Food and Drug Administration

U.S. Food and Drug Administration

The U.S. Food and Drug Administration (FDA or USFDA) is an agency of the United States Department of Health and Human Services and is responsible for regulating and supervising the safety of foods, dietary supplements, drugs, vaccines, biological medical products, blood products, medical devices, radiation-emitting devices, veterinary products, and cosmetics. The FDA also enforces section 361 of the Public Health Service Act and the associated regulations, including sanitation requirements on interstate travel as well as specific rules for control of disease on products ranging from pet turtles to semen donations for assisted reproductive medicine techniques.

The FDA is an agency within the United States Department of Health and Human Services responsible for protecting and promoting the nation's public health. The FDA is headquartered in Rockville, MD with 223 field offices supported by 13 laboratories located throughout the United States, the U.S. Virgin Islands, and Puerto Rico. In recent years the agency began undertaking a large-scale effort to consolidate its DC-metro area operations 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, MD. The first building, a 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 all of the Centers are located around the Washington, D.C., area as part of the Headquarters divisions, ORA and OCI are primarily field offices, with their workforce spread across the country. ORA is considered the "eyes and ears" of the agency, conducting the vast majority of the field work the Agency. 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 Judicial System. Each district comprises of 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.

OCI was established in 2002 to help relieve ORA of the burden of pursuing and proving criminal cases. Unlike ORA Investigators, OCI Special Agents are armed, and are not focused on the technical aspects of whether a regulated product meets the standards under the law. Rather, 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 (18 USC XXXX) 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 (21 USC XXX). OCI Special Agents often come from other criminal investigations backgrounds, and work closely with the FBI, US Assistant Attorney Generals, 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 much smaller branch, comprising of 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.

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

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 for FY 2009.

The FDA receives user fees submitted with New Drug Applications under the Prescription Drug User Fee Act (PDUFA); the company submitting an application pays a fee for the review of the new product. A similar process is used for medical devices under the Medical Device User Fee and Modernization Act (MDUFMA) and for animal drugs under a similar act. These fees are typically waived or reduced for small businesses.

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.

The programs for FDA 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.

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

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 the US are subject to inspection similar to other food firms, but quality controls for the bottled water industry are not nearly as stringent as those for municipal water supplies.

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

New drugs receive extensive scrutiny before FDA approval in a process called a New Drug Application or NDA. New drugs are available only by prescription by default. A change to Over the Counter (OTC) status is a separate process and the drug must be approved through an NDA first.

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. "Off-label use", using a drug for other than its approved purpose, is common in medical practice. Also, an advertisement must contain "fair balance" between the benefits and risks of a drug.

The term "off-label", often now used with a vaguely pejorative connotation, actually may mean only that the pharmaceutical company did not choose to invest in the lengthy and costly regimen of clinical trials required by the FDA in order to be able to add the particular application to the "uses" listed on the label. However it is entirely legal and professionally proper for physicians to prescribe the medication for any use for which there exists sufficient scientific research from any source, indicating it is or may be efficacious for that purpose. The test of propriety for off-label uses is whether the prescription meets the "standard of practice" among physicians.

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; 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.

Generic drugs are prescription drugs whose patent protection has expired, and therefore may be manufactured and marketed by other companies. For approval of a generic drug, the FDA requires scientific evidence that the generic drug is interchangeable or therapeutically equivalent with the originally approved drug. This is called an "ANDA" (Abbreviated New Drug Application).

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

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, 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.

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 brain pacemakers. 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. CDRH also conducts limited amounts of direct product testing.

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 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 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.

The FDA has been getting tougher on the cosmetic industry but it still lacks the power needed to properly oversee the industry. To begin the agency can’t require the safe testing of cosmetics by companies, has no systematic way of reviewing chemicals for safety, and doesn’t require that companies list all of their ingredients on the products label. In addition the agency has never defined what is meant by 'safe', so the companies are left to define safe for themselves as something that isn’t linked to cancer or something that doesn’t itch the skin, etc.

The Center for Veterinary Medicine (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 USDA.

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 Mad Cow Disease are also administered by CVM through inspections of feed manufacturers.

Up until the 20th century, there were few federal laws regulating the contents and sale of domestically produced food and pharmaceuticals, with one exception being the short-lived Vaccine Act of 1813. A patchwork of state laws provided varying degrees of protection against unethical sales practices, such as misrepresenting the ingredients of food products or therapeutic substances. 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. Although they had no regulatory powers, the Division published its findings from 1887 to 1902 in a ten-part series entitled Foods and Food Adulterants. Wiley used these findings, and alliances with diverse organizations such as state regulators, the General Federation of Women's Clubs, and national associations of physicians and pharmacists, to lobby for a new federal law to set uniform standards for food and drugs to enter into interstate commerce. 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 tetanus antitoxin was collected from a horse named Jim who also had diphtheria, 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", with that term referring to the addition of fillers of reduced "quality or strength", coloring to conceal "damage or inferiority," formulation with additives "injurious to health," or the use of "filthy, decomposed, or putrid" substances. 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 act also banned "misbranding" of food and drugs. 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, as well as by the creation of the Board of Food and Drug Inspection and the Referee Board of Consulting Scientific Experts as separate organizations within the USDA in 1907 and 1908 respectively. A 1911 Supreme Court decision ruled that the 1906 act did not apply to false claims of therapeutic efficacy, in response to which a 1912 amendment added "false and fraudulent" claims of "curative or therapeutic effect" to the Act's definition of "misbranded." However, these powers continued to be narrowly defined by the courts, which 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, cosmetics 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. The only way that the FDA could even seize the product was due to a misbranding problem: an "Elixir" was defined as a medication dissolved in ethanol, not the diethylene glycol used in the Elixir Sulfanilamide.

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. The law also authorized factory inspections and expanded enforcement powers, set new regulatory standards for foods, and brought cosmetics and therapeutic devices under federal regulatory authority. This law, though extensively amended in subsequent years, remains the central foundation of FDA regulatory authority to the present day.

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. While pre-market testing of drug efficacy was not authorized under the 1938 FD&C Act, subsequent amendments such as the Insulin Amendment and Penicillin Amendment did mandate potency testing for formulations of specific lifesaving pharmaceuticals. The FDA began enforcing its new powers against drug manufacturers who could not substantiate the efficacy claims made for their drugs, and the 1950 Court of Appeals ruling in Alberty Food Products Co. v. U.S. found that drug manufacturers could not evade the "false therapeutic claims" provision of the 1938 act by simply omitting the intended use of a drug from the drug's label. These developments confirmed extensive powers for the FDA to enforce post-marketing recalls of ineffective drugs. Much of the FDA's regulatory attentions in this era were directed towards abuse of amphetamines and barbiturates, but the agency also reviewed some 13,000 new drug applications between 1938 and 1962. While the science of toxicology was in its infancy at the start of this era, rapid advances in experimental assays for food additive and drug safety testing were made during this period by FDA regulators and others.

In 1959, Senator Estes Kefauver began holding congressional hearings into concerns about pharmaceutical industry practices, such as the perceived high cost and uncertain efficacy of many drugs promoted by manufacturers. There was significant opposition, however, to calls for a new law expanding the FDA's authority. This climate was rapidly changed by 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. Thalidomide had not been approved for use in the U.S. due to the concerns of an FDA reviewer, Frances Oldham Kelsey. However, thousands of "trial samples" had been sent to American doctors during the "clinical investigation" phase of the drug's development, which at the time was entirely unregulated by the FDA. Individual members of Congress cited the thalidomide incident in lending their support to expansion of FDA authority.

The 1962 Kefauver-Harris Amendment to the FD&C act 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. Drugs approved between 1938 and 1962 were also subject to FDA review of their efficacy, and to potential withdrawal from the market. Other important provisions of the 1962 amendments included the requirement that drug companies use the "established" or "generic" name of a drug along with the trade name, the restriction of drug advertising to FDA-approved indications, and expansion of FDA powers to inspect drug manufacturing facilities.

These reforms had the effect of delaying the time it took a drug to come to market. In the mid-1970s, 13 of the 14 drugs the FDA saw as most important to approve were on the market in other countries before the United States.

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. This act was intended to correct two unfortunate interactions between the new regulations mandated by the 1962 amendments, and existing patent law (which is not regulated or enforced by the FDA, but rather by the United States Patent and Trademark Office). Because the additional clinical trials mandated by the 1962 amendments significantly delayed the marketing of new drugs, without extending the duration of the manufacturer's patent, "pioneer" drug manufacturers experienced a decreased period of lucrative market exclusivity. On the other hand, the new regulations could be interpreted to require complete safety and efficacy testing for generic copies of approved drugs, and "pioneer" manufacturers obtained court decisions which prevented generic manufacturers from even beginning the clinical trial process while a drug was still under patent. The Hatch-Waxman Act was intended as a compromise between the "pioneer" and generic drug manufacturers which would reduce the overall cost of bringing generics to market and thus, it was hoped, reduce the long-term price of the drug, while preserving the overall profitability of developing new drugs.

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, and staged large protests, such as a confrontational October 11, 1988 action at the FDA campus which resulted in nearly 180 arrests. In August 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 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. The first of these new rules was the "IND exemption" or "treatment IND" rule, which allowed expanded access to a drug undergoing phase II or III trials (or in extraordinary cases even earlier) if it potentially represented a safer or better alternative to treatments currently available for terminal or serious illness. A second new rule, the "parallel track policy", allowed a drug company to set up a mechanism for access to a new potentially lifesaving drug by patients who for various reasons would be unable to participate in ongoing clinical trials. The "parallel track" designation could be made at the time of IND submission. The accelerated approval rules were further expanded and codified in 1992.

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.

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 .

A 2006 court case, Abigail Alliance v. von Eschenbach, would have forced radical changes in FDA regulation of unapproved drugs. The Abigail Alliance argued that the FDA must license drugs for use by terminally ill patients with "desperate diagnoses," after they have completed Phase I testing. 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.

The widely publicized recall of Vioxx, a non-steroidal anti-inflammatory drug now estimated to have contributed to fatal heart attacks in thousands of Americans, played a strong role in driving a new wave of safety reforms at both the FDA rulemaking and statutory levels. Vioxx was approved by the FDA in 1999, and was initially hoped to be safer than previous NSAIDs, due to its reduced risk of intestinal tract bleeding. However, a number of pre- and post-marketing studies suggested that Vioxx might increase the risk of myocardial infarction, and this was conclusively demonstrated by results from the APPROVe trial in 2004. 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.

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. The reasons for the death of clinical drug testing in children were multifactorial. For many drugs, children represented such a small proportion of the potential market, that drug manufacturers did not see such testing as cost-effective. Also, because children were thought to be ethically restricted in their ability to give informed consent, there were increased governmental and institutional hurdles to approval of these clinical trials, as well as greater concerns about legal liability. Thus, for decades, most medicines prescribed to children in the U.S. were done so in a non-FDA-approved, "off-label" manner, with dosages "extrapolated" from adult data through body weight and body-surface-area calculations.

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.

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

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. There are many criticisms and complaints lodged against the FDA from patients, economists, regulatory bodies, and the pharmaceutical industry. A $1.8 million 2006 Institute of Medicine report on pharmaceutical regulation in the U.S. found major deficiencies in the current FDA system for ensuring the safety of drugs on the American market. Overall, the authors called for an increase in the regulatory powers, funding, and independence of the FDA.

Nine FDA scientists appealed to then president-elect George W. Bush over pressure from management to manipulate data, mainly in relation to the review process for medical devices. These concerns were highlighted in the 2006 report on the agency as well.

Medical maggots represent the first living organism ever allowed by the Food and Drug Administration for production and marketing as a prescription medical device.

In June 2004, the FDA cleared leeches (Hirudo medicinalis) as the second living organism to be used in modern medicine as medical devices. Surgeons who do plastic and reconstructive surgery find leeches especially valuable when regrafting amputated appendages, such as fingers or toes. Severed veins in such cases often are too damaged or too small to reconnect. In these cases, pooled blood around a wound can threaten tissue survival. The primary function of leeches is to drain the pooled blood and increase the chances of survival of the tissue in reattached appendages.

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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. Food and Drug Administration (FDA) is an agency of the United States Department of Health and Human Services and is responsible for the safety regulation of most types of foods, dietary supplements, drugs, vaccines, biological medical products, blood products, medical devices, radiation-emitting devices, veterinary products, and cosmetics. The FDA also enforces section 361 of the Public Health Service Act and the associated regulations, including sanitation requirements on interstate travel as well as specific rules for control of disease on products ranging from animals sold as pets to donations of human blood and tissue.

A $1.8 million 2006 Institute of Medicine report on pharmaceutical regulation in the U.S. found major deficiencies in the 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.

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

The 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 and that therefore the FDA will take the action that will result in the least public condemnation of the FDA regardless of the health consequences.

Friedman has also argued that delays in the approval process have cost lives. Prior to passage of the Kefauver Harris Amendment in 1962, the average time from the filing of an investigational new drug application (IND) to approval was 7 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 1990, 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 expedited 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 accelerated approval mechanisms. For example, a "treatment IND" was issued for the first HIV drug, AZT, in 1985, and approval was granted 2 years later, in 1987. Three of the first 5 HIV medications were approved in the United States before they were approved in any other country.

In contrast, Nobel prize-winning economist Gary S. Becker has argued that FDA-required clinical trials for new drugs do contribute to high drug prices for consumers, and that dropping these requirements would hasten the development of new drugs because they would be cheaper to bring to market.

The FDA has been criticized for prohibiting dietary supplement manufacturers from making unsupported claims of effectiveness on the labels of their products. Manufacturers of supplements, which are considered foods for regulatory purposes, are allowed to make only limited "structure/function claims" and are prohibited from claiming that the supplement can prevent, cure, or mitigate a disease or condition unless the supplement undergoes actual testing of its safety and efficacy. Such unsupported claims of effectiveness are considered false advertising.

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.

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.

A $1.8 million 2006 Institute of Medicine report on pharmaceutical regulation in the U.S. found major deficiencies in the current FDA system for ensuring the safety of drugs on the American market. Overall, the authors called for an increase in the regulatory powers, funding, and independence of the FDA.

In the 1980s, Cutter Laboratories introduced a heat-treated version of Factor VIII concentrate in the US, designed to eliminate the risk of HIV transmission. However, Cutter continued to market the untreated product overseas, potentially spreading HIV while the safer product was marketed in the US.

Cutter initially had a voluntary agreement with the FDA to stop marketing the untreated product. However, when it became clear that Cutter was not complying with the agreement, the FDA ordered the company to cease marketing untreated blood products, stating: "It was unacceptable for them to ship that material overseas." At the same time, the FDA, according to Cutter's internal documents, asked that the issue be "quietly solved without alerting the Congress, the medical community and the public", leading to charges that the FDA was complicit in covering up Cutter's actions.

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. Rezulin (troglitazone) and Vioxx (rofecoxib) 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.

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 that may hide signs of spoilage from the consumer.

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 absorbed 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 ban 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.

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.

The journal Nature reported in 2005 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 disqualifying experts from serving on advisory committees if they had received financial compensation from a drug company potentially affected by the committee's recommendations.

The FDA has been criticized regarding delayed approval of foreign drugs to protect the US pharmaceutical companies from foreign competition. Eli Lilly's drug fluoxetine (Prozac) was the first serotonin-specific reuptake inhibitor to be approved by the FDA. Kali-Duphar, the Dutch manufacturer of another antidepressant fluvoxamine (Luvox), 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. Similarly, some critics argue that the FDA delayed the approval of Meroxyl (terephthalylidene dicamphor sulfonic acid), the most effective UV protectant (particularly against UV A) in clinical use to allow for US companies to develop competing products. Meroxyl has been available in Europe since 1991 but it only was approved in 2006 by the FDA and this delay allowed for Neutrogena to release helioplex which is a competitor for meroxyl. Helioplex differs from meroxyl in that it prevents the break down of avobenzone enhancing it's UV protection.

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, including men who have sex with men. The issue has been periodically revisited by the Blood Products Advisory Committee within the FDA Center for Biologics Evaluation and Research, and was last reconfirmed on May 24, 2007. Documentation from these meetings is available.

In April 2005, the FDA issued a statement asserting that cannabis plant had no medical value and should not be accepted as a medicine, despite a great deal of research suggesting the opposite. The supporters of medical cannabis legalization criticized the FDA's statement as a politically motivated one instead of one based on solid science. A group of congressmen led by Maurice Hinchey jointly wrote a letter to FDA's commissioner Andrew von Eschenbach, expressing their disapproval of the FDA's statement and pointed out the FDA's rejection of medical cannabis was inconsistent with the findings of the Institute of Medicine, which stated cannabis does have medical benefits. While the FDA has not approved marijuana it has approved THC (a compound found in cannabis) as an active ingredient for medicinal use . Critics argue that this approval is a politically motivated attempt to allow special interest groups to have patents over the substance , perhaps because the patents on previously patented competing substances have expired.

Nine FDA scientists appealed to Barack Obama over pressure from management to manipulate data, mainly in relation to the review process for medical devices. These concerns were highlighted in a 2006 report on the agency as well.

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National Agency for Food and Drug Administration and Control

The National Agency for Food and Drug Administration and Control (NAFDAC) is a Nigerian government agency responsible for regulating and controlling the manufacture, importation, exportation, advertisement, distribution, sale and use of food, drugs, cosmetics, medical devices, chemicals and prepackaged water.

Through the past two decades in Nigeria, the problem of adulterated and counterfeit drugs has been a very big issue, in fact counterfeit drugs were a major factor in contributing to death rates.over 150 children died in 1989 as a result of a formulation error in a drug.” Such problems led to the establishment of NAFDAC, which would help create a fake-drug-free environment. The intent was to ensure secure, effective, inexpensive, and high quality medicines. The problem of fake drugs was so severe that “neighboring countries such as Ghana and Sierra Leone officially banned the sale of drugs made in Nigeria.The issue of counterfeit drugs was so severe that “drugs were hawked even in commercial buses.” All these problems affected Nigeria as a whole, but the structure of NAFDAC is said to put the problems under control.

The formation of NAFDAC was inspired by a 1988 World Health Assembly resolution requesting countries' help in combating the global health threat posed by counterfeit pharmaceuticals, and amidst growing concerns about counterfeit and poorly-regulated drugs in Nigeria.

In December 1992, NAFDAC's first governing council was formed. The council was chaired by Ambassador Tanimu Saulawa. In January 1993, supporting legislation was approved as legislative Decree No. 15 of 1993. On January 1, 1994 NAFDAC was officially established as a “parastatal of the Federal Ministry of Health”.NAFDACC replaced an earlier Federal Ministry of Health body, the Directorate of Food and Drug Administration and Control, which had been deemed ineffective. This replacement was largely due to a lack of laws concerning fake drugs during the period the latter body was functional.

Three people from the general public are also represented on the council.

NAFDAC envisions that by making these functions known, that its actions will be apparent “in all sectors that deal with food, cosmetics, medical devices, bottled water, and chemicals to the extent of instilling extra need for caution and compulsion to respect and obey existing regulations both for healthy, living and knowledge of certain sanctions or default.". Despite the establishment of NAFDAC, the sale and use of fake drugs did not end.

NAFDAC ensures it maintains very close contact with a number of national and international organizations whose activities relate to the functions of NAFDAC. Such Organizations include the following.

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