Food and Drug Administration - History

Food and Drug Administration - History

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Food and Drug Administration - part of the Public Health Service of the Department of Health and Human Services. The FDA administers federal laws which prohibit the manufacture, shipment, or sale of impure or unsafe foods, drugs, cosmetics, medical devices, and other related items; and conducts research on their safety.


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Food and Drug Administration

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Food and Drug Administration (FDA), agency of the U.S. federal government authorized by Congress to inspect, test, approve, and set safety standards for foods and food additives, drugs, chemicals, cosmetics, and household and medical devices. First known as the Food, Drug, and Insecticide Administration when it was formed as a separate law enforcement agency in 1927, the FDA derives the greater part of its regulatory power from four laws: the Federal Food, Drug, and Cosmetic Act, which established safety and purity standards and provided for factory inspection and for legal remedy the Fair Packaging and Labeling Act, which required honest, informative, and standardized labeling of products the Radiation Control for Health and Safety Act, which was designed to protect consumers from possible excess radiation generated by X-ray machines, televisions, microwave ovens, and the like and the Public Health Service Act, which gave the FDA authority over vaccines and serums and justified the agency’s programs for milk sanitation and the inspection of restaurants and travel facilities.

Generally, the FDA is empowered to prevent untested products from being sold and to take legal action to halt sale of undoubtedly harmful products or of products which involve a health or safety risk. Through court procedure, the FDA can seize products and prosecute the persons or firms responsible for legal violation. FDA authority is limited to interstate commerce. The agency cannot control prices or directly regulate advertising except of prescription drugs and medical devices.

This article was most recently revised and updated by Lorraine Murray, Associate Editor.

Records of the Food and Drug Administration [FDA]

Established: In the Department of Agriculture, effective July 1, 1930, by the Agricultural Appropriation Act (46 Stat. 422), May 27, 1930.

Predecessor Agencies:

In the Department of Agriculture:

Food, Drug, and Insecticide Administration (FDIA, 1927-30)

Transfers: To Federal Security Agency by Reorganization Plan No. IV of 1940, effective June 30, 1940 to Department of Health, Education, and Welfare (HEW) by Reorganization Plan No. 1 of 1953, effective April 11, 1953 to Public Health Service (PHS), HEW, by HEW reorganization order, April 1, 1968 to newly established Consumer Protection and Environmental Health Service, PHS, HEW, by HEW reorganization plan, effective July 1, 1968 to operating health agency status within PHS, effective July 1, 1970, by HEW reorganization plan, January 16, 1970 with PHS to Department of Health and Human Services by Department of Education Organization Act (93 Stat. 695), October 17, 1979.

Functions: Enforces statutes and regulations promoting the purity, standard potency, and accurate labeling of foods, cosmetics, medicines, and other consumer products.

Related Records:
Record copies of publications of the Food and Drug Administration and its predecessors in RG 287, Publications of the U.S. Government.
Records of the Public Health Service, 1912-1968, RG 90.
Records of the Bureau of Agricultural and Industrial Chemistry, RG 97.
Records of the Consumer Product Safety Commission, RG 424.

88.2 General Records of the FDA and its Predecessors

History: Division of Chemistry established in the Department of Agriculture pursuant to provisions of its establishing act (12 Stat. 387), May 15, 1862. Began analysis of foods, drugs, and insecticides, 1883. Redesignated Bureau of Chemistry, effective July 1, 1901. Enforced an act of June 30, 1906 (34 Stat. 768), called the Food and Drugs Act for appropriations purposes.

Insecticide and Fungicide Board established by General Order 143, Department of Agriculture, December 22, 1910, to administer the Insecticide and Fungicide Act (36 Stat. 331), April 26, 1910, with associated analytical work vested in Bureau of Chemistry.

IFB superseded, July 1, 1927, by the Food, Drug, and Insecticide Administration, established on that date pursuant to the Agricultural Appropriation Act (44 Stat. 1002), January 18, 1927, absorbing also the regulatory functions of the Bureau of Chemistry, which was merged by the same act with the Bureau of Soils to form the Bureau of Chemistry and Soils. FDIA redesignated FDA, 1930. See 88.1.

Textual Records: Project schedules and reports on enforcement of the Food and Drugs Act, 1916-38. Index of articles seized because of violations of the Food and Drugs Act, 1908-39. Records relating to the Food and Drugs Act, including correspondence, 1919-37, with index charge and status cards, showing product status and charges against products, dealers, and manufacturers, 1907-38 and an index to manufacturers charged with violations, 1909-40. Records of the Food Standards Committee relating to investigations into the manufacture of food products, 1897-1938. Records relating to foreign food and drug legislation, 1910-40, with card index. Records concerning Consumers' Research, Inc., 1922-40. Summary information cards about seizure recommendations, 1907-38, and food product sample analyses, 1905-33. Import detention notices, 1908-38, and card index to import detention correspondence, 1906-42. Records relating to the proposed importation of medicinal and food substances, 1922-38. Records relating to an importer of chemicals used in fruit and vegetable sprays and pharmaceuticals, 1925-38. Allotment and disbursement ledgers, 1914-40. Reports, circulars, bulletins, and other records of committees engaged in the publication of the United States Pharmacopoeia, 1880-1940.

88.3 Records of the Bureau of Chemistry
1877-1943 (bulk 1877-1920)

Textual Records: Transcripts of hearings to determine the legal definition of whiskey, 1906-9. Records relating to a court case involving the seizure of a shipment of phenacetin (or acetphenetidin), 1906-14. Minutes of the Committee on Business Methods, 1907-13. Reports and correspondence relating to enforcement of the Food and Drugs Act ("Special File"), 1907-20. Letters sent to inspection districts, 1916-17. World War I project files on problems of conservation, preservation, and development of new food sources, 1917-19. Card index to publications and manuscripts of former staff members, 1900-43. Miscellaneous records, 1877-1910.

88.4 Records of the Board of Food and Drug Inspection

History: Established by order of the Secretary of Agriculture, April 25, 1907, to act on all questions arising from enforcement of the Food and Drugs Act of 1906. Interpreted the act and conducted hearings on alleged violations. Abolished, February 1, 1914, with functions divided between Bureau of Chemistry and Office of the Solicitor, Department of Agriculture.

Textual Records: Minutes of executive sessions, 1907-13. Index to hearings, 1907-13. Correspondence of the Chairman, 1908-10. Food inspection decisions, 1904-13. Transcripts of hearings on bleached flour, November 18-23, 1908. Notices of judgment obtained by the board, 1908-10. Reports by the Bureau of Chemistry, Solicitor of the Department of Agriculture, U.S. consuls abroad, and others, 1908-12. Records relating to recommendations on the seizure and condemnation of food and drug shipments on grounds of adulteration or mislabeling, 1908-12.

88.5 Records of the Referee Board of Consulting Scientific

History: Established by the Secretary of Agriculture, February 20, 1908, to report on the wholesome or deleterious character of foods and drugs. Discontinued after June 30, 1915.

Textual Records: Reports, food charts, blood analyses, and correspondence relating to the use of sulphur dioxide as a food preservative and to the use of alum in certain foods, 1911-13.

88.6 Records of the Supervising Tea Examiner and Successors

History: Established in the Department of the Treasury as head of the tea inspection service, to enforce the Tea Act (29 Stat. 604), March 2, 1897, and to provide expert assistance to the Secretary of the Treasury in setting standards of purity and quality for imported teas. Responsibility for administering the act transferred to the Bureau of Chemistry, July 1, 1920. Returned to FDIA by the Agriculture Appropriations Act of 1927 (44 Stat. 1003), January 15, 1927.

Textual Records: Periodic and special statistical reports, 1912- 37. Correspondence, 1913-29.

88.7 Records of the Food, Drug, and Insecticide Administration
and the Food and Drug Administration

Textual Records: Records of FDIA and FDA Commissioners relating to proposed food and drug legislation, 1927-40. FDA general correspondence, 1930-37, with index. Transcript of a hearing before the Senate Committee on Agriculture and Forestry concerning the administration of the Food and Drugs Act, June 3- 30, 1930. Reports, correspondence, and memorandums relating to a survey of orange beverages and the effects of shellac on animal organisms, 1935-36. Records of the Food Division, 1929-41, and of its Beverage Branch, 1907-45, concerning tests and analyses of foods. Import milk permit case files, 1927-41, with index, 1927- 45. Minutes, reports, correspondence, and memorandums relating to the work of the Division of Medicine with the National Research Council committees on medical research and on drugs and medical supplies, 1941-46. Advertising material for patent medicines and health devices, used to demonstrate the need for regulation of food and drug advertising, 1933-37. Printed notices of judgment in cases under section 4 of the Food and Drugs Act, 1908-43, and related partial index, 1922-37 and in cases under section 705 of the Federal Food, Drug, and Cosmetic Act of June 25, 1938 (52 Stat. 1040), 1940-54. Record set of FDA forms, 1950-77.

88.8 Records of the Philadelphia Field Station

Textual Records (in Philadelphia): Reports, correspondence, and memorandums relating to manufacturers and distributors of foods, drugs, and insecticides within its jurisdiction, 1906-46.

88.9 Textual Records (General)

Subject files, 1903-74. Drug reports, 1967-69. Hearing clerk records, 1961. Articles and speeches, 1916-64. Publications, 1917-68. Office of Public Information files, 1960-64. Food Standards Advisory Committee records, 1941-42. Records of the Federal Committee on Pest Control, 1946-64. Proceedings of conferences and National Food and Drug Council records, 1963-68. Citizens Advisory Committee files and other records, 1950-69. Radiation Registry of Physicians questionnaires and related records, 1960-78. Classified general subject files, 1945. Operational plans, 1966-74.

88.10 Motion Pictures (General)

Operation Plumbob, depicting FDA tests to determine effects of residual radiation (fallout) on commodities, 1957 (1 reel). FDA public service announcements on health and consumer fraud, 1966- 68 (3 reels).

88.11 Still Pictures (General)

Photographs: FDA personnel, 1968-77 (P, 480 images).

Photographs and Color Slides: FDA activities, including administration, laboratory analysis, and investigation, 1962-77 (A, 26,020 images).

Photographs and Lantern Slides: Regulatory and analytical functions of the FDA and its predecessors, including chemical analysis of drugs, investigations of fraudulent labeling of drugs, inspections of food products, and seizure and destruction of contaminated foods and manufacture of candy, liquor, and other commodities, 1885-1944 (GP, GB, GS, GN, 4,000 images).

Finding Aids: Shelf lists for series GB and GS.

Bibliographic note: Web version based on Guide to Federal Records in the National Archives of the United States. Compiled by Robert B. Matchette et al. Washington, DC: National Archives and Records Administration, 1995.
3 volumes, 2428 pages.

This Web version is updated from time to time to include records processed since 1995.


    • Food and Drug Administration
    • Office of Operations [10]
      • Office of Equal Employment Opportunity
      • Office of Human Resources
      • Office of Finance, Budget and Acquisition
      • Office of Information Management and Technology
        • Office of Informatics & Technology Innovation
          • Director: Taha A. Kass-Hout (also holds post of Chief Health Informatics Officer for the FDA) [11][12]

          Headquarters Edit

          FDA headquarters facilities are currently located in Montgomery County and Prince George's County, Maryland. [13]

          White Oak Federal Research Center Edit

          Since 1990, the FDA has had employees and facilities on 130 acres (53 hectares) of the White Oak Federal Research Center in the White Oak area of Silver Spring, Maryland. [6] [14] In 2001, the General Services Administration (GSA) began new construction on the campus to consolidate the FDA's 25 existing operations in the Washington metropolitan area, its headquarters in Rockville, and several fragmented office buildings. The first building, the Life Sciences Laboratory, was dedicated and opened with 104 employees in December 2003. As of December 2018, the FDA campus has a population of 10,987 employees housed in approximately 3,800,000 square feet (350,000 square metres) of space, divided into ten office and four laboratory buildings. The campus houses the Office of the Commissioner (OC), the Office of Regulatory Affairs (ORA), the Center for Drug Evaluation and Research (CDER), the Center for Devices and Radiological Health (CDRH), the Center for Biologics Evaluation and Research (CBER) and offices for the Center for Veterinary Medicine (CVM). [6]

          With the passing of the FDA Reauthorization Act of 2017, the FDA is projecting a 64% increase in employees to 18,000 over the next 15 years, and would like to add approximately 1,600,000 square feet (150,000 square metres) of office and special use space to their existing facilities. The National Capital Planning Commission approved a new master plan for this expansion in December 2018, [15] and construction is expected to be completed by 2035, dependent on GSA appropriations. [16]

          Field locations Edit

          Office of Regulatory Affairs Edit

          The Office of Regulatory Affairs is considered the agency's "eyes and ears," conducting the vast majority of the FDA's work in the field. Its employees, known as Consumer Safety Officers, or more commonly known simply as investigators, 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 20 districts. Districts are based roughly on the geographic divisions of the Federal court system. Each district comprises a main district office and a number of Resident Posts, which are FDA remote offices that serve a particular geographic area. ORA also includes the Agency's network of regulatory 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.

          Office of Criminal Investigations Edit

          The Office of Criminal Investigations was established in 1991 to investigate criminal cases. To do so, OCI employs approximately 200 Special Agents nationwide who, unlike ORA Investigators, are armed, have badges, and do not focus on technical aspects of the regulated industries. Rather, OCI agents pursue and develop cases when individuals and companies commit criminal actions, such as fraudulent claims or knowingly and willfully shipping known adulterated goods in interstate commerce. In many cases, OCI pursues cases involving violations of Title 18 of the United States Code (e.g., conspiracy, false statements, wire fraud, mail fraud), in addition to prohibited acts as defined in Chapter III of the FD&C Act. OCI Special Agents often come from other criminal investigations backgrounds, and frequently work closely with the Federal Bureau of Investigation, Assistant Attorney General, and even Interpol. OCI receives cases from a variety of sources—including ORA, local agencies, and the FBI, and works with ORA Investigators to help develop the technical and science-based aspects of a case.

          Other locations Edit

          The FDA has a number of field offices across the United States, in addition to international locations in China, India, Europe, the Middle East, and Latin America. [17]

          The FDA regulates more than US$2.4 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 these expenditures are for goods imported into the United States the FDA is responsible for monitoring imports. [18]

          The FDA's federal budget request for fiscal year (FY) 2012 totaled $4.36 billion, [7] while the proposed 2014 budget is $4.7 billion. [19] About $2 billion of this budget is generated by user fees. Pharmaceutical firms pay the majority of these fees, [19] which are used to expedite drug reviews. [20] 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. [21]

          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. [18]

          Emergency approvals (EUA) Edit

          Emergency Use Authorization (EUA) is a mechanism that was created to facilitate the availability and use of medical countermeasures, including vaccines, during public health emergencies such as the current COVID-19 pandemic.

          Regulations Edit

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

          In June 2018, the FDA released a statement regarding new guidelines to help food and drug manufacturers "implement protections against potential attacks on the U.S. food supply". [22] One of the new guidelines includes the Intentional Adulteration (IA) rule, which requires strategies and procedures by the food industry to reduce the risk of compromise in facilities and processes that are significantly vulnerable.

          The FDA also uses tactics of regulatory shaming, [23] mainly through online publication of non-compliance, warning letters, and "shaming lists." Regulation by shaming harnesses firms' sensitivity to reputational damage. For example, in 2018, the agency published an online "black list," in which it named dozens of branded drug companies that are supposedly using unlawful or unethical means to attempt to impede competition from generic drug companies. [24]

          The FDA frequently works with other federal agencies, including the Department of Agriculture, the Drug Enforcement Administration, Customs and Border Protection, and the Consumer Product Safety Commission. They also often work with local and state government agencies in performing regulatory inspections and enforcement actions.

          Food and dietary supplements Edit

          The regulation of food and dietary supplements by the Food and Drug Administration is governed by various statutes enacted by the United States Congress and interpreted by the FDA. Pursuant to the Federal Food, Drug, and Cosmetic Act and accompanying legislation, the FDA has authority to oversee the quality of substances sold as food in the United States, and to monitor claims made in the labeling of both the composition and the health benefits of foods.

          The FDA subdivides substances that it regulates as food into various categories—including foods, food additives, added substances (man-made substances that are not intentionally introduced into food, but nevertheless end up in it), and dietary supplements. Dietary supplements or dietary ingredients include vitamins, minerals, herbs, amino acids, and. enzymes. [25] Specific standards the FDA exercises differ from one category to the next. Furthermore, legislation had granted the FDA a variety of means to address violations of standards for a given substance category.

          Under the Dietary Supplement Health and Education Act of 1994 (DSHEA), the FDA is responsible for ensuring that manufacturers and distributors of dietary supplements and dietary ingredients meet the current requirements. These manufacturers and distributors are not allowed to advertise their products in an adulterated way, and they are responsible for evaluating the safety and labeling of their product. [26]

          The FDA has a “Dietary Supplement Ingredient Advisory List” that includes ingredients that sometimes appear on dietary supplements but need further evaluation further. [27] An ingredient is added to this list when it is excluded from use in a dietary supplement, does not appear to be an approved food additive or recognized as safe, and/or is subjected to the requirement for pre-market notification without having a satisfied requirement. [28]

          "FDA-Approved" vs. "FDA-Accepted in Food Processing" Edit

          The FDA does not approve applied coatings used in the food processing industry. [29] There is no review process to approve the composition of nonstick coatings nor does the FDA inspect or test these materials. Through their governing of processes, however, the FDA does have a set of regulations that cover the formulation, manufacturing, and use of nonstick coatings. Hence, materials like Polytetrafluoroethylene (Teflon) are not, and cannot be, considered as FDA Approved, rather, they are "FDA Compliant" or "FDA Acceptable".

          Medical countermeasures (MCMs) Edit

          Medical countermeasures (MCMs) are products such as biologics and pharmaceutical drugs that can protect from or treat the health effects of a chemical, biological, radiological, or nuclear (CBRN) attack. MCMs can also be used for prevention and diagnosis of symptoms associated with CBRN attacks or threats. [30] The FDA runs a program called the "FDA Medical Countermeasures Initiative" (MCMi), with programs funded by the federal government. It helps support "partner" agencies and organisations prepare for public health emergencies that could require MCMs. [30] [31]

          Medications Edit

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

          New medications Edit

          New drugs receive extensive scrutiny before FDA approval in a process called a new drug application (NDA). [32] Under the Trump administration, the agency has worked to make the drug-approval process go faster. [33] : 10 Critics, however, argue that the FDA standards are not sufficiently rigorous, allowing unsafe or ineffective drugs to be approved. [34] New drugs are available only by prescription by default. A change to over-the-counter (OTC) status is a separate process, and the drug must be approved through an NDA first. A drug that is approved is said to be "safe and effective when used as directed".

          Very rare limited exceptions to this multi-step process involving animal testing and controlled clinical trials can be granted out of compassionate use protocols. This was the case during the 2015 Ebola epidemic with the use, by prescription and authorization, of ZMapp and other experimental treatments, and for new drugs that can be used to treat debilitating and/or very rare conditions for which no existing remedies or drugs are satisfactory, or where there has not been an advance in a long period of time. The studies are progressively longer, gradually adding more individuals as they progress from stage I to stage III, normally over a period of years, and normally involve drug companies, the government and its laboratories, and often medical schools and hospitals and clinics. However, any exceptions to the aforementioned process are subject to strict review and scrutiny and conditions, and are only given if a substantial amount of research and at least some preliminary human testing has shown that they are believed to be somewhat safe and possibly effective.

          Advertising and promotion Edit

          The FDA's Office of Prescription Drug Promotion reviews and regulates prescription drug advertising and promotion through surveillance activities and issuance of enforcement letters to pharmaceutical manufacturers. Advertising and promotion for over-the-counter drugs is regulated by the Federal Trade Commission. The FDA also empowers third-party enforcer-firms to engage in some regulatory oversight, e.g. the FDA expects pharmaceutical companies to make sure that third-party suppliers and labs abide by the agency's health and safety guidelines. [35] : 4

          The drug advertising regulation [36] contains two broad requirements: (1) a company may advertise or promote a drug only for the specific indication or medical use for which it was approved by FDA. Also, an advertisement must contain a "fair balance" between the benefits and the risks (side effects) of a drug.

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

          Post-market safety surveillance Edit

          After NDA approval, the sponsor must then review and report to the FDA every single patient adverse drug experience it learns of. They must report unexpected serious and fatal adverse drug events within 15 days, and other events on a quarterly basis. [37] The FDA also receives directly adverse drug event reports through its MedWatch program. [38] These reports are called "spontaneous reports" because reporting by consumers and health professionals is voluntary.

          While this remains the primary tool of post-market safety surveillance, FDA requirements for post-marketing 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 called Risk Evaluation and Mitigation Strategies (REMS) for some drugs that require actions to be taken to ensure that the drug is used safely. [39] [40] For example, thalidomide can cause birth defects, but has uses that outweigh the risks if men and women taking the drugs do not conceive a child a REMS program for thalidomide mandates an auditable process to ensure that people taking the drug take action to avoid pregnancy many opioid drugs have REMS programs to avoid addiction and diversion of drugs. [39] The drug isotretinoin has a REMS program called iPLEDGE. [41]

          Generic drugs Edit

          Generic drugs are chemical and therapeutic equivalents of name-brand drugs whose patents have expired. [42] Approved generic drugs should have the same dosage, safety, effectiveness, strength, stability, and quality, as well as route of administration. In general, they are less expensive than their name brand counterparts, are manufactured and marketed by rival companies and, in the 1990s, accounted for about a third of all prescriptions written in the United States. [42] For a pharmaceutical company to gain approval to produce a generic drug, the FDA requires scientific evidence that the generic drug is interchangeable with or therapeutically equivalent to the originally approved drug. [43] This is called an Abbreviated New Drug Application (ANDA). [44] As of 2012, 80% of all FDA approved drugs are available in generic form. [ citation needed ]

          Generic drug scandal Edit

          In 1989, a major scandal erupted involving the procedures used by the FDA to approve generic drugs for sale to the public. [42] Charges of corruption in generic drug approval first emerged in 1988 during the course of an extensive congressional investigation into the FDA. The oversight subcommittee of the United States House Energy and Commerce Committee resulted from a complaint brought against the FDA by Mylan Laboratories Inc. of Pittsburgh. When its application to manufacture generics were subjected to repeated delays by the FDA, Mylan, convinced that it was being discriminated against, soon began its own private investigation of the agency in 1987. Mylan eventually filed suit against two former FDA employees and four drug-manufacturing companies, charging that corruption within the federal agency resulted in racketeering and in violations of antitrust law. "The order in which new generic drugs were approved was set by the FDA employees even before drug manufacturers submitted applications" and, according to Mylan, this illegal procedure was followed to give preferential treatment to certain companies. During the summer of 1989, three FDA officials (Charles Y. Chang, David J. Brancato, Walter Kletch) pleaded guilty to criminal charges of accepting bribes from generic drugs makers, and two companies (Par Pharmaceutical and its subsidiary Quad Pharmaceuticals) [45] pleaded guilty to giving bribes.

          Furthermore, it was discovered that several manufacturers had falsified data submitted in seeking FDA authorization to market certain generic drugs. Vitarine Pharmaceuticals of New York, which sought approval of a generic version of the drug Dyazide, a medication for high blood pressure, submitted Dyazide, rather than its generic version, for the FDA tests. In April 1989, the FDA investigated 11 manufacturers for irregularities and later brought that number up to 13. Dozens of drugs were eventually suspended or recalled by manufacturers. In the early 1990s, the U.S. Securities and Exchange Commission filed securities fraud charges against the Bolar Pharmaceutical Company, a major generic manufacturer based in Long Island, New York. [42]

          Over-the-counter drugs Edit

          Over-the-counter (OTC) are drugs like aspirin that do not require a doctor's prescription. [46] The FDA has a list of approximately 800 such 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 like ibuprofen. [47]

          Ebola treatment Edit

          In 2014, the FDA added an Ebola treatment being developed by Canadian pharmaceutical company Tekmira to the Fast Track program, but halted the phase 1 trials in July pending the receipt of more information about how the drug works. This was widely viewed as increasingly important in the face of a major outbreak of the disease in West Africa that began in late March 2014 and ended in June 2016. [48]

          Coronavirus (COVID-19) testing Edit

          During the coronavirus pandemic, FDA granted emergency use authorization for personal protective equipment (PPE), in vitro diagnostic equipment, ventilators and other medical devices. [49] [50]

          On March 18, FDA inspectors postponed most foreign facility inspections and all domestic routine surveillance facility inspections. [51] In contrast, the USDA's Food Safety and Inspection Service (FSIS) continued inspections of meatpacking plants, which resulted in 145 FSIS field employees who tested positive for COVID-19, and three who died. [52]

          Vaccines, blood and tissue products, and biotechnology Edit

          The Center for Biologics Evaluation and Research is the branch of the FDA responsible for ensuring the safety and efficacy of biological therapeutic agents. [53] These include blood and blood products, vaccines, allergenics, cell and tissue-based products, and gene therapy products. New biologics are required to go through a premarket approval process called a Biologics License Application (BLA), similar to that for drugs.

          The original authority for government regulation of biological products was established by the 1902 Biologics Control Act, with additional authority established by the 1944 Public Health Service Act. Along with these Acts, the Federal Food, Drug, and Cosmetic Act applies to all biologic products, as well. Originally, the entity responsible for regulation of biological products resided under the National Institutes of Health this authority was transferred to the FDA in 1972.

          Medical and radiation-emitting devices Edit

          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. [54] 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 neurostimulators. CDRH also oversees the safety performance of non-medical devices that emit certain types of electromagnetic radiation. Examples of CDRH-regulated devices include cellular phones, airport baggage screening equipment, television receivers, microwave ovens, tanning booths, and laser products.

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

          "FDA-Cleared" vs "FDA-Approved" Edit

          Clearance requests are required for medical devices that prove they are "substantially equivalent" to the predicate devices already on the market. Approved requests are for items that are new or substantially different and need to demonstrate "safety and efficacy", for example they may be inspected for safety in case of new toxic hazards. Both aspects need to be proved or provided by the submitter to ensure proper procedures are followed. [55]

          Cosmetics Edit

          Cosmetics are regulated by the Center for Food Safety and Applied Nutrition, the same branch of the FDA that regulates food. Cosmetic products are not, in general, subject to premarket approval by the FDA unless they make "structure or function claims" that make them into drugs (see Cosmeceutical). However, all color additives must be specifically FDA approved before manufacturers can include them in cosmetic products sold in the U.S. The FDA regulates cosmetics labeling, and cosmetics that have not been safety tested must bear a warning to that effect. [56]

          According to the industry advocacy group the American Council on Science and Health, though the cosmetic industry is predominantly responsible in ensuring the safety of its products, the FDA also has the power to intervene when necessary to protect the public but in general does not require pre-market approval or testing. The ACSH says that companies are required to place a warning note on their products if they have not been tested and that experts in cosmetic ingredient reviews also play a role in monitoring safety through influence on the use of ingredients, but also lack legal authority. According to the ACSH, overall the organization has reviewed about 1,200 ingredients and has suggested that several hundred be restricted, but there is no standard or systemic method for reviewing chemicals for safety and a clear definition of what is meant by 'safety' so that all chemicals are tested on the same basis. [57]

          Veterinary products Edit

          The Center for Veterinary Medicine (CVM) is a center of the FDA that regulates food additives and drugs that are given to animals. [58] CVM regulates animal drugs, animal food including pet animal, and animal medical devices. The FDA's requirements to prevent the spread of bovine spongiform encephalopathy are also administered by CVM through inspections of feed manufacturers. [59] CVM does not regulate vaccines for animals these are handled by the United States Department of Agriculture. [60]

          Tobacco products Edit

          The FDA regulates tobacco products with authority established by the 2009 Family Smoking Prevention and Tobacco Control Act. [61] This Act requires color warnings on cigarette packages and printed advertising, and text warnings from the U.S. Surgeon General. [62]

          The nine new graphic warning labels were announced by the FDA in June 2011 and were scheduled to be required to appear on packaging by September 2012. The implementation date is uncertain, due to ongoing proceedings in the case of R.J. Reynolds Tobacco Co. v. U.S. Food and Drug Administration. [63] R.J. Reynolds, Lorillard, Commonwealth Brands, Liggett Group and Santa Fe Natural Tobacco Company have filed suit in Washington, D.C. federal court claiming that the graphic labels are an unconstitutional way of forcing tobacco companies to engage in anti-smoking advocacy on the government's behalf. [64]

          A First Amendment lawyer, Floyd Abrams, is representing the tobacco companies in the case, contending requiring graphic warning labels on a lawful product cannot withstand constitutional scrutiny. [65] The Association of National Advertisers and the American Advertising Federation have also filed a brief in the suit, arguing that the labels infringe on commercial free speech and could lead to further government intrusion if left unchallenged. [66] In November 2011, Federal judge Richard Leon of the U.S. District Court for the District of Columbia temporarily halted the new labels, likely delaying the requirement that tobacco companies display the labels. The U.S. Supreme Court ultimately could decide the matter. [67]

          In July 2017, the FDA announced a plan that would reduce the current levels of nicotine permitted in tobacco cigarettes. [68]

          Regulation of living organisms Edit

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

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

          The FDA also requires milk to be pasteurized to remove bacteria. [ citation needed ]

          International Cooperation Edit

          In February 2011, President Barack Obama and Canadian Prime Minister Stephen Harper issued a "Declaration on a Shared Vision for Perimeter Security and Economic Competitiveness" [69] [70] and announced the creation of the Canada-United States Regulatory Cooperation Council (RCC) "to increase regulatory transparency and coordination between the two countries.” [71]

          Under the RCC mandate, the FDA and Health Canada undertook a "first of its kind" initiative by selecting "as its first area of alignment common cold indications for certain over-the-counter antihistamine ingredients (GC 2013-01-10)." [72]

          A more recent example of the FDA's international work is their 2018 cooperation with regulatory and law-enforcement agencies worldwide through Interpol as part of Operation Pangea XI. [73] [74] The FDA targeted 465 websites that illegally sold potentially dangerous, unapproved versions of opioid, oncology, and antiviral prescription drugs to U.S. consumers. The agency focused on transaction laundering schemes in order to uncover the complex online drug network. [75]

          The FDA carries out research and development activities to develop technology and standards that support its regulatory role, with the objective of resolving scientific and technical challenges before they become impediments. The FDA's research efforts include the areas of biologics, medical devices, drugs, women's health, toxicology, food safety and applied nutrition, and veterinary medicine. [76]

          The FDA has collected a large amount of data through the decades. The OpenFDA project was created to enable easy access of the data for the public and was officially launched in June 2014. [77] [78]

          Up until the 20th century, there were few federal laws regulating the contents and sale of domestically produced food and pharmaceuticals, with one exception being the short-lived Vaccine Act of 1813. The history of the FDA can be traced to the latter part of the 19th century and the U.S. Department of Agriculture's Division of Chemistry, later its Bureau of Chemistry. Under Harvey Washington Wiley, appointed chief chemist in 1883, the Division began conducting research into the adulteration and misbranding of food and drugs on the American market. Wiley's advocacy came at a time when the public had become aroused to hazards in the marketplace by muckraking journalists like Upton Sinclair, and became part of a general trend for increased federal regulations in matters pertinent to public safety during the Progressive Era. [79] The Biologics Control Act of 1902 was put in place after a diphtheria antitoxin—derived from tetanus-contaminated serum—was used to produce a vaccine that caused the deaths of thirteen children in St. Louis, Missouri. The serum was originally collected from a horse name Jim who had contracted tetanus.

          In June 1906, President Theodore Roosevelt signed into law the Pure Food and Drug Act of 1906, also known as the "Wiley Act" after its chief advocate. [79] The Act prohibited, under penalty of seizure of goods, the interstate transport of food that had been "adulterated". The Act applied similar penalties to the interstate marketing of "adulterated" drugs, in which the "standard of strength, quality, or purity" of the active ingredient was not either stated clearly on the label or listed in the United States Pharmacopeia or the National Formulary. [80]

          The responsibility for examining food and drugs for such "adulteration" or "misbranding" was given to Wiley's USDA Bureau of Chemistry. [79] Wiley used these new regulatory powers to pursue an aggressive campaign against the manufacturers of foods with chemical additives, but the Chemistry Bureau's authority was soon checked by judicial decisions, which narrowly defined the bureau's powers and set high standards for proof of fraudulent intent. [79] In 1927, the Bureau of Chemistry's regulatory powers were reorganized under a new USDA body, the Food, Drug, and Insecticide Administration. [81] This name was shortened to the Food and Drug Administration (FDA) three years later. [82]

          By the 1930s, muckraking journalists, consumer protection organizations, and federal regulators began mounting a campaign for stronger regulatory authority by publicizing a list of injurious products that had been ruled permissible under the 1906 law, including radioactive beverages, the mascara Lash lure which caused blindness, and worthless "cures" for diabetes and tuberculosis. The resulting proposed law was unable to get through the Congress of the United States for five years, but was rapidly enacted into law following the public outcry over the 1937 Elixir Sulfanilamide tragedy, in which over 100 people died after using a drug formulated with a toxic, untested solvent. [83]

          President Franklin Delano Roosevelt signed the Federal Food, Drug, and Cosmetic Act into law on June 24, 1938. The new law significantly increased federal regulatory authority over drugs by mandating a pre-market review of the safety of all new drugs, as well as banning false therapeutic claims in drug labeling without requiring that the FDA prove fraudulent intent. Soon after passage of the 1938 Act, the FDA began to designate certain drugs as safe for use only under the supervision of a medical professional, and the category of "prescription-only" drugs was securely codified into law by the Durham-Humphrey Amendment in 1951. These developments confirmed extensive powers for the FDA to enforce post-marketing recalls of ineffective drugs. [79]

          Outside of the US, the drug thalidomide was marketed for the relief of general nausea and morning sickness, but caused birth defects and even the death of thousands of babies when taken during pregnancy. [84] American mothers were largely unaffected as Dr. Frances Oldham Kelsey of the FDA refused to authorize the medication for market. In 1962, the Kefauver-Harris Amendment to the FD&C Act was passed, which represented a "revolution" in FDA regulatory authority. [85] The most important change was the requirement that all new drug applications demonstrate "substantial evidence" of the drug's efficacy for a marketed indication, in addition to the existing requirement for pre-marketing demonstration of safety. This marked the start of the FDA approval process in its modern form.

          These reforms had the effect of increasing the time, and the difficulty, required to bring a drug to market. [86] One of the most important statutes in establishing the modern American pharmaceutical market was the 1984 Drug Price Competition and Patent Term Restoration Act, more commonly known as the "Hatch-Waxman Act" after its chief sponsors. The act extended the patent exclusivity terms of new drugs, and tied those extensions, in part, to the length of the FDA approval process for each individual drug. For generic manufacturers, the Act created a new approval mechanism, the Abbreviated New Drug Application (ANDA), in which the generic drug manufacturer need only demonstrate that their generic formulation has the same active ingredient, route of administration, dosage form, strength, and pharmacokinetic properties ("bioequivalence") as the corresponding brand-name drug. This Act has been credited with, in essence, creating the modern generic drug industry. [87]

          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. [88] 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. [89] All of the initial drugs approved for the treatment of HIV/AIDS were approved through these accelerated approval mechanisms. [90] Frank Young, then commissioner of the FDA, was behind the Action Plan Phase II, established in August 1987 for quicker approval of AIDS medication. [91]

          In two instances, state governments have sought to legalize drugs that the FDA has not approved. Under the theory that federal law, passed pursuant to Constitutional authority, overrules conflicting state laws, federal authorities still claim the authority to seize, arrest, and prosecute for possession and sales of these substances, [ citation needed ] even in states where they are legal under state law. The first wave was the legalization by 27 states of laetrile in the late 1970s. This drug was used as a treatment for cancer, but scientific studies both before and after this legislative trend found it to be ineffective. [92] [93] The second wave concerned medical marijuana in the 1990s and 2000s. Though Virginia passed legislation allowing doctors to recommend cannabis for glaucoma or the side effects of chemotherapy, a more widespread trend began in California with the Compassionate Use Act of 1996.

          Historical first: FDA and Endo Pharmaceutical's Opana ER (2017) Edit

          When the FDA requested Endo Pharmaceuticals on June 8, 2017, to remove oxymorphone hydrochloride from the market, it was the first such request in FDA history. [94]

          Critical Path Initiative Edit

          The Critical Path Initiative [95] is the 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. [96]

          Patients' rights to access unapproved drugs Edit

          The Compassionate Investigational New Drug program was created after Randall v. U.S. ruled in favor of Robert C. Randall in 1978, creating a program for medical marijuana. [97]

          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. [98] The case won an initial appeal in May 2006, but that decision was reversed by a March 2007 rehearing. The US Supreme Court declined to hear the case, and the final decision denied the existence of a right to unapproved medications.

          Critics of the FDA's regulatory power argue that the FDA takes too long to approve drugs that might ease pain and human suffering faster if brought to market sooner. The AIDS crisis created some political efforts to streamline the approval process. However, these limited reforms were targeted for AIDS drugs, not for the broader market. This has led to the call for more robust and enduring reforms that would allow patients, under the care of their doctors, access to drugs that have passed the first round of clinical trials. [99] [100]

          Post-marketing drug safety monitoring Edit

          The widely publicized recall of Vioxx, a non-steroidal anti-inflammatory drug (NSAID) 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. [101]

          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 [102] for reforms in the FDA's procedures for pre- and post-market drug safety regulation.

          In 2006, a Congressional 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 medicine medical 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. [103] [104] Some of the committee's recommendations were incorporated into drafts of the PDUFA IV amendment, which was signed into law as the Food and Drug Administration Amendments Act of 2007. [105]

          As of 2011, Risk Minimization Action Plans (RiskMAPS) have been created to ensure risks of a drug never outweigh the benefits of that drug within the post-marketing period. This program requires that manufacturers design and implement periodic assessments of their programs' effectiveness. The Risk Minimization Action Plans are set in place depending on the overall level of risk a prescription drug is likely to pose to the public. [106]

          Pediatric drug testing Edit

          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. [ citation needed ] 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. Children react differently to the drugs because of many reasons, including size, weight, etc. There were several reasons that few medical trials were done with children. For many drugs, children represented such a small proportion of the potential market, that drug manufacturers did not see such testing as cost-effective. [107]

          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. [107]

          An initial attempt by the FDA to address this issue was the 1994 FDA Final Rule on Pediatric Labeling and Extrapolation, which allowed manufacturers to add pediatric labeling information, but required drugs that had not been tested for pediatric safety and efficacy to bear a disclaimer to that effect. However, this rule failed to motivate many drug companies to conduct additional pediatric drug trials. In 1997, the FDA proposed a rule to require pediatric drug trials from the sponsors of New Drug Applications. However, this new rule was successfully preempted in federal court as exceeding the FDA's statutory authority. [107]

          While this debate was unfolding, Congress used the Food and Drug Administration Modernization Act of 1997 to pass incentives that gave pharmaceutical manufacturers a six-month patent term extension on new drugs submitted with pediatric trial data. The Best Pharmaceuticals for Children Act of 2007 reauthorized these provisions and allowed the FDA to request NIH-sponsored testing for pediatric drug testing, although these requests are subject to NIH funding constraints. 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. [107]

          Priority review voucher (PRV) Edit

          The priority review voucher is a provision of the Food and Drug Administration Amendments Act of 2007, which awards a transferable "priority review voucher" to any company that obtains approval for a treatment for a neglected tropical diseases. The system was first proposed by Duke University faculty David Ridley, Henry Grabowski, and Jeffrey Moe in their 2006 Health Affairs paper: "Developing Drugs for Developing Countries". [108] President Obama signed into law the Food and Drug Administration Safety and Innovation Act of 2012 which extended the authorization until 2017. [109]

          Rules for generic biologics Edit

          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, [ citation needed ] while the enzyme replacement therapy drug Cerezyme costs $200,000 per year, and must be taken by Gaucher's Disease patients for life. [110]

          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. This precluded 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. [110]

          Mobile medical applications Edit

          In 2013, a guidance was issued to regulate mobile medical applications and protect users from their unintended use. This guidance distinguishes the apps subjected to regulation based on the marketing claims of the apps. [111] Incorporation of the guidelines during the development phase of these apps has been proposed for expedited market entry and clearance. [112]

          The FDA has regulatory oversight over a large array of products that affect the health and life of American citizens. [79] As a result, the FDA's powers and decisions are carefully monitored by several governmental and non-governmental organizations. A $1.8 million 2006 Institute of Medicine report on pharmaceutical regulation in the U.S. found major deficiencies in the current FDA system for ensuring the safety of drugs on the American market. Overall, the authors called for an increase in the regulatory powers, funding, and independence of the FDA. [113] [114]

          Nine FDA scientists appealed to then president-elect Barack Obama over pressures from management, experienced during the George W. Bush presidency, to manipulate data, including in relation to the review process for medical devices. Characterized as "corrupted and distorted by current FDA managers, thereby placing the American people at risk," these concerns were also highlighted in the 2006 report [113] on the agency as well. [115]

          The FDA has also been criticized from the opposite viewpoint, as being too tough on industry. According to an analysis published on the website of the libertarian Mercatus Center, many feel the FDA oversteps its regulatory powers, and undermines small business and small farms in favor of large corporations. Three of the FDA restrictions under their analysis are the permitting of new drugs and devices, the control of manufacturer speech, and the imposition of prescription requirements. The authors argue that in the increasingly complex and diverse food marketplace, the FDA is not equipped to adequately regulate or inspect food. [116] [ verification needed ]

          However, in an indicator that the FDA may be too lax in their approval process, in particular for medical devices, a 2011 study by Dr. Diana Zuckerman and Paul Brown of the National Research Center for Women and Families, and Dr. Steven Nissen of the Cleveland Clinic, published in the Archives of Internal Medicine, showed that most medical devices recalled in the last five years for "serious health problems or death" had been previously approved by the FDA using the less stringent, and cheaper, 510(k) process. In a few cases, the devices had been deemed so low-risk that they did not need FDA regulation. Of the 113 devices recalled, 35 were for cardiovascular health purposes. [117]

          Kefauver-Harris Drug Amendments of 1962

          Greater public interest in drug legislation allowed Congress to pass major changes, making the rules for getting a drug to market much stricter. Instead of merely demonstrating safety, the Kefauver-Harris Drug Amendments required producers to provide substantial evidence showing that the drug was effective for the purpose for which it was intended.

          This was revolutionary because it required rigorous proof consisting of well-controlled studies.

          The Secretary of the FDA also established new requirements for the testing and investigation of new drugs, including obtaining informed consent from study subjects.

          Food and Drug Administration (FDA)

          The Food and Drug Administration (FDA) is an executive branch agency, the beneficiary of vast legislative powers delegated to it by Congress. It is also the repository of powers not delegated by Congress that FDA has usurped beyond the limits of its enabling statute throughout its 68 year history. The Commissioner of FDA sits at the pleasure of the President. The FDA is one of the largest and most powerful federal bureaucracies. It regulates over $1 trillion dollars of goods. The products under its jurisdiction account for 25 cents of every dollar spent by American consumers. FDA has approximately ten thousand employees and 26 district offices across the United States. The United States Attorneys and federal marshals are at its disposal and can obtain search and seizure warrants to be exercised without any advance notice against any company that sells a food, dietary supplement, drug, or medical device in the United States.

          To understand how FDA has acquired so much power in a government designedly of limited powers, we have to appreciate the agency&rsquos place in history. Indeed, we have to start with the origins of American constitutional government, 151 years before the FDA came into existence, to appreciate the perversion of the Framers&rsquo plan effected by the modern FDA. We must follow America&rsquos late 18th Century rejection of the arbitrary will of King George III, its embrace of a written Constitution where the law and a system of separation of powers and checks and balances were supposed to prevent the accumulation of tyrannical power in any one set of hands. We must then observe the rise of independent regulatory commissions in the Twentieth Century and how those commissions united legislative, executive, and judicial powers into single hands in violation of our founding principles. We must then come to see how FDA in particular exemplifies the arbitrary rule of people in power over the rule of law.

          FDA approves "the pill"

          The Food and Drug Administration (FDA) approves the world’s first commercially produced birth-control pill𠄾novid-10, made by the G.D. Searle Company of Chicago, Illinois.

          Development of “the pill,” as it became popularly known, was initially commissioned by birth-control pioneer Margaret Sanger and funded by heiress Katherine McCormick. Sanger, who opened the first birth-control clinic in the United States in 1916, hoped to encourage the development of a more practical and effective alternative to contraceptives that were in use at the time.

          In the early 1950s, Gregory Pincus, a biochemist at the Worcester Foundation for Experimental Biology, and John Rock, a gynecologist at Harvard Medical School, began work on a birth-control pill. Clinical tests of the pill, which used synthetic progesterone and estrogen to repress ovulation in women, were initiated in 1954. On May 9, 1960, the FDA approved the pill, granting greater reproductive freedom to American women.

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          In: Clinical Therapeutics , Vol. 29, No. 1, 01.2007, p. 1-16.

          Research output : Contribution to journal › Article › peer-review

          T1 - The history and contemporary challenges of the US food and drug administration

          N2 - Background: The year 2006 marks the 100th anniversary of the regulatory agency now known as the US Food and Drug Administration (FDA), the first consumer protection agency of the federal government and arguably the most influential regulatory agency in the world. The FDA thus plays an integral role in the use of pharmaceuticals, not only in the United States but worldwide. Objective: The goal of this review was to present an overview of the FDA and place its current role in the perspectives of history and contemporary needs. Methods: Relevant materials for this review were identified through a search of the English-language literature indexed on MEDLINE (through 2006) using the main search terms United States Food and Drug Administration, FDA, history of the FDA, drug approvals, drug legislation, and FDA legislation. Results from the initial searches were then explored further. Results: The statute that created the bureau which later became the FDA established this agency to prohibit interstate commerce of adulterated foods, drinks, and drugs. The Food, Drug, and Cosmetic Act that replaced it in 1938, and subsequent food and drug laws and amendments, expanded the FDA's responsibilities to cosmetics, medical devices, biological products, and radiation-emitting products. These amendments have also established the FDA as a mainly preventive regulatory agency that relies chiefly on premarket control. As such, the FDA has played an important role in shaping the modern pharmaceutical industry by making the scientific approach and the clinical trial process the standard for establishing safety and efficacy and by making rigorous scientific analysis the predominant component of the process for pharmaceutical regulation. Conclusions: As shown in this review, the evolution of the FDA can be described as a series of "crisis-legislation-adaptation" cycles: a public health crisis promoted the passage of congressional legislation, which was then followed by implementation of the law by the FDA. However, the crises the FDA faces currently are likely to be overcome only under strong and permanent leadership willing to redefine the role and procedures of the FDA with an open mind.

          AB - Background: The year 2006 marks the 100th anniversary of the regulatory agency now known as the US Food and Drug Administration (FDA), the first consumer protection agency of the federal government and arguably the most influential regulatory agency in the world. The FDA thus plays an integral role in the use of pharmaceuticals, not only in the United States but worldwide. Objective: The goal of this review was to present an overview of the FDA and place its current role in the perspectives of history and contemporary needs. Methods: Relevant materials for this review were identified through a search of the English-language literature indexed on MEDLINE (through 2006) using the main search terms United States Food and Drug Administration, FDA, history of the FDA, drug approvals, drug legislation, and FDA legislation. Results from the initial searches were then explored further. Results: The statute that created the bureau which later became the FDA established this agency to prohibit interstate commerce of adulterated foods, drinks, and drugs. The Food, Drug, and Cosmetic Act that replaced it in 1938, and subsequent food and drug laws and amendments, expanded the FDA's responsibilities to cosmetics, medical devices, biological products, and radiation-emitting products. These amendments have also established the FDA as a mainly preventive regulatory agency that relies chiefly on premarket control. As such, the FDA has played an important role in shaping the modern pharmaceutical industry by making the scientific approach and the clinical trial process the standard for establishing safety and efficacy and by making rigorous scientific analysis the predominant component of the process for pharmaceutical regulation. Conclusions: As shown in this review, the evolution of the FDA can be described as a series of "crisis-legislation-adaptation" cycles: a public health crisis promoted the passage of congressional legislation, which was then followed by implementation of the law by the FDA. However, the crises the FDA faces currently are likely to be overcome only under strong and permanent leadership willing to redefine the role and procedures of the FDA with an open mind.

          FDA and Clinical Trials

          While the FDA does not conduct clinical trials, it has the responsibility of protecting clinical trial participants and making sure data is available to the public on The FDA’s Office of Good Clinical Practice oversees the ethical treatment of participants in clinical trials.

          The agency also oversees and regulates clinical-trial protocols called Good Clinical Practice (GCP). Researchers for drug companies and others conducting clinical trials refer to these protocols when designing each phase of their clinical trials, particularly if these trials are funded by the National Institutes of Health.

          In January 2017, the NIH and FDA required all NIH-funded clinical trial staff be trained in GCP. These principles help assure the safety, integrity, and quality of clinical trials, according to the FDA.

          Food and Drug Administration

          The Food and Drug Administration (FDA) is an executive branch agency, the beneficiary of vast legislative powers delegated to it by Congress. It is also the repository of powers not delegated by Congress that FDA has usurped beyond the limits of its enabling statute throughout its 68 year history. The Commissioner of FDA sits at the pleasure of the President. The FDA is one of the largest and most powerful federal bureaucracies. It regulates over $1 trillion dollars of goods. The products under its jurisdiction account for 25 cents of every dollar spent by American consumers. FDA has approximately ten thousand employees and 26 district offices across the United States. The United States Attorneys and federal marshals are at its disposal and can obtain search and seizure warrants to be exercised without any advance notice against any company that sells a food, dietary supplement, drug, or medical device in the United States.

          To understand how FDA has acquired so much power in a government designedly of limited powers, we have to appreciate the agency&rsquos place in history. Indeed, we have to start with the origins of American constitutional government, 151 years before the FDA came into existence, to appreciate the perversion of the Framers&rsquo plan effected by the modern FDA. We must follow America&rsquos late 18th Century rejection of the arbitrary will of King George III, its embrace of a written Constitution where the law and a system of separation of powers and checks and balances were supposed to prevent the accumulation of tyrannical power in any one set of hands. We must then observe the rise of independent regulatory commissions in the Twentieth Century and how those commissions united legislative, executive, and judicial powers into single hands in violation of our founding principles. We must then come to see how FDA in particular exemplifies the arbitrary rule of people in power over the rule of law.

          The Framers of our Constitution prohibited the federal government from delegating legislative power from the duly elected representatives of Congress to any other entity. They warned that if legislative power were combined with executive power, or if legislative power were combined with judicial power, our republic would become an oligarchy and the rights of the people would be sacrificed to achieve the selfish ends of those who govern.

          In February of 1776, a pamphlet came to be published in Philadelphia that would outsell every other up to that time in the American colonies and would achieve resounding popularity throughout Europe. It was Common Sense. Written anonymously by Thomas Paine, that pamphlet became the most influential tract in revolutionary America. In it Paine explained the quintessential defining principle of our polity, the very reason why we could not endure the arbitrary will of King George III and would rebel to form a new nation. He begged for revolution against Great Britain because the King had usurped rights and powers of the people and had replaced the rule of law with his arbitrary will. Paine wrote:

          But where . . . is the King of America? I&rsquoll tell you Friend, he reigns above, and doth not make havoc of mankind like the Royal Brute of Britain. Yet that we may not appear to be defective in earthly honors, let a day be solemnly set apart for proclaiming the charter . . . . that in America the law is King. For as in absolute governments the King is law, so in free countries the law ought to be King and there ought to be no other.

          The defining principle of the American republic was that governments are instituted among men to protect the rights of the governed, that to accomplish that task governmental powers must be limited and defined in written law and separated in the hands of independent legislative, executive, and judicial departments with a system of checks and balances to prevent the accumulation of the separate powers into any single department. The French philosopher Montesquieu argued for the separation of powers in his 1748 treatise The Spirit of the Laws. That book greatly influenced the founding fathers, as did endorsements of the doctrine by John Locke and other British Whig writers of the 18th Century. Historian Forrest McDonald explains that all leading politicos of the Founding Era &ldquocould recite central points of Montesquieu&rsquos doctrine of separation of powers as if it had been a catechism.&rdquo In The Spirit of the Laws Montesquieu wrote:

          [T]here is no liberty if the power of judging be not separated from the legislative and executive powers. Were it joined with the legislative, the life and liberty of the subject would be exposed to arbitrary control, for the judge would then be the legislator. Were it joined to the executive power, the judge might behave with all the violence of an oppressor . . . . There would be an end of everything were the same man, or the same body . . . to exercise those three powers . . . of enacting laws . . . of executing [laws]. . . and . . . of judging the crimes or differences of individuals . . . .

          In Federalist No. 47, James Madison argued for the rule of law over the arbitrary will of those in power, explaining that our Constitution would define &ldquoa government of laws and not of men.&rdquo The phrase, common among the founding generation, meant that there was to be no place in government for the exercise of arbitrary will over the lives, liberties, or properties of the American people. Just as we were to be ruled by laws, our law itself was to be the product of separate, competing legislative, executive, and judicial power centers never were any two of those powers to be combined in a single center. Madison wrote, &ldquo[t]he accumulation of all powers, legislative, executive, and judicial, in the same hands, whether of one, few, or many, and whether hereditary, self-appointed, or elected, may justly be pronounced the very definition of tyranny.&rdquo Typical of the Federalists who advocated ratification of the Constitution, Alexander Hamilton explained that the separation of powers was &ldquoitself, in every rational sense, and to every useful purpose, A BILL OF RIGHTS.&rdquo It would deny a single department autonomous governance. It would keep abuse of power in check by humbling those in government with the need to satisfy the dictates of competing power centers.

          Like Montesquieu, the Framers viewed political liberty as a condition in which citizens are free from arbitrary power and can expect to be secure in their persons and property. As Montesquieu put it in The Spirit of the Laws, &ldquo[t]he political liberty of the subject is a tranquility of mind, arising from the opinion each person has of his safety.&rdquo Concentration of two or more of the three classes of power&ndashlegislative, executive, judicial&ndashin a single organ of government would destroy that tranquility for reasons that John Adams expressed succinctly in a pamphlet published in 1776: &ldquoBecause a single assembly, possessed of all the powers of government, would make arbitrary laws for their own interest, execute all laws arbitrarily for their own interest, and adjudge all controversies in their own favor.&rdquo

          Indeed, liberty depends on the secure knowledge that the rule of law governs over the arbitrary will of those in power. The separation of powers assures that no single power center may create, execute, and judge the law but must obtain the consent of the other, independent power centers to achieve those ends. When the separation of powers and the system of checks and balances is gone, so is the security needed for the preservation of liberty from the arbitrary will of those in government.

          From 1787 until 1937, the constitutional law of this country prohibited administrators from possessing combined legislative, executive, and judicial powers, but for the last 69 years, the Separation of Powers doctrine has been largely abandoned in favor of oligarchic rule by the independent regulatory commissions. That rule has produced rights violations, massive transfers of wealth from private to public hands, government protectionism for industry leaders over new market entrants, vast corruption, and explosive growth in the size and scope of the federal government. The independent regulatory commissions, and the FDA in particular, are destroying free enterprise and individual liberty in America.

          So what happened in 1937 to undue the Framers&rsquo constitutional design, the separation of powers doctrine?

          Accepting the Republican nomination for President in 1928, Herbert Hoover with great exuberance and confidence predicted, &ldquoWe in America today are nearer to the final triumph over poverty than ever before in the history of any land. The poorhouse is vanishing from us.&rdquo Eight months later, on October 29, 1929, the stock market crashed signaling the start of the Great Depression, an economic collapse that reverberated worldwide. From 1929 to 1933, the United States gross national product declined from $104 billion to $56 billion. By 1933, unemployment reached 33% (roughly 16 million Americans out of work). President Hoover lost his re-election bid to Franklin Delano Roosevelt on Roosevelt&rsquos promise of a New Deal to end widespread poverty through government largesse.

          Shortly after his inauguration in March of 1933, President Roosevelt proposed laws that granted sweeping legislative, executive, and judicial powers to new executive branch agencies. Although the Supreme Court upheld many of these laws, it refused to do so in the 1935 A.L.A. Schechter Poultry Corp. v. U.S. decision. Schechter Poultry struck down Roosevelt&rsquos National Industrial Recovery Act of 1933. A unanimous Court held that Title I of the NIRA constituted an &ldquounconstitutional delegation of legislative power to the executive.&rdquo Chief Justice Charles Evans Hughes wrote for the Court: &ldquoCongress is not permitted to abdicate or to transfer to others the essential legislative function with which it is thus vested.&rdquo In a concurrence, Justice Benjamin Cardozo referred to the industrial code provisions of the NIRA as &ldquodelegation [of power] running riot.&rdquo The Court thus demanded adherence to the separation of powers doctrine embodied in the Constitution.

          The Court&rsquos actions did not sit well with President Roosevelt. Following his re-election to office and preceding his plans for the enactment of additional executive branch agencies invested with legislative, executive, and judicial powers, President Roosevelt proposed the Judiciary Reorganization Act of 1937. The Act would give President Roosevelt the power to appoint an extra Supreme Court Justice for every sitting Justice over the age of 70 and six months. Six of the Justices on the High Court were over 70 and six months. The Justices predisposed against delegation had held a slim one vote majority (5 to 4). Roosevelt&rsquos threatened court packing plan never was enacted but the threat alone provoked the desired response. It produced what the media of that day referred to as &ldquothe switch in time that saved nine.&rdquo Justice Owen J. Roberts who favored the conservative wing of the Court (the so-called Four Horsemen, Justices James Clark McReynolds George Sutherland Willis Van DeVanter and Pierce Butler) voted with the liberal wing of the Court (the so-called Three Musketeers, Justices Louis Brandeis Benjamin Cardozo and Harlan Stone). Within a year, conservative Justices Van DeVanter and Sutherland retired, replaced by the pro-New Deal Justices Hugo Black and Stanley Reed.

          That shift in the Court&rsquos alignment led to the near total erosion of the separation of powers doctrine, resulting in massive legislative delegations of power to independent regulatory commissions, among them the U.S. Food and Drug Administration.

          Over the years independent regulatory commissions have not only come to exercise powers intended to be vested in Congress but they have also become legislatures themselves&ndashpromulgating regulations that exceed statutory limits and running roughshod over individual liberties designedly protected by the Bill of Rights. The rule of law has been replaced by the arbitrary will of unelected and unaccountable federal bureaucrats. The FDA is an excellent case in point.

          Congressional delegations of legislative power to FDA, and FDA usurpations of power, often occur following either a real or supposed public health crisis involving a regulated product.

          Federal drug regulation was of trifling import until 1937. In that year an attempt by the Massengill Company to reformulate a sulfa drug into a liquid form resulted in the deaths of 107 children. The company sold the liquid drug in a syrup that included diethylene glycol as a solvent. That is anti-freeze. Although Massengill was convicted of gross negligence, the Roosevelt administration, feeling its oats after the &ldquoswitch in time that saved nine,&rdquo called for adoption of the Food, Drug and Cosmetic Act of 1938. That law required companies to submit New Drug Applications (NDA&rsquos) before introducing new pharmaceuticals into interstate commerce. In concessions to the leading drug makers, the law grandfathered as lawful all drugs then on the market and created costly safety testing barriers to entry. Each NDA had to document tests that proved a drug safe at recommended dosages. NDAs were automatically approved sixty days after submission unless FDA determined the safety testing insufficient.

          Before 1962, FDA regulated drug safety but not drug efficacy. Then in 1961 thousands of deformed newborns began appearing across Europe&ndashvictims of the sedative thalidomide. Although existing law included safety reviews that would presumably prevent the sale of thalidomide in the United States, FDA, the pharmaceutical industry, and sympathetic members of Congress argued for expanded FDA powers based on the thalidomide catastrophe. The Kefauver-Harris Drug Amendments became law in 1962. Under the 1938 Act, NDAs were approved unless FDA acted to deny them. Under the 1962 Act, NDAs were denied unless FDA acted to approve them. For an NDA to be granted, FDA had to conclude that the new drug was safe and effective. With the support of the pharmaceutical industry, FDA translated the law into a Byzantine system of clinical trial proofs, not involving product testing by the FDA but involving redundant inquiries and demands for proof at the discretion of agency regulators. The new drug approval process went from a short sixty day to a six month or more review, and the cost from discovery to approval rose from a few million dollars to over $138 million per drug (that cost has now risen to $1.6 billion per drug). The day of the government protected monopolist had arrived for the drug industry.

          The 1962 Act also transferred to FDA from FTC jurisdiction over drug advertising&ndasha move urged by the pharmaceutical industry because it lacked the kind of influence over FTC that it had long enjoyed over FDA. The bill codified cGMPs, another barrier to entry into the drug market, and gave FDA expanded inspection powers, yet another barrier. The drug industry lobbied for the bill.

          The same year FDA acquired vast new powers to regulate drugs, it tried to expand its drug regulation to eliminate a burgeoning new source of competition for drugs, dietary supplements. Evidence began to reveal that dietary ingredients had therapeutic effects. The far sighted in the pharmaceutical industry and at the FDA perceived a competitive threat emerging to drug regulation from the sale of dietary ingredients at above RDA doses. To counter that threat, and without the slightest grant of legislative authority from Congress, FDA published regulations setting minimum and maximum potency levels for dietary supplements. The regulations were withdrawn in the face of strong public protest.

          Four years later, FDA returned to the subject. Again without any grant of legislative authority, FDA published a rule that any dietary supplement exceeding 150% of the RDA for a vitamin or mineral would automatically be regulated as a drug. Once declared a drug, the supplement could not be lawfully marketed in the United States without FDA drug approval. The dietary supplement industry challenged the rule in federal court with mixed results. Public outcry against the rule reached a fever pitch. On April 22, 1976, after intense public lobbying against the rule, Senator William Proxmire introduced an amendment to the Heart and Lung Act and the amended Act became law. It prohibited FDA from classifying a vitamin or a mineral as a drug based on its potency.

          Undaunted, FDA tried yet again to rid the market of vitamins in the 1970s by claiming on a case by case basis that they were adulterated based on their potency. The federal courts refused to cooperate with this attempt at an end-run around the Proxmire Amendment. FDA tried another approach in the 1970s. It declared supplements to be unapproved Food Additives. Under the Food Additives provision of the FDCA, no food additive may be sold unless the manufacturer proves it safe to FDA&rsquos satisfaction. In this way, FDA planned to make proving the safety of supplements so difficult that it would drive them out of the market. FDA&rsquos position was a logical absurdity: Single ingredient dietary supplements were food additives because the ingredients were added to a gelatin capsule which was, FDA said with a wink and a smirk, a food. The federal courts rejected this effort. The United States Court of Appeals for the First Circuit described FDA&rsquos approach as &ldquononsensical.&rdquo The United States Court of Appeals for the Seventh Circuit described FDA&rsquos position as an &ldquoAlice in Wonderland&rdquo approach.

          Then in 1980, FDA was back at it. This time FDA issued a proposed over-the-counter drug monograph for vitamins and minerals, declaring potencies above the RDA to fall within the scope of the monograph. Substantial public opposition killed this proposal.

          Most notably from the codification of the Kefauver-Harris Amendments of 1962 to the present, FDA has repeatedly exceeded the limits of its statutory authority to bring about changes designed to protect drug companies from competition. Many times those changes have come at the cost of human life. Courts have occasionally held FDA&rsquos actions unlawful. Rarely has FDA respected court decisions against its exercise of authority. The agency&rsquos usual course is either to ignore court orders or to render them ineffectual through the adoption of new rules, policies, or approaches that achieve the ends FDA desires through different means. The FDA&rsquos lack of respect for the rule of law, its destruction of the rule of law itself, was a consequence predicted by the Framers of the Constitution who warned against delegation of legislative powers.

          Since 1962, people within the FDA itself and outside the agency have complained bitterly that FDA is unduly influenced by drug companies. The complaining parties are many, have excellent reputations for honesty, and have spoken against their own economic interests and at considerable personal risk of FDA retaliation. FDA has approved numerous drugs over the objections of its drug safety officers. A significant number of those drugs have been withdrawn from the market following occurrence of the very harms predicted by FDA&rsquos drug safety officers. The following drugs are among those FDA allowed into the market over the objections of its drug safety officers. Each of the drugs was subsequently withdrawn from the market when the predicted harms actually occurred: GlaxoSmithKline&rsquos Lotronex for irritable bowel syndrome American Home Products&rsquo Redux, a diet aid Bayer Corporation&rsquos Raxav, an antibiotic Roche&rsquos Posicor, a blood pressure medication Wyeth-Ayersts&rsquo Duract, a painkiller and Warner-Lambert&rsquos Rezulin, a diabetes drug.

          In 1987, an FDA supervisor named Charles Chang received expensive gifts (including a fur coat and a videocassette recorder) from drug company lobbyists in exchange for making sure that their drugs were assigned to subordinates Chang knew to be quick reviewers. Through his assignment of work, Chang manipulated the approval schedule to the advantage of those who gave him bribes. Given a tip to investigate the corruption by Barr Laboratories, the Department of Justice and the FBI uncovered corrupt practices within the agency&rsquos generic drug division. The sting landed Chang in federal prison and caused 42 others and 10 companies to be convicted on charges of fraud and corruption. The scandal shook congressional confidence in FDA. It brought down the FDA Commissioner Frank Young who resigned in November 1989. Although FDA was clearly in the wrong, senior management at the agency resented Barr Laboratories disclosures to the Justice Department, FBI, and Congress. Commissioner David Kessler authorized repeated inspections of Barr Laboratories&rsquo facilities and delayed approvals for its drugs then in the pipeline.

          In 1997, the drug Rezulin was approved by FDA for the treatment of Type 2 diabetes over objections from several FDA drug safety officers that Rezulin significantly increased liver enzyme levels and would cause liver failure and death. Complaining that politics ruled over science at the agency, the FDA&rsquos drug safety officer Robert Misbin resigned. Frustrated with FDA management for approving Rezulin despite its lethal dangers, Misbin said he knew people would die and did &ldquonot want to stay around for what&rsquos going to happen.&rdquo Not willing to sit idly by while the bodies piled up, Misbin complained to Congress. The FDA retaliated by giving Misbin his first negative job performance review and commenced an internal investigation against him. Members of Congress condemned FDA&rsquos actions. Misbin was not the first FDA scientist to be persecuted for complaining about Rezulin safety problems. FDA Internal Affairs interrogated Dr. Leo Lutwak, whom they also accused of leaking data on Rezulin. FDA Internal Affairs investigated Dr. John Gueriguian, the original scientist in charge of FDA&rsquos review of the Rezulin trials, after he also insisted that Rezulin was too dangerous to be sold. Doctors Gueriguian and Lutwak retired from FDA rather than face the costly investigations. Lutwak told CBS News, &ldquoIn my own agency I&rsquom treated like&hellipI&rsquom treated worse than a criminal! I&rsquom accused, I&rsquom threatened, I&rsquom taken away from my work.&rdquo CBS News also reported that two researchers at Warner-Lambert who conducted clinical trials on Rezulin claimed the company told them to downplay problems with the drug. FDA documents showed tests of the drug found liver enzyme levels six times normal, but Warner-Lambert reported levels of &ldquo2 to 3 times&hellipnormal,&rdquo a figure the company later acknowledged to be incorrect.

          Rezulin was withdrawn from the market after it was associated with 391 deaths, including 63 from liver failure. According to Warner-Lambert records, a senior FDA official, Dr. G. Alexander Fleming, offered to &ldquoease out&rdquo any FDA medical officer who exposed doubts about a Rezulin safety study.

          In 1999, FDA approved the GlaxoSmithKline drug Lotronex for the treatment of irritable bowel syndrome over FDA safety officers&rsquo objections. In November of 2000, Glaxo withdrew the drug from the market after reports of several deaths, the removal of a patient&rsquos colon, and bowel surgeries. Despite Lotronex&rsquos safety problems, FDA worked with GlaxoSmithKline to achieve a return of the drug to the market. It did so in the face of new studies showing that the drug increased patient risk of a life-threatening condition called ischemic colitis. Glaxo internal memos revealed that FDA&rsquos Center for Drug Evaluation and Research had been working with the manufacturer to assist it in managing media inquiries and in structuring the composition of a drug advisory committee panel to be favorable to the drug. The editor of The Lancet, Dr. Richard Horton, condemned FDA&rsquos actions saying, &ldquothis story reveals not only dangerous failings in a single drug&rsquos approval and review process but also the extent to which the FDA, its Center for Drug Evaluation and Research in particular, has become the servant of industry.&rdquo

          In 2001, Dr. Rudolph M. Widmark, who had been a drug safety officer at the FDA until 1997, told the Los Angeles Times, &ldquo[t]he basic message [in the new drug review process] is to approve. The people in charge don&rsquot say, &lsquoShould we approve this drug?&rsquo They say, &lsquoHey, how can we get this drug approved?'&rdquo

          Before 1995, FDA approved 60 percent of all new drug applications. By the end of that decade and to the present, the agency has approved over 80% of all new drug applications.

          In December of 2003, the British Medicines and Healthcare Products Regulatory Agency (England&rsquos equivalent of our FDA) warned physicians in that country not to prescribe the anti-depressants Zoloft, Lexapro, Celexa, Luvox, Effexor, Serzone, Remeron, and Paxil to patients under 18 years of age. The British agency concluded that the anti-depressants were unsafe for juveniles and young adults because they increased the risk of suicidal behavior and hostility. FDA&rsquos lead expert on the safety of antidepressants, Dr. Andrew Mosholder, agreed with the British agency. He found a statistically significant increased risk of suicidal behavior among children taking those drugs. Children were 1.89 times more likely to become suicidal on those drugs than on placebo. When he voiced his views to his superiors at FDA, he was removed from the February 2004 advisory panel considering the safety of the drugs and was made the subject of a criminal investigation. Facing adverse publicity, FDA convened a second advisory panel seven months later in September of 2004 and recommended warning labels. FDA refused to take the drugs off the market for juveniles and young adults despite mounting evidence that the drugs were ineffective and dangerous.

          In November of 2004, the Associate Director of FDA&rsquos Office of Drug Safety, Dr. David J. Graham, testified under the Whistleblower&rsquo Act before the Senate Finance Committee. He explained that the largest drug companies in the world exercised undue influence over FDA senior management. He said that repeatedly&ndashover safety staff objections&ndashFDA had approved unsafe drugs. In an interview he had in the September/October 2005 edition of Fraud magazine, Dr. Graham explained that he and other senior drug safety officers at FDA had urged the agency not to approve Vioxx, an arthritis drug manufactured by Merck, because it would substantially increase the risk of heart attack and stroke. FDA approved the drug over those objections. Some 20 million Americans took Vioxx. An estimated 140,000 suffered heart attacks, and, of those, 60,000 died.

          Dr. Graham testified about FDA attempts to keep him from testifying before Congress concerning the FDA&rsquos decision to put Vioxx on the market despite its lethal effects. In an interview on my radio program Health Law and Politics on the Talk Star Radio Network, Dr. Graham explained that the then FDA Commissioner, Lester A. Crawford, on the eve of Graham&rsquos testimony before the Senate urged Graham not to testify but to take instead a position Crawford would create for him as an aide to the Commissioner. Crawford invited Graham to advise him on FDA&rsquos drug approval process at a higher pay grade. Graham declined. He said FDA management then orchestrated a media campaign, calls to his lawyer and to members of Congress, all designed to cause those contacted to distrust Graham and view him as inept.

          In his Fraud magazine interview, Dr. Graham stated that &ldquoFDA is inherently biased in favor of the pharmaceutical industry. It views industry as its client, whose interests it must represent and advance.&rdquo Graham also charged that &ldquoFDA has a well-established history of suppressing its scientists, of pressuring them to change their recommendations and conclusions if they are unfavorable about a drug and retaliates against those scientists who don&rsquot buckle under FDA pressure and threats.&rdquo

          Dr. Graham explained that the drug Serevent, for asthma, still on the market, was the subject of significant objection by FDA drug safety officers yet was approved nonetheless. The drug creates a four-fold increase in the risk of death from asthma. Dr. Graham speculates that this drug may be responsible for many asthma deaths around the world.

          In the case of the drug Arava, for rheumatoid arthritis, also on the market, Dr. Graham and a colleague recommended against approval of the drug because it substantially increased the risk of acute liver failure. Dr. Graham reports that he and his colleague at FDA &ldquowere severely pressured to change our review, even to the point of being screamed at by a senior FDA manager while&rdquo Dr. Graham&rsquos supervisor (and that of his colleague) &ldquolooked on and did nothing to stop the abuse.&rdquo

          Although one would think the Vioxx debacle would have humbled FDA, please think again. On April 1, 2004, FDA approved the Sanofi-Aventis antibiotic Ketek despite warnings from four FDA drug safety officers (Dr. Charles Cooper, Dr. David Ross, Dr. Rosemary Johann-Liang, and Dr. David Graham) that the evidence supporting the drug was highly suspicious. FDA investigators found that Sanofi failed to disclose safety dangers that FDA drug safety officers later discovered. FDA&rsquos Dr. Cooper wrote, &ldquoI tried to argue that given Aventis&rsquos track record in which they have proven themselves to be untrustworthy that we have to consider the possibility that they are intentionally doing a poor job of collecting . . . data.&rdquo FDA approved the drug despite those warnings and had the temerity to argue against the drug&rsquos withdrawal from the market based on the allegedly fraudulent data. Ketek has been implicated in fourteen incidents of liver failure, including four liver failure deaths. It remains on the market.

          FDA frequently uses advisory committees comprised of scientists to evaluate drug safety and make recommendations on drug approvals. Members often have financial interests related to the products or topics under review. FDA routinely waives those conflicts of interest. This year the National Research Center for Women and Families published the results of a study conducted by the organization of FDA&rsquos Advisory Committee process. The National Research Center evaluated advisory committee meeting transcripts from January 1998 through December 2005. Among the findings:

          Many advisory committees recommended approval for almost every product they review, usually unanimously.

          Committee members describe pressure to conform and to recommend approval, and they candidly admit that their votes for approval may not be consistent with their concerns about safety and effectiveness.

          The FDA almost always approves products recommended for approval but also often approves products that advisory committees reject.

          Also this year the Union of Concerned Scientists revealed the results of a survey of senior scientists at FDA. 18.4% of 997 FDA scientists surveyed said that they had been asked for non-scientific reasons to inappropriately exclude or alter technical information or their conclusions in FDA scientific documents. 61% knew of cases where HHS or FDA political appointees have inappropriately injected themselves into FDA determinations or actions. 60% knew of cases where commercial interests have inappropriately induced or attempted to induce the reversal, withdrawal, or modification of FDA determinations or actions. Only half believe &ldquoFDA is acting effectively to protect the public health.&rdquo 20% said they have been asked directly by FDA decision makers to provide incomplete, inaccurate, or misleading information to the public, regulated industry, media, or elected senior government officials.

          To make matters worse, the FDA Center for Drug Evaluation and Research is now principally funded by the very drug companies it is supposed to regulate. Since 1992 over 50% of the funding for FDA&rsquos drug center has come from the drug companies themselves via fees paid under the Prescription Drug User Fees Act. Dr. Graham states, &ldquo[w]hen Congress passed this law I suppose it&rsquos possible that it didn&rsquot realize that PDUFA would lead to FDA becoming a captive of the industry it&rsquos supposed to regulate. However, that is what has happened, and to a disastrous end.&rdquo

          The pharmaceutical lobby not only affects FDA regulation of drugs but also FDA regulation of foods and dietary supplements. Truthful speech concerning the disease treatment effects of dietary ingredients is censored by the FDA. In 1990, Congress passed the Nutrition Labeling and Education Act. In that Act, Congress provided that foods and dietary supplements could make claims concerning the effects of dietary ingredients on disease without obtaining FDA drug approval. From 1990 until 1999, FDA refused to implement the NLEA health provision in case after case. Among the claims FDA censored from 1991 to 1993 was the claim that folic acid reduced the risk of neural tube defect births. An estimated 2,500 preventable neural tube defect births occurred each year FDA&rsquos censorship remained in place. Finally, on the eve of testifying before Congress and under intense public pressure and a law suit brought by my firm, Dr. David Kessler relented and allowed a claim for folic acid. FDA had refused to allow that claim despite the fact that the Centers for Disease Control and Prevention and the Public Health Service each recommended publicly that women of childbearing age consume 400 micrograms of folic acid daily before becoming pregnant to reduce their risk of having a neural tube defect birth.

          In 1999, the United States Court of Appeals for the D.C. Circuit held FDA&rsquos censorship of four nutrient-disease relationship claims (including a folic acid claim/neural tube defect claim an antioxidant vitamin/cancer risk reduction claim a fiber/colorectal cancer risk reduction claim and an omega-3 fatty acid/heart disease claim) unconstitutional under the First Amendment. The Court ordered FDA to favor disclosure of nutrient-disease information over its suppression and to allow the claims if they could be rendered nonmisleading with disclaimers. That landmark decision, Pearson v. Shalala, has opened the door to qualified health claims but FDA has been fast at work trying to close the door at every turn.

          On remand, FDA refused to allow any of the claims the Pearson court held unconstitutionally suppressed. Four federal court decisions later, all against FDA, the claims have finally been allowed along with a half dozen others. Many well-backed claims, like the glucosamine and chondroitin sulfate/osteoarthritis claim, have been suppressed by FDA to protect the makers of non-steroidal anti-Inflammatory drugs from competition.

          Moreover, in Whitaker v. Thompson II FDA succeeded in undermining the NLEA and the Pearson decision. It argued, contrary to the legislative history, that Congress intended health claims not to embrace every nutrient-disease relationship but only disease risk reduction claims. Every nutrient-disease treatment claim was, FDA argued, a drug claim that may not be communicated to the public even if true unless the dietary ingredient is approved as a drug (at $1.6 billion a pop, an economic impossibility). The Whitaker court upheld FDA&rsquos interpretation. Based on that win, the FDA now forbids reliance on almost all science concerning the treatment effects of nutrients and limits claims to nutrient disease risk reduction. The effect has been to foreclose all but a select few claims from being made. Thus, FDA has regained the censorship it was denied in Pearson. It once again favors censorship as the rule and disclosure as the rare exception&ndashthe very First Amendment violation the Pearson court condemned.

          Watch the video: Φυσική ανοσία ή ανοσία ? Βασιλακόπουλος, Iωαννιδης, Αρβανίτης