Food and Drug Administration
Agency overview
Formed	1906[1]
Preceding agencies	Food, Drug, and Insecticide Administration (July 1927 to July 1930) Bureau of Chemistry, USDA (July 1901 through July 1927) Division of Chemistry, USDA (established 1862)
Jurisdiction	Federal government of the United States
Headquarters	White Oak Campus, 10903 New Hampshire Avenue, Silver Spring, Maryland 20993 39°02′07″N 76°58′59″W / 39.03528°N 76.98306°W / 39.03528; -76.98306
Employees	9,300 (2008)
Annual budget	$2.3 billion (2008)
Agency executive	Margaret Hamburg, Commissioner of Food and Drugs[2]
Parent agency	Department of Health and Human Services
Child agencies	Center for Biologics Evaluation and Research Center for Devices and Radiological Health Center for Drug Evaluation and Research Center for Food Safety and Applied Nutrition Center for Tobacco Products Center for Veterinary Medicine National Center for Toxicological Research Office of Criminal Investigations Office of Regulatory Affairs
Website
U.S. Food and Drug Administration - Homepage

The Food and Drug Administration (FDA or USFDA) is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments. The FDA is responsible for protecting and promoting public health through the regulation and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), veterinary products, and cosmetics.

The FDA also enforces other laws, notably Section 361 of the Public Health Service Act and associated regulations, many of which are not directly related to food or drugs. These include sanitation requirements on interstate travel and control of disease on products ranging from certain household pets to sperm donation for assisted reproduction.

The FDA is led by the Commissioner of Food and Drugs, appointed by the President with the advice and consent of the Senate. The Commissioner reports to the Secretary of Health and Human Services. The 21st and current Commissioner is Dr. Margaret A. Hamburg. She has served as Commissioner since February 2009.

The FDA has its headquarters at White Oak, Maryland.^[3] The agency also has 223 field offices and 13 laboratories located throughout the 50 states, the United States Virgin Islands, and Puerto Rico.^[4] In 2008, the FDA started opening offices in foreign countries, including China, India, Costa Rica, Chile, Belgium, and the United Kingdom.^[5]

Organization[link]

The FDA comprises several offices and centers. There are

• Office of the Commissioner

• Center for Biologics Evaluation and Research

• Center for Devices and Radiological Health (CDRH)
  • Office of the Center Director
  • Office of Communication, Education, and Radiation Programs
  • Office of Compliance
  • Office of Device Evaluation
  • Office of In Vitro Diagnostic Device Evaluation and Safety
  • Office of Management Operations
  • Office of Science and Engineering Laboratories
  • Office of Surveillance and Biometrics

• Center for Drug Evaluation and Research (CDER)
  • Office of the Center Director
    • Advisory Committee Staff
    • Controlled Substance Staff
      • Uncontrolled regulations
  • Office of Compliance
    • Division of Compliance Risk Management and Surveillance
    • Division of Manufacturing and Product Quality
    • Division of New Drugs and Labeling Compliance
    • Division of Scientific Investigations
  • Office of Medical Policy
    • Division of Drug Marketing, Advertising and Communications
  • Office of New Drugs
  • Office of Nonprescription Products
  • Office of Oncology Drug Products
    • Radioactive Drug Research Committee (RDRC) Program
  • Office of Pharmaceutical Science
    • Office of Biotechnology Products
    • Office of Generic Drugs
    • Office of New Drugs Quality Assessment
    • Office of Testing and Research
      • Division of Applied Pharmacology Research
      • Division of Pharmaceutical Analysis
      • Division of Product Quality Research
        • Informatics and Computational Safety Analysis Staff (ICSAS)
  • Office of Surveillance and Epidemiology (formerly Office of Drug Safety)
  • Office of Translational Sciences
    • Office of Biostatistics
    • Office of Clinical Pharmacology
      • Pharmacometrics Staff
  • Division of Drug Information
    • FDA Pharmacy Student Experiential Program
  • Botanical Review Team
  • Maternal Health Team

• Center for Food Safety and Applied Nutrition
• Center for Tobacco Products
• Center for Veterinary Medicine
• National Center for Toxicological Research
• Office of Regulatory Affairs

In recent years, the agency began undertaking a large-scale effort to consolidate its operations in the Washington Metropolitan Area from its main headquarters in Rockville and several fragmented office buildings in the vicinity to the former site of the Naval Ordnance Laboratory in the White Oak area of Silver Spring, Maryland.^[3][6] When the FDA arrived, the site was renamed from the White Oak Naval Surface Warfare Center to the Federal Research Center at White Oak. The first building, the Life Sciences Laboratory, was dedicated and opened with 104 employees on the campus in December 2003. The project is slated to be completed by 2013.

While most of the Centers are located around the Washington, D.C., area as part of the Headquarters divisions, two offices - the Office of Regulatory Affairs (ORA) and the Office of Criminal Investigations (OCI) - are primarily field offices with a workforce spread across the country.

The Office of Regulatory Affairs is considered the "eyes and ears" of the agency, conducting the vast majority of the FDA's work in the field. Consumer Safety Officers, more commonly called Investigators, are the individuals who inspect production and warehousing facilities, investigate complaints, illnesses, or outbreaks, and review documentation in the case of medical devices, drugs, biological products, and other items where it may be difficult to conduct a physical examination or take a physical sample of the product. The Office of Regulatory Affairs is divided into five regions, which are further divided into 13 districts. Districts are based roughly on the geographic divisions of the federal court system. Each district comprises a main district office, and a number of Resident Posts, which are FDA offices located away from the district office to serve a particular geographic area. ORA also includes the Agency's network of laboratories, which analyze any physical samples taken. Though samples are usually food-related, some laboratories are equipped to analyze drugs, cosmetics, and radiation-emitting devices.

The Office of Criminal Investigations was established in 1991 to investigate criminal cases. Unlike ORA Investigators, OCI Special Agents are armed, and are not focused on the technical aspects of the regulated industries. OCI agents pursue and develop cases where criminal actions have occurred, such as fraudulent claims, or knowingly and willfully shipping known adulterated goods in interstate commerce. In many cases, OCI will pursue cases where Title 18 violations have occurred (e.g. conspiracy, false statements, wire fraud, mail fraud), in addition to prohibited acts as defined in Chapter III of the FD&C Act. OCI Special Agents often come from other criminal investigations backgrounds, and work closely with the Federal Bureau of Investigation, Assistant Attorney General, and even Interpol. OCI will receive cases from a variety of sources, including ORA, local agencies, and the FBI, and will work with ORA investigators to help develop the technical and science-based aspects of a case. OCI is a smaller branch, comprising about 200 agents nationwide.

The FDA frequently works in conjunction with other federal agencies including the Department of Agriculture, Drug Enforcement Administration, Customs and Border Protection, and Consumer Product Safety Commission. Often local and state government agencies also work in cooperation with the FDA to provide regulatory inspections and enforcement action.

Scope and funding[link]

The FDA regulates more than $1 trillion worth of consumer goods, about 25% of consumer expenditures in the United States. This includes $466 billion in food sales, $275 billion in drugs, $60 billion in cosmetics and $18 billion in vitamin supplements. Much of the expenditures is for goods imported into the United States; the FDA is responsible for monitoring a third of all imports.^[7]

The FDA's federal budget request for fiscal year (FY) 2008 (October 2007 through September 2008) totaled $2.1 billion, a $105.8 million increase from what it received for fiscal year 2007.^[8] In February 2008, the FDA announced that the Bush Administration's FY 2009 budget request for the agency was just under $2.4 billion: $1.77 billion in budget authority (federal funding) and $628 million in user fees. The requested budget authority was an increase of $50.7 million more than the FY 2008 funding - about a three percent increase. In June 2008, Congress gave the agency an emergency appropriation of $150 million for FY 2008 and another $150 million.^[7]

Most federal laws concerning the FDA are part of the Food, Drug and Cosmetic Act,^[9] (first passed in 1938 and extensively amended since) and are codified in Title 21, Chapter 9 of the United States Code. Other significant laws enforced by the FDA include the Public Health Service Act, parts of the Controlled Substances Act, the Federal Anti-Tampering Act, as well as many others. In many cases these responsibilities are shared with other federal agencies.

Regulatory programs[link]

Regulation of therapeutic goods in the United States
Prescription drugs Over-the-counter drugs
Law Federal Food, Drug, and Cosmetic Act Comprehensive Drug Abuse Prevention and Control Act of 1970 Controlled Substances Act Prescription Drug Marketing Act Drug Price Competition and Patent Term Restoration Act Hatch-Waxman exemption
Government agencies Department of Health and Human Services -Food and Drug Administration- Department of Justice -Drug Enforcement Administration-
Process Drug discovery Drug design Drug development New drug application Investigational new drug Clinical trial (Phase I, II, III, IV) Randomized controlled trial Pharmacovigilance Abbreviated New Drug Application Fast track approval Off-label use
International coordination International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use Uppsala Monitoring Centre World Health Organization Council for International Organizations of Medical Sciences Single Convention on Narcotic Drugs
Non-governmental organizations Institute of Medicine Research on Adverse Drug events And Reports
v t e

The programs for safety regulation vary widely by the type of product, its potential risks, and the regulatory powers granted to the agency. For example, the FDA regulates almost every facet of prescription drugs, including testing, manufacturing, labeling, advertising, marketing, efficacy and safety, yet FDA regulation of cosmetics is focused primarily on labeling and safety. The FDA regulates most products with a set of published standards enforced by a modest number of facility inspections. Inspection observations are documented on Form 483.

Food and dietary supplements[link]

The Center for Food Safety and Applied Nutrition is the branch of the FDA that is responsible for ensuring the safety and accurate labeling of nearly all food products in the United States.^[10] One exception is meat products derived from traditional domesticated animals, such as cattle and chickens, which fall under the jurisdiction of the United States Department of Agriculture Food Safety and Inspection Service. Products that contain minimal amounts of meat are regulated by FDA, and the exact boundaries are listed in a memorandum of understanding between the two agencies. However, medicines and other products given to all domesticated animals are regulated by the FDA through a different branch, the Center for Veterinary Medicine. Other consumables that are not regulated by the FDA include beverages containing more than 7% alcohol (regulated by the Bureau of Alcohol, Tobacco, Firearms and Explosives in the Department of Justice), and non-bottled drinking water (regulated by the United States Environmental Protection Agency (EPA)).

CFSAN's activities include establishing and maintaining food standards, such as standards of identity (for example, what the requirements are for a product to be labeled, "yogurt") and standards of maximum acceptable contamination. CFSAN also sets the requirements for nutrition labeling of most foods. Both food standards and nutrition labeling requirements are part of the Code of Federal Regulations.

The Dietary Supplement Health and Education Act of 1994 mandated that the FDA regulate dietary supplements as foods, rather than as drugs. Therefore, dietary supplements are not subject to safety and efficacy testing and there are no approval requirements. The FDA can take action against dietary supplements only after they are proven to be unsafe. Manufacturers of dietary supplements are permitted to make specific claims of health benefits, referred to as "structure or function claims" on the labels of these products. They may not claim to treat, diagnose, cure, or prevent disease and must include a disclaimer on the label.^[11]

Bottled water is regulated in America by the FDA.^[12] State governments also regulate bottled water. Tap water is regulated by state and local regulations, as well as the United States EPA. FDA regulations of bottled water generally follow the guidelines established by the EPA, and new EPA rules automatically apply to bottled water if the FDA does not release an explicit new rule.^[13]

Drugs[link]

The Center for Drug Evaluation and Research has different requirements for the three main types of drug products: new drugs, generic drugs and over-the-counter drugs. A drug is considered "new" if it is made by a different manufacturer, uses different excipients or inactive ingredients, is used for a different purpose, or undergoes any substantial change. The most rigorous requirements apply to "new molecular entities": drugs that are not based on existing medications.

New drugs[link]

New drugs receive extensive scrutiny before FDA approval in a process called a New Drug Application or NDA. New drugs are available only by prescription by default. A change to over-the-counter (OTC) status is a separate process, and the drug must be approved through an NDA first. A drug that is approved is said to be "safe and effective when used as directed."

Advertising and promotion[link]

The FDA reviews and regulates prescription drug advertising and promotion. (Other kinds of advertising, including for over-the-counter drugs, are regulated by the Federal Trade Commission). The drug advertising regulation^[14] contains two key requirements. Under most circumstances, a company may advertise a drug only for the specific indication or medical use for which it was approved. Also, an advertisement must contain "fair balance" between the benefits and the risks of a drug.

The term off-label refers to drug usage for indications other than those approved by the FDA.

Postmarket safety surveillance[link]

After approval of an NDA, the sponsor must review and report to the FDA every patient adverse drug experience of which it learns. Unexpected serious and fatal adverse drug events must be reported within 15 days, and other events on a quarterly basis.^[15] The FDA also receives directly adverse drug event reports through its MedWatch program.^[16] These reports are called "spontaneous reports" because reporting by consumers and health professionals is voluntary. While this remains the primary tool of postmarket safety surveillance, FDA requirements for postmarketing risk management are increasing. As a condition of approval, a sponsor may be required to conduct additional clinical trials, called Phase IV trials. In some cases, the FDA requires risk management plans for some drugs that may provide for other kinds of studies, restrictions, or safety surveillance activities.

Generic drugs[link]

Generic drugs are chemical equivalents of name-brand drugs whose patents have expired.^[17] In general, they are less expensive than their name brand counterparts, are manufactured and marketed by other companies and, in the 1990s, accounted for about a third of all prescriptions written in the United States.^[17] For approval of a generic drug, the U.S. Food and Drug Administration (FDA) requires scientific evidence that the generic drug is interchangeable with or therapeutically equivalent to the originally approved drug.^[18] This is called an "ANDA" (Abbreviated New Drug Application).

Generic drug scandal[link]

In 1989, a major scandal erupted involving the procedures used by the FDA to approve generic drugs for sale to the public.^[17] Charges of corruption in generic drug approval first emerged in 1988, in the course of an extensive congressional investigation into the FDA. The oversight subcommitee of the United States House Energy and Commerce Committee resulted from a complaint brought against the FDA by Mylan Laboratories Inc. of Pittsburgh. When its application to manufacture generics were subjected to repeated delays by the FDA, Mylan, convinced that it was being discriminated against, soon began its own private investigation of the agency in 1987. Mylan eventually filed suit against two former FDA employees and four drug-manufacturing companies, charging that corruption within the federal agency resulted in racketeering and in violations of antitrust law. "The order in which new generic drugs were approved was set by the FDA employees even before drug manufacturers submitted applications" and, according to Mylan, this illegal procedure was followed to give preferential treatment to certain companies. During the summer of 1989, three FDA officials (Charles Y. Chang, David J. Brancato, Walter Kletch) pleaded guilty to criminal charges of accepting bribes from generic drugs makers, and two companies (Par Pharmaceutical and its subsidiary Quad Pharmaceuticals)^[19] pleaded guilty to giving bribes. Furthermore, it was discovered that several manufacturers had falsified data submitted in seeking FDA authorization to market certain generic drugs. Vitarine Pharmaceuticals of New York, which sought approval of a generic version of the drug Dyazide, a medication for high blood pressure, submitted Dyazide, rather than its generic version, for the FDA tests. In April 1989, the FDA investigated 11 manufacturers for irregularities; and later brought that number up to 13. Dozens of drugs were eventually suspended or recalled by manufacturers. In the early 1990s, the U.S. Securities and Exchange Commission filed "securities fraud charges against the Bolar Pharmaceutical Company, a major generic manufacturer based in Long Island, New York.^[17]

Over-the-counter drugs[link]

Over-the-counter (OTC) drugs are drugs and combinations that do not require a doctor's prescription. The FDA has a list of approximately 800 approved ingredients that are combined in various ways to create more than 100,000 OTC drug products. Many OTC drug ingredients had been previously approved prescription drugs now deemed safe enough for use without a medical practitioner's supervision.^[20]

Vaccines, blood and tissue products, and biotechnology[link]

The Center for Biologics Evaluation and Research is the branch of the FDA responsible for ensuring the safety and efficacy of biological therapeutic agents.^[21] These include blood and blood products, vaccines, allergenics, cell and tissue-based products, and gene therapy products. New biologics are required to go through a premarket approval process similar to that for drugs. The original authority for government regulation of biological products was established by the 1902 Biologics Control Act, with additional authority established by the 1944 Public Health Service Act. Along with these Acts, the Federal Food, Drug, and Cosmetic Act applies to all biologic products, as well. Originally, the entity responsible for regulation of biological products resided under the National Institutes of Health; this authority was transferred to the FDA in 1972.

Medical and radiation-emitting devices[link]

The Center for Devices and Radiological Health (CDRH) is the branch of the FDA responsible for the premarket approval of all medical devices, as well as overseeing the manufacturing, performance and safety of these devices.^[22] The definition of a medical device is given in the FD&C Act, and it includes products from the simple toothbrush to complex devices such as implantable brain pacemakers. CDRH also oversees the safety performance of non-medical devices that emit certain types of electromagnetic radiation. Examples of CDRH-regulated devices include cellular phones, airport baggage screening equipment, television receivers, microwave ovens, tanning booths, and laser products.

CDRH regulatory powers include the authority to require certain technical reports from the manufacturers or importers of regulated products, to require that radiation-emitting products meet mandatory safety performance standards, to declare regulated products defective, and to order the recall of defective or noncompliant products. CDRH also conducts limited amounts of direct product testing.

FDA-Cleared vs FDA-Approved[link]

Clearance requests are for medical devices that prove they are "substantially equivalent" to the predicate devices already on the market. Approved requests are for items that are new or substantially different and need to demonstrate "safety and efficacy", for example it may be inspected for safety in case of new toxic hazards. Both aspects need to be proved or provided by the submitter to ensure proper procedures are followed.^[23]

Cosmetics[link]

Cosmetics are regulated by the Center for Food Safety and Applied Nutrition, the same branch of the FDA that regulates food. Cosmetic products are not in general subject to premarket approval by the FDA unless they make "structure or function claims", which make them into drugs (see Cosmeceutical). However, all color additives must be specifically approved by the FDA before they can be included in cosmetic products sold in the U.S. The labelling of cosmetics is regulated by the FDA, and cosmetics that have not been subjected to thorough safety testing must bear a warning to that effect.

Cosmetic products[link]

Though the cosmetic industry is predominantly responsible in ensuring the safety of its products, the FDA also has the power to intervene when necessary to protect the public but in general does not require pre-market approval or testing. Companies are required to place a warning note on their products if they have not been tested. Experts in cosmetic ingredient reviews also play a role in monitoring safety through influence on the use of ingredients, but also lack legal authority. Overall the organization has reviewed about 1,200 ingredients and has suggested that several hundred be restricted, but there is no standard or systemic method for reviewing chemicals for safety and a clear definition of what is meant by ‘safety’ so that all chemicals are tested on the same basis.^[24]

Veterinary products[link]

The Center for Veterinary Medicine (CVM) is the branch of the FDA that regulates food, food additives, and drugs that are given to animals, including food animals and pets. CVM does not regulate vaccines for animals; these are handled by the United States Department of Agriculture.

CVM's primary focus is on medications that are used in food animals and ensuring that they do not affect the human food supply. The FDA's requirements to prevent the spread of bovine spongiform encephalopathy are also administered by CVM through inspections of feed manufacturers.

Tobacco products[link]

Since the Family Smoking Prevention and Tobacco Control Act became law in 2009, the FDA also has had the authority to regulate tobacco products.^[25]

In 2009, Congress passed a law requiring color warnings on cigarette packages and on printed advertising, in addition to text warnings from the U.S. Surgeon General.^[26]

The nine new graphic warning labels were announced by the FDA in June 2011 and are required to appear on packaging by September 2012.^[27] R.J. Reynolds, Lorillard, Commonwealth Brands Inc., Liggett Group LLC and Santa Fe Natural Tobacco Company Inc. have filed suit in Washington, D.C. federal court claiming that the graphic labels are an unconstitutional way of forcing tobacco companies to engage in anti-smoking advocacy on the government's behalf.^[28] A First Amendment lawyer, Floyd Abrams, is representing the tobacco companies in the case, contending requiring graphic warning labels on a lawful product cannot withstand constitutional scrutiny.^[29] The Association of National Advertisers and the American Advertising Federation have also filed a brief in the suit, arguing that the labels infringe on commercial free speech and could lead to further government intrusion if left unchallenged.^[30] In November 2011, Federal judge Richard Leon of the U.S. District Court for the District of Columbia temporarily halted the new labels, likely delaying the requirement that tobacco companies display the labels. The U.S. Supreme Court ultimately could decide the matter.^[31]

Regulation of living organisms[link]

With acceptance of premarket notification 510(k) k033391 in January 2004, the FDA granted Dr. Ronald Sherman permission to produce and market medical maggots for use in humans or other animals as a prescription medical device. Medical maggots represent the first living organism allowed by the Food and Drug Administration for production and marketing as a prescription medical device.

In June 2004, the FDA cleared Hirudo medicinalis (medicinal leeches) as the second living organism to be used as a medical devices.

Science and research programs[link]

In addition to its regulatory functions, the FDA carries out research and development activities to develop technology and standards that support its regulatory role, with the objective of resolving scientific and technical challenges before the become impediments. The FDA's research efforts include the areas of biologics, medical devices, drugs, women's health, toxicology, food safety and applied nutrition, and veterinary medicine.^[32]

History[link]

Up until the 20th century, there were few federal laws regulating the contents and sale of domestically produced food and pharmaceuticals, with one exception being the short-lived Vaccine Act of 1813. The history of the FDA can be traced to the latter part of the 19th century and the U.S. Department of Agriculture's Division of Chemistry (later Bureau of Chemistry). Under Harvey Washington Wiley, appointed chief chemist in 1883, the Division began conducting research into the adulteration and misbranding of food and drugs on the American market. Wiley's advocacy came at a time when the public had become aroused to hazards in the marketplace by muckraking journalists like Upton Sinclair, and became part of a general trend for increased federal regulations in matters pertinent to public safety during the Progressive Era.^[33] The 1902 Biologics Control Act was put in place after diphtheria antitoxin was collected from a horse named Jim who contracted tetanus, resulting in several deaths.

In June 1906, President Theodore Roosevelt signed into law the Food and Drug Act, also known as the "Wiley Act" after its chief advocate.^[33] The Act prohibited, under penalty of seizure of goods, the interstate transport of food that had been "adulterated". The act applied similar penalties to the interstate marketing of "adulterated" drugs, in which the "standard of strength, quality, or purity" of the active ingredient was not either stated clearly on the label or listed in the United States Pharmacopoeia or the National Formulary.^[34] The responsibility for examining food and drugs for such "adulteration" or "misbranding" was given to Wiley's USDA Bureau of Chemistry.^[33] Wiley used these new regulatory powers to pursue an aggressive campaign against the manufacturers of foods with chemical additives, but the Chemistry Bureau's authority was soon checked by judicial decisions, which narrowly defined the bureau's powers and set high standards for proof of fraudulent intent.^[33] In 1927, the Bureau of Chemistry's regulatory powers were reorganized under a new USDA body, the Food, Drug, and Insecticide organization. This name was shortened to the Food and Drug Administration (FDA) three years later.^[35]

By the 1930s, muckraking journalists, consumer protection organizations, and federal regulators began mounting a campaign for stronger regulatory authority by publicizing a list of injurious products that had been ruled permissible under the 1906 law, including radioactive beverages, the mascara Lash lure, which caused blindness, and worthless "cures" for diabetes and tuberculosis. The resulting proposed law was unable to get through the Congress of the United States for five years, but was rapidly enacted into law following the public outcry over the 1937 Elixir Sulfanilamide tragedy, in which over 100 people died after using a drug formulated with a toxic, untested solvent.^[36] President Franklin Delano Roosevelt signed the new Food, Drug, and Cosmetic Act (FD&C Act) into law on June 24, 1938. The new law significantly increased federal regulatory authority over drugs by mandating a pre-market review of the safety of all new drugs, as well as banning false therapeutic claims in drug labeling without requiring that the FDA prove fraudulent intent. Soon after passage of the 1938 Act, the FDA began to designate certain drugs as safe for use only under the supervision of a medical professional, and the category of "prescription-only" drugs was securely codified into law by the 1951 Durham-Humphrey Amendment. These developments confirmed extensive powers for the FDA to enforce post-marketing recalls of ineffective drugs.^[33]

In 1959, the thalidomide tragedy, in which thousands of European babies were born deformed after their mothers took that drug - marketed for treatment of nausea - during their pregnancies,^[37] led to the 1962 Kefauver-Harris Amendment to the FD&C Act, which represented a "revolution" in FDA regulatory authority.^[38] The most important change was the requirement that all new drug applications demonstrate "substantial evidence" of the drug's efficacy for a marketed indication, in addition to the existing requirement for pre-marketing demonstration of safety. This marked the start of the FDA approval process in its modern form.

These reforms had the effect of increasing the time required to bring a drug to market.^[39] One of the most important statutes in establishing the modern American pharmaceutical market was the 1984 Drug Price Competition and Patent Term Restoration Act, more commonly known as the "Hatch-Waxman Act" after its chief sponsors. The act extended the patent exclusivity terms of new drugs, and tied those extensions, in part, to the length of the FDA approval process for each individual drug. For generic manufacturers, the Act created a new approval mechanism, the Abbreviated New Drug Application (ANDA), in which the generic drug manufacturer need only demonstrate that their generic formulation has the same active ingredient, route of administration, dosage form, strength, and pharmacokinetic properties ("bioequivalence") as the corresponding brand-name drug. This act has been credited with in essence creating the modern generic drug industry.^[40]

Concerns about the length of the drug approval process were brought to the fore early in the AIDS epidemic. In the mid- and late 1980s, ACT-UP and other HIV activist organizations accused the FDA of unnecessarily delaying the approval of medications to fight HIV and opportunistic infections.^[41] Partly in response to these criticisms, the FDA issued new rules to expedite approval of drugs for life threatening diseases, and expanded pre-approval access to drugs for patients with limited treatment options.^[42] All of the initial drugs approved for the treatment of HIV/AIDS were approved through these accelerated approval mechanisms.^[43]

In two instances, state governments have sought to legalize drugs that have not been approved by the FDA. Because federal law passed pursuant to Constitutional authority overrules conflicting state laws^{[citation needed]}, federal authorities still claim the authority to seize, arrest, and prosecute for possession and sales of these substances, even in states where they are legal under state law. The first wave was the legalization by 27 states of laetrile in the late 1970s. This drug was used as a treatment for cancer, but scientific studies both before and after this legislative trend found it to be ineffective.^[44][45] The second wave concerned medical marijuana in the 1990s and 2000s (decade). Though Virginia passed a law with limited effect in 1979, a more widespread trend began in California in 1996.

Recent and ongoing reforms[link]

Critical Path Initiative[link]

The Critical Path Initiative^[46] is FDA's effort to stimulate and facilitate a national effort to modernize the sciences through which FDA-regulated products are developed, evaluated, and manufactured. The Initiative was launched in March 2004, with the release of a report entitled Innovation/Stagnation: Challenge and Opportunity on the Critical Path to New Medical Products.^[47]

Patients' rights to access unapproved drugs[link]

A 2006 court case, Abigail Alliance v. von Eschenbach, would have forced radical changes in FDA regulation of unapproved drugs. The Abigail Alliance argued that the FDA must license drugs for use by terminally ill patients with "desperate diagnoses," after they have completed Phase I testing.^[48] The case won an initial appeal in May 2006, but that decision was reversed by a March 2007 rehearing. The US Supreme Court declined to hear the case, and the final decision denied the existence of a right to unapproved medications.

Critics of the FDA's regulatory power argue that the FDA takes too long to approve drugs that might ease pain and human suffering faster if brought to market sooner. The AIDS crisis created some political efforts to streamline the approval process. However, these limited reforms were targeted for AIDS drugs, not for the broader market. This has led to the call for more robust and enduring reforms that would allow patients, under the care of their doctors, access to drugs that have passed the first round of clinical trials.^[49][50]

Post-marketing drug safety monitoring[link]

The widely publicized recall of Vioxx, a non-steroidal anti-inflammatory drug now estimated to have contributed to fatal heart attacks in thousands of Americans, played a strong role in driving a new wave of safety reforms at both the FDA rulemaking and statutory levels. Vioxx was approved by the FDA in 1999, and was initially hoped to be safer than previous NSAIDs, due to its reduced risk of intestinal tract bleeding. However, a number of pre- and post-marketing studies suggested that Vioxx might increase the risk of myocardial infarction, and this was conclusively demonstrated by results from the APPROVe trial in 2004.^[51] Faced with numerous lawsuits, the manufacturer voluntarily withdrew it from the market. The example of Vioxx has been prominent in an ongoing debate over whether new drugs should be evaluated on the basis of their absolute safety, or their safety relative to existing treatments for a given condition. In the wake of the Vioxx recall, there were widespread calls by major newspapers, medical journals, consumer advocacy organizations, lawmakers, and FDA officials^[52] for reforms in the FDA's procedures for pre- and post- market drug safety regulation.

In 2006, a congressionally requested committee was appointed by the Institute of Medicine to review pharmaceutical safety regulation in the U.S. and to issue recommendations for improvements. The committee was composed of 16 experts, including leaders in clinical medicinemedical research, economics, biostatistics, law, public policy, public health, and the allied health professions, as well as current and former executives from the pharmaceutical, hospital, and health insurance industries. The authors found major deficiencies in the current FDA system for ensuring the safety of drugs on the American market. Overall, the authors called for an increase in the regulatory powers, funding, and independence of the FDA.^[53][54] Some of the committee’s recommendations have been incorporated into drafts of the PDUFA IV bill, which was signed into law in 2007.^[55]

Pediatric drug testing[link]

Prior to the 1990s, only 20% of all drugs prescribed for children in the United States were tested for safety or efficacy in a pediatric population. This became a major concern of pediatricians as evidence accumulated that the physiological response of children to many drugs differed significantly from those drugs' effects on adults. There were several reasons that not many medical trials were done with children. For many drugs, children represented such a small proportion of the potential market, that drug manufacturers did not see such testing as cost-effective. Also, because children were thought to be ethically restricted in their ability to give informed consent, there were increased governmental and institutional hurdles to approval of these clinical trials, as well as greater concerns about legal liability. Thus, for decades, most medicines prescribed to children in the U.S. were done so in a non-FDA-approved, "off-label" manner, with dosages "extrapolated" from adult data through body weight and body-surface-area calculations.^[56]

An initial attempt by the FDA to address this issue was the 1994 FDA Final Rule on Pediatric Labeling and Extrapolation, which allowed manufacturers to add pediatric labeling information, but required drugs that had not been tested for pediatric safety and efficacy to bear a disclaimer to that effect. However, this rule failed to motivate many drug companies to conduct additional pediatric drug trials. In 1997, the FDA proposed a rule to require pediatric drug trials from the sponsors of New Drug Applications. However, this new rule was successfully preempted in federal court as exceeding the FDA's statutory authority. While this debate was unfolding, Congress used the 1997 Food and Drug Administration Modernization Act to pass incentives that gave pharmaceutical manufacturers a six-month patent term extension on new drugs submitted with pediatric trial data. The act reauthorizing these provisions, the 2002 Best Pharmaceuticals for Children Act, allowed the FDA to request NIH-sponsored testing for pediatric drug testing, although these requests are subject to NIH funding constraints. Most recently, in the Pediatric Research Equity Act of 2003, Congress codified the FDA's authority to mandate manufacturer-sponsored pediatric drug trials for certain drugs as a "last resort" if incentives and publicly funded mechanisms proved inadequate.^[56]

Rules for generic biologics[link]

Since the 1990s, many successful new drugs for the treatment of cancer, autoimmune diseases, and other conditions have been protein-based biotechnology drugs, regulated by the Center for Biologics Evaluation and Research. Many of these drugs are extremely expensive; for example, the anti-cancer drug Avastin costs $55,000 for a year of treatment, while the enzyme replacement therapy drug Cerezyme costs $200,000 per year, and must be taken by Gaucher's Disease patients for life. Biotechnology drugs do not have the simple, readily verifiable chemical structures of conventional drugs, and are produced through complex, often proprietary techniques, such as transgenic mammalian cell cultures. Because of these complexities, the 1984 Hatch-Waxman Act did not include biologics in the Abbreviated New Drug Application (ANDA) process, in essence precluding the possibility of generic drug competition for biotechnology drugs. In February 2007, identical bills were introduced into the House to create an ANDA process for the approval of generic biologics, but were not passed.^[57]

Criticisms[link]

Wikinews has related news: Obama calls food safety system a 'hazard to public health'

The FDA currently has regulatory oversight over a large array of products that affect the health and life of American citizens.^[33] As a result, the FDA's powers and decisions are carefully monitored by several governmental and non-governmental organizations. A $1.8 million 2006 Institute of Medicine report on pharmaceutical regulation in the U.S. found major deficiencies in the current FDA system for ensuring the safety of drugs on the American market. Overall, the authors called for an increase in the regulatory powers, funding, and independence of the FDA.^[58][59]

Nine FDA scientists appealed to then president-elect Barack Obama over pressures from management, experienced during the George W. Bush presidency, to manipulate data, including in relation to the review process for medical devices. Characterized as "corrupted and distorted by current FDA managers, thereby placing the American people at risk," these concerns were also highlighted in the 2006 report^[58] on the agency as well.^[60]

The FDA has also been criticized from the opposite viewpoint, as being too tough on industry. According to an analysis published on the website of the libertarian Mercatus Center as well as published statements by economists, medical practitioners, and concerned consumers, many feel the FDA oversteps its regulatory powers and undermines small business and small farms in favor of large corporations. Three of the FDA restrictions under analysis are the permitting of new drugs and devices, the control of manufacturer speech, and the imposition of prescription requirements. The authors argue that in the increasingly complex and diverse food marketplace, the FDA is not equipped to adequately regulate or inspect food.^[61]

However, in an indicator that the FDA may be too lax in their approval process, in particular for medical devices, a 2011 study by Dr. Diana Zuckerman and Paul Brown of the National Research Center for Women and Families, and Dr. Steven Nissen of the Cleveland Clinic, published in the Archives of Internal Medicine, showed that most medical devices recalled in the last five years for “serious health problems or death” had been previously approved by the FDA using the less stringent, and cheaper, 510(k) process. In a few cases the devices had been deemed so low-risk that they did not need FDA regulation. Of the 113 devices recalled, 35 were for cardiovascular health purposes.^[62]

In 1956 the FDA had moved for the burning of William Reich's books and research materials, which is seen as one of the worst examples of censorship in U.S. history.^[63][64]

See also[link]

	Food portal
	Government of the United States portal
	Health and fitness portal
	Law portal
	Medicine portal

• 100,000,000 Guinea Pigs: Dangers in Everyday Foods, Drugs, and Cosmetics (book)
• Criticism of the Food and Drug Administration
• Drug Efficacy Study Implementation
• European Medicines Agency
• FDA Food Safety Modernization Act
• Food Administration^{[disambiguation needed ]}
• Food and Drug Administration Amendments Act of 2007
• International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)
• Inverse benefit law
• Investigational Device Exemption
• Kefauver Harris Amendment
• Medicines and Healthcare products Regulatory Agency (UK)
• Pharmaceutical company
• The Food Defect Action Levels, an FDA publication

References[link]

Further reading[link]

• Michael Givel (December 2005) Philip Morris’ FDA Gambit: Good for Public Health? Journal of Public Health Policy (26): pp. 450–468.
• Philip J. Hilts. Protecting America's Health: The FDA, Business, and One Hundred Years of Regulation. New York: Alfred E. Knopf, 2003. ISBN 0-375-40466-X
• Thomas J. Moore. Prescription for Disaster: The Hidden Dangers in Your Medicine Cabinet. New York: Simon & Schuster, 1998. ISBN 0-684-82998-3.
• Bartley Madden (July 2010) Free To Choose Medicine: How Faster Access to New Drugs Would Save Countless Lives and End Needless Suffering Chicago: The Heartland Institute, 2010. ISBN 978-1-934791-32-5

External links[link]

Wikimedia Commons has media related to: Food and Drug Administration (United States)

• Food & Drug Administration homepage
• Strategic Plan (in XML)^{[dead link]} - from StratML
• Biologics Centennial: 100 Years of Biologics Regulation^{[dead link]} – from the Food and Drug Administration Home Page
• U.S. FDA CDER Home Page – the Center for Drug Evaluation and Research
• CBER – Center for Biologics Evaluation and Research, FDA
• Past FDA Commissioners
• Agency Presentations

Coordinates: 39°02′07″N 76°58′59″W / 39.03534°N 76.98309°W / 39.03534; -76.98309

v t e Commissioners of Food and Drugs Harvey W. Wiley Carl L. Alsberg Charles A. Browne Walter G. Campbell Paul P. Dunbar Charles W. Crawford George P. Larrick James L. Goddard Herbert L. Ley Charles C. Edwards Alexander M. Schmidt Donald Kennedy Jere E. Goyan Arthur H. Hayes Jr. Frank Edward Young David Aaron Kessler Jane E. Henney Mark McClellan Lester Crawford Andrew von Eschenbach Margaret Hamburg

v t e Agencies of the United States Department of Health and Human Services Secretary of Health and Human Services Deputy Secretary of Health and Human Services Secretariate staff offices Office of the Secretary of Health and Human Services Office of the Deputy Secretary of Health and Human Services Office of Inspector General Organizations under the Assistant Secretary for Health Office of the Assistant Secretary for Health Public Health Service Office of Public Health and Science Administration for Children and Families Administration on Aging Agency for Healthcare Research and Quality Agency for Toxic Substances and Disease Registry Centers for Disease Control and Prevention Centers for Medicare and Medicaid Services Food and Drug Administration Health Resources and Services Administration Indian Health Service National Institutes of Health Substance Abuse and Mental Health Services Administration Public Health Service Commissioned Corps (Surgeon General) Programs National Toxicology Program

v t e Food and Drug Administration of the United States Divisions Center for Biologics Evaluation and Research Center for Devices and Radiological Health Center for Drug Evaluation and Research Center for Food Safety and Applied Nutrition Center for Tobacco Products Center for Veterinary Medicine National Center for Toxicological Research Office of Criminal Investigations Office of Regulatory Affairs Major Acts Family Smoking Prevention and Tobacco Control Act FDA Modernization Act of 1997 Federal Food, Drug, and Cosmetic Act Food Safety Modernization Act Prescription Drug User Fee Act Pure Food and Drug Act Title 21 Regulations & Rules Administrative Law  • Title 21 of the Code of Federal Regulations (CFR) Federal Journal  • Federal Register (FR) Federal Law  • Title 21 of the United States Code (U.S.C.) Commissioners Harvey W. Wiley Carl L. Alsberg Charles A. Browne Walter G. Campbell Paul P. Dunbar Charles W. Crawford George P. Larrick James L. Goddard Herbert L. Ley Charles C. Edwards Alexander M. Schmidt Donald Kennedy Jere E. Goyan Arthur H. Hayes Jr. Frank Edward Young David Aaron Kessler Jane E. Henney Mark McClellan Lester Crawford Andrew von Eschenbach Margaret Hamburg

A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.^[1][2]

Classification[link]

Medications can be classified in various ways,^[3] such as by chemical properties, mode or route of administration, biological system affected, or therapeutic effects. An elaborate and widely used classification system is the Anatomical Therapeutic Chemical Classification System (ATC system). The World Health Organization keeps a list of essential medicines.

A sampling of classes of medicine includes:

1. Antipyretics: reducing fever (pyrexia/pyresis)
2. Analgesics: reducing pain (painkillers)
3. Antimalarial drugs: treating malaria
4. Antibiotics: inhibiting germ growth
5. Antiseptics: prevention of germ growth near burns, cuts and wounds

[edit] Types of medications (type of pharmacotherapy)

For the gastrointestinal tract (digestive system)[link]

• Upper digestive tract: antacids, reflux suppressants, antiflatulents, antidopaminergics, proton pump inhibitors (PPIs), H₂-receptor antagonists, cytoprotectants, prostaglandin analogues
• Lower digestive tract: laxatives, antispasmodics, antidiarrhoeals, bile acid sequestrants, opioid

[edit] For the cardiovascular system

• General: β-receptor blockers ("beta blockers"), calcium channel blockers, diuretics, cardiac glycosides, antiarrhythmics, nitrate, antianginals, vasoconstrictors, vasodilators, peripheral activators
• Affecting blood pressure (antihypertensive drugs): ACE inhibitors, angiotensin receptor blockers, α blockers, calcium channel blockers
• Coagulation: anticoagulants, heparin, antiplatelet drugs, fibrinolytics, anti-hemophilic factors, haemostatic drugs
• Atherosclerosis/cholesterol inhibitors: hypolipidaemic agents, statins.

For the central nervous system[link]

Drugs affecting the central nervous system include: hypnotics, anaesthetics, antipsychotics, antidepressants (including tricyclic antidepressants, monoamine oxidase inhibitors, lithium salts, and selective serotonin reuptake inhibitors (SSRIs)), antiemetics, anticonvulsants/antiepileptics, anxiolytics, barbiturates, movement disorder (e.g., Parkinson's disease) drugs, stimulants (including amphetamines), benzodiazepines, cyclopyrrolones, dopamine antagonists, antihistamines, cholinergics, anticholinergics, emetics, cannabinoids, and 5-HT (serotonin) antagonists.

For pain and consciousness (analgesic drugs)[link]

The main classes of painkillers are NSAIDs, opioids and various orphans such as paracetamol.

For musculo-skeletal disorders[link]

The main categories of drugs for musculoskeletal disorders are: NSAIDs (including COX-2 selective inhibitors), muscle relaxants, neuromuscular drugs, and anticholinesterases.

[edit] For the eye

• General: adrenergic neurone blocker, astringent, ocular lubricant
• Diagnostic: topical anesthetics, sympathomimetics, parasympatholytics, mydriatics, cycloplegics
• Anti-bacterial: antibiotics, topical antibiotics, sulfa drugs, aminoglycosides, fluoroquinolones
• Antiviral drug:
• Anti-fungal: imidazoles, polyenes
• Anti-inflammatory: NSAIDs, corticosteroids
• Anti-allergy: mast cell inhibitors
• Anti-glaucoma: adrenergic agonists, beta-blockers, carbonic anhydrase inhibitors/hyperosmotics, cholinergics, miotics, parasympathomimetics, prostaglandin agonists/prostaglandin inhibitors. nitroglycerin

[edit] For the ear, nose and oropharynx

sympathomimetics, antihistamines, anticholinergics, NSAIDs, steroids, antiseptics, local anesthetics, antifungals, cerumenolyti

[edit] For the respiratory system

bronchodilators, NSAIDs, anti-allergics, antitussives, mucolytics, decongestants
corticosteroids, Beta2-adrenergic agonists, anticholinergics, steroids

[edit] For endocrine problems

androgens, antiandrogens, gonadotropin, corticosteroids, human growth hormone, insulin, antidiabetics (sulfonylureas, biguanides/metformin, thiazolidinediones, insulin), thyroid hormones, antithyroid drugs, calcitonin, diphosponate, vasopressin analogues

[edit] For the reproductive system or urinary system

antifungal, alkalising agents, quinolones, antibiotics, cholinergics, anticholinergics, anticholinesterases, antispasmodics, 5-alpha reductase inhibitor, selective alpha-1 blockers, sildenafils, fertility medications

[edit] For contraception

• Hormonal contraception
• Ormeloxifene
• Spermicide

[edit] For obstetrics and gynecology

NSAIDs, anticholinergics, haemostatic drugs, antifibrinolytics, Hormone Replacement Therapy (HRT), bone regulators, beta-receptor agonists, follicle stimulating hormone, luteinising hormone, LHRH
gamolenic acid, gonadotropin release inhibitor, progestogen, dopamine agonists, oestrogen, prostaglandins, gonadorelin, clomiphene, tamoxifen, Diethylstilbestrol

[edit] For the skin

emollients, anti-pruritics, antifungals, disinfectants, scabicides, pediculicides, tar products, vitamin A derivatives, vitamin D analogues, keratolytics, abrasives, systemic antibiotics, topical antibiotics, hormones, desloughing agents, exudate absorbents, fibrinolytics, proteolytics, sunscreens, antiperspirants, corticosteroids

[edit] For infections and infestations

antibiotics, antifungals, antileprotics, antituberculous drugs, antimalarials, anthelmintics, amoebicides, antivirals, antiprotozoals

[edit] For the immune system

vaccines, immunoglobulins, immunosuppressants, interferons, monoclonal antibodies

[edit] For allergic disorders

anti-allergics, antihistamines, NSAIDs

[edit] For nutrition

tonics, electrolytes and mineral preparations (including iron preparations and magnesium preparations), parenteral nutritional supplements, vitamins, anti-obesity drugs, anabolic drugs, haematopoietic drugs, food product drugs

[edit] For neoplastic disorders

cytotoxic drugs, therapeutic antibodies, sex hormones, aromatase inhibitors, somatostatin inhibitors, recombinant interleukins, G-CSF, erythropoietin

[edit] For diagnostics

contrast media

[edit] For euthanasia

An euthanaticum is used for euthanasia and physician-assisted suicide.

Euthanasia is not permitted by law in many countries, and consequently medicines will not be licensed for this use in those countries.

Administration[link]

Administration is the delivery of a pharmaceutical drug to a patient.

It can be performed in various dosage forms such as pills, tablets, or capsules.

There are also many variations in the routes of administration, including intravenous (into the blood through a vein) and oral administration (through the mouth).

They can be administered all at once as a bolus, at frequent intervals or continuously. Frequencies are often abbreviated from Latin, such as every 8 hours reading Q8H from Quaque VIII Hora.

Legal considerations[link]

Depending upon the jurisdiction, medications may be divided into over-the-counter drugs (OTC) which may be available without special restrictions, and prescription only medicine (POM), which must be prescribed by a licensed medical practitioner. The precise distinction between OTC and prescription depends on the legal jurisdiction. A third category, behind-the-counter medications (BTMs), is implemented in some jurisdictions. BTMs do not require a prescription, but must be kept in the dispensary, not visible to the public, and only be sold by a pharmacist or pharmacy technician. Doctors may also prescribe prescription drugs for off-label use - purposes which the drugs were not originally approved for by the regulatory agency. The Classification of Pharmaco-Therapeutic Referrals helps guide the referral process between pharmacists and doctors.

The International Narcotics Control Board of the United Nations imposes a world law of prohibition of certain medications. They publish a lengthy list of chemicals and plants whose trade and consumption (where applicable) is forbidden. OTC medications are sold without restriction as they are considered safe enough that most people will not hurt themselves accidentally by taking it as instructed. Many countries, such as the United Kingdom have a third category of pharmacy medicines which can only be sold in registered pharmacies, by or under the supervision of a pharmacist.

For patented medications, countries may have certain mandatory licensing programs which compel, in certain situations, a medication's owner to contract with other agents to manufacture the drug. Such programs may deal with the contingency of a lack of medication in the event of a serious epidemic of disease, or may be part of efforts to ensure that disease treating drugs, such as AIDS drugs, are available to countries which cannot afford the drug owner's price.

Prescription practice[link]

Drugs which are prescription only are regulated as such because they can impose adverse effects and should not be used unless necessary. Medical guidelines and clinical trials required for approval are used to help inform doctors' prescription of these drugs, but errors can happen. Reasons to not prescribe drugs such as interactions or side effects are called contraindications.

Errors include overprescription and polypharmacy, misprescription, contraindication and lack of detail in dosage and administrations instructions. In 2000 the definition of a prescription error was studied using a Delphi method conference; the conference was motivated by ambiguity in the what a prescription error and a need to use a uniform definition in studies.^[4]

Development[link]

Drug development is the process by which a drug is created. Drugs can be extracted from natural products (pharmacognosy) or synthesized through chemical processes. The drug's active ingredient will be combined with a "vehicle" such as a capsule, cream, or liquid which will be administered through a particular route of administration. Child-resistant packaging will likely be used in the ultimate package sold to the consumer.

Blockbuster drug[link]

A blockbuster drug is a drug generating more than $1 billion of revenue for its owner each year.^[5][when?]

A report from URCH Publishing estimated that about one third of the pharma market by value is accounted for by blockbusters. About 125 products are blockbusters. The top seller was Lipitor, a cholesterol-lowering medication marketed by Pfizer with sales of $12.5 billion.

In 2009 there were a total of seven new blockbuster drugs, with combined sales of $9.8 billion.

Beyond this purely arbitrary financial consideration,

"In the pharmaceutical industry, a blockbuster drug is one that achieves acceptance by prescribing physicians as a therapeutic standard for, most commonly, a highly prevalent chronic (rather than acute) condition. Patients often take the medicines for long periods."^[6]

The birth control pill Enovid was the first modern drug taken by those not ill for a highly prevalent chronic condition. The focus on highly profitable drugs for chronic conditions and resulting de-emphasis of one-time acute treatment drugs has led to occasional shortages of antibiotics or vaccines, such as the influenza vaccine shortage in the United States.

Leading blockbuster drugs[link]

^*Sales are for the 12 months preceding June 30, 2011.

Environmental impact[link]

Since the 1990s water contamination by pharmaceuticals has been an environmental issue of concern.^[8] Most pharmaceuticals are deposited in the environment through human consumption and excretion, and are often filtered ineffectively by wastewater treatment plants which are not designed to manage them. Once in the water they can have diverse, subtle effects on organisms, although research is limited. Pharmaceuticals may also be deposited in the environment through improper disposal, runoff from sludge fertilizer and reclaimed wastewater irrigation, and leaky sewage.^[8] In 2009 an investigative report by Associated Press concluded that U.S. manufacturers had legally released 271 million pounds of drugs into the environment, 92% of which was the antiseptics phenol and hydrogen peroxide. It could not distinguish between drugs released by manufacturers as opposed to the pharmaceutical industry. It also found that an estimated 250 million pounds of pharmaceuticals and contaminated packaging were discarded by hospitals and long-term care facilities.^[9]

Pharmacoenvironmentology is a branch of pharmacology and a form of pharmacovigilance which deals entry of chemicals or drugs into the environment after elimination from humans and animals post-therapy. It deals specifically with those pharmacological agents that have impact on the environment via elimination through living organisms subsequent to pharmacotherapy, while Ecopharmacology is concerned with the entry of chemicals or drugs into the environment through any route and at any concentration disturbing the balance of ecology (ecosystem), as a consequence. Ecopharmacology is a broad term that includes studies of “PPCPs” irrespective of doses and route of entry into environment.^[10][11][12]

Ecopharmacovigilance is the science and activities associated with the detection, evaluation, understanding and prevention of adverse effects of pharmaceuticals in the environment. This is close to the WHO definition of pharmacovigilance, the science aiming to capture any adverse effects of pharmaceuticals in humans after use.^[13]

The term Environmental Persistent Pharmaceutical Pollutants (EPPP) was suggested in the 2010 nomination of pharmaceuticals and environment as an emerging issue to Strategic Approach to International Chemicals Management (SAICM) by the International Society of Doctors for the Environment (ISDE).

History[link]

Ancient pharmacology[link]

Using plants and plant substances to treat all kinds of diseases and medical conditions is believed to date back to prehistoric medicine.

The Kahun Gynaecological Papyrus, the oldest known medical text of any kind, dates to about 1800 BC and represents the first documented use of any kind of medication.^[14][15] It and other medical papyri describe Ancient Egyptian medical practices, such as using honey to treat infections.

Ancient Babylonian medicine demonstrate the use of prescriptions in the first half of the 2nd millennium BC. Medicinal creams and pills were employed as treatments.^[16]

On the Indian subcontinent, the Atharvaveda, a sacred text of Hinduism whose core dates from the 2nd millennium BC, although the hymns recorded in it are believed to be older, is the first Indic text dealing with medicine. It describes plant-based medications to counter diseases.^[17] The earliest foundations of ayurveda were built on a synthesis of selected ancient herbal practices, together with a massive addition of theoretical conceptualizations, new nosologies and new therapies dating from about 400 BC onwards.^[18] The student of Āyurveda was expected to know ten arts that were indispensable in the preparation and application of his medicines: distillation, operative skills, cooking, horticulture, metallurgy, sugar manufacture, pharmacy, analysis and separation of minerals, compounding of metals, and preparation of alkalis.

The Hippocratic Oath for physicians, attributed to 5th century BC Greece, refers to the existence of "deadly drugs", and ancient Greek physicians imported medications from Egypt and elsewhere.^[19]

The first drugstores were created in Baghdad in the 8th century AD. The injection syringe was invented by Ammar ibn Ali al-Mawsili in 9th century Iraq. Al-Kindi's 9th century AD book, De Gradibus, developed a mathematical scale to quantify the strength of drugs.^[20]

The Canon of Medicine by Ibn Sina (Avicenna), who is considered the father of modern medicine,^[21] reported 800 tested drugs at the time of its completion in 1025 AD.^{[citation needed]} Ibn Sina's contributions include the separation of medicine from pharmacology, which was important to the development of the pharmaceutical sciences.^[22] Islamic medicine knew of at least 2,000 medicinal and chemical substances.^[23]

Medieval pharmacology[link]

Medieval medicine saw advances in surgery, but few truly effective drugs existed, beyond opium and quinine. Folklore cures and potentially poisonous metal-based compounds were popular treatments. Theodoric Borgognoni, (1205–1296), one of the most significant surgeons of the medieval period, responsible for introducing and promoting important surgical advances including basic antiseptic practice and the use of anaesthetics. Garcia de Orta described some herbal treatments that were used.

Modern pharmacology[link]

For most of the 19th century, drugs were not highly effective, leading Oliver Wendell Holmes, Sr. to famously comment in 1842 that "if all medicines in the world were thrown into the sea, it would be all the better for mankind and all the worse for the fishes".^[24]:21

During the First World War, Alexis Carrel and Henry Dakin developed the Carrel-Dakin method of treating wounds with an irrigation, Dakin's solution, a germicide which helped prevent gangrene.

In the inter-war period, the first anti-bacterial agents such as the sulpha antibiotics were developed. The Second World War saw the introduction of widespread and effective antimicrobial therapy with the development and mass production of penicillin antibiotics, made possible by the pressures of the war and the collaboration of British scientists with the American pharmaceutical industry.

Medicines commonly used by the late 1920s included aspirin, codeine, and morphine for pain; digitalis, nitroglycerin, and quinine for heart disorders, and insulin for diabetes. Other drugs included antitoxins, a few biological vaccines, and a few synthetic drugs. In the 1930s antibiotics emerged: first sulfa drugs, then penicillin and other antibiotics. Drugs increasingly became "the center of medical practice".^[24]:22 In the 1950s other drugs emerged including corticosteroids for inflammation, rauwolfia alkloids as tranqulizers and antihypertensives, antihistamines for nasal allergies, xanthines for asthma, and typical antipsychotics for psychosis.^[24]:23-24 As of 2008, thousands of approved drugs have been developed. Increasingly, biotechnology is used to discover biopharmaceuticals.^[24] Recently, multi-disciplinary approaches have yielded a wealth of new data on the development of novel antibiotics and antibacterials and on the use of biological agents for antibacterial therapy.^[25]

In the 1950s new psychiatric drugs, notably the antipsychotic chlorpromazine, were designed in laboratories and slowly came into preferred use. Although often accepted as an advance in some ways, there was some opposition, due to serious adverse effects such as tardive dyskinesia. Patients often opposed psychiatry and refused or stopped taking the drugs when not subject to psychiatric control.

Governments have been heavily involved in the regulation of drug development and drug sales. In the U.S., the Elixir Sulfanilamide disaster led to the establishment of the Food and Drug Administration, and the 1938 Federal Food, Drug, and Cosmetic Act required manufacturers to file new drugs with the FDA. The 1951 Humphrey-Durham Amendment required certain drugs to be sold by prescription. In 1962 a subsequent amendment required new drugs to be tested for efficacy and safety in clinical trials.^[24]:24-26

Until the 1970s, drug prices were not a major concern for doctors and patients. As more drugs became prescribed for chronic illnesses, however, costs became burdensome, and by the 1970s nearly every U.S. state required or encouraged the substitution of generic drugs for higher-priced brand names. This also led to the 2006 U.S. law, Medicare Part D, which offers Medicare coverage for drugs.^[24]:28-29

As of 2008, the United States is the leader in medical research, including pharmaceutical development. U.S. drug prices are among the highest in the world, and drug innovation is correspondingly high. In 2000 U.S. based firms developed 29 of the 75 top-selling drugs; firms from the second-largest market, Japan, developed eight, and the United Kingdom contributed 10. France, which imposes price controls, developed three. Throughout the 1990s outcomes were similar.^[24]:30-31

See also[link]

References[link]

External links[link]

• WHO Model List of Essential Medicines
• New Medicines Database | PHRMA
• Informations and Leaflets of approved pharmaceutical drugs | Diagnosia
• SuperCYP: Database for Drug-Cytochrome- and Drug-Drug-interactions