RU486, however, in September of 2000, it specifically mandated the use of misoprostol as a necessary part of the chemical abortion procedure.⁽⁶⁶⁾ Searle never sought approval for this use, and its label (package insert) is inconsistent with this use.

Information published in trade and medical journals indicates that the FDA is seeking to get Searle to change its label to endorse this use.⁽⁶⁷⁾ If the FDA is successful is pressuring Searle to make such a change, the FDA will force Searle to accept a use of its product if finds objectionable and which could expose it to potentially serious liability.

How has the drug been received?

Despite enormous media hype and claims by the abortion industry that there is great demand for the drug, all available evidence indicates that RU486 has not been the breakthrough product the pills supporters dreamed of.

At least thirty of the nation's major colleges and universities, including Princeton, Boston University, the University of Michigan, the University of North Carolina (Chapel Hill), the University of Oklahoma,⁽⁶⁸⁾ Florida State University, and UCLA, have indicated they will not offer the drug to their students.⁽⁶⁹⁾ Yale University is the only major university that has publicly indicated plans to make RU486 available on its campus.⁽⁷⁰⁾

Though Danco, the distributor, reported it had received hundreds of orders, and abortion groups like Planned Parenthood said that it had been swamped with calls from women asking about the pill shortly after approval, the New York Times reported that most of the orders came from clinics already offering abortion and that many of the women who called were confused about what RU486 was or how it worked, believing it was a pill that could be taken at any stage of pregnancy to make the baby magically disappear.⁽⁷¹⁾ Other reasons behind the reluctance of individual doctors to prescribe the pill are the time involved in counseling⁽⁷²⁾ and the expense of ultrasound equipment and training.⁽⁷³⁾

Even among experienced abortionists, enthusiasm has not been universal. Despite years of advocacy and a recent "massive educational program," only two-thirds of the National Abortion Federation's 360 "member facilities" were indicating to the Federation in September of 2000 that they would be offering the drug.⁽⁷⁴⁾ Some of those planning to offer RU486 still believe surgical abortions are better because they are quicker, less painful, and involve fewer office visits and are telling their patients so.⁽⁷⁵⁾

The price of an RU486/PG abortion, with Danco charging $270 for a single dose of the RU486 pills, is also an issue with abortion clinics.⁽⁷⁶⁾ The chemical option becomes even more expensive once the additional cost of three office visits, lab work, and counseling is factored in [to say nothing of the cost of one, maybe two ultrasounds], forcing the clinic to offer the RU486/PG method at a loss or to charge a rate substantially higher than that of a corresponding surgical procedure.⁽⁷⁷⁾

^{Click Here for Extensive Research on RU-486.}

1. FDA "Approval Letter Mifeprex™ (mifepristone) Tablets," September 28, 2000, available at www.fda.gov/cder/drug/infopage/mifepristone . FDA release, "FDA Approved Mifepristone for the Termination of Early Pregnancy," September 28, 2000, available at www.fda.gov/bbs/topics/NEWS/NEW00737.html .

2. FDA, "Office Memo to Population Council," September 28, 2000, at www.fda.gov/cder/drug/infopage/mifepristone/memo.pdf .

3. FDA, "Patient Agreement" for Mifeprex (mifepristone) tablets, available at www.fda.gov/cder/drug/infopage/mifepristone/patientagreement.pdf .

4. FDA, "Prescriber's Agreement, for Mifeprex (Mifepristone) Tablets, available at www.fda.gov/cder/drug/infopage/mifepristone/patientagreement.pdf .

5. FDA, "Prescriber's Agreement, for Mifeprex (Mifepristone) Tablets, available at www.fda.gov/cder/drug/infopage/mifepristone/patientagreement.pdf .

6. Danco Laboratories, "Prescribing Information," Mifeprex Early Option Pill packet, available from Danco Laboratories, P.O. Box 4816, New York, NY 10185, or from FDA website at www.fda.gov/cder/drug/infopage/mifepristone (comprised of "Mifepristone Label," "Medication Guide," and "Patient Agreement").

7. Jean Marbella, "FDA fuels abortion pill debate," Baltimore Sun, June 12, 2000.

8. Letter from American College of Obstetricians and Gynecologists and American Medical Association to Jane Henney, FDA Commissioner, July 24, 2000.

9. Nancy Gibbs, "The Abortion Pill," TIME, October 9, 2000, p. 43.

10. FDA, "Mifepristone Approval Letter," September 28, 2000, available at www.fda.gov/cder/foi/appletter/200/20687appltr.htm and FDA, "Office Memo to Population Council," September 28, 2000, at www.fda.gov/cder/drug/infopage/mifepristone .

11. FDA, "Office Memo to Population Council," September 28, 2000, at www.fda.gov/cder/drug/infopage/mifepristone/memo.pdf, p. 5.

12. FDA, "Office Memo to Population Council," September 28, 2000, at www.fda.gov/cder/drug/infopage/mifepristone/memo.pdf, p. 5.

13. FDA, "Office Memo to Population Council," September 28, 2000, at www.fda.gov/cder/drug/infopage/mifepristone/memo.pdf, p. 5.

14. FDA, "Office Memo to Population Council," September 28, 2000, at www.fda.gov/cder/drug/infopage/mifepristone/memo.pdf, pp. 2-3.

15. Carole Joffe, "Medical Abortion and the Potential for New Abortion Providers: A Cautionary Tale," Journal of the American Medical Women's Association, Vol. 55, No. 3 (Supplement 2000), pp. 151-154. See also Sherry Kay Stolberg, "FDA Adds Hurdles in Approval of Abortion Pill," New York Times, June 8, 2000.

16. Carole Joffe, "Reactions to Medical Abortion Among Providers of Surgical Abortion: An Early Snapshot," Family Planning Perspectives, Vo. 31, No. 1 (January-February 2000), pp. 35-38.

17. National Abortion Federation News Release, Statement of Vicki Saporta, Executive Director, "National Abortion Federation Opposes Legislation That Would Impose Restrictions on Mifepristone (RU-486) Already Rejected As Medically Unnecessary by the FDA," February 6, 2001.

18. Maureen Paul, et al, "Appendix: National Abortion Federation 1998 Clinical Policy Guidelines," republished in A Clinician's Guide to Medical and Surgical Abortion (New York: Churchill Livingstone, 1999), p. 256.

19. Mifeprex "Prescriber's Agreement Form" available at www.fda.gov/cder/drug/infopage/mifepristone/prescriberagreement.pdf . See also FDA "Office Memo to Population Council," www.fda.gov/cder/drug/infopage/mifepristone/memo.pdf , pp. 4-5.

20. FDA "Office Memo to Population Council," www.fda.gov/cder/drug/infopage/mifepristone/memo.pdf , p. 6.

21. Carole Joffe, "Reactions to Medical Abortion Among Providers of Surgical Abortion: An Early Snapshot," Family Planning Perspectives, Vo. 31, No. 1 (January-February 2000), pp. 35-38.

22. Thomas H. Maugh II, "Abortion Drug Is Safe, U.S. Study Finds," Los Angleles Times, April 30, 1998, p. A4.

23. Irving M. Spitz, C. Wayne Bardin, Lauri Benton, and Ann Robbins, "Early Pregnancy Termination with Mifepristone and Misoprostol in the United States," New England Journal of Medicine, Vol. 338, No. 18 (April 30, 1998), pp. 1241-1247.

24. Mifeprex label, available at www.fda.gov/cder/foi/label/2000/20687lbl.pdf Also see O.M Avrech, et al, "Mifepristone (RU486) alone or in combination with a prostaglandin analogue for termination of early pregnancy: a review," Fertility & Sterility, Vol 56 (1991), pp. 385-293.

25. Maureen Paul, et al, A Clinician's Guide to Medical and Surgical Abortion (New York: Churchill Livingstone, 1999), pp. 41, 50.

26. Irving M. Spitz, C. Wayne Bardin, Lauri Benton, and Ann Robbins, "Early Pregnancy Termination with Mifepristone and Misoprostol in the United States," New England Journal of Medicine, Vol. 338, No. 18 (April 30, 1998), pp. 1241-1247.

27. F. Gary Cunningham, et al, "Chapter 32: Ectopic Pregnancy," Williams Obstetrics, 19^th ed. (Norwalk, CT: Appleton & Lange, 1993), pp. 691-719, particularly, pp. 696, 705..

28. FDA "Mifepristone Hearing" transcript of Reproductive Health Drugs Advisory Committee meeting, July 19, 1996, pp. 48-49, available at www.fda.gov/ohrms/dockets/ac/96/transcpt . C. Wayne Bardin, the doctor who oversaw the new drug application for the Population Council, told the FDA advisory panel that 65% of all "adverse events" that were reported were observed during the 4-5 hours the women spent in the clinic after taking the misoprostol.

29. The case of Dr. Mark Louviere, reported in the September 24, 1995 edition of the Waterloo Courier (p. F3), is instructive. Louviere's patient was fortunate that he recognized her danger and rushed her to emergency surgery.

30. 21 CFR 314.500-314.560

31. Christine Gorman, "Let's not be too hasty," TIME, September 19, 1994 (Vol. 144, No. 12); available at www.time.com/time/magazine/archive/1994/940919/940919.medicine.html .

32. Department of Health and Human Services, Food and Drug Administration, Final Rule, 21 CFR, Parts 314 and 601, "New Drug, Antibiotic, and Biologic Product Regulations; Accelerated Approval," Federal Register, 57 FR 58942, December 11, 1992.

33. FDA, "Office Memo to Population Council," September 28, 2000, at www.fda.gov/cder/drug/infopage/mifepristone/memo.pdf, p. 6.

34. Department of Health and Human Services, Food and Drug Administration, Final Rule, 21 CFR, parts 314 and 601, "New Drug, Antibiotic, and Biologic Product Regulations; Accelerated Approval," Federal Register, 57 FR 58942, December 11, 1992.

35. FDA, "Press Release on Mifepristone Approval," available at www.fda.gov/bbs/topics/NEWS/NEW00737.html .

36. 36. William J. Clinton, "Memorandum for the Secretary of Health and Human Services; Subject: Importation of RU-486," January 22, 1993.

37. Transcript of FDA Advisory Panel, "Mifepristone for..." July 19, 1996, p. ....

38. FDA, "Approvable Letter for Mifepristone 2/18/96" [FDA typo, should read 9/18/96], available at www.fda.gov/cder/foi/nda/2000/2087_Mifepristone_approvableltr.pdf .

39. Sarah Lueck, "Groups Offer Abortion-Drug Variations," Wall Street Journal, October 30. 2000, p. B2.

40. Irving M. Spitz, C. Wayne Bardin, Lauri Benton, and Ann Robbins, "Early Pregnancy Termination with Mifepristone and Misoprostol in the United States," New England Journal of Medicine, Vol. 338, No. 18 (April 30, 1998), pp. 1241-1247.

41. FDA, "Mifepristone Medication Guide,"available at www.fda.gov/cder/drug/infopage/mifepristone/medguide.htm.

42. Philip P. Pan, "Chinese To Make RU-486 For U.S.," Washington Post, October 12, 2000, p. A1.

43. Rep. Chris Smith (R-NJ) raises a similar concern in AP reporter Paul Recer's wire story "Abortion Pill," October 13, 2000.

44. Rachel Zimmerman, "Awaiting Green Light, Abortion Pill Venture Keeps to the Shadows," Wall Street Journal, September 5, 2000.

45. Rachel Zimmerman, "Awaiting Green Light, Abortion-Pill Venture Keeps to the Shadows," Wall Street Journal, September 5, 2000. Zimmerman quotes internal documents saying that Danco expects to be used for 29% of all abortions in the U.S. after 4 years. With annual abortions now running about 1.3 million a year (according to the Alan Guttmacher Institute, quoted in the New York Times, 12/30/00), even this optimistic prediction would represent only about 385,000 sales a year, a relatively small demand in the large U.S. pharmaceutical market. See AP, "Novartis tops Merck in global drug sales," Bergen Record, March 24, 1999.

46. Michael Cullen, Medical Director, U.S., Searle, "Important Drug Warning Concerning Unapproved Use of Intravaginal or Oral Misoprostol in Pregnant Women for Induction of Labor or Abortion," Letter to Health Care Practitioners, August 23, 2000. In an earlier letter, Searle Vice President Charles L. Fry, specifically said that Searle did not want its product used in conjunction with RU486 for abortion ("Searle Against Use Of Its Drug in Abortion" Letter to the Editor, Wall Street Journal, March 19, 1993, p. A11).

47. Melissa Glim, "Pharmacia's Actions Could Stall RU486 Availability," Physician's Weekly, Vol. XVII, No. 43 (November 13, 2000). Available on line at www.physweekly.com/archive/00/11_13_00/itn2.html .

48. FDA "Office Memo to Population Council," www.fda.gov/cder/drug/infopage/mifepristone/memo.pdf , p. 6.

49. Philip P. Pan, "Chinese To Make RU-486 For U.S.," Washington Post, October 12, 2000, p. A1.

50. Letter from Rep. Tom Bliley (R-VA), Chair of the U.S. House Commerce Committee, to Jane Henney, M.D., FDA Commissioner, September 25, 2000.

51. Rep. Chris Smith (R-NJ) raises this sort of concern in AP reporter Paul Recer's wire story, "Abortion Pill," AP Financial, October 13, 2000.

52. Aaron Zitner, "RU-486 Firm Tied to Impurities," Los Angeles Times, October 20, 2000.

53. Letters from Rep. Tom Bliley, Chair, U.S. House of Representatives Commerce Commitee, to Jane Henney, M.D., Commissioner, Food and Drug Administration, October 18, 2000, and November 1, 2000.

54. Letter from Rep. Tom Bliley, Chair, U.S. House of Representatives Commerce Commitee, to Jane Henney, M.D., Commissioner, Food and Drug Administration, October 18, 2000, p.4.

55. Letter from Rep. Tom Bliley, Chair, U.S. House of Representatives Commerce Commitee, to Jane Henney, M.D., Commissioner, Food and Drug Administration, October 18, 2000, p. 4.

56. Letter from Rep. Tom Bliley, Chair, U.S. House of Representatives Commerce Committee, to Jane Henney, M.D., Commissioner, Food and Drug Administration, October 18, 2000, p. 5.

57. Regina Sitruk-Ware, a representative of Exelgyn, the current French supplier, told a 1998 Population Council sponsored conference that the Chinese synthesis for the abortion pill is different from the one developed by the French and said only that the pills are "very similar." See "Strategy for the introduction of Mifepristone," Population Council and The Wellcome Trust Conference, Towards Safe and Effective Use of Medical Abortion, Bermuda, January 10-13, 1998, Report of Meeting, p. 16.

58. Lawrence Lader, A Private Matter (New York: Prometheus Books, 1995), p. 227.

59. FDA, "Mifepristone Approval Letter," September 28, 2000, pp. 2-3. Available at www.fda.gov/cder/foi/appletter/200/20687appltr.htm .

60. Associated Press, "Iowa 'abortion pill' test heralded as a success," Des Moines Register, September 2, 1995. Dr. Mark Louviere, "Group lied when it said 'abortion pill' test resulted in no complications," Waterloo Courier, September 24, 1995, p. F3. Tom Carney, "'Abortion pill' test goes awry for one patient," Des Moines Register, September 21, 1995, p. 1M.

61. Carol Jouzaitis, "Doctor's abortion-drug technique draws fire," Chicago Tribune, September 12, 1994, Section 1, pp. 1, 14.

62. Statement of Vicki Saporta, Executive Director, National Abortion Federation, February 6, 2001.

63. Mifeprex Label, available at www.fda.gov/cder/foi/label/2000/20687lbl.htm .

64. Michael A. Friedman, M.D., "Manufacturer's Warning Regarding Unapproved Uses of Misoprostol," New England Journal of Medicine, Vol. 344, No. 1 (January 4, 2001), p. 61.

65. Charles L. Fry, Letter to the Editor, "Searle Against Use of Its Drug in Abortion," Wall Street Journal, March 19, 1993, p. A11.

66. Mifeprex Label, available at www.fda.gov/cder/foi/label/2000/20687lbl.htm .

67. "Searle/FDA Cytotec Labeling Negotiations Continue Ahead Of Mifeprex Launch," F-D-C Reports "The Pink Sheet," October 9, 2000, p. 11.

68. "RU-486 availability on campuses" USA Today, available at www.usatoday.com/news/health/2001-04-17.abortion-pill-campus.htm . See also "RU-486 debate replaying on college campuses," USA Today, available at www.usatoday.com/news/health/2001-04-17.pill.htm .

69. Robert Gold, "Many schools opt not to offer RU-486 pill" Michigan Daily, November 27, 2000, via COMTEX Newswire, 11/27/00.

70. Darlene Superville, "Abortion Pill-Colleges," Associated Press, April 17, 2001.

71. Gina Kolata, "Wary Doctors Spurn New Abortion Pill," New York Times, November 14, 2000, pp. D1,7.

72. Gina Kolata, "Wary Doctors Spurn New Abortion Pill," New York Times, November 14, 2000, pp. D1,7.

73. Carole Joffe, "Medical Abortion in social context," Supplement to American Journal of Obstetrics & Gynecology, vol. 83, no. 2 (August 2000), pp. 512-513. See also Carole Joffe, "Reactions to Medical Abortion Among Providers of Surgical Abortion: An Early Snapshot," Family Planning Perspectives, Vo. 31, No. 1 (January-February 2000), pp. 35-38.

74. National Abortion Federation, "Statement" September 18, 2000.

75. Gina Kolata, "Wary Doctors Spurn New Abortion Pill," New York Times, November 14, 2000, p. D7.

76. Rachel Zimmerman, "Wrangling Over Abortion Intensifies as RU486 Pill Nears the Market," Wall Street Journal, November 14, 2000, p. B1.

77. Gina, Kolata, "As Abortion Rate Decreases, Clinics Compete for Patients," New York Times, December 30, 2000.