Food and Drug Administration
Encyclopedia
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 supplement
s, prescription
and over-the-counter
pharmaceutical drugs (medications), vaccine
s, biopharmaceutical
s, blood transfusion
s, medical device
s, 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 pet
s 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
.The agency also has 223 field offices and 13 laboratories
located throughout the 50 states
, the United States Virgin Islands
, and Puerto Rico
. In 2008, the FDA started opening offices in foreign countries, including China
, India
, Costa Rica
, Chile
, Belgium
, and the United Kingdom
.
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
. 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.
. 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.
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. 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.
Most federal laws concerning the FDA are part of the Food, Drug and Cosmetic Act, (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.
is the branch of the FDA which is responsible for ensuring the safety and accurate labeling of nearly all food products in the United States. 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 which 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 which 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 supplement
s 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.
Bottled water is regulated in America by the FDA. 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.
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 which are not based on existing medications.
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."
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 contains two key requirements. Under most circumstances, a company may only advertise a drug for the specific indication or medical use for which it was approved. Also, an advertisement must contain "fair balance" between the benefits and risks of a drug.
The term off-label refers to drug usage for indications other than those approved by the FDA.
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.
The FDA also receives directly adverse drug event reports through its MedWatch
program.
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.
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. This is called an "ANDA" (Abbreviated New Drug Application).
In 1989, a major scandal erupted involving the procedures used by the FDA to approve generic drugs for sale to the public. 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) 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.
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.
is the branch of the FDA responsible for ensuring the safety and efficacy of biological therapeutic agents. 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.
(CDRH) is the branch of the FDA responsible for the premarket approval of all medical device
s, as well as overseeing the manufacturing, performance and safety of these devices. 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 pacemaker
s. CDRH also oversees the safety performance of non-medical devices which emit certain types of electromagnetic radiation
. Examples of CDRH-regulated devices include cellular phones, airport baggage screening equipment
, television receivers
, microwave oven
s, tanning booth
s, 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.
requests are for medical devices that are exactly like those already on the market. Approved requests are for items that are completely new and need to be inspected for safety in case of new hazards. Both aspects need to be proved or provided by the submitter to ensure proper procedures are followed.
, the same branch of the FDA that regulates food. Cosmetic products are not generally 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 which have not been subjected to thorough safety testing must bear a warning to that effect.
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 does not generally 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.
(CVM) is the branch of the FDA which 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.
became law in 2009, the FDA also has had the authority to regulate tobacco products
.
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.
The nine new graphic warning labels were announced by the FDA in June 2011 and are required to appear on packaging by September 2012. 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.
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. 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. 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.
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.
to develop technology and standards which 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.
. 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
. 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. The Act prohibited, under penalty of seizure of goods, the interstate transport of food which 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. The responsibility for examining food and drugs for such "adulteration" or "misbranding" was given to Wiley's USDA Bureau of Chemistry. 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. 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.
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 which 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. 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.
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, led to the 1962 Kefauver-Harris Amendment to the FD&C Act, which represented a "revolution" in FDA regulatory authority. 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. 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 importantly 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 essentially creating the modern generic drug industry.
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. 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. All of the initial drugs approved for the treatment of HIV/AIDS were approved through these accelerated approval mechanisms.
In two instances, state governments have sought to legalize drugs which have not been approved by the FDA. Because federal law passed pursuant to Constitutional authority overrules conflicting state laws, 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. The second wave concerned medical marijuana in the 1990s and 2000s. Though Virginia passed a law with limited effect in 1979, a more widespread trend began in California in 1996.
, 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. 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.
now estimated to have contributed to fatal heart attack
s 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. 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 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. Some of the committee’s recommendations have been incorporated into drafts of the PDUFA IV bill which was signed into law in 2007.
, 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.
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 which 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 which 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.
, autoimmune disease
s, 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, essentially 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.
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.
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 on the agency as well.
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.
However, in an indicator that the FDA may be too lax in their approval process, particularly 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.
In 1956 the FDA had moved for the burning of William Reich's books and research materials, which is seen as arguably one of the worst examples of censorship
in U.S. history.
Also the testing process of the TAVI aortic valve replacement device, in use in Europe since 2007 and still clinical trials in the United States, has left patients without an alternative to open heart surgery, which is too risky for many elderly patients.
Government agency
A government or state agency is a permanent or semi-permanent organization in the machinery of government that is responsible for the oversight and administration of specific functions, such as an intelligence agency. There is a notable variety of agency types...
of the United States Department of Health and Human Services
United States Department of Health and Human Services
The United States Department of Health and Human Services is a Cabinet department of the United States government with the goal of protecting the health of all Americans and providing essential human services. Its motto is "Improving the health, safety, and well-being of America"...
, one of the United States federal executive departments
United States Federal Executive Departments
The United States federal executive departments are among the oldest primary units of the executive branch of the federal government of the United States—the Departments of State, War, and the Treasury all being established within a few weeks of each other in 1789.Federal executive...
. The FDA is responsible for protecting and promoting public health
Public health
Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals" . It is concerned with threats to health based on population health...
through the regulation
Regulation
Regulation is administrative legislation that constitutes or constrains rights and allocates responsibilities. It can be distinguished from primary legislation on the one hand and judge-made law on the other...
and supervision of food safety
Food safety
Food safety is a scientific discipline describing handling, preparation, and storage of food in ways that prevent foodborne illness. This includes a number of routines that should be followed to avoid potentially severe health hazards....
, tobacco products
Tobacco products
After tobacco has been processed, it is used to produce a number of different products.- Chewing tobacco :Chewing is one of the oldest ways of consuming tobacco leaves. Native Americans in both North and South America chewed the fresh leaves of the plant, frequently mixed with lime. Modern chewing...
, dietary supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
s, prescription
Prescription drug
A prescription medication is a licensed medicine that is regulated by legislation to require a medical prescription before it can be obtained. The term is used to distinguish it from over-the-counter drugs which can be obtained without a prescription...
and over-the-counter
Over-the-counter drug
Over-the-counter drugs are medicines that may be sold directly to a consumer without a prescription from a healthcare professional, as compared to prescription drugs, which may be sold only to consumers possessing a valid prescription...
pharmaceutical drugs (medications), vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...
s, biopharmaceutical
Biopharmaceutical
Biopharmaceuticals are medical drugs produced using biotechnology. They include proteins , nucleic acids and living microorganisms like virus and bacteria where the virulence of viruses and bacteria is reduced by the process of attenuation, they can be used for therapeutic or in vivo diagnostic...
s, blood transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
s, medical device
Medical device
A medical device is a product which is used for medical purposes in patients, in diagnosis, therapy or surgery . Whereas medicinal products achieve their principal action by pharmacological, metabolic or immunological means. Medical devices act by other means like physical, mechanical, thermal,...
s, electromagnetic radiation
Electromagnetic radiation
Electromagnetic radiation is a form of energy that exhibits wave-like behavior as it travels through space...
emitting devices (ERED), veterinary products
Veterinary medicine
Veterinary Medicine is the branch of science that deals with the prevention, diagnosis and treatment of disease, disorder and injury in non-human animals...
, and cosmetics
Cosmetics
Cosmetics are substances used to enhance the appearance or odor of the human body. Cosmetics include skin-care creams, lotions, powders, perfumes, lipsticks, fingernail and toe nail polish, eye and facial makeup, towelettes, permanent waves, colored contact lenses, hair colors, hair sprays and...
.
The FDA also enforces other laws, notably Section 361 of the Public Health Service Act
Public Health Service Act
The Public Health Service Act is a United States federal law enacted in 1944. The full act is captured under Title 42 of the United States Code "The Public Health and Welfare", Chapter 6A "Public Health Service"....
and associated regulations, many of which are not directly related to food or drugs. These include sanitation
Sanitation
Sanitation is the hygienic means of promoting health through prevention of human contact with the hazards of wastes. Hazards can be either physical, microbiological, biological or chemical agents of disease. Wastes that can cause health problems are human and animal feces, solid wastes, domestic...
requirements on interstate travel
Commerce Clause
The Commerce Clause is an enumerated power listed in the United States Constitution . The clause states that the United States Congress shall have power "To regulate Commerce with foreign Nations, and among the several States, and with the Indian Tribes." Courts and commentators have tended to...
and control of disease on products ranging from certain household pet
Pet
A pet is a household animal kept for companionship and a person's enjoyment, as opposed to wild animals or to livestock, laboratory animals, working animals or sport animals, which are kept for economic or productive reasons. The most popular pets are noted for their loyal or playful...
s to sperm donation
Sperm donation
Sperm donation is the provision by a man, , of his sperm, with the intention that it be used to impregnate a woman who is not usually the man's sexual partner, in order to produce a child....
for assisted reproduction.
The FDA is led by the Commissioner of Food and Drugs, appointed by the President
President of the United States
The President of the United States of America is the head of state and head of government of the United States. The president leads the executive branch of the federal government and is the commander-in-chief of the United States Armed Forces....
with the advice and consent
Advice and consent
Advice and consent is an English phrase frequently used in enacting formulae of bills and in other legal or constitutional contexts, describing a situation in which the executive branch of a government enacts something previously approved of by the legislative branch.-General:The expression is...
of the Senate
United States Senate
The United States Senate is the upper house of the bicameral legislature of the United States, and together with the United States House of Representatives comprises the United States Congress. The composition and powers of the Senate are established in Article One of the U.S. Constitution. Each...
. The Commissioner reports to the Secretary of Health and Human Services. The 21st and current Commissioner is Dr. Margaret A. Hamburg
Margaret A. Hamburg
Dr. Margaret Ann Hamburg is an American physician and medical/public health administrator. She currently serves as Commissioner of the U.S. Food and Drug Administration....
. She has served as Commissioner since February 2009.
The FDA has its headquarters
Headquarters
Headquarters denotes the location where most, if not all, of the important functions of an organization are coordinated. In the United States, the corporate headquarters represents the entity at the center or the top of a corporation taking full responsibility managing all business activities...
at White Oak, Maryland
White Oak, Maryland
White Oak is a census-designated place and an unincorporated area in Montgomery County, Maryland, United States.-Geography:As an unincorporated area, White Oak's boundaries are not officially defined...
.The agency also has 223 field offices and 13 laboratories
Laboratory
A laboratory is a facility that provides controlled conditions in which scientific research, experiments, and measurement may be performed. The title of laboratory is also used for certain other facilities where the processes or equipment used are similar to those in scientific laboratories...
located throughout the 50 states
U.S. state
A U.S. state is any one of the 50 federated states of the United States of America that share sovereignty with the federal government. Because of this shared sovereignty, an American is a citizen both of the federal entity and of his or her state of domicile. Four states use the official title of...
, the United States Virgin Islands
United States Virgin Islands
The Virgin Islands of the United States are a group of islands in the Caribbean that are an insular area of the United States. The islands are geographically part of the Virgin Islands archipelago and are located in the Leeward Islands of the Lesser Antilles.The U.S...
, and Puerto Rico
Puerto Rico
Puerto Rico , officially the Commonwealth of Puerto Rico , is an unincorporated territory of the United States, located in the northeastern Caribbean, east of the Dominican Republic and west of both the United States Virgin Islands and the British Virgin Islands.Puerto Rico comprises an...
. In 2008, the FDA started opening offices in foreign countries, including China
People's Republic of China
China , officially the People's Republic of China , is the most populous country in the world, with over 1.3 billion citizens. Located in East Asia, the country covers approximately 9.6 million square kilometres...
, India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
, Costa Rica
Costa Rica
Costa Rica , officially the Republic of Costa Rica is a multilingual, multiethnic and multicultural country in Central America, bordered by Nicaragua to the north, Panama to the southeast, the Pacific Ocean to the west and the Caribbean Sea to the east....
, Chile
Chile
Chile ,officially the Republic of Chile , is a country in South America occupying a long, narrow coastal strip between the Andes mountains to the east and the Pacific Ocean to the west. It borders Peru to the north, Bolivia to the northeast, Argentina to the east, and the Drake Passage in the far...
, Belgium
Belgium
Belgium , officially the Kingdom of Belgium, is a federal state in Western Europe. It is a founding member of the European Union and hosts the EU's headquarters, and those of several other major international organisations such as NATO.Belgium is also a member of, or affiliated to, many...
, and the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
.
Organization
The FDA comprises several offices and centers. There are- Office of the Commissioner
- Center for Biologics Evaluation and ResearchCenter for Biologics Evaluation and ResearchThe Center for Biologics Evaluation and Research is one of six main centers for the U.S. Food and Drug Administration , which is a part of the U.S. Department of Health and Human Services. The current Director of CBER is Dr. Karen Midthun, M.D...
- Center for Devices and Radiological HealthCenter for Devices and Radiological HealthThe Center for Devices and Radiological Health is the branch of the United States Food and Drug Administration responsible for the premarket approval of all medical devices, as well as overseeing the manufacturing, performance and safety of these devices...
(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 ResearchCenter for Drug Evaluation and ResearchThe Center for Drug Evaluation and Research is a division of the U.S. Food and Drug Administration that monitors most drugs as defined in the Food, Drug, and Cosmetic Act. Some biological products are also legally considered drugs, but they are covered by the Center for Biologics Evaluation and...
(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 Communications8
- 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
- Office of the Center Director
- Center for Food Safety and Applied NutritionCenter for Food Safety and Applied NutritionThe Center for Food Safety and Applied Nutrition is the branch of the United States Food and Drug Administration that regulates food, dietary supplements, and cosmetics .-Area of regulation:...
- Center for Tobacco ProductsCenter for Tobacco ProductsThe Center for Tobacco Products ' was established by the Food and Drug Administration as a result of the Family Smoking Prevention and Tobacco Control Act signed by President Obama in June 2009....
- Center for Veterinary MedicineCenter for Veterinary MedicineThe Center for Veterinary Medicine is a branch of the U.S. Food and Drug Administration that regulates the manufacture and distribution of food, food additives, and drugs that will be given to animals. These include animals from which human foods are derived, as well as food additives and drugs...
- National Center for Toxicological ResearchNational Center for Toxicological ResearchThe National Center for Toxicological Research is the branch of the United States Food and Drug Administration which conducts research to define biological mechanisms of action underlying the toxicity of products regulated by the FDA....
- Office of Regulatory AffairsOffice of Regulatory AffairsThe Office of Regulatory Affairs is the part of the U.S. Food and Drug Administration that enforces the laws governing biologics, cosmetics, drugs, food, medical devices, radiation-emitting electronic devices, tobacco products, and veterinary products which may have potentially harmful side...
In recent years, the agency began undertaking a large-scale effort to consolidate its operations in the Washington Metropolitan Area
Washington Metropolitan Area
The Washington Metropolitan Area is the metropolitan area centered on Washington, D.C., the capital of the United States. The area includes all of the federal district and parts of the U.S...
from its main headquarters in Rockville and several fragmented office buildings in the vicinity to the former site of the Naval Ordnance Laboratory
Naval Ordnance Laboratory
The Naval Ordnance Laboratory , now disestablished, formerly located in White Oak, Maryland was the site of considerable work that had practical impact upon world technology. The White Oak site of NOL has now been taken over by the Food and Drug Administration.-History:The U.S...
in the White Oak area of Silver Spring, Maryland
Silver Spring, Maryland
Silver Spring is an unincorporated area and census-designated place in Montgomery County, Maryland, United States. It had a population of 71,452 at the 2010 census, making it the fourth most populous place in Maryland, after Baltimore, Columbia, and Germantown.The urbanized, oldest, and...
. 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.
Washington, D.C.
Washington, D.C., formally the District of Columbia and commonly referred to as Washington, "the District", or simply D.C., is the capital of the United States. On July 16, 1790, the United States Congress approved the creation of a permanent national capital as permitted by the U.S. Constitution....
, 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
Federal Bureau of Investigation
The Federal Bureau of Investigation is an agency of the United States Department of Justice that serves as both a federal criminal investigative body and an internal intelligence agency . The FBI has investigative jurisdiction over violations of more than 200 categories of federal crime...
, Assistant Attorney General, and even Interpol
Interpol
Interpol, whose full name is the International Criminal Police Organization – INTERPOL, is an organization facilitating international police cooperation...
. 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
United States Department of Agriculture
The United States Department of Agriculture is the United States federal executive department responsible for developing and executing U.S. federal government policy on farming, agriculture, and food...
, Drug Enforcement Administration
Drug Enforcement Administration
The Drug Enforcement Administration is a federal law enforcement agency under the United States Department of Justice, tasked with combating drug smuggling and use within the United States...
, Customs and Border Protection
U.S. Customs and Border Protection
U.S. Customs and Border Protection is a federal law enforcement agency of the United States Department of Homeland Security charged with regulating and facilitating international trade, collecting import duties, and enforcing U.S. regulations, including trade, customs and immigration. CBP is the...
, and Consumer Product Safety Commission
Consumer Product Safety Commission
The United States Consumer Product Safety Commission is an independent agency of the United States government created in 1972 through the Consumer Product Safety Act to protect "against unreasonable risks of injuries associated with consumer products." The CPSC is an independent agency that does...
. Often local and state government agencies also work in cooperation with the FDA to provide regulatory inspections and enforcement action.
Scope and funding
The FDA regulates more than $1 trillion worth of consumer goods, about 25% of consumer expenditures in the United StatesUnited States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
. 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.
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. 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.
Most federal laws concerning the FDA are part of the Food, Drug and Cosmetic Act, (first passed in 1938 and extensively amended since) and are codified in Title 21, Chapter 9 of the United States Code
Title 21 of the United States Code
Title 21 of the United States Code governs Food and Drugs in the United States Code.-Title 21 — Food and Drugs:Title 21 has 26 chapters: — Adulterated or Misbranded Foods or Drugs — [Teas] — Filled Milk...
. Other significant laws enforced by the FDA include the Public Health Service Act
Public Health Service Act
The Public Health Service Act is a United States federal law enacted in 1944. The full act is captured under Title 42 of the United States Code "The Public Health and Welfare", Chapter 6A "Public Health Service"....
, parts of the Controlled Substances Act
Controlled Substances Act
The Controlled Substances Act was enacted into law by the Congress of the United States as Title II of the Comprehensive Drug Abuse Prevention and Control Act of 1970. The CSA is the federal U.S. drug policy under which the manufacture, importation, possession, use and distribution of certain...
, the Federal Anti-Tampering Act, as well as many others. In many cases these responsibilities are shared with other federal agencies.
Regulatory programs
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
The Center for Food Safety and Applied NutritionCenter for Food Safety and Applied Nutrition
The Center for Food Safety and Applied Nutrition is the branch of the United States Food and Drug Administration that regulates food, dietary supplements, and cosmetics .-Area of regulation:...
is the branch of the FDA which is responsible for ensuring the safety and accurate labeling of nearly all food products in the United States. 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
United States Department of Agriculture
The United States Department of Agriculture is the United States federal executive department responsible for developing and executing U.S. federal government policy on farming, agriculture, and food...
Food Safety and Inspection Service
Food Safety and Inspection Service
The Food Safety and Inspection Service , an agency of the United States Department of Agriculture , is the public health agency responsible for ensuring that the nation's commercial supply of meat, poultry, and egg products is safe, wholesome, and correctly labeled and packaged...
. Products which 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
Center for Veterinary Medicine
The Center for Veterinary Medicine is a branch of the U.S. Food and Drug Administration that regulates the manufacture and distribution of food, food additives, and drugs that will be given to animals. These include animals from which human foods are derived, as well as food additives and drugs...
. Other consumables which are not regulated by the FDA include beverages containing more than 7% alcohol (regulated by the Bureau of Alcohol, Tobacco, Firearms and Explosives
Bureau of Alcohol, Tobacco, Firearms and Explosives
The Bureau of Alcohol, Tobacco, Firearms and Explosives is a federal law enforcement organization within the United States Department of Justice...
in the Department of Justice
United States Department of Justice
The United States Department of Justice , is the United States federal executive department responsible for the enforcement of the law and administration of justice, equivalent to the justice or interior ministries of other countries.The Department is led by the Attorney General, who is nominated...
), and non-bottled drinking water (regulated by the United States Environmental Protection Agency
United States Environmental Protection Agency
The U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...
(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
The Food Defect Action Levels
The Food Defect Action Levels: Levels of natural or unavoidable defects in foods that present no health hazards for humans is a publication of the United States Food and Drug Administration's Center for Food Safety and Applied Nutrition detailing acceptable levels of food contamination from sources...
. 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
Code of Federal Regulations
The Code of Federal Regulations is the codification of the general and permanent rules and regulations published in the Federal Register by the executive departments and agencies of the Federal Government of the United States.The CFR is published by the Office of the Federal Register, an agency...
.
The Dietary Supplement Health and Education Act of 1994 mandated that the FDA regulate dietary supplement
Dietary supplement
A dietary supplement, also known as food supplement or nutritional supplement, is a preparation intended to supplement the diet and provide nutrients, such as vitamins, minerals, fiber, fatty acids, or amino acids, that may be missing or may not be consumed in sufficient quantities in a person's diet...
s 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.
Bottled water is regulated in America by the FDA. 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.
Drugs
The Center for Drug Evaluation and ResearchCenter for Drug Evaluation and Research
The Center for Drug Evaluation and Research is a division of the U.S. Food and Drug Administration that monitors most drugs as defined in the Food, Drug, and Cosmetic Act. Some biological products are also legally considered drugs, but they are covered by the Center for Biologics Evaluation and...
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 which are not based on existing medications.
New drugs
New drugs receive extensive scrutiny before FDA approval in a process called a New Drug ApplicationNew drug application
The New Drug Application is the vehicle in the United States through which drug sponsors formally propose that the Food and Drug Administration approve a new pharmaceutical for sale and marketing...
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
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
Federal Trade Commission
The Federal Trade Commission is an independent agency of the United States government, established in 1914 by the Federal Trade Commission Act...
).
The drug advertising regulation contains two key requirements. Under most circumstances, a company may only advertise a drug for the specific indication or medical use for which it was approved. Also, an advertisement must contain "fair balance" between the benefits and risks of a drug.
The term off-label refers to drug usage for indications other than those approved by the FDA.
Postmarket safety surveillance
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.
The FDA also receives directly adverse drug event reports through its MedWatch
MedWatch
MedWatch is the Food and Drug Administration’s reporting system for an adverse event or sentinel event, founded in 1993. An adverse event is any undesirable experience associated with the use of a medical product...
program.
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
Postmarketing surveillance
Postmarketing surveillance is the practice of monitoring the safety of a pharmaceutical drug or device after it has been released on the market and is an important part of the science of pharmacovigilance...
, 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
Generic drugs are chemical equivalents of name-brand drugs whose patents have expired. Generally, 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.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. This is called an "ANDA" (Abbreviated New Drug Application).
Generic drug scandal
In 1989, a major scandal erupted involving the procedures used by the FDA to approve generic drugs for sale to the public. 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.
Mylan Laboratories Inc.
Mylan Inc. is a global generic and specialty pharmaceuticals company headquartered in Canonsburg, Pennsylvania. In 2007, Mylan acquired a controlling interest in India-based Matrix Laboratories Limited, a top producer of active pharmaceutical ingredients for generic drugs, and the generics...
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
Par Pharmaceutical
Par Pharmaceutical develops, manufactures and markets generic and branded specialty pharmaceuticals. Par was founded in 1978 and initially traded on the New York Stock Exchange in 1987...
and its subsidiary Quad Pharmaceuticals) 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
Dyazide
Dyazide is the brand name for a drug marketed by GlaxoSmithKline used to treat hypertension and edema . Dyazide is a combination of triamterene and hydrochlorothiazide...
, 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.
Over-the-counter drugs
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
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
's supervision.
Vaccines, blood and tissue products, and biotechnology
The Center for Biologics Evaluation and ResearchCenter for Biologics Evaluation and Research
The Center for Biologics Evaluation and Research is one of six main centers for the U.S. Food and Drug Administration , which is a part of the U.S. Department of Health and Human Services. The current Director of CBER is Dr. Karen Midthun, M.D...
is the branch of the FDA responsible for ensuring the safety and efficacy of biological therapeutic agents. 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
Biologics Control Act
The Biologics Control Act was passed in the United States on July 1, 1902 after two incidents involving the deaths of children caused by contaminated vaccines. The first involved the horse named Jim whose tetanus-contaminated serum was used to produce a diphtheria antitoxin that caused the deaths...
, with additional authority established by the 1944 Public Health Service Act
Public Health Service Act
The Public Health Service Act is a United States federal law enacted in 1944. The full act is captured under Title 42 of the United States Code "The Public Health and Welfare", Chapter 6A "Public Health Service"....
. Along with these Acts, the Federal Food, Drug, and Cosmetic Act
Federal Food, Drug, and Cosmetic Act
The United States Federal Food, Drug, and Cosmetic Act , is a set of laws passed by Congress in 1938 giving authority to the U.S. Food and Drug Administration to oversee the safety of food, drugs, and cosmetics. A principal author of this law was Royal S. Copeland, a three-term U.S. Senator from...
applies to all biologic products, as well. Originally, the entity responsible for regulation of biological products resided under the National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
; this authority was transferred to the FDA in 1972.
Medical and radiation-emitting devices
The Center for Devices and Radiological HealthCenter for Devices and Radiological Health
The Center for Devices and Radiological Health is the branch of the United States Food and Drug Administration responsible for the premarket approval of all medical devices, as well as overseeing the manufacturing, performance and safety of these devices...
(CDRH) is the branch of the FDA responsible for the premarket approval of all medical device
Medical device
A medical device is a product which is used for medical purposes in patients, in diagnosis, therapy or surgery . Whereas medicinal products achieve their principal action by pharmacological, metabolic or immunological means. Medical devices act by other means like physical, mechanical, thermal,...
s, as well as overseeing the manufacturing, performance and safety of these devices. The definition of a medical device is given in the FD&C Act, and it includes products from the simple toothbrush
Toothbrush
The toothbrush is an oral hygiene instrument used to clean the teeth and gums that consists of a head of tightly clustered bristles mounted on a handle, which facilitates the cleansing of hard-to-reach areas of the mouth. Toothpaste, which often contains fluoride, is commonly used in conjunction...
to complex devices such as implantable brain pacemaker
Brain pacemaker
"Brain pacemakers" are used to treat people who suffer from epilepsy, Parkinson's disease, major depression and other diseases. The pacemaker is a medical device that is implanted into the brain to send electrical signals into the tissue. Depending on the area of the brain that is targeted, the...
s. CDRH also oversees the safety performance of non-medical devices which emit certain types of electromagnetic radiation
Electromagnetic radiation
Electromagnetic radiation is a form of energy that exhibits wave-like behavior as it travels through space...
. Examples of CDRH-regulated devices include cellular phones, airport baggage screening equipment
Airport security
Airport security refers to the techniques and methods used in protecting airports and aircraft from crime.Large numbers of people pass through airports. This presents potential targets for terrorism and other forms of crime due to the number of people located in a particular location...
, television receivers
Television
Television is a telecommunication medium for transmitting and receiving moving images that can be monochrome or colored, with accompanying sound...
, microwave oven
Microwave oven
A microwave oven is a kitchen appliance that heats food by dielectric heating, using microwave radiation to heat polarized molecules within the food...
s, tanning booth
Tanning booth
A tanning booth is a device that emits ultraviolet radiation, usually for the purpose of a cosmetic tan. They are very similar to a tanning bed, but the design is such that it is intended to be used while standing up, rather than lying down....
s, and laser products
Laser
A laser is a device that emits light through a process of optical amplification based on the stimulated emission of photons. The term "laser" originated as an acronym for Light Amplification by Stimulated Emission of Radiation...
.
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
ClearanceClearance
A clearance can refer to:* in chess, A positional move, where a player moves a piece occupying a certain square away, replacing it with an allied piece that will strengthen the player's position....
requests are for medical devices that are exactly like those already on the market. Approved requests are for items that are completely new and need to be inspected for safety in case of new hazards. Both aspects need to be proved or provided by the submitter to ensure proper procedures are followed.
Cosmetics
Cosmetics are regulated by the Center for Food Safety and Applied NutritionCenter for Food Safety and Applied Nutrition
The Center for Food Safety and Applied Nutrition is the branch of the United States Food and Drug Administration that regulates food, dietary supplements, and cosmetics .-Area of regulation:...
, the same branch of the FDA that regulates food. Cosmetic products are not generally subject to premarket approval by the FDA unless they make "structure or function claims", which make them into drugs (see Cosmeceutical
Cosmeceutical
Cosmeceuticals refers to the combination of cosmetics and pharmaceuticals. Cosmeceuticals are cosmetic products with biologically active ingredients purporting to have medical or drug-like benefits....
). 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 which have not been subjected to thorough safety testing must bear a warning to that effect.
Cosmetic products
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 does not generally 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.
Veterinary products
The Center for Veterinary MedicineCenter for Veterinary Medicine
The Center for Veterinary Medicine is a branch of the U.S. Food and Drug Administration that regulates the manufacture and distribution of food, food additives, and drugs that will be given to animals. These include animals from which human foods are derived, as well as food additives and drugs...
(CVM) is the branch of the FDA which 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
United States Department of Agriculture
The United States Department of Agriculture is the United States federal executive department responsible for developing and executing U.S. federal government policy on farming, agriculture, and food...
.
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
Bovine spongiform encephalopathy
Bovine spongiform encephalopathy , commonly known as mad-cow disease, is a fatal neurodegenerative disease in cattle that causes a spongy degeneration in the brain and spinal cord. BSE has a long incubation period, about 30 months to 8 years, usually affecting adult cattle at a peak age onset of...
are also administered by CVM through inspections of feed manufacturers.
Tobacco products
Since the Family Smoking Prevention and Tobacco Control ActFamily Smoking Prevention and Tobacco Control Act
The Family Smoking Prevention and Tobacco Control Act, is a United States federal law that gives the Food and Drug Administration the power to regulate the tobacco industry...
became law in 2009, the FDA also has had the authority to regulate tobacco products
Tobacco products
After tobacco has been processed, it is used to produce a number of different products.- Chewing tobacco :Chewing is one of the oldest ways of consuming tobacco leaves. Native Americans in both North and South America chewed the fresh leaves of the plant, frequently mixed with lime. Modern chewing...
.
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.
The nine new graphic warning labels were announced by the FDA in June 2011 and are required to appear on packaging by September 2012. R.J. Reynolds
R.J. Reynolds
Richard Joshua "R. J." Reynolds was an American businessman and founder of the R. J. Reynolds Tobacco Company....
, Lorillard, Commonwealth Brands Inc., Liggett Group LLC and Santa Fe Natural Tobacco Company
Santa Fe Natural Tobacco Company
The Santa Fe Natural Tobacco Company is a tobacco manufacturer based in Santa Fe, New Mexico, best known for its production of the Natural American Spirit cigarette brand....
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.
A First Amendment lawyer, Floyd Abrams
Floyd Abrams
Floyd Abrams is an American attorney at Cahill Gordon & Reindel. He is an expert on constitutional law, and many arguments in the briefs he has written before the United States Supreme Court have been adopted as United States Constitutional interpretative law as it relates to the First Amendment...
, is representing the tobacco companies in the case, contending requiring graphic warning labels on a lawful product cannot withstand constitutional scrutiny. 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. 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.
Regulation of living organisms
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
In addition to its regulator functions, the FDA carries out research and development activitiesScience policy of the United States
-Agencies involved in science policy:Science policy in the United States is the responsibility of many organizations throughout the federal government...
to develop technology and standards which 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.
History
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 1813Vaccine Act of 1813
The Vaccine Act of 1813 was an Act of the Twelfth Congress of the United States to encourage vaccination against smallpox. It was passed 27-Feb-1813 and repealed 4-May-1822. The Act was the first federal law concerning consumer protection and pharmaceuticals.Dr...
. 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
Muckraker
The term muckraker is closely associated with reform-oriented journalists who wrote largely for popular magazines, continued a tradition of investigative journalism reporting, and emerged in the United States after 1900 and continued to be influential until World War I, when through a combination...
journalists like Upton Sinclair
Upton Sinclair
Upton Beall Sinclair Jr. , was an American author who wrote close to one hundred books in many genres. He achieved popularity in the first half of the twentieth century, acquiring particular fame for his classic muckraking novel, The Jungle . It exposed conditions in the U.S...
, and became part of a general trend for increased federal regulations in matters pertinent to public safety during the Progressive Era
Progressive Era
The Progressive Era in the United States was a period of social activism and political reform that flourished from the 1890s to the 1920s. One main goal of the Progressive movement was purification of government, as Progressives tried to eliminate corruption by exposing and undercutting political...
. The 1902 Biologics Control Act
Biologics Control Act
The Biologics Control Act was passed in the United States on July 1, 1902 after two incidents involving the deaths of children caused by contaminated vaccines. The first involved the horse named Jim whose tetanus-contaminated serum was used to produce a diphtheria antitoxin that caused the deaths...
was put in place after diphtheria
Diphtheria
Diphtheria is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane on the tonsils, pharynx, and/or nasal cavity...
antitoxin was collected from a horse named Jim who contracted tetanus, resulting in several deaths.
In June 1906, President Theodore Roosevelt
Theodore Roosevelt
Theodore "Teddy" Roosevelt was the 26th President of the United States . He is noted for his exuberant personality, range of interests and achievements, and his leadership of the Progressive Movement, as well as his "cowboy" persona and robust masculinity...
signed into law the Food and Drug Act
Pure Food and Drug Act
The Pure Food and Drug Act of June 30, 1906, is a United States federal law that provided federal inspection of meat products and forbade the manufacture, sale, or transportation of adulterated food products and poisonous patent medicines...
, also known as the "Wiley Act" after its chief advocate. The Act prohibited, under penalty of seizure of goods, the interstate transport of food which 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. The responsibility for examining food and drugs for such "adulteration" or "misbranding" was given to Wiley's USDA Bureau of Chemistry. 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. 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.
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 which had been ruled permissible under the 1906 law, including radioactive beverages
Radithor
Radithor was a patent medicine that is a well known example of radioactive quackery. It consisted of triple distilled water containing at a minimum each of the radium 226 and 228 isotopes.-History:...
, the mascara
Mascara
Mascara is a cosmetic commonly used to enhance the eyes. It may darken, thicken, lengthen, and/or define the eyelashes. Normally in one of three forms—liquid, cake, or cream—the modern mascara product has various formulas; however, all contain the same basic components of pigments, oils, waxes, and...
Lash lure, which caused blindness, and worthless "cures" for diabetes and tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
. 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. President Franklin Delano Roosevelt signed the new Food, Drug, and Cosmetic Act
Federal Food, Drug, and Cosmetic Act
The United States Federal Food, Drug, and Cosmetic Act , is a set of laws passed by Congress in 1938 giving authority to the U.S. Food and Drug Administration to oversee the safety of food, drugs, and cosmetics. A principal author of this law was Royal S. Copeland, a three-term U.S. Senator from...
(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
Prescription drug
A prescription medication is a licensed medicine that is regulated by legislation to require a medical prescription before it can be obtained. The term is used to distinguish it from over-the-counter drugs which can be obtained without a prescription...
" drugs was securely codified into law by the 1951 Durham-Humphrey Amendment
Durham-Humphrey Amendment
The Durham-Humphrey Amendment explicitly defined two specific categories for medications, legend and over-the-counter . This amendment was co-sponsored by former vice president and senator Hubert H. Humphrey Jr., who was a pharmacist in South Dakota before beginning his political career...
. These developments confirmed extensive powers for the FDA to enforce post-marketing recalls of ineffective drugs.
In 1959, the thalidomide
Thalidomide
Thalidomide was introduced as a sedative drug in the late 1950s that was typically used to cure morning sickness. In 1961, it was withdrawn due to teratogenicity and neuropathy. There is now a growing clinical interest in thalidomide, and it is introduced as an immunomodulatory agent used...
tragedy, in which thousands of European babies were born deformed after their mothers took that drug - marketed for treatment of nausea - during their pregnancies, led to the 1962 Kefauver-Harris Amendment to the FD&C Act, which represented a "revolution" in FDA regulatory authority. 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. One of the most important statutes in establishing the modern American pharmaceutical market was the 1984 Drug Price Competition and Patent Term Restoration Act
Drug Price Competition and Patent Term Restoration Act
-Overview:The Drug Price Competition and Patent Term Restoration Act, informally known as the "Hatch-Waxman Act" [Public Law 98-417], is a 1984 United States federal law which established the modern system of generic drugs...
, more commonly known as the "Hatch-Waxman Act" after its chief sponsors. The act extended the patent exclusivity terms of new drugs, and importantly 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
Pharmacokinetics
Pharmacokinetics, sometimes abbreviated as PK, is a branch of pharmacology dedicated to the determination of the fate of substances administered externally to a living organism...
properties ("bioequivalence") as the corresponding brand-name drug. This act has been credited with essentially creating the modern generic drug industry.
Concerns about the length of the drug approval process were brought to the fore early in the AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
epidemic. In the mid- and late 1980s, ACT-UP and other HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
activist organizations accused the FDA of unnecessarily delaying the approval of medications to fight HIV and opportunistic infections. 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. All of the initial drugs approved for the treatment of HIV/AIDS were approved through these accelerated approval mechanisms.
In two instances, state governments have sought to legalize drugs which have not been approved by the FDA. Because federal law passed pursuant to Constitutional authority overrules conflicting state laws, 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. The second wave concerned medical marijuana in the 1990s and 2000s. Though Virginia passed a law with limited effect in 1979, a more widespread trend began in California in 1996.
Critical Path Initiative
The Critical Path Initiative 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.Patients' rights to access unapproved drugs
A 2006 court case, Abigail Alliance v. von EschenbachAbigail Alliance v. von Eschenbach
Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach was resolved in early 2008 when the Supreme Court of the United States declined to hear the appeal...
, 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. 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
Criticism of the Food and Drug Administration
Numerous governmental and non-governmental organizations have criticized the U. S. Food and Drug Administration of either over- or under- regulation. The U.S...
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.
Post-marketing drug safety monitoring
The widely publicized recall of Vioxx, a non-steroidal anti-inflammatory drugNon-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs, usually abbreviated to NSAIDs or NAIDs, but also referred to as nonsteroidal anti-inflammatory agents/analgesics or nonsteroidal Anti-inflammatory medicines , are drugs with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory...
now estimated to have contributed to fatal heart attack
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
s 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. 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 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
Institute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...
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
Biostatistics
Biostatistics is the application of statistics to a wide range of topics in biology...
, law, public policy, public health, and the allied health professions, as well as current and former executives from the pharmaceutical, hospital, and health insurance
Health insurance
Health insurance is insurance against the risk of incurring medical expenses among individuals. By estimating the overall risk of health care expenses among a targeted group, an insurer can develop a routine finance structure, such as a monthly premium or payroll tax, to ensure that money is...
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. Some of the committee’s recommendations have been incorporated into drafts of the PDUFA IV bill which was signed into law in 2007.
Pediatric drug testing
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 consentInformed consent
Informed consent is a phrase often used in law to indicate that the consent a person gives meets certain minimum standards. As a literal matter, in the absence of fraud, it is redundant. An informed consent can be said to have been given based upon a clear appreciation and understanding of the...
, there were increased governmental and institutional hurdles to approval of these clinical trials, as well as greater concerns about legal liability
Legal liability
Legal liability is the legal bound obligation to pay debts.* In law a person is said to be legally liable when they are financially and legally responsible for something. Legal liability concerns both civil law and criminal law. See Strict liability. Under English law, with the passing of the Theft...
. 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.
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 which 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 which 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.
Rules for generic biologics
Since the 1990s, many successful new drugs for the treatment of cancerCancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
, autoimmune disease
Autoimmunity
Autoimmunity is the failure of an organism to recognize its own constituent parts as self, which allows an immune response against its own cells and tissues. Any disease that results from such an aberrant immune response is termed an autoimmune disease...
s, and other conditions have been protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
-based biotechnology drugs
Biologics
A biologic is a medicinal product such as a vaccine, blood or blood component, allergenic, somatic cell, gene therapy, tissue, recombinant therapeutic protein, or living cells that are used as therapeutics to treat diseases...
, regulated by the Center for Biologics Evaluation and Research
Center for Biologics Evaluation and Research
The Center for Biologics Evaluation and Research is one of six main centers for the U.S. Food and Drug Administration , which is a part of the U.S. Department of Health and Human Services. The current Director of CBER is Dr. Karen Midthun, M.D...
. 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
Enzyme replacement therapy
Enzyme replacement therapy is a medical treatment replacing an enzyme in patients in whom that particular enzyme is deficient or absent. Usually this is done by giving the patient an intravenous infusion containing the enzyme...
drug Cerezyme
Imiglucerase
Imiglucerase is a medication used in the treatment of Gaucher's disease.It is a recombinant DNA-produced analogue of human β-glucocerebrosidase....
costs $200,000 per year, and must be taken by Gaucher's Disease
Gaucher's disease
Gaucher's disease is a genetic disease in which a fatty substance accumulates in cells and certain organs.Gaucher's disease is the most common of the lysosomal storage diseases. It is caused by a hereditary deficiency of the enzyme glucosylceramidase. The enzyme acts on the fatty acid...
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
Drug Price Competition and Patent Term Restoration Act
-Overview:The Drug Price Competition and Patent Term Restoration Act, informally known as the "Hatch-Waxman Act" [Public Law 98-417], is a 1984 United States federal law which established the modern system of generic drugs...
did not include biologics in the Abbreviated New Drug Application (ANDA) process, essentially 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.
Criticisms
The FDA currently has regulatory oversight over a large array of products that affect the health and life of American citizens. 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 MedicineInstitute of Medicine
The Institute of Medicine is a not-for-profit, non-governmental American organization founded in 1970, under the congressional charter of the National Academy of Sciences...
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.
Nine FDA scientists appealed to then president-elect Barack Obama
Barack Obama
Barack Hussein Obama II is the 44th and current President of the United States. He is the first African American to hold the office. Obama previously served as a United States Senator from Illinois, from January 2005 until he resigned following his victory in the 2008 presidential election.Born in...
over pressures from management, experienced during the George W. Bush
George W. Bush
George Walker Bush is an American politician who served as the 43rd President of the United States, from 2001 to 2009. Before that, he was the 46th Governor of Texas, having served from 1995 to 2000....
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 on the agency as well.
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
Mercatus Center
The Mercatus Center at George Mason University in the United States is a non-profit market-oriented research, education, and outreach think tank affiliated with the Koch family. It works with policy experts, lobbyists, and government officials to connect academic learning and real-world practice...
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.
However, in an indicator that the FDA may be too lax in their approval process, particularly for medical devices, a 2011 study by Dr. Diana Zuckerman
Diana Zuckerman
Diana M. Zuckerman is an expert on national health policy, particularly in women's health. She is the President of the National Research Center for Women & Families as well as the Cancer Prevention and Treatment Fund.-Life and work:...
and Paul Brown of the National Research Center for Women and Families
National Research Center for Women and Families
The National Research Center for Women & Families is a Washington, DC-based non-profit organization founded in 1999. It uses objective, research-based information to encourage new, more effective programs and policies that promote the health and safety of women, children, and families. The...
, and Dr. Steven Nissen of the Cleveland Clinic
Cleveland Clinic
The Cleveland Clinic is a multispecialty academic medical center located in Cleveland, Ohio, United States. The Cleveland Clinic is currently regarded as one of the top 4 hospitals in the United States as rated by U.S. News & World Report...
, 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.
In 1956 the FDA had moved for the burning of William Reich's books and research materials, which is seen as arguably one of the worst examples of censorship
Censorship
thumb|[[Book burning]] following the [[1973 Chilean coup d'état|1973 coup]] that installed the [[Military government of Chile |Pinochet regime]] in Chile...
in U.S. history.
Also the testing process of the TAVI aortic valve replacement device, in use in Europe since 2007 and still clinical trials in the United States, has left patients without an alternative to open heart surgery, which is too risky for many elderly patients.
See also
- 100,000,000 Guinea Pigs: Dangers in Everyday Foods, Drugs, and Cosmetics100,000,000 Guinea Pigs100,000,000 Guinea Pigs: Dangers in Everyday Foods, Drugs, and Cosmetics is a book written by Arthur Kallet and F.J. Schlink first released in 1933 by the Vanguard Press and manufactured in the United States of America...
(book) - Criticism of the Food and Drug AdministrationCriticism of the Food and Drug AdministrationNumerous governmental and non-governmental organizations have criticized the U. S. Food and Drug Administration of either over- or under- regulation. The U.S...
- Drug Efficacy Study ImplementationDrug Efficacy Study ImplementationDrug Efficacy Study Implementation was a program begun by the Food and Drug Administration in the 1960s after the requirement that all drugs be efficacious as well as safe. The DESI program was intended to classify all pre-1962 drugs that were already on the market as either effective,...
- European Medicines AgencyEuropean Medicines AgencyThe European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
- FDA Food Safety Modernization ActFDA Food Safety Modernization ActThe FDA Food Safety Modernization Act was signed into law by President Obama on January 4th, 2011. It aims to ensure the U.S. food supply is safe by shifting the focus of federal regulators from responding to contamination to preventing it...
- Food AdministrationFood AdministrationFood Administration may refer to various past and present organizations with responsibilities related to food in numerous countries and international organizations:- Argentina :...
- Food and Drug Administration Amendments Act of 2007Food and Drug Administration Amendments Act of 2007On September 27, 2007, President of the United States George W. Bush signed the Food and Drug Administration Amendments Act of 2007 into law. This new law is an important step for the Food and Drug Administration . It reviewed, expanded, and reaffirmed several existing pieces of legislation...
- International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH)
- Inverse benefit lawInverse benefit lawThe Inverse Benefit Law states that the ratio of benefits to harms among patients taking new drugs tends to vary inversely with how extensively a drug is marketed...
- Investigational Device ExemptionInvestigational Device ExemptionAn Investigational Device Exemption allows the investigational device to be used in a clinical study in order to collect safety and effectiveness data required to support a Premarket Approval application or a...
- Kefauver Harris AmendmentKefauver Harris AmendmentThe U.S. Kefauver Harris Amendment or "Drug Efficacy Amendment" is a 1962 amendment to the Federal Food, Drug, and Cosmetic Act.It introduced a requirement for drug manufacturers to provide proof of the effectiveness and safety of their drugs before approval...
- Medicines and Healthcare products Regulatory AgencyMedicines and Healthcare products Regulatory AgencyThe Medicines and Healthcare products Regulatory Agency is the UK government agency which is responsible for ensuring that medicines and medical devices work and are acceptably safe....
(UK) - Pharmaceutical companyPharmaceutical companyThe pharmaceutical industry develops, produces, and markets drugs licensed for use as medications. Pharmaceutical companies are allowed to deal in generic and/or brand medications and medical devices...
- The Food Defect Action LevelsThe Food Defect Action LevelsThe Food Defect Action Levels: Levels of natural or unavoidable defects in foods that present no health hazards for humans is a publication of the United States Food and Drug Administration's Center for Food Safety and Applied Nutrition detailing acceptable levels of food contamination from sources...
, an FDA publication
Further reading
- 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
- Food & Drug Administration homepage
- Strategic Plan (in XML) - from StratML
- Biologics Centennial: 100 Years of Biologics Regulation 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