Three general types of Internet pharmacies sell prescription drugs directly to consumers. First, some Internet pharmacies operate much like traditional drugstores, selling a wide range of prescription drugs and requiring consumers to submit a prescription from their physicians before their orders are filled. In some instances, these Internet pharmacies are affiliated with traditional chain drug stores. Second, other Internet pharmacies may sell a more limited range of drugs, often specializing in certain lifestyle medications, such as those that treat sexual dysfunction or assist in weight control. These Internet pharmacies typically require consumers to fill out an online medical history questionnaire in place of a traditional examination by a physician, and issue a prescription after a physician affiliated with the pharmacy reviews the questionnaire. Still other Internet pharmacies dispense drugs without a prescription. In the United States, the practice of pharmacy is regulated by state boards of pharmacy, which establish and enforce standards intended to protect the public. State boards of pharmacy also license pharmacists and pharmacies. To legally dispense a prescription drug, a licensed pharmacist working in a licensed pharmacy must be presented a valid prescription from a licensed health care professional. The requirement that drugs be prescribed and dispensed by licensed professionals helps ensure patients receive the proper dose, take the medication correctly, and are informed about warnings, side effects, and other important information about the drug. Under the Federal Food, Drug, and Cosmetic Act (FDCA), as amended, FDA is responsible for ensuring the safety, effectiveness, and quality of domestic and imported drugs. To do so, FDA establishes standards for the safety, effectiveness, and manufacture of drugs that must be met before they are approved for the U.S. market. To gain approval, a drug manufacturer must demonstrate that a drug is safe and effective, and that the manufacturing methods and controls that will be used in the specific facility where it will be manufactured meet FDA standards. The same drug manufactured in another facility not approved by FDA—such as a foreign- made version of an approved drug—may not be sold legally in the United States. Drugs are subject to other statutory and regulatory standards relating to purity, labeling, manufacturing, and packaging. Failure to meet these standards could result in a drug being considered adulterated or misbranded and therefore illegal for sale, which could result in FDA enforcement action. The FDCA requires that drugs be dispensed with labels that include the name of the prescriber, directions for use, and cautionary statements, among other things. A drug is considered misbranded if its labeling or container is misleading, or if the label fails to include required information. Prescription drugs dispensed without a prescription are also considered misbranded. In addition, if a drug is susceptible to deterioration and must, for example, be maintained in a temperature-controlled environment, it must be packaged and labeled in accordance with regulations and manufacturer standards. Drugs must also be handled to prevent adulteration, which may occur, for example, if held under unsanitary conditions leading to possible contamination. FDA-approved drugs manufactured in foreign countries, including those sold over the Internet, are subject to the same requirements as domestic drugs. Further, imported drugs may be denied entry into the United States if they “appear” to be unapproved, adulterated, or misbranded, among other things. While the importation of such drugs may be illegal, FDA has allowed individuals to bring small quantities of certain drugs into the United States for personal use under certain circumstances. Internet pharmacies pose challenges for regulators. State boards of pharmacy in many states have reported difficulty identifying Internet pharmacies located outside of their borders and have limited ability and authority to investigate and act against pharmacies that do not comply with state pharmacy laws when they are identified. In 2000, nearly half of the state boards had identified consumer complaints against Internet pharmacies or reported problems with Internet pharmacies not complying with state pharmacy laws. Additionally, state medical boards have reported receiving complaints about physicians prescribing drugs over the Internet without performing an examination of the patient. Federal agencies have taken steps to stop the illegal sales of prescription drugs and other substances by Internet pharmacies. For example, FDA has taken enforcement actions against Internet pharmacies; the Department of Justice has prosecuted Internet pharmacies and physicians for dispensing medications without a valid prescription; and DEA has investigated Internet pharmacies for illegal distribution of controlled substances. We were able to obtain the majority of prescription drugs we targeted for purchase from a wide variety of domestic and foreign Internet pharmacies without providing a prescription. Five U.S. and all 18 Canadian pharmacies from which we obtained drug samples required a patient-provided prescription, whereas the remaining 24 U.S. and all 21 other foreign pharmacies from which we obtained samples either provided a prescription based on an online medical questionnaire or had no prescription requirement. Although we obtained samples of most of the drugs we targeted for purchase, some drugs, such as those with special safety restrictions and narcotics, were available from fewer sources or were more difficult to obtain. We obtained 1 or more samples of 11 of the 13 drugs we targeted, both with and without a patient-provided prescription. In total, we placed 90 orders—each with a different Internet pharmacy in the United States, Canada, and other foreign countries—and received 68 samples. Drug samples we received from other foreign pharmacies came from Argentina, Costa Rica, Fiji, India, Mexico, Pakistan, Philippines, Spain, Thailand, and Turkey. Most of the drugs—45 of 68—were obtained without a patient- provided prescription. These included drugs for which physician supervision is of particular importance due to the possibility of severe side effects, such as Accutane, or the high potential for abuse and addiction, such as the narcotic painkiller hydrocodone. (See table 2.) Although most of the samples we received were obtained without a patient- provided prescription, prescription requirements varied. Five U.S. and all 18 Canadian pharmacies from which we obtained drug samples required the patient to provide a prescription. The remaining 24 U.S. pharmacies generally provided a prescription based on a general medical questionnaire filled out online by the patient. Questionnaires requested information on the patient’s physical characteristics, medical history, and condition for which drugs were being purchased. Several pharmacy Web sites indicated that a U.S.-licensed physician reviews the completed questionnaire and issues a prescription. The other foreign Internet pharmacies we ordered from generally had no prescription requirements, and many did not seek information regarding the patient’s medical history or condition. The process for obtaining a drug from many of these pharmacies involved only selecting the desired medication and submitting the necessary billing and shipping information. (See table 3.) While we obtained samples of most of the drugs we targeted for purchase on the Internet, certain drugs were more widely available and easier to purchase than others. The top selling drugs Celebrex (a pain reliever), Lipitor (a cholesterol-lowering drug), Viagra (a medication for male sexual dysfunction), and Zoloft (an antidepressant) were available from multiple pharmacies. We placed 10 orders for each of these four drugs with little difficulty. Other drugs were available from fewer sources or were more difficult to obtain. Some of our orders for drugs with special safety restrictions were more closely scrutinized. For example, one order we placed for Accutane was declined by a U.S. pharmacy. Accutane is an acne medication that may cause birth defects and serious mental disturbances leading to suicide among some users. The pharmacy indicated that it declined our order because the physician was not included on a national registry of qualified prescribers. Similarly, one U.S. and one Canadian Internet pharmacy declined our order for Clozaril. According to its manufacturer, patients taking Clozaril, an antipsychotic medication, must have ongoing blood tests to monitor for the development of a fatal blood disorder that can occur during treatment. The U.S. pharmacy that declined our order indicated that Clozaril should not have been offered for sale on its Web site, and the Canadian pharmacy indicated that more stringent prescription requirements prevented it from dispensing the drug to patients outside of Canada. Narcotic pain medications—OxyContin, Percocet, and Vicodin—were also less readily available. Despite extensive searching of Internet pharmacy sites, we found few that sold these drugs without a prescription. Other factors also hindered our ability to purchase these drugs. For example, some pharmacies that advertised the narcotics did not actually sell them. Rather, they attempted to substitute a different, often less potent and nonnarcotic drug once the order was placed. In addition, several pharmacies that offered narcotics required payment by means that were beyond our scope, such as check, bank transfers, or “e-gold” exchanges. We were able to place orders for the generic version of Vicodin at several U.S. pharmacies; however, some of these pharmacies required not only an online medical questionnaire, but also a telephone consultation with a pharmacy-designated physician in order to obtain a prescription. Finally, we were able to place only one order for a drug purporting to be OxyContin, and only after locating the source by paying a membership fee and joining an Internet pharmacy drug club, which referred us to the site. We identified several problems associated with the handling, FDA-approval status, and authenticity of the 21 drug samples we received from other foreign Internet pharmacies. None included required pharmacy labels that provided patient instructions for use, and few provided warning information. Thirteen were shipped improperly, were packaged unconventionally, or arrived damaged. Manufacturers reported that most of the samples they reviewed at our request from other foreign pharmacies were not approved by FDA for the United States—although most had a comparable chemical composition to the product we ordered—and 4 were either counterfeit products or otherwise not comparable to the product we ordered.