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The Food and Drug Administration (FDA) is an agency of the United States Department of Health and Human Services and is responsible for regulating food, dietary supplements, drugs, biological medical products, blood products, medical devices, radiation-emitting devices, veterinary products, and cosmetics in the United States.

Organization

The FDA is an agency within the United States Department of Health and Human Services.

Currently, the FDA is divided into eight major centers and offices:

• The Center for Food Safety and Applied Nutrition (CFSAN)
• The Center for Drug Evaluation and Research (CDER)
• The Center for Biologics Evaluation and Research (CBER)
• The Center for Devices and Radiological Health (CDRH)
• The Center for Veterinary Medicine (CVM)
• The National Center for Toxicological Research (NCTR)
• The Office of Regulatory Affairs (ORA)
• The Office of the Commissioner (OC)

Leadership

The FDA is led by Commissioner Andrew von Eschenbach, who was confirmed by the Senate on December 7 2006 after serving as Acting Commissioner for fourteen months. Von Eschenbach succeeded Lester Crawford, who resigned on September 23 2005, just two months after his final Senate confirmation.

Authorization and regulatory mandate

As an administrative agency in the executive branch of the government of the United States of America, the FDA derives all of its authority and jurisdiction from various acts of the United States Congress. The main source of the FDA's authority is the Federal Food, Drug, and Cosmetic Act. This act gave the FDA various responsibilities including the responsibility of ensuring that no adulterated or misbranded food, drug or medical devices enters into interstate commerce.

The FDA has the power to regulate a multitude of products in a manner that ensures the safety of the American public and the effectiveness of marketed food, medical, and cosmetic products. Regulations may take several forms, including but not limited to outright ban, controlled distribution, and controlled marketing. Additionally, the FDA sets the standards under which individuals may be licensed to prescribe drugs or other medical devices. Regulatory enforcement is carried out by Consumer Safety Officers within the Office of Regulatory Affairs and criminal matters are handled by special agents within the Office of Criminal Investigations (OCI).

Regulation of food and dietary supplements

The Center for Food Safety and Applied Nutrition 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 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 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, and Firearms in the U.S. Department of the Treasury), and non-bottled drinking water (regulated by the Environmental Protection Agency).

The Dietary Supplement Health and Education Act of 1994 mandated that the FDA regulate dietary supplements as foods, rather than as drugs. Therefore, dietary supplements are not subject to safety and efficacy testing prior to approval, and the FDA can take action against dietary supplements only after they are proven to be unsafe. However, the 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.

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. Water bottlers in America must make their facilities available to yearly compliance checks by FDA officials, to document that required protocols are followed. Regulated water quality control in the bottled water industry is not nearly as publicly accountable or transparent as municipal water works, due to the emphasis on drug regulation in the FDA budget.

Regulation of cosmetics

Cosmetics are regulated by the Center for Food Safety and Applied Nutrition, the same branch of the FDA that regulates food. Cosmetic products are not generally subject to pre-market approval by the FDA. 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 labeling 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.

Regulation of drugs

The Center for Drug Evaluation and Research is the branch of the FDA responsible for ensuring the safety and efficacy of new prescription and over-the-counter drugs, overseeing the labeling and marketing of drugs, and regulating the manufacturing and packaging of drugs. The FDA defines a drug as safe and effective for a specific indication if the clinical benefits to the patient are felt to outweigh any health risks the drug might pose. Once a drug has been approved for use, physicians may prescribe it for any indication, referred to as "off label use" and are not restricted to the indications approved by the FDA. The drug may not be marketed for any use other than FDA-approved indications.

The drug approval process

The FDA does not directly test the drugs it regulates. Instead, it is the responsibility of the company seeking to bring a new drug to market, the drug's "sponsor", to submit information to the FDA proving that a new drug is safe and effective. Initially, a U.S.-based researcher or sponsoring company submits an "investigational new drug" (IND) application to the FDA, which includes pre-clinical data about the drug. Approval of this application allows the drug to be shipped across state lines for clinical trials. Once the sponsor has conducted sufficient trials to demonstrate the safety and efficacy of the drug, they submit that information, along with information on manufacturing specifications, drug stability and bioavailablility, and suggested packaging and labeling, as a "new drug application" (NDA) to the FDA. The NDA is then reviewed by teams of FDA employees, including physicians, statisticians, chemists, pharmacologists, and other scientists who assess the validity of the sponsor's claims. FDA inspectors also examine the facilities in which the sponsor intends to manufacture the drug.

The NDA review process is complex, but there are three general outcomes for most drugs after the initial review. First, the FDA may accept the sponsor's application in its entirety and approve the drug for marketing in the U.S. Second, a drug may be declared "approvable," meaning that minor concerns must be worked out between the FDA and the sponsor prior to full approval. For example, the sponsor may be required to provide additional information, or change the proposed labelling of the drug. The FDA may also make approval contingent on an agreement by the manufacturer to conduct specific post-approval studies. Finally, a drug can be declared "not approvable", meaning that the FDA reviewers did not agree that the submitted studies were sufficient to prove the drug's safety and efficacy.

The Prescription Drug User Fee Amendment Program

The Prescription Drug User Fee Amendments (PDUFA) program, established in 1993, allows the FDA to collect fees from drug companies in connection with certain IND and NDA submissions. In 2007, the FDA is expected to collect $259,300,000 in industry user fees. The user fees were intended to allow the FDA to add staff and improve the speed of drug approvals, although the effects of this arrangement on the approval process and on FDA impartiality are controversial (see Criticism).

Accelerated approval processes

The traditional FDA approval process requires that a drug's sponsor prove clinical efficacy of a drug. Because studies showing clear clinical outcomes may take a long time to conduct, the FDA has a special approval track for potentially lifesaving drugs directed at diseases for which satisfactory treatments are lacking. In this track, a drug may receive approval based on its effect on "surrogate markers". For example, a new medication for highly drug-resistant HIV might be approved on the accelerated track if, in short-term trials, it was shown to decrease HIV viral load and increase serum CD4 T-cell counts in AIDS patients, without causing major adverse effects. Under the traditional process, the sponsor would have to show that the drug prevented hospitalizations or saved lives in large, long-term, randomized trials comparing the new drug to older ones.

Following passage of the Drug Price Competition and Patent Term Restoration Act of 1984, the FDA established an abbreviated approval process for manufacturers who wish to produce generic versions of off-patent, previously approved drugs. Generic drug manufacturers are only required to show that the active ingredient in their version of a drug is chemically identical to that of the previously approved drug, that its formulation shows bioequivalence to the previously approved formulation in small human trials, and that the manufacturing, packaging, and labeling of the drug meet FDA standards. There is currently no abbreviated process for approving generic "biologic" agents, such as vaccines or antibody-based drugs.

Regulation of tobacco as a drug

In the 1990s, while under the leadership of former Commissioner David Aaron Kessler, the FDA attempted to regulate tobacco as a pharmaceutical. The courts determined in FDA v. Brown & Williamson Tobacco Corp. that the FDA did not have Congressional authority to regulate tobacco.

Regulation of biologics and blood products

The Center for Biologics Evaluation and Research 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, protein-based therapeutic agents, cell and tissue-based products, and gene therapy products. New biologics are required to go through a pre-market 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.

Regulation of medical devices and radiation-emitting devices

The Center for Devices and Radiological Health (CDRH) is the branch of the FDA responsible for the premarket approval of all medical devices, as well as overseeing the manufacturing, performance and safety of these devices. 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 pacemakers. The 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 ovens, tanning booths, and laser products.

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

Regulation of veterinary products

The Center for Veterinary Medicine is the branch of the FDA which regulates food additives and drugs that are given to animals, including agricultural animals and pets.

Enabling legislation

• 1902 — Biologics Control Act
• 1906 — Pure Food and Drug Act
• 1938 — Federal Food, Drug, and Cosmetic Act
• 1944 — Public Health Service Act
• 1951 — Food, Drug, and Cosmetics Act Amendments PL 82–215
• 1953 — Flammable Fabrics Act PL 83–88
• 1960 — Federal Hazardous Substances Labeling Act PL 86–613
• 1962 — Food, Drug, and Cosmetics Act Amendments PL 87–781
• 1965 — Federal Cigarette Labeling and Advertising Act PL 89–92
• 1966 — Fair Packaging and Labeling Act PL 89–755
• 1966 — Child Protection Act PL 89–756
• 1970 — Federal Cigarette Labeling and Advertising Act Amendments PL 91–222
• 1972 — Consumer Products Safety Act PL 92–573
• 1976 — Medical Device Regulation Act PL 94–295
• 1986 — Comprehensive Smokeless Tobacco Health Education Act PL 99–252
• 1988 — Anti–drug Abuse Act PL 100–690
• 1990 — Nutrition Labeling and Education Act PL 101–535
• 1992 — Prescription Drug User Fee Act PL 102–571
• 1997 — Food and Drug Modernization Act 105-115
• 2002 — Bioterrorism Act 107-188
• 2002 — Medical Device User Fee and Modernization Act (MDUFMA) PL 107-250
• 2002 — Best Pharmaceuticals for Children Act PL 107-109
• 2003 — Animal Drug User Fee Act PL 108-130
• 2003 — Pediatrict Research Equity Act PL 108-155
• 2004 — Project BioShield Act 108-276
• 2004 — Minor Use and Minor Species Animal Health Act PL 108-282
• 2004 — Food Allergen Labeling and Consumer Protection Act PL 108-282

History

Selected history establishing public need

• 1862 — President Lincoln appoints chemist, Charles M. Wetherill to the Department of Agriculture. This appointment led to the Bureau of Chemistry.
• 1906 — Upton Sinclair's The Jungle is published: this contributes to the creation of the FDA which received power through the 1906 Pure Food and Drug Act under Theodore Roosevelt.
• 1927 — The "Bureau of Chemistry" is reorganized into two separate entities. Regulatory functions are located in the "Food, Drug, and Insecticide Administration", and non-regulatory research is located in the "Bureau of Chemistry and Soils".
• 1930 — The name of the "Food, Drug, and Insecticide Administration" is shortened to "Food and Drug Administration" (FDA) under an agricultural appropriations act.
• 1937 — Over 100 people died after consuming a raspberry-flavored sulfa elixir which had been rushed to market by the S.E. Massengill Company without any testing. About 70 percent of the elixir was diethylene glycol, which is now known to be poisonous (related to antifreeze). However, the FDA was able to remove the sulfa elixir from the market because elixirs at the time were to contain alcohol as a solvent (not diethylene glycol).
• 1938 — The resulting sulfa elixir scandal and public outcry led to the passage of the Federal Food, Drug, and Cosmetic Act of 1938, which gave the FDA the power to preapprove all new drugs introduced into interstate commerce.
• 1959 — During a 10-week period leading up to Thanksgiving, the FDA recalled cranberry crops that may have been exposed to a weed killer, aminotriazole, which was known to cause cancer. The FDA sampled 3653 batches amounting to over 33,000,000 pounds of cranberries and cranberry products. Samples that were deemed safe and did not contain the weed killer were stamped with FDA approval.
• 1960 — Frances Oldham Kelsey, who was in charge of reviewing new drug applications, refused to allow Thalidomide in the United States market. Already being manufactured and sold throughout Europe, Kelsey insisted there was not enough evidence of the drug's safety. Receiving pressure from thalidomide manufacturers, Kelsey would not budge.
• 1961 — November, Germany takes thalidomide, known as kevadon, off the market after several thousand newborns suffered the teratogenic effects — they were born with grave congenital abnormalities.
• 1962 - Partly in response to the thalidomide tragedy, the Kefauver Harris Amendment to the Federal Food, Drug, and Cosmetic Act of 1938 are passed. These laws regulate the marketing and licensure of new drugs. For the first time, rational requirements for the approval of new drugs are enforceable by law.
• 1982 — Cyanide poisoning in Tylenol (a brand of the over-the-counter drug acetaminophen) capsules results in many deaths, leading the FDA to begin tamper-resistant packaging.
• 1990 — The FDA promulgates regulations banning "gifts of substantial value" from drug companies to doctors. Minor gifts (like meals, tickets, and travel) are not banned.
• 1992 — Congress passes a new law creating a faster approvals process to legalize new drugs. The FDA must hire more reviewers and speed up reviews without sacrificing proper study and testing. The drug industry must pay "user fees" with every new drug application. A drug is given "fast-track" status if it meets a medical need not currently being met by any medication. Approval times drop from 30 to 12 months on average. 60% of new drugs come on the market in the U.S. first, before other countries. Before this law, when the approval process was slower, more new drugs came out in other countries first.
• 1997 — The FDA loosens restrictions on consumer advertising. Drug companies are allowed to spend less time describing risks and side effects on TV commercials. A large increase in TV drug ads caused a large increase in drug sales within months.

Historical list of FDA Commissioners

• Andrew von Eschenbach — current commissioner
• Lester Crawford 7/2005 - 9/2005
• Mark McClellan 11/2002 - 3/2004
• Jane E. Henney 1/1999 - 1/2001
• David Aaron Kessler 11/1990 - 2/1997
• Frank Edward Young 7/1984 - 12/1989
• Arthur Hull Hayes 4/1981 - 9/1983
• Jere E. Govan 10/1979 - 1/1981
• Donald Kennedy 4/1977 - 6/1979
• Alexander M. Schmidt 7/1973 - 10/1976
• Charles C. Edwards 12/1969 - 3/1973
• Herbert L. Ley 7/1968 - 12/1969
• James L. Goddard 1/1966 - 7/1968
• George P. Larrick 8/1954 - 12/1965
• Charles W. Crawford 6/1951 - 7/1954
• Paul P. Dunbar 5/1944 - 5/1951
• Walter G. Campbell 7/1927 - 4/1944 and 7/1921 - 6/1924
• Charles A. Browne 7/1924 - 6/1927
• Carl L. Alsberg 12/1912 - 7/1921
• Harvey W. Wiley 1/1907 - 3/1912

Court cases

Abigail Burroughs v. von Eschenbach, 2001-2007

Abigail Burroughs was a college student diagnosed with head and neck cancer. During the later phases of her treatment, Abigail's father, Frank Burroughs, sued the FDA for access to cetuximab, case of Abigail Alliance for Better Access to Developmental Drugs v. von Eschenbach. At that time, cetuximab was only available experimentally for patients participating in colon cancer clinical trials. The argument made by the Abigail Alliance in court is that terminal cancer patients have a Constitutionally protected right to access to experimental medications before the FDA approves them. Specifically, the Abigail Alliance argues that the FDA should license drugs for use by terminally ill patients with "desperate diagnoses," after they have completed Phase I testing.

In May, 2006, the U.S. Court of Appeals for the District of Columbia ruled in favor of the Abigail Alliance, and found that the US Constitution protects the right of terminally ill patients to access treatments that are not approved by the FDA. On March 1, 2007, the U.S. Court of Appeals was scheduled to rehear the case at the request of the FDA. This case has the potential to radically alter the conduct of clinical cancer research, since the initial Court of Appeals ruling essentially condones unfettered access to experimental drugs by terminally ill patients, who would then have little incentive to enter Phase II and Phase III clinical trials testing new cancer drugs. While clinical trials restrict access by terminally ill patients to new drugs, they also protect patients by collecting safety and efficacy data on new drugs under controlled circumstances. The expected success rate of cancer drugs at the Phase I stage of clinical testing is 6%. Implementing the changes proposed by the Abigail Alliance could have the potential to expose terminally ill patients to the toxicity of many unapproved treatments, with a very low expected success rate. From its inception, the US Government has charged the FDA with a mission of overseeing testing of new drugs. Challenges to this core definition, as in the Abigail Alliance court case, would likely require broad changes to the FDA's operating mandate. The Americal Society of Clinical Oncology (ASCO) filed an amicus brief to the U.S. Court of Appeals in advance of the March 1 hearing, supporting the FDA. ASCO proposes that the Constitution does not guarantee the right to access unapproved medications, and that the court case threatens the cancer clinical trial enterprise.

Criticism

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The FDA, as a component of the executive branch of the US government, does not create drug regulatory policy. The legislative branch of government sets the policies in the form of laws, and the FDA then administers these laws. The FDA also seeks public comments on controversial topics; experts in particular fields are appointed to Advisory Committees (see above), and the FDA consults these committees for answers to important questions.

Over-regulation

A diverse group of critics claim that the FDA possesses excessive regulatory authority.

Criticism: FDA causes more harm than good

There are trade-offs in regard to regulation. Increase the safety standards increases lag time for drugs to come to market, therefore there is some suffering and deaths during that time that could have been averted if the standard were more relaxed. However, decreasing the safety standards allows dangerous drugs to come to market that would otherwise not have, therefore also causing some suffering and deaths. In trying to prevent bad drugs from coming to market, good drugs are slowed from coming to market. The question is at what level to set the standards so that more suffering is alleviated than caused. Many believe that more harm than good is caused by the FDA. Many economists who have studied the FDA would agree with Milton Friedman who said "“The FDA has done enormous harm to the health of the American public by greatly increasing the costs of pharmaceutical research, thereby reducing the supply of new and effective drugs, and by delaying the approval of such drugs as survive the tortuous FDA process.” These economists advocate liberalization, ranging from gradual decontrol to outright abolition of the FDA, as advocated by Friedman. The Nobel prize-winning economist Milton Friedman has claimed that the regulatory process is inherently biased against approval of some worthy drugs, because the adverse effects of wrongfully banning a useful drug are undetectable, while the consequences of mistakenly approving a harmful drug are highly publicised.

Criticism: FDA regulation leads to delays in drug approval

FDA critics such as Nobel prize-winnning economist Milton Friedman acknowledge that the lengthy FDA approval process has saved lives in individual cases, such as that of thalidomide, but argue that "there's enormous evidence that they have caused more deaths by late approvals than they have saved by early approval." Prior to passage of the Kefauver Harris Amendment of 1962, the average time from the filing of an investigational new drug application (IND) to approval was seven months. By 1998, it took an average of 7.3 years from the date of filing to approval. Prior to the 1990s, the mean time for new drug approvals was shorter in Europe than in the United States, although that difference has since disappeared.

Concerns about the length of the drug approval process were brought to the fore early in the AIDS epidemic. In the 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, and staged large protests, such as a confrontational October 11, 1988 action at the FDA campus which resulted in nearly 180 arrests. In August of 1990, Dr. Louis Lasagna, then chairman of a presidential advisory panel on drug approval, estimated that thousands of lives were lost each year due to delays in approval and marketing of drugs for cancer and AIDS. Partly in response to these criticisms, the FDA introduced procedures to expedite approval of drugs for life threatening diseases, and exanded 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 accelerated approval mechanisms. For example, a "treatment IND" was issued for the first HIV drug, AZT, in 1985, and approval was granted just two years later in 1987. Three of the first five drugs targeting HIV were approved in the United States before they were approved in any other country. </ref>

Criticism: FDA regulation contributes to the high cost of drugs

Studies published in 2003 by Joseph DiMasi and colleagues estimated an average cost of approximately $800 million to bring a new "first-in class" drug to market, while a 2006 study estimated the cost to be $500 million to $2 billion. The consumer advocacy group Public Citizen, using a different methodology, estimated the average cost for development of all new drugs to be under $200 million, about 29% of which is spent on FDA-required clinical trials. Dimasi himself rejects the claim that high drug development costs are responsible for high drug prices. As he wrote in a published letter, "At the time that drug prices are determined, the associated R&D spending for a drug is a sunk cost. Basic economic logic tells us that R&D costs do not determine prices."

In contrast, Nobel prize winning economist Gary S. Becker has written that FDA-required clinical trials for new drugs do contribute to high drug prices for consumers. Prior to the passing of the Kefhauver-Harris Amedment, drugs were only required to obtain FDA certification for safety. That 1962 amendment introduced new regulations went beyond safety standards and required that drugs be proven to be effective, as well, to the FDA. Rejecting government-imposed price controls as a solution to lowering prices, Becker advocates eliminating the regulations introduced in 1962, which would make drugs cheaper to bring to market. He says that this reduced cost in bringing drugs to market will increase the introduction of new drugs, especially from small biotech firms that do not have the capital to invest in extended efficacy trials. Becker says that this will result in more drugs coming to market to compete with each other and will therefore result in lower prices. He says though efficiacy trials would not be mandatory, "fear of lawsuits and the desire to maintain a good reputation would sometimes induce companies to conduct many trials before marketing highly invasive medicines.".

Criticism: FDA regulations reduced the number of new drugs introduced and reduce research spending

A study by Steven N. Wiggins compared pre-1962 data with date after 1962 through the 1970's and found that the 1962 regulations drastically reduced the number of new drugs introduced as well as reduced the amount of research spending. They found that regulations have reduced the rate of introduction of new drugs by 60%. They find a "steep trade-off" between requiring greater certainty about a drugs effectiveness and the rate of new drug introductions.

Criticism: FDA regulations disallow drug reimportation

Some claim that the FDA unjustly opposes importation of cheaper drugs from foreign sources, which is held to be an anti-competitive policy that keeps drug prices artificially high in the United States. Prices of almost all pharmaceutical drugs in Europe are significantly lower than in the United States.

Representatives of the pharmaceutical industry, which supports importation restrictions, respond that the lower prices are often due to government imposed price caps, not because of "competition" between markets.

Criticism: FDA is slow in granting over-the-counter status

An article in the libertarian magazine Reason argued that the FDA should be more aggressive about switching medications to over-the-counter status. They argue that the prescription requirement causes consumers to spend time and money on unnecessary doctor's visits. In the past, the FDA has lagged behind regulator agencies in other major industrialized nations in switching drugs from prescription to over-the-counter status. Unlike some nations, the U.S. does not have a pharmacist-dispensed "behind the counter status" for drugs which are not yet deemed appropriate for over-the counter status, but which do not require a doctor visit for safe and effective usage by patients.

Criticism: FDA restricts free speech in food and drug labeling

The FDA has been criticized for prohibiting dietary supplement manufacturers from making "drug claims" on the labels of their products. Manufacturers of supplements (which are considered foods for regulatory purposes) are only allowed to make limited claims regarding how the supplement affects the structure or function of the body (structure/function claims), and are prohibited from stating that the supplement can prevent, cure, or mitigate a disease or condition.

One critic, Representative Ron Paul (R-TX), introduced a bill on November 10 2005 titled the "Health Freedom Protection Act " (H.R. 4284), which proposes to stop "the FDA from censoring truthful claims about the curative, mitigative, or preventative effects of dietary supplements, and adopts the federal court’s suggested use of disclaimers as an alternative to censorship. Other critics, such as the Life Extension Foundation, claim that the prohibitions are a violation of the Constitutional right to free speech.

The FDA also prevents providers of foods from making certain "drug claims." For example, the FDA threatened legal action against cherry juice manufacturers for labels with claims such as "If you're plagued with chronic pain of arthritis, headaches, or even gout, pros say a daily bowl of cherries could ease your ache without side effects," and "cherries are packed with... a natural chemical that not only flushes cancer-causing substances out of the body, but also helps stunt the growth of cancerous cells."

Under-regulation

In contrast to those who see the FDA as a source of excessive regulation, other critics believe that the FDA does not regulate strictly enough. According to this view, the FDA allows unsafe drugs on the market because of pressure from pharmaceutical companies, fails to ensure safety in drug storage and labelling, and allows the use of dangerous agricultural chemicals, food additives, and food processing techniques.

Criticism: FDA approves unsafe drugs

Some critics believe that the FDA has been too willing to overlook safety concerns in approving new drugs, and is slow to withdraw approved drugs once evidence shows them to be unsafe. Troglitazone and rofecoxib (trade name Vioxx) are high-profile examples of drugs approved by the FDA which were later withdrawn from the market for posing unacceptable risks to patients.

Troglitazone is a diabetes drug that was also available abroad at the time the FDA approved it. Post-marketing safety data indicated that the drug had dangerous side-effects (in this case liver failure). The drug was pulled off that market in the UK in 1997, but was not withdrawn by the FDA until 2000, before which time it is claimed that thousands of Americans were injured or killed by the drug.

In the case of Vioxx, a pre-approval study indicated that a group taking the drug had four times the risk of heart attacks when compared to another group of patients taking another anti-inflammatory, naproxen. The FDA approval board accepted the manufacturer's argument that this was due to a previously unknown cardioprotective effect of naproxen, rather than a risk of Vioxx, and the drug was approved. In 2005, the results of a randomized, placebo-controlled study showed that Vioxx users suffered a higher rate of heart attacks and other cardiovascular disorders than patients taking no medication at all. Faced with numerous lawsuits, the manufacturer voluntarily withdrew it from the market in 2004. 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.

David Graham, a scientist in the Office of Drug Safety within the CDER, testified to Congress that he was pressured by his supervisors not to warn the public about dangers of drugs like Vioxx. He argued that an inherent conflict of interest exists when the office responsible for post-approval monitoring of drug safety is controlled by the same organization which initially approved those same drugs as safe and effective. In a 2006 survey sponsored by the Union of Concerned Scientists, almost one-fifth of FDA scientists said they "have been asked, for non-scientific reasons, to inappropriately exclude or alter technical information or their conclusions in a FDA scientific document."

Criticism: FDA approves unsafe food additives and processing technologies

Food safety advocates have criticized the FDA for allowing meat manufacturers to use carbon monoxide gas mixtures during the packaging process to prevent discoloration of meat, a process which may hide signs of spoilage from the consumer. The irradiation of food for purposes of safety and longer shelf life is regulated by the FDA. The FDA has concluded that such irradiation is safe, but places a consumer advisory label on all irradiated food.

The FDA has been criticised for allowing the use of recombinant bovine growth hormone (rBGH) in dairy cows. rBGH-treated cows secrete higher levels of insulin-like growth factor 1 (IGF-1) in their milk than do untreated cows. IGF-1 signalling is thought to play a role in sustaining the growth of some tumors, although there is little or no evidence that exogenously absobed IGF could promote tumor growth. The FDA approved rBGH for use in dairy cows in 1993, after concluding that humans drinking such milk were unlikely to absorb biologically significant quantities of bovine IGF-1. A 1999 report of the European Commission Scientific Committee on Veterinary Measures relating to Public Health noted that scientific questions persist regarding the theoretical health risks of milk from rBGH-treated cows, particularly for feeding to infants. Since 1993, all EU countries have maintained a moratorium on rBGH use in dairy cattle.

The FDA has also been criticised for permitting the routine use of antibiotics in healthy domestic animals to promote their growth, a practice which contributes to the evolution of antibiotic-resistant strains of bacteria. The FDA has taken recent steps to limit the use of antibiotics in farm animals. In September 2005, the FDA withdrew approval for the use of the fluoroquinolone antibiotic enrofloxacin (trade name Baytril) in poultry, out of concern that this practice could promote bacterial resistance to important human antibiotics such as ciprofloxacin.

The FDA has received criticism for its approval of certain coal tar derived food dyes such as FDC yellow 5 and 6, which are banned in most European countries. However, many studies of these compounds have failed to demonstrate heath risks. For example, a Japanese group found in 1987 that tartrazine was not carcinogenic even after being fed to mice for two years. In addition, a German group found in 1989 that Sunset Yellow did not induce mutations that could lead to cancer in laboratory animals.

FDA bias

Criticism: Pharmaceutical companies have excessive influence over the FDA

Critics have disputed the claim that the Prescription Drug User Fee Amendment has improved the speed of drug approvals. The advocacy group Consumer Union has claimed that the primary effect of this program has been to increase the influence of the pharmaceutical industry on FDA policy, similar to the effect meat industry user fees have had on the USDA.

A 2005 investigation by reporters from the prestigious science journal Nature found that 70% of FDA panels writing clinical guidelines on prescription drug usage contained at least one member with financial links to drug companies whose products were covered by those guidelines. In the most egregious instance, every member of a panel which recommended the use of epoeitin alfa in HIV patients had received money from a manufacturer of that drug. On March 21, 2007, the FDA announced new guidelines for disqualifying experts from serving or voting on advisory committees if they had received financial compensation from a drug company potentially affected by the committee's recccomendations.

The FDA has been criticized regarding its delayed approval of foreign drugs to protect the US pharmaceutical companies from foreign competition. Eli Lilly's Fluoxetine was the first SSRI to be approved by the FDA. Kali-Duphar, the Dutch manufacturer of another antidepressant fluvoxamine, had first attempted to apply for FDA review in the early 1980s (much earlier than Eli Lilly) but fluvoxamine was not approved until the rights were bought by the US pharmaceutical company Reid Rowell. Critics have suggested that the FDA was attempting to protect Eli-Lilly's fluoxetine so it could gain a foothold in the US market before approving fluvoxamine.

Criticism: FDA discriminates against homosexuals in blood donation

Blood collecting organizations, such as the American Red Cross, have policies in accordance with FDA guidelines that prohibit accepting blood donations from any "male who has had sex with another male since 1977, even once". The inclusion of homo- and bisexual men on the prohibited list has created some controversy, but the FDA and Red Cross cite the need to protect blood recipients from HIV as justification for the continued ban. Even with PCR-based testing of blood products, a "window period" may still exist in which an HIV-positive unit of blood would test negative. All potential donors from HIV high risk groups are deferred for this reason. The issue has been periodically revisited by the Blood Products Advisory Committee within the FDA Center for Biologics Evaluation and Research. Documentation from these meetings is available.

See also

• Institute of Food and Agricultural Sciences (IFAS)
• Frances Oldham Kelsey
• Kefauver Harris Amendment
• RAFT Program (pharmaceutical)
• Drug Efficacy Study Implementation
• Investigational Device Exemption
• European Medicines Agency
• Health Canada
• Japan Ministry of Health
• Pharmaceutical company

Further reading

• Philip J. Hilts, Protecting America's Health: The FDA, Business, and One Hundred Years of Regulation, ISBN 0-375-40466-X

References

1. FDCA Section 301 at FDA website
2. http://www.cfsan.fda.gov/~lrd/cfsan4.html Overview of the Center for Food Safety and Applied Nutrition
3. Text of the Dietary Supplement Health and Education Act of 1994. Accessed 5 Feb 2007.
4. Title 21 of the Code of Federal regulations
5. http://www.dwrf.info/documents/recent_dev_bw_quality.pdf
6. http://www.fda.gov/cder/regulatory/applications/default.htm
7. Information about the PDUFA program is publicly available
8. http://www.fda.gov/cber/about.htm
9. http://www.fda.gov/cdrh/radhealth/initiative/rhprogram.pdf 2005 report of the CDRH Radiological Health Program Core Group
10. http://www.fda.gov/oc/history/elixir.html
11. Abigal Alliance Citizen Petition to FDA
12. "The Society for Clinical Trials opposes US legislation to permit marketing of unproven medical therapies for seriously ill patients". Clin Trials. 3 (2): 154–7. 2006. PMID 16773958.
13. Okie S (2006). "Access before approval--a right to take experimental drugs?". N Engl J Med. 355 (5): 437–40. PMID 16885545.
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15. Amicus brief by ASCO, filed February 2007
16. Klein, Daniel B. Economists Against the FDA (September 2000). The Freeman. Vol. 50 No. 9.
17. Friedman, Milton & Rose (1979). Free to Choose. New York: Harcourt Brace Jovanovich. ISBN 0-15-133481-1.
18. TAKE IT TO THE LIMITS: Milton Friedman on Libertarianism. Transcript from television show filmed February 10, 1999. Retrieved from Hoover Institution website.
19. . Theory, Evidence and Examples of FDA Harm, citing Peltzman, S. 1973. An Evaluation of Consumer Protection Legislation: The 1962 Drug Amendments. Journal of Political Economy 81, no. 5: 1049–91. Reprinted in Chicago Studies in Political Economy, edited by George J. Stigler, 303–48. Chicago, University of Chicago Press, 1988. and Thomas, L. G. 1990. Regulation and Firm Size: FDA Impacts on Innovation. Rand Journal of Economics 21, no. 4: 497–517.
20. http://www.diahome.org/content/abstract/1999/d334969.pdf Healy, Elaine, and Kenneth Kaitin. 1999. The European Agency for the Evaluation of Medicinal Product’s Centralized Procedure for Product Approval: Current Status. Drug Information Journal 33: 969–78.
21. http://www.actupny.org/documents/cron-88.html ACT-UP NY timeline
22. Faster Approval of AIDS Drugs Is Urged, The New York Times, August 16, 1990, Thursday, Late Edition - Final, Section B; Page 12, Column 4; National Desk, 830 words, By ROBERT PEAR, Special to The New York Times, WASHINGTON, Aug. 15
23. http://www.fda.gov/oashi/aids/expanded.html FDA Website: Expanded Access and Expedited Approval of New Therapies Related to HIV/AIDS
24. http://www.fda.gov/fdac/special/newdrug/speeding.html FDA report on accelerated approval process
25. http://www.fda.gov/bbs/topics/NEWS/NEW00519.html FDA press release on 3TC approval
26. DiMasi J. "The value of improving the productivity of the drug development process: faster times and better decisions". Pharmacoeconomics. 20 Suppl 3: 1–10. PMID 12457421.
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28. Adams C, Brantner V. "Estimating the cost of new drug development: is it really 802 million dollars?". Health Aff (Millwood). 25 (2): 420–8. PMID 16522582.
29. 2001 Public Citizen Report on Drug Development Costs
30. Public Citizen response to 2003 DiMasi papers.
31. DiMasi JA (2006). "What's time got to do with it?". Health Aff (Millwood). 25 (4): 1188. PMID 16835212. {{cite journal}}: Unknown parameter |month= ignored (help)
32. Becker, Gary. Power to the Patients. AEI-Brookings Joint Center Policy Matters 04-15. Originally published in The Milken Institute Review, 2nd quarter 2004.
33. Becker, Gary S. Get the FDA Out of the Way, and Drug Prices Will Drop, Business Week Magazine, September 16, 2002
34. Wiggens, Steven N. (1981) Product Quality Regulation and New Drug Introductions: Some New Evidence from the 1970s. Review of Economics and Statistics 63: 615–19
35. http://www.stopfda.org/june99-ripoff.htm
36. http://www.phrma.org/issues/researchdev/index.cfm
37. "Locking Up Life-Saving Drugs", by Kerry Howley. Published in Reason, August/September 2005. Accessed 23 Feb 2007.
38. International Rx-to-OTC-Switch Forecasts 2004-2008. Kline and Company. www.klinegroup.com.
39. "Free Speech and Dietary Supplements" by Representative Ron Paul, Before the US House of Representatives, November 10, 2005
40. http://www.lewrockwell.com/paul/paul288.html Free Speech and Dietary Supplements
41. http://www.lef.org/featured-articles/consumer_alert_091905.htm
44. ^ David Graham's 2004 testimony to Congress
45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=11087881&query_hl=10&itool=pubmed_docsum The VIGOR study (Pubmed)
46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15713943&query_hl=10&itool=pubmed_docsum The APPROVe study (Pubmed)
47. 2006 Union of Concerned Scientists survey of FDA Scientists
48. http://www.post-gazette.com/pg/06050/657804.stm
49. http://www.fda.gov/opacom/catalog/irradbro.html "Food Irradiation: A Safe Measure", U.S. Food and Drug Administration, January 2000
50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=2203142&query_hl=2&itool=pubmed_DocSum Abstract of report in Science regarding the pending FDA approval of recombinant bovine growth hormone
51. http://ec.europa.eu/food/fs/sc/scv/out19_en.html 1999 report of the European Commission Scientific Committee on Veterinary Measures relating to Public Health
52. Myllys V, Honkanen-Buzalski T, Huovinen P, Sandholm M, Nurmi E (1994). "Association af changes in the bacterial ecology of bovine mastitis with changes in the use of milking machines and antibacterial drugs". Acta Vet Scand. 35 (4): 363–9. PMID 7676918.{{cite journal}}: CS1 maint: multiple names: authors list (link)
53. http://www.fda.gov/cvm/FQWithdrawal.html FDA statement on withdrawal of Baytril for use in poultry
54. Maekawa A, Matsuoka C, Onodera H, Tanigawa H, Furuta K, Kanno J, Jang J, Hayashi Y, Ogiu T (1987). "Lack of carcinogenicity of tartrazine (FD & C Yellow No. 5) in the F344 rat". Food Chem Toxicol. 25 (12): 891–6. PMID 3692395.{{cite journal}}: CS1 maint: multiple names: authors list (link)
55. Wever J, Münzner R, Renner H (1989). "Testing of sunset yellow and orange II for genotoxicity in different laboratory animal species". Environ Mol Mutagen. 13 (3): 271–6. PMID 2651119.{{cite journal}}: CS1 maint: multiple names: authors list (link)
56. Carpenter D.; et al. (2003). "Approval times for new drugs: does the source of funding for FDA staff matter?". Health Affairs (Millwood). Suppl Web Exclusives:W3: 618–24. PMID 15506165. {{cite journal}}: Explicit use of et al. in: |author= (help)
57. http://www.consumersunion.org/pub/campaigndrugcosts/004249.html Consumer Union statement about PDUFA IV
58. http://www.azcentral.com/arizonarepublic/business/articles/0223biz-meat0223.html Recent USDA inspection guideline changes have ignited strong reaction from meat industry institute
59. http://www.nature.com/news/2005/051017/full/4371070a.html
60. FDA press release on new conflict-of-interest guidelines for Advisory Committee members
61. Schlesser, Jerry. "Drugs Available Abroad". Gale Research, 1991.
62. http://www.harbus.org/main.cfm?include=detail&storyid=171199&page=2 2002 article in The Harbus regarding the blood donor guideline controversy
63. http://www.fda.gov/cber/faq/bldfaq.htm CBER blood products FAQ
64. http://www.fda.gov/ohrms/dockets/ac/acmenu.htm FDA advisory committee documents

External links

Food & Drug Administration Websites

• Food and Drug Administration Home Page
  • 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

Selected news coverage

• Frontline: Dangerous Prescription: watch online |PBS
• US drug safety checks 'slack' from the BBC News
• FDA Scientists Pressured to Exclude, Alter Findings; Scientists Fear Retaliation for Voicing Safety Concerns from the Union of Concerned Scientists.

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