A Brief History of the Center for Drug Evaluation and Research - Slide Show
A Brief History of the
Center for Drug Evaluation and Research
Harvey Wiley, the Chief Chemist of the Bureau of Chemistry
During the 1902 annual meeting of the American Pharmaceutical Association, Harvey Wiley, the Chief Chemist of the Bureau of Chemistry, announced the formation of a Drug Laboratory within his organization. Wiley intended the Laboratory to assist with standardizing pharmaceuticals and unifying analytical results.
One of the nominees to lead this function was Lyman Frederic Kebler, the Chief Chemist at Smith Kline and French and a recognized expert in the detection of drug adulteration. Appointed Director of the Drug Laboratory in November 1902, he assumed the duties in March 1903.
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One of the covers Collier's used in its campaign for the Pure Food and Drugs Act of 1906
Initially, the Drug Laboratory worked on a variety of projects. One of the first was an investigation of the reagents used by the Bureau, which Kebler soon learned were not completely pure. The Laboratory spent much of its time in search of methods to improve pharmaceutical analyses. Kebler also alerted the public to problems with the drug supply in general.
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Carl Alsberg, Chief Chemist, Bureau of Chemistry
Three years later, behind the long-time lobbying of Wiley, the Pure Food and Drugs Act became law; this prohibited interstate commerce of mislabeled and adulterated drugs and food. Wiley himself emphasized food-related issues as a greater health concern, but he gave some attention to patent medicines and prescription drugs; his successor, Carl Alsberg, elevated the importance of drug matters.
By 1908 the Drug Laboratory underwent its first of what would be many major reorganizations. Renamed the Drug Division, it was divided into four laboratories: the Drug Inspection Laboratory, directed by George Hoover; the Synthetic Products Laboratory which W.O. Emery headed; the Essential Oils Laboratory, under E.K. Nelson; and the Pharmacological Laboratory, directed by William Salant. Kebler remained the Division Director
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Drug Division, Essential Oils Laboratory
The main focus of the Essential Oils Laboratory was the analysis of oils used therapeutically either alone or in combination with other chemicals, such as root-beer extract and oil of wintergreen. The Synthetic Products Laboratory was responsible for examinations of synthetic remedies, including the popular headache mixtures, and active ingredients in crude drug products.
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Radol was exposed as a hoax in 1908. The makers of this nostrum tried to cash in on people's fascination with radioactivity.
The Pharmacological Laboratory investigated the physiological effects of drugs on animals. Most of their early efforts centered on caffeine, a subject of great interest to Wiley. Finally, the Drug Inspection Laboratory was the principal enforcement arm of the Division. For example, from 1909-1910 this Laboratory scrutinized over 900 domestic drug samples, around 1000 imported drugs, and recommended prosecution of 115 samples.
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Representative Swagar Sherley was a Representative from Kentucky and Chairman of the House Committee on Appropriations.
One of the first major challenges to drug regulation under the 1906 Act came in 1910. The Bureau had seized a large quantity of "Johnson's Mild Combination Treatment for Cancer," a worthless product that bore false therapeutic claims on its label. When the case came to trial, the judge determined that claims made for effectiveness were not within the scope of the Pure Food and Drugs Act, and ruled against the government.
In 1912, Congress issued corrective legislation. The Sherley Amendment brought therapeutic claims within the jurisdiction of the Pure Food and Drugs Act, but required the Bureau to prove those claims to be false and fraudulent before they would be judged as illegal.
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Bureau analysts received their samples from field inspectors such as John Earnshaw, pictured here in an extract packing plant in 1910.
By this time, the scope of the Drug Inspection Laboratory's work had grown. For example, they investigated methodologies for the determination of morphine, nitroglycerin, and other drugs in combination preparations. Also, the Laboratory collaborated with the U.S. Pharmacopeia (USP) in a study of drug standards. The work of the Division of Drugs was not limited to domestic drug problems. They also studied imported drugs and chemicals and imported products of dubious therapeutic value. The Division also spent considerable time on an investigation of contaminated chloroform. Several manufacturers had been distributing chloroform in tin containers, which was prone to decompose into a substandard product compared to USP chloroform stored in glass.
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Though the 1906 Act led many patent medicines to abandon narcotics rather than label them, it was less sucessful in corralling exaggerated claims.In the mid 1910s, the Division of Drugs added two new components. The Pharmacognosy Laboratory was created in 1914. In addition to investigating crude drug products, this Laboratory studied improvements in crude drug processing to reduce waste. In 1916 the Division established an office to investigate false and fraudulent labeling of drugs. This effort stemmed directly from the Sherley Amendment and was directed by M.W. Glover, a physician on detail from the U. S. Public Health Service (USPHS).
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Lyman Kebler in the laboratory, circa 1922.
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George Hoover (38) in a group shot, May, 1923
In 1923, the Office of Drug Control replaced both the Office of Drug Administration and the Division of Drugs. Directed by George Hoover and organized in parallel with the new Office of Food Control, the Office was responsible for all work in the control of drugs, including crude drugs, manufactured drug ingredients, drug preparations, and patent medicines.
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Some of the official reference standards that the FDA's predecessors provided.
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A pharmaceutical manufacturer's control room around the early 1940s.
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James J. Durrett, M.D., Ph.G., Chief, Drug Control 1928-1931.
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FDA's Pharmacological Laboratory
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FDA pharmacologist James C. Munch dictates results of an animal toxicity test.
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Theodore Klumpp(standing) leads a meeting at FDA. He left FDA in 1941 for the American Medical Association and two years later became the president of Winthrop-Stearns.
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In 1943 FDA began testing penicillin as part of the wartime development program. The first NDAs for this drug (some of which derived from this strain of P. notatum) were approved in September of that year.
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Drug Inspectors Conference - 1946
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The emergence of fatal blood dyscrasias associated with chloramphenicol in the early 1950s led to the search for better adverse reaction reporting.
Drug regulation farther down in the distribution system came under scrutiny in 1955, when FDA undertook a pilot study of adverse drug reaction reporting. In cooperation with the American Society of Hospital Pharmacists, the American Medical Association, and others, the study focused on reactions reported by hospitals and pharmacists. Adverse reaction reporting at this time was voluntary and reports normally were scarce.
This study blossomed into a more ambitious effort in 1957, a large-scale system for voluntary reporting to assist with post-marketing evaluation of new drugs. By 1963 the study had evolved into a voluntary reporting system with almost 200 participating hospitals.
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The biggest drug enforcement problem at this time was the illegal distribution of barbiturates and amphetamines. FDA responded by training drug inspectors in undercover techniques.
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Included on these shelves of the Bureau of Chemistry around 1910 were the Bulletins and Circulars in which bureau scientists published much of their research.
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Drug plant inspector (right) checks the working drug formula against the master formula.
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Kelsey receiving the award from President John F. Kennedy in 1962.
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Sadusk chaired the Department of Preventive Medicine and Community Health at George Washington University before he joined FDA. Under Sadusk, the Bureau of Medicine consisted of four Divisions: Medical Review, directed by Howard Weinstein, New Drugs, directed by Smith, Research and Reference, under George Saiger, and Veterinary Medical, which was headed by Charles Durbin.
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Robert Roe (second from right, standing) and Daniel Banes (far right, standing) are pictured here at a 1961 joint conference between the FDA and the Food Law Institute
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Rep. Fountain on a visit to Research Triangle Park, NC.
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Among the products that came under intense scrutiny through DESI were preparations with multiple antiinfective ingredients, such as this one.
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Over-the-counter (OTC) drugs
In May 1972, FDA applied the principle of a retrospective review to over-the-counter (OTC) drugs. The structure for this OTC review would necessarily be different than that of the prescription drug review, mainly because of the vast array of available OTC products -- hundreds of thousands of different preparations. The OTC review focused on active ingredients, around 1,000 different items, and panels of experts were convened to evaluate these drugs. The agency would publish the results as a series of monographs in the Code of Federal Regulations, specifying the active ingredients, restrictions on formulations, and labeling by therapeutic category.
FDA formed seventeen panels, consisting of seven voting members (medical, dental, and scientific experts) and non-voting representatives for industry and consumers. The panels were responsible for arranging the drugs into three categories: safe and effective, unsafe and/or ineffective (which should no longer be marketed), and probably safe and effective but needing further testing to establish significant proof. The review is ongoing. The agency eventually decided that drugs in the last category, like those in the second, would be taken off the market until sufficient proof dictated otherwise.
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A chemist in the Antibiotic Chemistry Branch uses a transparent "dry box" with built-in rubber gloves
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FDA Commisioner James Goddard swears in 65 physicians on 10 July 1966 for various assignments in the Bureau of Medicine including DESI, investigational drug and new drug review, and adverse reaction reporting.
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An inspector checks ampules for extraneous matte on a plant's inpection line. in 1969 FDA proposed the first major GMP revisions since 1963
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Summary of early work at the National Center for Drug Analysis
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HEW Secretary Joseph A. Califano
A renewed push for changes in drug regulation began at the highest level of the Department. HEW Secretary Joseph Califano felt that, for such changes to be effective, they had to be made through legislation rather than administrative policy. The initial bill, introduced in Congress on March 17, 1978, was titled the Drug Regulation Reform Act.
It contained nine main provisions: to increase consumer protection, encourage drug innovation, increase consumer information, protect patient rights, improve FDA enforcement, promote competition and cost savings through generic drugs, increase FDA's public accountability, make additional drugs available, and encourage research and training. The effort during 1978 was unsuccessful, but the bill was reintroduced the following year. The Senate approved the bill in September 1979, but the House did not take action and the measure died.
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In March 1979 FDA suspended both labeling and manufacturing requirements for emergency production of potassium iodide, intended for those in the vicinity of the Three Mile Island nuclear emergency.
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Hemin and chenodiol were the first two orphan drugs recognized under the 1983 Act.
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Charles Roberts of the Center for Drugs and Biologics examines an AIDS testing kit, which FDA approved in 1985.
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The 1980s witnessed increasing concern for drug regulation by patient advocacy groups, exemplified here by a 1988 protest at the Parklawn Building in Rockville by the AIDS Coalition to Unleash Power.
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In the Spring of 1988 the Public Health Service sent this pamphlet to over 100 million households in the U.S.
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Also at this time, CDER established the Office of Generic Drugs to assume responsibility for review of ANDAs, which had been located in the Office of Drug Standards. In addition, the Generic Drugs Advisory Committee was formed to assist the Office of Generic Drugs with approval issues. This Committee advised the Office on scientific and technical matters related to the safety and effectiveness of generic drugs. In the wake of the convictions of five FDA reviewers for unlawful contacts with regulated industry, Congress passed the Generic Drug Enforcement Act in 1992. This law provided a variety of penalties for illegal acts involved with ANDA approvals
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In March 1990 HHS Secretary Louis Sullivan appointed a committee, headed by former FDA Comissioner Charles Edwards, to review the agency's mission, structure, priorities, staffing, and budget. One committee member resigned when he was selected by President Bush as the Commissioner-designate: David Kessler.
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Advisory committees have been an important element in drug review since the 1960s. Pictured here is a meeting of the Oncologic Drugs Advisory Committee.
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Through the years, responsibilities within FDA for drug regulation have undergone major changes. Most of these came as a result of innovations in drug development and additions to legislative authority. When Lyman Kebler was hired in 1902, he was basically a one-man bureau who had corrupt reagents and half a desk to fight the most egregious offenses of a largely unregulated industry. As of 1994, CDER was the largest headquarters component of FDA, consisting of almost 1500 men and women working in several buildings. The complexity and challenges of drug review are multiplying as the sophistication of drug design and manufacturing increases, which speaks to the importance of maintaining a well-trained and adequately supported group of agency drug officials, for the good of the public health.
End of Slide Show
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