# Presentation: 588808

##  U.S. Food and Drug AdministrationCentennial Celebration1906-2006

-  U.S. Food and Drug AdministrationCentennial Celebration1906-2006

## Overview

- Early Food and Drug Regulation
- Early Decades
- Decades of Growth
- Decades of Achievements
- Next Century

## Enacting a Federal Law

- Prompted by a new scientific “revolution”
- Radium and X-rays
- Microbes to create wine and cheese
- Pasteurization to preserve milk
- New foods, e.g. oleomargarine
- Vaccines and vaccinations to protect against disease
- 1902 Biologics Control Act

**Notes:**
In the late 19th century America witnessed a revolution in science.  Frenchman Louis Pasteur's discovery of microbes lay at the heart of the revolution while German scientist William Roentgen's discovery of the x-ray also  opened up new opportunities in science, medicine, and commerce.   Radium, discovered by Marie Curie was quickly put to use therapeutically for the treatment of tumors.    Microbes were harnessed to create a domestic wine and cheese industry;  and the pasteurization of milk helped children nutritionally, but also helped prevent the spread of disease.   New foods, such as baking powder, and oleomargarine changed WHAT America ate, as new processing methods, including refrigerated and canned foods changed HOW America ate.   In 1902 the Biologics Control Act was passed to protect the public from unsafe vaccines, serums, and antitoxins as children and adults began to accept vaccination as a viable and effective public health measure.

## Enacting a Federal Law

- State statutes inadequate
- Local industry protection
- Wisconsin cheese
- Vermont maple syrup
- Prosecuted retailers not manufacturers for violations
- Food and drug standards varied under state laws

**Notes:**
Regulation of food in the United States dates from early colonial times. 
The first general law against food adulteration in the US was enacted in Massachusetts in 1784.  Gradually, other states passed a variety of food and drug statutes.  As the country expanded, it became clear that a national law was needed.  Many states had no laws or lacked enforcement.  Products meeting requirements in one state could be illegal in adjoining states.  Variations in labeling requirements became intolerable.  From 1879 to 1906 more than 100 food and drug bills were introduced in the US Congress

Adulteration and misbranding of foods and drugs had long been a fixture in the American cultural landscape, though the egregiousness of the problems seemed to have increased by the late 19th century (or at least they became more identifiable) 
Conditions in the US food and drug industries at the end of the 19th century can hardly be imagined today.  Changes from an agricultural to an industrial economy made it necessary to provide the rapidly increasing city population with food from distant areas.  But sanitation was primitive in the light of modern standards.  Ice was still the principal means of refrigeration, use of chemical preservatives and toxic colors was virtually uncontrolled.

Federal controls over the drug supply began with inspection of imported drugs in 1848.

## Harvey Wiley‘Father of the Food and Drugs Act’ and the ‘Crusading Chemist’

**Notes:**
In 1883, Dr. Wiley left Purdue University to become chief of the Bureau of Chemistry of the US Department of Agriculture.  One of his first official acts was to expand studies of food adulteration begun in the 1870s.  

## Poison Squad

**Notes:**
In 1902 Dr. Wiley started research with human volunteers to determine the effects of food preservatives on digestion and health. Overnight the press made the "Poison Squad" a national sensation. Even the minstrel shows had songs about the squad -- offically designated the "Hygienic Table." Chemicals fed to the young men included borax; salicylic, sulphurous, and benzoic acids; and formaldehyde. The experiments went on for 5 years. Wiley and the public became convinced that chemical preservatives should be used in food only when necessary; that the burden of proving safety should fall on the producer; and that none should be used without informing the consumer on the label -- basic principles of today's law and regulations. 
"O, they may get over it but they'll never look the same, That kind of bill of fare would drive most men insane.Next week he'll give them mothballs, a la Newburgh or else plain;O, they may get over it but they'll never look the same." 
Chorus from "Song of the Poison Squad,"Lew Dockstader's Minstrels, October 1903 While at the Bureau of Chemistry, Dr. Wiley started research with human volunteers to determine the effects of food preservatives on digestion and health
	The press dubbed the volunteers the “Poison Squad”

## Patent Medicines

- Buyer beware
- Boastful and extravagant claims
- Alcohol as the main ingredient
- Addictive and dangerous ingredients

**Notes:**
While Wiley was attracting attention to food issues, journalists of the period were writing about the dangers in patent medicines of the day.  Thousands of so called patent medicines such as “kick-a-poo Indian Sagwa” and Warners Cure for Diabetes reflected both the limited medical knowledge of the period and public acceptance of the doctrine that the buyer should look out for himself.  Medicines containing such drugs as opium, morphine, heroin, and cocaine were sold without restriction.  Labeling gave no hint of their presence.  Labels did not list ingredients and warnings against misuse were unheard of.  What information the public received came frequently from bitter experience.

Ethical dimensions became more apparent in the early 20th century when scientific understanding increased and real cures were developed.  The "patent medicines" were a constant danger to millions who believed their false promises but had little else to rely on for serious ailments.  Typical products  claimed to renovate the stomach, liver, and to cure cancer diabetes, gallstones, and weak hearts

## A Public Outcry for a New Law

- Upton Sinclair’s book,  _The _Jungle, drew attention to adulterated meat
- Meat sales dropped by 1/3
- Roosevelt was persuaded to sign Pure Food and Drugs Act on June 30, 1906 along with the Meat Inspection Act
- 1906 Act transformed a scientific bureau into a regulatory agency that would become FDA

**Notes:**
While Wiley was stumping for a law, muckraking journalists such as Samuel Hopkins Adams exposed in vivid detail the hazards of the marketplace. In fact, the nauseating condition of the meat-packing industry that Upton Sinclair captured in The Jungle was the final precipitating force behind both a meat inspection law and a comprehensive food and drug law. (A poster of the 1913 movie adaptation of Sinclair's novel is pictured at right, courtesy of the Sinclair Archives, Lilly Library, Indiana University, through James Harvey Young's Pure Food: Securing the Federal Food and Drugs Act of 1906.) Since 1879, nearly 100 bills had been introduced in Congress to regulate food and drugs; on 30 June 1906 President Roosevelt signed the Food and Drugs Act, known simply as the Wiley Act, a pillar of the Progressive era. 

Wiley came to lead a diverse coalition of groups and organizations in support of a federal food and drugs statute.  FDA continues to rely on many of these same groups as partners in our work today

## 1906 Pure Food and Drugs Act

- “Adulteration” and “Misbranding
- Prohibited interstate transport of unlawful products
- New labels
- Sanctioned drug standards
- Recruitment

**Notes:**
This act, which the Bureau of Chemistry was charged to administer, prohibited the interstate transport of unlawful food and drugs under penalty of seizure of the questionable products and/or prosecution of the responsible parties. The basis of the law rested on the regulation of product labeling rather than pre-market approval. Drugs, defined in accordance with the standards of strength, quality, and purity in the United States Pharmacopoeia and the National Formulary, could not be sold in any other condition unless the specific variations from the applicable standards were plainly stated on the label. Foods were not defined according to analogous standards, but the law prohibited the addition of any ingredients that would substitute for the food, conceal damage, pose a health hazard, or constitute a filthy or decomposed substance. Interpretations of the food provisions in the law led to many, sometimes protracted, court battles. If the manufacturer opted to list the weight or measure of a food, this had to be done accurately. Also, the food or drug label could not be false or misleading in any particular, and the presence and amount of eleven dangerous ingredients, including alcohol, heroin, and cocaine, had to be listed. 

## Early Decades

- 1906-1938

## Achievements Under the 1906 Act

- Revolutionized food supply
- Encouraged better sanitation in food processing
- Discouraged use of chemical preservatives
- Revolutionized drug labeling with regard to ingredients
- Presence of federal food and drug inspector encouraged compliance

**Notes:**
Achievements under the 1906 Act.   In the first decade after its passage, the nation's food supply underwent a revolution.  Accurate drug labels protected Americans from products with dangerous ingredients, including alcohol and morphine.  Chemists worked to create methods of analysis to address the worst violations of the new food and drug statute.  Inspectors coached food producers into compliance with the law, and failing that, they took them to court and began winning precedent-setting verdicts.   Once producers realized that the playing field was level, more producers became profitable.

##  Limitations of the 1906 Act

- No provision for food quality or standardized labeling
- Consumers had no way of knowing that the products were of low quality

**Notes:**
Salad Bouquet for use "like vinegar," Peanut Spred with few peanuts, and Bred Spred, with a low fruit content and high pectin content were heavily advertised and sold well during the Depression. Consumers had no way of knowing that the products were of low quality.
How did this happen? In World War I, there had been quite a marked expansion in the industry to supply our Allies, esp. the British, as well as our own military with jams, jellies, and preserves. After the war, the overbuilt industry had to go after volume sales with low prices. The development of refined pectin under the Douglas patents made it possible to make much better preserves without using green fruit, but it also make it possible to make sugar and water alone jell. In the marketplace, standards spiraled downward. The consumer could not depend on the labeling or the appearance of the product to guarantee its contents or quality. The only official food standards were voluntary "advisory" standards of the Bureau of Chemistry, forerunner of the present U.S. Food and Drug Administration. As an old-timer described the situation, "there never was a product made but some gosh darn fool could make it worse and sell it for less." The market for fabricated foods under this "distinctive name" proviso grew rapidly following the 1929 stock market crash.
Preserves were not the only consumer products caught in a downward economic spiral in which the incentive was to make products worse. Canned fruit and vegetable manufacturers finally went to Congress and got the so-called "Canner's Amendment (McNary-Mapes) enacted in 1930 which allowed the establishment and enforcement of canned foods, excluding meat and milk products. Substandard products could be sold but did have to carry a so-called "crepe" label--a black label announcement that announced that while a product was good food, it was poor quality.

## Limitations of the 1906 Act

- What’s hidden behind the label?

**Notes:**
Chicken and Glass –White meat is displayed in a thin layer in front of the glass—the dark meat is hidden behind the label

## Limitations of the 1906 ActFraudulent packaging – fill of container

**Notes:**
“fill of container” regulations are still in force today.  These bottles would have been recognized by consumers as 2 oz extract bottles, but they have been altered by the glass manufacturer to hold a single ounce.

## Limitations of the 1906 ActCrazy Crystals Radio Advertising

**Notes:**
Radio advertising made it possible to again make extravagant curative claims on products while the labeling met the requirements of the law.  Radio claims were so outrageous that it looked as if we were returning to the patent medicine era.

## A Turning Point

- Elixir Sulfanilamide
- First wonder drug
- Used untested “solvent” DEG
- Proved deadly

**Notes:**
Languishing in Congress for five years, the bill that would replace the 1906 was ultimately enhanced and passed in the wake of a therapeutic disaster in 1937. A Tennessee drug company marketed a form of the new sulfa wonder drug that would appeal to pediatric patients, Elixir Sulfanilamide. However, the solvent in this untested product was a highly toxic chemical analogue of antifreeze; over 100 people died, many of whom were children.  The public outcry not only reshaped the drug provisions of the new law to prevent such an event from happening again, it propelled the bill itself through Congress. This was neither the first nor the last time Congress presented a public health bill to a president only after a therapeutic disaster. FDR (signed the Food, Drug, and Cosmetic Act on 25 June 1938.

## Federal Food, Drug, and Cosmetic Act 1938

*	*
- Pre-market safety approval of all new drugs
- Prohibited false therapeutic claims for drugs
- Drugs labeled with adequate directions for safe use
- Food standards “in the interests of consumers”
- Cosmetics and medical devices under FDA’s jurisdiction

**Notes:**
For the first time, manufacturers were required to provide evidence of product safety before distributing new human and animal drugs
Food standards were established in the interest of consumers, a fact that distinguishes FDA’s statute from any other food and drug statute around the globe

The new law brought cosmetics and medical devices under control, and it required that drugs be labeled with adequate directions for safe use. Moreover, it mandated pre-market approval of all new drugs, such that a manufacturer would have to prove to FDA that a drug were safe before it could be sold. It irrefutably prohibited false therapeutic claims for drugs, although a separate law granted the Federal Trade Commission jurisdiction over drug advertising. The act also corrected abuses in food packaging and quality, and it mandated legally enforceable food standards. Tolerances for certain poisonous substances were addressed. The law formally authorized factory inspections, and it added injunctions to the enforcement tools at the agency's disposal.

## Decades of Growth

- 1940s – 1960s

**Notes:**
1927 - The Food, Drug, and Insecticide Administration was formed

1931 - Renamed in 1931 as the Food and Drug Administration

1940 - FDA transferred from USDA to the Federal Security Agency (FSA)

1953 - FSA became the Department of Health, Education, and Welfare -- now the Department of Health and Human Services

## Establishment of Food Standards

**Notes:**
Provisions for food standards and new drug reviews were at the heart of our growth during this period, along with advances in all kinds of science.

## New Drug Applications

- Required growth in scientific expertise
- Hiring of review scientists

**Notes:**
- NDA -- Pre-market approval of new drugs to insure that they were safe, required the creation of a New Drug Division within FDA, which had to develop new expertise in pharmaceutical evaluation.   The agency began to hire and train scientists, not to work in chemistry labs, but to work behind desks, evaluating paperwork submitted by firms seeking to market a new drug.

This is the formal step a drug sponsor takes to ask that the FDA consider approving a new drug for marketing in the United States. An NDA includes all animal and human data and analyses of the data, as well as information about how the drug behaves in the body and how it is manufactured.
When an NDA comes in, the FDA has 60 days to decide whether to file it so that it can be reviewed. The FDA can refuse to file an application that is incomplete. For example, some required studies may be missing. In accordance with the Prescription Drug User Fee Act (PDUFA), the FDA's Center for Drug Evaluation and Research (CDER) expects to review and act on at least 90 percent of NDAs for standard drugs no later than 10 months after the applications were received. The review goal is six months for priority drugs. (See "The Role of User Fees.")
The Tufts Center for the Study of Drug Development in Boston estimates that about 1 in 5 drugs that enter clinical testing ultimately are approved by the FDA.
How often the FDA meets with a drug sponsor varies, but the two most common meeting points are at the end of Phase 2 clinical trials and pre-NDA--right before a new drug application is submitted.
At the end of Phase 2, the FDA and sponsors try to come to an agreement on how the large-scale studies in Phase 3 should be done. The pre-NDA meeting is for discussing what the FDA expects to see in the application.
There is also continuous interaction throughout the review process. For example, over roughly six years, the sponsor Merck Research Laboratories of West Point, Pa., and the FDA had a half-dozen face-to-face meetings and about 28 teleconferences regarding the asthma drug Singulair (montelukast sodium).
In 1992, Merck submitted an IND for Singulair so that it could begin conducting studies in humans. After clinical trials were complete, the company submitted a new drug application in February 1997. The FDA approved Singulair in February 1998.
"It's the clinical trials that take so long--usually several years," says Sandra Kweder, M.D., deputy director for the Office of New Drugs in CDER. "The emphasis on speed for FDA mostly relates to review time and timelines of being able to meet with sponsors during a drug's development," she says.

## Drug Abuse

- From the 1940s to the 1960s, the abuse of amphetamines and barbiturates required more regulatory effort by FDA than all other drug problems combined
- 1965 Drug Abuse Control Amendments brought relief

**Notes:**
Enforcement of the new law came swiftly. Within two months of the passage of the act, the FDA began to identify drugs such as the sulfas that simply could not be labeled for safe use directly by the patient--they would require a prescription from a physician. The ensuing debate by the FDA, industry, and health practitioners over what constituted a prescription and an over-the-counter drug was resolved in the Durham-Humphrey Amendment of 1951. From the 1940s to the 1960s, the abuse of amphetamines and barbiturates required more regulatory effort by FDA than all other drug problems combined. Furthermore, the new law ushered in a flood of new drugs applications, over 6,000 in the first nine years, and 13,000 by 1962.

llegal sales of amphetamines and barbiturates occupied more regulatory concern at FDA than all other drug problems combined from the 1940s to the 1960s. Interdiction in some venues required undercover tactics, as indicated here by these two inspectors posing as truck drivers.

1965 - Congress gave the FDA enhanced control over amphetamines, barbiturates, hallucinogens, and other drugs of considerable abuse potential in the Drug Abuse Control Amendments of 1965. That function was consolidated with similar responsibilities in 1968 under an organization that gave rise to the Drug Enforcement Administration 

## Amendments – 1950s

- Durham-Humphrey Amendment of 1951 required Rx legend
- Food Additives Amendment of 1958 and Color Additives Amendments of 1960 --Delaney Clause
- Appropriate tests

**Notes:**
Durham-Humphrey Amendment of 1951
required human drugs which cannot be safely used without medical supervision must be dispensed only on the prescription of a licensed practitioner, and must bear the Rx legend 

Delaney Clause - Food Additives Amendment of 1958 had an impact too, Following hearings in the early 1950s under Representative James Delaney, a series of laws addressing pesticide residues (1954), food additives (1958), and color additives (1960) gave the FDA much tighter control over the growing list of chemicals entering the food supply, putting the onus on manufacturers to establish their safety. Since drugs used in animal feed were also considered additives they were subject to the provisions of the food additive petition process.

The Delaney Clause prohibiting carcinogenic food additives was modified by the DES proviso in 1962, named for diethylstilbestrol, a hormone used against miscarriages in humans and to promote growth in food-producing animals. The proviso permitted the use of possible carcinogens in such animals as long as residues of the product did not remain in edible tissues.

## A Disaster Averted Thalidomide

- Sedative sold over-the-counter in Europe
- Treated morning sickness during pregnancy
- Produced birth defects in European babies
- FDA received application for marketing in the US
- Reviewer Frances Kelsey had concerns
- Delay in approval prevented its being sold in US

**Notes:**
As with the 1938 act, a therapeutic disaster compelled passage of the new law; in this case the disaster was narrowly averted. Thalidomide, a sedative that was never approved in this country, produced thousands of grossly deformed newborns in Western Europe. Dr. Francis Kelsey, an FDA medical officer, is credited with keeping the drug off the U.S. market, and increasing public support for stronger drug regulation.   She is shown here with President Kennedy awarding her the Civilian Medal of Honor, the highest civilian award in the government.

## Drug Regulation Changes

- New drug approvals based on safety AND efficacy
- Required GMPs and later GLPs
- New controls over Rx advertising
- New patient protection policies
- Retrospective reviews of drugs approved for safety alone between 1938-1960
- DESI Drug Review
- OTC Review

**Notes:**
Thalidomide led to some really significant changes, especially in drug regulation, not just in the US but around the globe as well.  Thalidomide caused all countries with food and drug statutes to make similar measures to tighten control over the marketing of new drugs.  And these new requirements were upheld by the US Supreme Court.

Drug Regulation Changes -- passage of the 1962 Kefauver-Harris amendments in the wake of the thalidomide crisis, required FDA to approve new drugs that were not only safe, but effective as well.   In order to do that, FDA began to set standards for the manufacturing and testing of new products as a guide to "good manufacturing" and "good laboratory" practices, known as GMP and GLP regulations.   FDA acted with new authorities to ensure the accuracy and adequacy of prescription Rx advertising.  Under the Act, it also instituted some of the earliest government assurances that patients who participated in clinical research trials would be protected.  

Finally, one of the most important provisions of the law was the provision for the retrospective review of drugs--both over-the-counter (OTC) and Rx (DESI)--that had been approved between 1938 and 1960 for safety alone.   Many ingredients, such as hexachlorophene, disappeared from products on drug-store shelves, while many prescription drugs also disappeared, making way for a whole new generation of pharmaceutical products that were truly effective.  Some of these include better heart and blood pressure medications, new anti-depressants, and a whole host of drugs that are now recognized as indispensable in the modern practice of medicine as witnessed by the government's new Medicare Prescription Drug Benefit program.

## Amendments – 1960s

- Kefauver-Harris Amendments - *the most significant changes in the Food, Drug and Cosmetic Act*
- Premarket efficacy and safety
- Good manufacturing practices
- Prescription drug advertising

**Notes:**
A new drug law in that year, the Kefauver-Harris Amendments, derived in large part from hearings held by Senator Estes Kefauver. As with the 1938 act, a therapeutic disaster compelled passage of the new law; in this case the disaster was narrowly averted. The new law mandated efficacy as well as safety before a drug could be marketed, required FDA to assess the efficacy of all drugs introduced since 1938, instituted stricter agency control over drug trials (including a requirement that patients involved must give their informed consent), transferred from the Federal Trade Commission to the FDA regulation of prescription drug advertising, established good manufacturing practices by the drug industry, and granted the FDA greater powers to access company production and control records to verify those practices. 

## Amendments – 1960s

- DES proviso in 1962 modified the Delaney Clause
- Fair Packaging and Labeling Act of 1966
- 1968 Animal Drug Amendments

**Notes:**
In 1962, the Delaney Clause was modified to permit the FDA to approve the use of carcinogenic compounds in food-producing animals if certain conditions were met. "The FDA felt that food-producing animals could be exposed to carcinogenic drugs and not necessarily pass cancer-causing chemicals on to humans," says Woodrow Knight, Ph.D., director of the CVM's Division of Production Drugs.
The modification to the Delaney Clause is known as the "Diethylstilbestrol (DES) Proviso," named for a hormone approved in 1954 to promote growth in cattle and sheep. DES had also been approved much earlier in humans. It was thought to prevent miscarriages in women, but the hormone later was linked to vaginal cancers in the daughters of women who were treated with the drug during pregnancy.
Under the DES Proviso, the FDA could approve a carcinogen for food animal use if the concentration of any residue remaining in the edible tissues was so low that it presented an insignificant risk of cancer to consumers.
But measuring drug residues was a problem. Standard tests at that time were not very sophisticated, and regulators were concerned that drug residues in foods might exist in dangerous levels and just couldn't be measured.
Using advances in analytical chemistry, FDA scientists developed techniques to measure minute concentrations of residues, says Knight. "They were able to measure parts per billion or even per trillion." These techniques led to a 1987 regulation called the Sensitivity-of-Method procedures, or SOM. The regulation defines an insignificant risk of cancer as a 1 in 1 million increase in risk, and spells out how to measure the residue concentration.
Although DES was banned for use in people and animals in the 1970s, the DES Proviso remains in effect. SOM procedures are used to determine acceptable residue concentrations of new animal drugs in food produced from animals.
Safety and Effectiveness
Under the Federal FD&C Act of 1938, manufacturers of human or animal drugs only had to show that their products were safe. In 1962, amendments to the act required them to show that their products were also effective. The 1962 amendments generally did not distinguish between human and animal drugs; in 1968, Congress passed legislation to strengthen provisions of the act that pertained to the regulation of animal drugs. Animal drugs, medicated feeds, and food additives were required to be safe for the animal they were intended to be used in and, in the case of food-producing animals, safe for human consumption and safe for the environment. Effectiveness was required to be shown by substantial evidence from one or more adequate and well-controlled studies.
1960 Color Additive Amendment requires manufacturers to prove color additives used in foods, drugs and cosmetics are safe. 
1960 Federal Hazardous Substances Labeling Act, requires certain hazardous household products have warning labels. 
1962 Thalidomide, a new sleeping pill, is found to have caused birth defects in thousands of babies in Western Europe. Dr. Francis Kelsey, an FDA medical officer, is credited with keeping the drug off the U.S. market, and increasing public support for stronger drug regulation.
1962 Kefauver-Harris New Drug Amendments require drug manufacturers to prove their products are safe and effective before marketing. 
 1962 Consumer Bill of Rights is presented to Congress by President John F. Kennedy. Included are the right to safety, the right to be informed, the right to choose, and the right to be heard.
1965 Drug Abuse Control Amendments address problems caused by abuse of depressants, stimulants and hallucinogens.
1966 Fair Packaging and Labeling Act requires all consumer products sold across state lines be honestly and completely labeled.
1968 Animal Drug Amendments make approval and regulation of new animal drugs and medicated feeds more efficient.
1969 FDA establishes sanitation programs for milk, shellfish, food services, and interstate travel facilities, and for preventing poisoning and accidents.

## Decades of Achievements 

- 1970s to Present

## Modern FDA

**Notes:**
PUZZLE PIECE SLIDE -- In the 1970s, the pieces of what we consider to be the modern FDA came together.   The Drug Enforcement Agency (now the DEA) was created from FDA's old Bureau of Drug Abuse and Enforcement.   The Environmental Protection Agency (EPA) took over many of FDA's pesticide and pesticide residue programs.  And the consumer product responsibilities FDA had assumed over the years, were relocated in the Consumer Product Safety Commission (CPSC).    

The product bureaus became Centers;  FDA's Office of Regulatory Affairs was created and regional offices were opened in 10 cities around the country to compliment the Department of Health, Education and Welfare (now DHHS) offices in the same cities.

## 1976 Medical Device Amendments

- Medical devices be classified according to their comparative risk, and regulated accordingly
- Three classes of medical devices, each requiring a different level of regulatory scrutiny--up to pre-market approval

**Notes:**
The 1976 Medical Device Amendments Become Law 
While the Cooper Committee recommendations were being debated in Congress during 1972 and 1973, pacemaker failures were reported. And in 1975, hearings took place on problems that had been reported with the Dalkon Shield intrauterine device, which caused thousands of reported injuries. Those two incidents helped underscore the need for the Medical Device Amendments, enacted in 1976.
President Gerald R. Ford, in signing the law, said, "The Medical Device Amendments of 1976 eliminate the deficiencies that accorded FDA 'horse and buggy' authority to deal with 'laser age' problems." He added, "I welcome this legislation and commend the FDA, who identified the need, cooperated in its development, and finally, will be entrusted with its enforcement." 
The 1976 amendments defined devices similarly to drugs, but noted that drugs cause a chemical reaction in the body, whereas devices do not. They called for all devices to be divided into classes, with varying amounts of control required in each one.
Tongue depressors, for example, would fall under general controls of the types already existing (Class I); wheelchairs would be subjected to performance standards when general controls were deemed insufficient to assure product safety and effectiveness (Class II); while artificial hearts would be required to go through pre-market approval (Class III). The agency's first device performance standard was developed for impact-resistant lenses in eyeglasses and sunglasses.
The final provisions of the 1976 amendments closely resemble the Cooper Committee recommendations. In addition to the medical device inventory and classification requirements, Class III device manufacturers were required to notify the FDA prior to marketing. New devices that were substantially equivalent to pre-1976 devices could be marketed immediately, subject to any existing or future requirements for that type of device.
Good Manufacturing Practice (GMP) regulations also were authorized at that time. These are a set of procedures to ensure that devices are manufactured to be safe and effective through quality design, manufacture, labeling, testing, storage, and distribution.
"The development of the GMP regulation included significant interaction with the medical device industry, which resulted in a set of requirements that stood the test of time for 20 years," recalls David M. Link, former director of the FDA's then Bureau of Medical Devices, at a 20th anniversary of the medical device law. Link, who served as bureau director between 1974 and 1980, said it is a gratifying reflection that "a number of the processes initiated in the late 70s are still in place."
During the 1980s, spectacular growth began to occur in the related field of medical diagnostic devices, which aid in the detection of diseases and other conditions, such as pregnancy.
"It was an exciting time to be in FDA and the bureau," says Victor Zafra, former acting director of the Bureau of Medical Devices from 1980 to 1982, "because many of the initial policies and regulations were developed at that time." Zafra remembers approval of the first monoclonal antibody in vitro diagnostic test kit, as well as extended-wear soft contact lenses.
With the development of electronic technology came a host of new products and, with them, potential harmful radiation exposure. But the tools to solve their potential dangers, as recognized by the act--training, research, and state collaboration--were perceived as less enforcement-oriented than the traditional FDA approach to regulation. Responsibility for radiation product activities fell under the agency's then Bureau of Radiological Health, which was combined in 1982 with the Bureau of Medical Devices and renamed the CDRH.
"Consequently, there was the challenge of preserving these 'softer' radiation programs and at the same time building a credible compliance program in the new center," says John C. Villforth, who served as director of the CDRH from 1982 to 1990. The most important challenge facing the new organization, he emphasized, was the merging of the two bureaus into a single center.
"Both bureaus had a similar culture in that they were involved with 'things' as opposed to foods or drugs," he said, "and so there was a reasonable fit in the disciplines--primarily physical sciences and engineering--that were needed to regulate the combined programs."
But Mark Barnett, the CDRH's assistant director for education and communications since its inception in 1982, says it isn't just the emphasis on physics and engineering that distinguishes medical devices and radiological equipment from drugs.
"The safety of most medical devices depends to a large degree on their being used properly," he says. "That's true in the case of a surgeon implanting a prosthetic device in a patient's body, an anesthesiologist operating a complex gas delivery machine, or a diabetic patient using a blood glucose monitor at home. And so, with devices," he adds, "an important part of our job is to educate health care practitioners and patients about safe use."
Villforth adds, "I believe the melding of the talents of both bureaus into the combined center was responsible for the success that CDRH has maintained over the years."
The Medical Device Amendments also gave the FDA authority to deal with the notification, repair, replacement, and refund of defective devices, and the agency was authorized to ban any device that presents a substantial deception or substantial unreasonable risk of injury or illness. Thus, the final law greatly strengthened the FDA's authority to regulate medical devices, but retained the fundamental concept of the Cooper Committee report that regulation should be carefully tailored to the type of device involved.

## Achievements -- Last 25 Years

- Development of accelerated techniques for drug approval, beginning with drugs for AIDS
- Encouraged the development of drugs for rare or untreatable diseases

**Notes:**
Through numerous amendments to the FD&CA over the years, FDA’s responsibilities were expanded or clarified, evolving to FDA’s current programs covering foods, human drugs, biologics, medical devices and radiological health, animal drugs and feeds, supporting toxicological research, and counterterrorism, combination products, international programs, pediatrics, and women’s health.
Hemin and chenodiol were the first two orphan drugs recognized under the 1983 Act. 

Drug responsibilities increased in several ways in the mid-1980s. The Orphan Drug Act of 1983 employed several means to promote development of products for rare diseases. Among the provisions of this law, the sponsors of drug candidates could petition the agency for assistance in planning animal and clinical protocols. Also, the sponsor was allowed seven years of marketing protection for unpatentable products, and the law provided a 50 percent tax credit for investigation expenses. As a result of this Act, in early 1983 an Orphan Product Development office was established in the Office of the Commissioner, under Marion Finkel. Also in 1983, Congress passed the Federal Anti-Tampering Act in the wake of the Tylenol poisonings. This law amended the U.S. Code to provide penalties for tampering with or threatening to tamper with any product covered by the Food, Drug, and Cosmetic Act. 

The structure of the Office of Compliance changed in 1986, resulting in five Divisions: Drug Labeling Compliance, Drug Quality Evaluation, Scientific Investigations, Regulatory Affairs, and Manufacturing and Product Quality. The Office of Consumer and Professional Affairs, formed after the merger of the Bureau of Drugs and the Bureau of Biologics, was abolished in 1987. Also in 1987, Paul Parkman became the Director of the Center for Drugs and Biologics, and Gerald Meyer became his deputy. 
1970 FDA requires the first patient package insert; oral contraceptives must contain information for the patient about specific risks and benefits. 
1971 National Center for Toxicological Research established. Its mission: to examine the biological effects of chemicals in the environment.
1972 New Over-the-Counter Drug Review enhances the safety, effectiveness and appropriate labeling of drugs sold without a prescription.
1976 Medical Device Amendments establish regulations that increase the regulatory and surveillance control of FDA and increase the safety and effectiveness of medical devices, including diagnostic products. 
1976 Vitamins And Minerals Amendments ("Proxmire Amendments") stop FDA from establishing standards limiting potency of vitamins and minerals in food supplements or regulating them as drugs based solely on potency. 

## Achievements -- Last 25 Years

- Protected consumers from individually imported counterfeit, unapproved and unsafe drugs
- Helped develop globally acceptable standards for various aspects of drug development

## Achievements -- Last 25 Years

- Reforms
- Increase availability of generic drugs
- Modernize drug manufacturing
- Strengthen the safety of marketed medicines

**Notes:**
The Drug Price Competition and Patent Term Restoration Act of 1984 gave FDA the authority to accept abbreviated new drug applications (ANDAs) for generic versions of post-1962 drugs. The first approved ANDA was for generic disopyramide, marketed as Norpace and used in the treatment of cardiac arrhythmias. As a result of this legislation, several Divisions in the Office of Drug Standards added branches to assist with the review of ANDAs. The law also provided manufacturers with the opportunity to apply for an extra five years of patent protection to make up for time lost during the FDA approval process. 

## Achievements -- Last 25 Years

- More informative Food Label – NLEA
- Health Claims/Qualified Health Claims for Foods
- Dietary Supplements
- Securing the nation’s food supply from unintentional and intentional contamination (bioterrorism)

**Notes:**
Assured that genetically modified foods are safe before sold
Made the food label more informative and helpful in avoiding transfat, potential allergens and selecting a healthy diet
Constantly tested freshly prepared meals for traces of pesticides and other contaminants.
Worked with consumer groups and industry to develop new nutrition labeling for foods.

## Achievements -- Last 25 Years

- Assured that X-ray machines, television sets and microwave ovens are safe
- Assured that every mammogram taken in the United States is of the highest quality and interpreted by well-trained specialists

## Achievements -- Last 25 Years

- Strengthened animal feed safeguards to help prevent the spread of BSE in the U.S. cattle herd
- High safety and effectiveness standards for animal drugs

## Program User Fees

- PDUFA
- Doubled the efficiency of drug reviews without compromising standards
- MDUFMA
- ADUFA of 2003

**Notes:**
User fees are not a new concept. FDA has charged fees for color certification and insulin certification for more than 40 years. FDA first considered drug review fees in 1971 when the General Accounting Office recommended to Congress that FDA charge such fees. GAO's report cited the authority federal agencies were given to levy user fees under the Independent The road to gaining FDA approval to market a new prescription drug or biologic can be a lengthy one. By law, FDA must review clinical test results for any new drug or biologic to ensure the product is safe and effective. Because of staff shortages, limited resources, and incomplete submitted applications, it takes an average of 22 months for approval from the time companies apply to market products. But that is changing. 
Resources provided by the Prescription Drug User Fee Act of 1992 will help FDA shorten review time significantly over the next five years. The agency has started collecting "user fees"--charges levied on pharmaceutical companies for certain new drug and biologic applications, drug products, and manufacturing establishments covered under the act. FDA will use these funds to hire more reviewers to assess applications. At the same time, the agency is streamlining drug and biologic review processes. 
FDA hopes to employ about 600 new drug reviewers and support staff by the end of fiscal year 1997, nearly half of whom are now on the job. To support these new staffers, the agency expects to collect more than $325 million in user fees over the five years covered by the 1992 act. Unless Congress renews the act, the user fee law will expire at the end of FY 1997. 
New employees are working in either FDA's Center for Drug Evaluation and Research or Center for Biologics Evaluation and Research. They include medical officers, chemists, microbiologists, and pharmacologists, along with other professionals and support staff. They also are helping FDA with its backlog of overdue applications.As of Nov. 30, 1994, FDA had cleared all but nine applications from the backlog. Agency officials say the backlog should be completely eliminated ahead of the mid-1995 target date. 
As for new applications, FDA aims to reduce review times to 12 months for "standard" applications and to six months for "priority" applications. Applications for drugs similar to those already marketed are designated standard, while priority applications represent drugs offering significant advances over existing treatments. (Drugs for AIDS and cancer typically fall into the priority category.) Goals for shortening review times and for hiring more staff will be phased in gradually over the five-year statutory period. 
User fees are funding a way to accelerate reviews through use of computer technology. Through this program, dubbed the "Smart Initiative," FDA is establishing standards for the software drug companies use in preparing data for submission to the agency. Eventually electronic data submission is expected to virtually eliminate the need for huge paper submissions and also to reduce the application review time. In a 1994 pilot program, FDA was able to approve electronic submissions 11 months faster than similar submissions on paper. 
Although FDA is accelerating its review time, the agency remains committed to high review standards. Newly initiated programs are helping ensure the quality and integrity of the review process. Offices Appropriation Act of 1952. But after weighing pros and cons--such as whether fees would burden small businesses or be passed on by firms that pay them in the form of higher prices--FDA's parent agency, the former Department of Health, Education, and Welfare, rejected the proposal. 
The idea of FDA user fees resurfaced beginning in 1982 but failed to gain significant support. In 1992, things changed. 
As budget proceedings for FY 1993 began, FDA Commissioner David A. Kessler, M.D., testified before Congress that the user fee issue was one of critical importance to FDA's future and that it should be considered "very seriously." FDA worked with the pharmaceutical industry to create performance goals and determine what fees would be needed to reach those goals. Though earlier fee suggestions encompassed numerous FDA-regulated products, the final proposal included only prescription drugs and certain biologics. (Biologics exempted were whole blood products or blood components for transfusion, some human therapies made from bovine blood products, allergenic extract products, and in vitro diagnostics. 

## Next Century

- A Vision

## Strategic Goals for the 21st Century

- Improve product quality, safety, and availability through better manufacturing and product oversight
- Enhance patient and consumer protection and empower them with better information about regulated products

## Strategic Goals for the 21st Century

- Increase access to innovative products and technologies to improve health
- Transform FDA business operations, systems, and infrastructure to support FDA’s Mission in the 21st Century

**Notes:**
Picture shows optically variable coating.

## Vision for the Next Century

- Critical Path Initiative
- Transform medical product development
- Keep pace with expected medical advances

## Vision for the Next Century

- State-of-the-art sciences for progress with incurable diseases
- Regulatory expertise to enforce product standards and facilitate scientific progress to advance global public health

## Vision for the Next Century

- Ensuring Food Defense and Food Safety
- Improving Nutrition
- Improving Dietary Supplement Safety
- Ensuring Cosmetics and Color Additive Safety

**Notes:**
The food industry and the technologies used in food production and packaging are constantly evolving.  And although the U.S. food supply is among the world's safest, new trends in food production, transportation, storage and consumption have brought with them new public health concerns.  
CFSAN continues to consider the effects of  increased demand for fresh foods . . . foods traveling long distances . . . Americans eating outside the home more frequently . . . and new kinds of food contaminants.  What’s more, sources of food contamination are almost as numerous and varied as the contaminants themselves.   These include everything from pre-harvest conditions to contamination introduced during processing, packaging, transportation, and preparation. 
And so, CFSAN enters its next hundred years, its focus is on five principal areas:
Food Defense
Food Safety
Nutrition
Dietary Supplements
Cosmetic Safety

In addition to staying on the cutting edge of science and consumer concerns and regulatory responsibilities related to these ever-evolving concerns, CFSAN continues to consider how other societal and regulatory trends will impact their mission today and for the future:
Obesity.  This growing crisis is associated with increased risk of serious illness and death.  With accurate and useful food labeling being a key CFSAN objective, the Center will be looking at ways to enhance the food label. In addition, CFSAN will increase consumer education efforts toward reducing obesity and overweight and increasing health and nutrition overall.
Continued Food Safety Efforts.  With more foods from more sources, CFSAN will continue to monitor the food supply to ensure safe standards.
Ensuring that genetically modified foods are safe.
Good manufacturing practices for dietary supplements.  This will ensure that consumers are protected from products that are not pure or don’t contain what is claimed on the label.
Food Allergen Labeling.  All domestically manufactured and imported packaged food products that are labeled on or after January 1, 2006, are required to identify in plain English any ingredient that is, or contains protein from, any of the eight major food allergens: milk, eggs, fish, Crustacean shellfish, tree nuts, peanuts, wheat, or soybeans.  CFSAN is working on standards for use of the term “gluten-free” on food labels and will continue to monitor emerging food allergen issues.
Working with industry to enhance food safety systems for preventing food terrorism and enabling rapid response and containment. Overall, these proactive prevention efforts will also prepare CFSAN to respond to new food safety issues as they arise. 

## Celebrating 100 Years of Public Service

**Notes:**
Food and 

## Contact Us! 

**Notes:**
The public can influence FDA decisions by:
Commenting on proposed rules
Participating in meetings with Agency decision makers
Serving on FDA Advisory Committees
Filing citizen petitions
Participating in public meetings

FDA employs more than 10.000 employees, many of whom are medical doctors and scientists.
FDA is located in 49 states and Puerto Rico

Contact us: FDA #

## Slide 45

## Optional Slides

## Significant Milestones in Food and Drug Law

- PHS Act
- Biologics Control Act of 1902
- Pure Food and Drugs Act of 1906
- Federal Food, Drug and Cosmetic Act of 1938
- Durham-Humphrey Amendment of 1951
- Food Additives Amendment 1958
- Kefauver-Harris Drug Amendments of 1962
- Animal Drug Amendments of 1968
- Medical Device Amendments of 1976
- Infant Formula Act of 1980
- Nutrition Labeling and Education Act of 1990
- Dietary Supplement Health Education Act of 1994
- Bioterrorism Act of 2002Food Allergen Labeling and Consumer Protection Act of 2006

**Notes:**
- Other significant milestones include PDUFA, FDAMA