On August 24, 2006, the Food and Drug Administration (FDA) announced the approval of an application to switch Plan B, an emergency contraceptive, from a prescription-only drug to an over-the-counter (OTC) drug for women 18 years of age and older. Plan B will only be sold OTC in pharmacies or healthcare clinics. It will continue to be dispensed as a prescription drug for women 17 years old and younger. Both men and women will be able to purchase Plan B, but all individuals will need to show the pharmacist identification for proof of age before purchasing the OTC version. Anonymous shoppers will be used to test compliance with the age restriction. A booklet will be distributed with Plan B that explains proper use of the drug. The manufacturer, Barr Pharmaceuticals, began shipping the OTC version of the drug to U.S. pharmacies early in November 2006. Approval of the switch to OTC for Plan B has been controversial. Critics believe that initial policy decisions made by the Bush Administration regarding Plan B were based on political and ideological considerations rather than on sound science. Conservative religious and pro-life groups believe that readily available Plan B may increase the occurrence of unsafe sexual activity and that such a drug should be used only under the supervision of a healthcare professional. Their primary concern with Plan B, however, is that it might prevent the implantation of the embryo in the uterus, which, for those who believe human life begins at conception, would constitute an abortion. However, the medical community does not consider prevention of implantation to be an abortion, and FDA does not classify Plan B as an abortion drug. Although the precise mechanism of action remains undetermined, scientific evidence suggests that prevention of ovulation or fertilization is the most likely mode of action for Plan B, rather than prevention of implantation of a developing embryo. This report discusses the FDA approval of Plan B as a prescription drug, as well as the more recent and controversial FDA approval of Plan B as an OTC drug. Legal issues regarding the recent FDA decision are also discussed as well as various state policies that affect access to emergency contraceptives. In addition, the report discusses the Department of Justice guidelines for the treatment of sexual assault victims, which have been criticized by numerous organizations because they do not mention offering emergency contraception to female rape victims. The DOJ guidelines were the focus of legislation introduced in the 109 th Congress. Lastly, this report discusses the likely impact of the FDA Plan B OTC decision. Emergency contraception is a therapy that may prevent pregnancy for women who have had unprotected sexual intercourse. There are two methods of emergency contraceptive therapy: insertion of an intrauterine devise, or IUD, within five days of intercourse; or, ingestion of a pill containing the hormones commonly found in the contraceptive pill. Although hormonal emergency contraception is often referred to as the "morning-after pill," it can be given up to 72 hours after unprotected intercourse and can involve taking more than one pill. Reasons for using emergency contraception include problems with a contraceptive (condom breakage, missed pill), sexual assault, or exposure to an agent which may cause a birth defect (e.g., live vaccine, cytotoxic drug, or radiation). The current approach to emergency conception began with the recognition in the 1920s that estrogen prevented pregnancy in mammals. In the mid-1960s, a Dutch physician gave high-dose estrogen to a 13-year-old rape victim in order to prevent pregnancy. During the 1960s and 1970s high-dose estrogen became the standard emergency contraceptive treatment. In the early 1970s, Canadian physician A. Albert Yuzpe began studying emergency contraception and published his first study in 1974. The Yuzpe method used conventional birth control pills, a combination of estrogen and progestin, taken in two doses 12 hours apart. In 1984, the United Kingdom became the first country to approve such a combination pill regimen as an emergency contraceptive. In January 2001, the United Kingdom began allowing pharmacies to dispense emergency contraception without a prescription. In April 2005, an emergency contraceptive (Plan B, a progestin-only pill) was approved by the Canadian government for use by all women without a prescription. Emergency contraceptive pills are used by women in more than 100 countries; in over 40 countries the pills are sold without prescription either by a pharmacist or OTC (see Table 1 , below). Following the 1974 publication by Yuzpe, physicians often instructed patients to take multiple pills from a standard one-cycle oral contraceptive package for emergency contraception; this is referred to as an "off-label" use of the drug. On February 25, 1997, a notice in the Federal Register stated that the Commissioner of FDA had concluded that certain oral contraceptives are safe and effective for use as emergency contraception and asked manufacturers to submit a new drug application for this use. In 1998, FDA approved Preven for use as an emergency contraceptive available by prescription. Preven utilized the Yuzpe method; two pills, containing estrogen and progestin, taken 12 hours apart. A 1993 study conducted on about 800 women in Hong Kong found that use of progestin alone was somewhat more effective for emergency contraception than the Yuzpe method and had fewer side effects. In 1998, the World Health Organization (WHO) followed up with a larger international trial using almost 2,000 women comparing the Yuzpe method and a progestin-only pill. The WHO trial found that progestin alone was significantly more effective than the Yuzpe method at preventing pregnancy, and caused fewer side effects. Most importantly, for either method, the WHO trial found that the earlier the pill is taken, the better it works. In the WHO trial, the progestin-alone regimen reduced the risk of pregnancy by 85% when taken within 72 hours of intercourse. Progestin prevented 95% of expected pregnancies when taken within 24 hours, 85% when taken between 25 and 48 hours, and 58% when taken between 49 and 72 hours. In contrast, Yuzpe reduced the risk of pregnancy by 57% when taken within 72 hours. Yuzpe prevented 77% of expected pregnancies when taken within 24 hours, 36% for 25 to 48 hours, and 31% for 49 to 72 hours. WHO also found that the Yuzpe method resulted in significantly more side effects than progestin alone. The incidence of nausea was 50% with Yuzpe and 23% with progestin. Vomiting with Yuzpe was 3 times higher than with progestin (19% vs. 6%), which is significant as women who vomit after taking the first combination pill may need to take an extra dose. On July 28, 1999, FDA approved Plan B, a progestin-only emergency contraceptive, for use by prescription. Plan B consists of two pills each containing 0.75 mg of levonorgestrel (a progestin). One pill is taken as soon as possible after unprotected intercourse and the second is taken 12 hours later. The FDA-approved labeling for Plan B states that it is 89% effective if taken within three days (72 hours) after unprotected sex. In other words, 7 of every 8 women who would have become pregnant will not become pregnant. As mentioned earlier, Plan B is even more effective (95%) if taken within 24 hours of unprotected sex. In humans, the fertile days when sexual intercourse can result in pregnancy include the five days before ovulation (release of the egg from the ovary) and the day of ovulation. Although the precise mechanism of action by which Plan B prevents pregnancy remains undetermined, scientific evidence suggests that prevention of ovulation or fertilization is the most likely mode of action for Plan B, rather than prevention of implantation. The active ingredient in Plan B, levonorgestrel, has been used in birth control pills for more than 35 years. Emergency contraception is not as effective as the regular use of oral contraceptives. However, the higher dose of levonorgestrel in Plan B works like a birth control pill to prevent pregnancy, most probably by stopping ovulation. Several studies indicate that hormonal emergency contraception interferes with the events in the ovary that lead up to release of the egg. Plan B may also interfere with fertilization by altering the transport of sperm and/or egg within the female reproductive system. In one study, administration of levonorgestrel after sexual intercourse reduced the number of sperm within the uterus, increased the pH of the uterine fluid (which immobilized sperm), and increased the viscosity of cervical mucus (which impeded entry of sperm into the uterus). It is possible that Plan B may inhibit implantation of the fertilized egg within the uterus by altering the endometrium (the uterine lining). Three studies of hormonal emergency contraception in human subjects found alterations in the endometrium, but whether such changes had an impact on implantation was "open to question." Four other studies found either negligible or no alterations in the endometrium. However, in the case of levonorgestrel, "publications in refereed journals do not support the hypothesis that it alters endometrial receptivity or impedes implantation." In addition, studies in the rat and monkey indicate that levonorgestrel does not disrupt post-fertilization events such as implantation. Plan B is not effective after the embryo has implanted in the uterus and therefore cannot interfere with an established pregnancy, which is defined as an embryo implanted in a uterus. Plan B is used before a pregnancy can be diagnosed. Plan B does not use the same active ingredient as Mifeprex (also known as the abortion pill, RU-486, or mifepristone). Mifeprex (in combination with misoprostol) is used after a positive pregnancy test to terminate an early pregnancy (up through seven weeks). The fact that there are relatively few side effects for Plan B was a major factor in the approval of OTC status for this drug.