amount.26 The Court ruled that Red 32 could not be used after March 1, 1959. The decision had a wide impact; it affected the use of all coal-tar dyes not only in foods but in drugs and cosmetics. As a result of the ruling, the food, drug and cosmetic industry called for a revision of the Act to allow tolerances to be set for safe use of colors. The FDA was in favor of such a change and had sent a letter proposing such to the House Committee on Interstate and Foreign Commerce on June 27, 1958 and again on February 19, 1959. However, although legislation regarding the use of all color additives would not be passed until 1960, this emergency legislation was passed in 1959 to allow the orange growers to continue use of FD&C Red No. 2. XV. INSECTICIDE AMENDMENTS OF 1959 The Pesticide Chemical Amendments of 1954 established controls on residues of pesticides left on fresh fruits and vegetables. Subsequent to its enactment, new forms of chemical insecticides were developed for use in agriculture which were not covered by the existing provisions. These new insecticides were nematocides, defoliants, dessicants, and plant regulators. In 1959, Congress passed legislation which brought these chemicals under the 1954 Pesticide Chemical Amendments.27 XVI. COLOR ADDITIVE AMENDMENTS OF 1960 In 1960, Congress revised the provisions of the 1938 Food, Drug, and Cosmetic Act regarding the use of color additives. One of the major provisions of the Amendment was the requirement that the conditions for safe use of a color additive be established by regulation. The new law placed on the manufacturer the burden of proof that a color additive was safe for the intended use whereas before it had been up to the Government to prove an additive was unsafe. The regulations regarding use of an additive could set forth tolerance limitations which specified the maximum amount of the additive permitted to remain on or in the product. In addition, the Amendment also required all color additives to be batch-certified unless exempted by the Secretary of HEW. These color additives already on the market were allowed up to two-and-a-half years to obtain FDA approval. Premarket testing and batch certification had previously been required only for coal-tar dyes. A change was also made in the existing requirement that a coal-tar dye could be used only if found to be harmless in any amount. The new legislation allowed the use of any coal-tar dye or any other color additive if it could be established that the substance was safe for the intended use, a change in the Food, Drug, and Cosmetic Act which was supported by both spokesmen from industry and HEW. The cosmetic industry had a particular interest in the provision as the FDA had recently removed 14 dyes used for coloring lipstick from the list of approved coal-tar dyes even though many of the dyes were considered safe as they were being used. The controversial Delaney Clause which prohibited use of any food additives known to produce cancer in man or animals was applied to 28 Flemming v. Florida Citrus Exchange, 358 U.S. 153, cert. denied, 358 U.S. 948. 27 73 Stat. 286, 86th Cong., 1st sess.; Aug. 7, 1959. color additives. Many industry spokesmen who opposed the Delaney Clause in 1958 also opposed its inclusion in the Color Additives Amendments. However, the Secretary of HEW testified strongly supporting application of the Delaney Clause to color additives.28 The preponderance of scientific evidence clearly dictates our position: our advocacy of the anticancer proviso in the proposed color additives amendment is based on the simple fact that no one knows how to set a safe tolerance for substances in human foods when those substances are known to cause cancer when added to the diet of animals. XVII. THE DRUG AMENDMENTS OF 1962 (THE KEFAUVER-HARRIS The Drug Amendments of 1962 were, like the 1938 Act, enacted into law following a serious drug incident, the "thalidomide disaster" 29 Use of thalidomide, a sedative, by pregnant women can cause a severe deformity of the child called phocomelia. Although the drug was never approved by the FDA for commercial marketing, it was distributed to doctors for experimental purposes. A 1962 survey by the FDA showed the drug was given to 3,879 women of child-bearing age, nine of whom gave birth to a malformed child. Legislation to achieve many of the objectives of the 1962 Amendments, like the 1938 legislation, was pending before the Congress when the thalidomide incident occurred. Unlike the 1938 Act, however, the Drug Amendments of 1962 did not represent an entire revision of current law or the drafting of a completely new proposal. Instead, the legislation extended, expanded, and strengthened the regulatory authority of the Food and Drug Administration, particularly as to prescription drugs. The Food and Drug Administration had taken the position that the 1938 law was defective in the following ways: 30 1. The producer of a new drug did not have to establish that his product would be effective, as well as safe, for its intended uses. 2. FDA had to work against deadlines of 60 and 180 days to prevent the automatic approval of new drug products. 3. There were no provisions requiring regular record keeping and reporting of clinical and other experience with new drugs. 4. The FDA could not remove a new drug from the market unless it could prove that it was an unsafe product; it was not enough just to show that new developments had drawn the question of the drug's safety into issue. 5. There were inadequate controls over the distribution and use of investigational drugs, as the thalidomide episode showed. 6. Prescription drug advertising was virtually unregulated. 7. Trade names for products were being used without proper reference to generic or established names, resulting in confusion for the medical profession. 28 House of Representatives. Committee on Interstate and Foreign Commerce, Subcommittee on Public Health and Environment. Report on Color Additive Amendments of 1958, 86th Cong., 2d sess.; June 7. 1960. 20 76 Stat. 780, 87th Cong., 2d sess.; Oct. 10, 1962. 30 Hearings before a Subcommittee of the House Committee on Government Operations on Drug Safety; statement by George P. Larrick, Commissioner, Food and Drug Administration; Mar. 24, 1964. 56-782 O 7522 8. The quality of "old" drugs was not assured, as it was with "new drugs". 9. Only five classes of antibiotic drugs were subject to routine batchtesting and certification. 10. Factory inspection authority was severely restrictive. The changes brought about by the 1962 Amendments included the following: 1. The Food and Drug Administration was authorized to establish for drugs, by regulation, current good manufacturing practices. Drugs which are not manufactured under conforming methods or in conforming facilities are considered adulterated. 2. The factory inspection authority was widely expanded to all matters bearing on violations of the Act. Included within the reach of this authority are data concerning the qualifications of technical and professional personnel employed by the manufacturer. Each establishment must be inspected at least once every two years. 3. Every manufacturer had to register annually with the Department of Health, Education, and Welfare. This provision aids in identifying and inspecting all places where drugs are manufactured, and aids in certain enforcement areas. Drugs coming from non-registered plants are deemed misbranded. 4. The Amendments provided that a new drug cannot be marketed until the FDA approves it as having met the statutory requirements for safety and efficacy. The 1938 law permitted automatic clearance of drugs through lapse of time without FDA action. Approval was now conditioned upon the showing of "substantial evidence" of efficacy, and the burden for proof rested with the manufacturer. 5. Labeling now took on a material bearing on the matter of new drug approval-it must not be false or misleading in an particular. This prohibition relates to the claimed effects of such drugs, as well as to other aspects of labeling. 6. The Secretary of HEW, on finding an imminent hazard to the public health, could immediately suspend a new drug approval, with the manufacturer afforded an expedited hearing. 7. Withdrawal from the market of a previously approved drug could be made for any one of the following reasons: (a) if its labeling is found to be false or misleading in any particular and it is not corrected within a reasonable time after notice.from FDA; (b) if, after reevaluation in the light of new evidence, its safety cannot be established or its claimed efficacy is not supported by substantial evidence; (c) if, after reevaluation in the light of new evidence, it is found that manufacturing facilities, methods, or controls employed in manufacturing or packaging do not conform with standards of good manufacturing practices and are not changed after a reasonable period of time; and (d) if the manufacturer fails to establish a system of maintaining adequate records, fails to make required reports, or refuses to give the FDA access to such records. 8. With respect to drugs already on the market, the manufacturer was now required to report promptly to the FDA information con cerning adverse effects and other clinical experience or data relating in any way to safety and efficacy. 9. New authority was granted to prevent the testing of investigational new drugs, including antibiotics, on humans unless specified safety conditions are met, including: submission of reports of preclinical testing, including animal studies and the obtaining of signed agreements from investigators that clinical work will only be done under personal supervision and experimental drugs will not be supplied to others. 10. Manufacturers who sought an exemption for investigational drugs had to secure from their scientific investigators assurance that they would obtain informed consent from the persons to whom the drugs or controls are to be administered or from their legal representatives (with certain exceptions). 11. Exemptions for experimental drugs from the new drug procedures were conditioned upon the keeping of records and the making of reports. This requirement would enable the FDA to evaluate the safety and efficacy of the drug in the event that a New Drug Application was filed at some later date. 12. All human antibiotics became subject to batch-testing and certification. This provision added 30 additional groups to the five previously subject to this procedure. 13. Changes were made in labeling requirements. The quantity of all active ingredients and specified inactive ingredients must be stated. Labels have to bear the established name of the drug designated under the name standardization authority provided for in the Act, or certain other official or common names where an established name has not been designated. 14. Prescription-drug advertising is required to show the established name (in half-size type similar to that for any other name used, such as a trade name), the quantitative formula to the same extent it is required on the label, and a true and nonmisleading brief summary of adverse effects, contra-indications, efficacy, and other information for the guidance of physicians. A much cited weakness in the 1938 law was the requirement that drugs had only to be shown safe before marketing; there were no requirements for the manufacturer to prove that his product_was effective (efficacious) as well. However, in testimony before a Committee of Congress, FDA Commissioner George Larrick noted that the FDA, since 1938, had assessed the effectiveness of certain products when making safety determinations in the case of drugs for use in lifethreatening or grave diseases: 31 Basically we were saying that the dangerous characteristics of many drugs were such that they would automatically be outlawed unless they had some lifesaving or other very benefiscal aspects that out-weighed those dangers. Where the FDA could not establish that the product was unsafe, the manufacturer was free to proceed to market the product. In short, under the 1938 statute the manufacturer had the burden of proof that the product was safe, while the Government had the burden of proof 31 Hearings on Drug Safety; House Intergovernmental Relations Subcommittee, pt. 1 pp. 185-86; Mar. 24, 1964. to disprove efficacy. The 1962 Amendments now required the manufacturer to show both safety and efficacy. Prior to 1962, the manufacturer was also under no obligation to report any information on adverse findings, after the product was introduced into the market, that would cast doubt on or disprove the safety of the product. The 1962 Amendment required the manufacturer to keep the FDA advised of adverse experience and other data which would shed light on the status of the manufacturer's product. An important feature of the 1962 Act was the provision which enabled the Food and Drug Administration to require tests of efficacy for every product which was subject to the new drug provisions of the 1938 Act. In short, an efficacy review-which is still going oncould be made with respect to every new drug introduced between 1938 and 1962. XVIII. ANIMAL DRUG AMENDMENTS OF 1968 In 1968, legislation was passed to consolidate provisions of the Federal Food, Drug, and Cosmetic Act with respect to the regulation of new animal drugs.32 Both the House and the Senate reports on the Amendment pointed out that, in many cases, the requirements for clearance of new drugs for administration to animals were more complicated than the clearance procedures for drugs for human beings. The reports expressed a need for simplification of the clearance procedures because the existing procedures had led to long delays in the clearance of new animal drugs. Prior to the Amendment, a drug which was intended for use in animal feeds was regulated both as a new drug under the new drug requirements of the Act and as a food additive. This meant that the drug must be cleared under the procedures of both sections of the law. Where the product was a combination of drugs containing a certifiable antibiotic, the product was also regulated under the antibiotic section of the Federal Food, Drug, and Cosmetic Act. The Amendment added a new section to the Act, "new animal drugs", to consolidate into one place the various parts of the Act which related to drugs for administration to animals and to animal feeds. containing new drugs (including antibiotics). A definition for "new animal drug" and "animal drug" was also added by the Amendment. During the Congressional consideration of the proposed legislation, an attempt was made by the House Committee on Interstate and Foreign Commerce to change the existing provisions of the Act regarding the export of animal drugs and feeds. The bill, as reported from that Committee, contained a provision to exempt those new animal drugs and feeds intended for export from the requirements of the Act. New, more lenient requirements were proposed for those products. The requirements were that the animal drug or feed must (1) comply with the law of that foreign country; (2) comply with the specifications of the foreign purchaser; and (3) be labeled for export. The Senate Committee on Labor and Public Welfare was opposed to this amendment and it was omitted in Conference. Any new animal drug intended for export must comply fully with the requirements of the Federal Food, Drug, and Cosmetic Act. 32 82 Stat. 342, 90th Cong., 2d sess.; July 13, 1968. |