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: 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 1 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 on— could 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. 282 Stat. 342, 90th Cong., 2d sess.; July 13, 1968. XIX. THE DRUG LISTING ACT OF 1972 As of 1972, the Food and Drug Administration had no ready means of determining what drugs were actually being manufactured and commercially distributed by establishments registered under the Food, Drug, and Cosmetic Act except by periodic inspection of the establishments. In an effort to increase the FDA's regulatory tools in this area, legislation was introduced in the 92nd Congress to provide for a current listing of each drug manufactured, prepared, propagated, compounded, or processed by a registrant under the Act. During the hearings on the proposed legislation, the Commissioner of the FDA stated that availability of a current inventory of drugs would substantially assist in the enforcement of Federal laws requiring that drugs be pure, safe, effective, and properly labeled. The legislation under consideration was passed and signed into public law on August 16, 1972.33 The Drug Listing Act required manufacturers and processors of drugs to submit to the Secretary a list of all drugs manufactured or processed for commercial distribution. Any drug contained in the list which is subject to the requirements of the Act for new drugs, insulin, antibiotics, or animal drugs must be accompanied by a reference to the authority for marketing and a copy of all labeling for the drug. Those prescription drugs not subject to these specific requirements must be accompanied by a copy of the current labeling, and a representative sampling of advertisements for the product. Over-the-counter drugs not subject to requirements for new drugs, insulin, antibiotics, or animal drugs must be accompanied by the label and package insert and a representative sampling of any other labeling for the drug. In the case of those drugs (prescription or over-the-counter) not subject to the special requirements of the Act, a quantitative listing of all active ingredients is to be submitted. The submission of a quantitative listing of all ingredients (including inactive ingredients) of a particular drug may be required if deemed necessary to carry out the purposes of the Act. The manufacturer or processor may also be required to state why he has determined a particular product is not subject to the requirements for new drugs, insulin, antibiotics or new animal drugs. Supplemental filings are required every six months if there has been a material change in any information previously submitted, if a drug is introduced for commercial distribution after the previous filing, if a drug has been discontinued, or if a previously discontinued drug is reintroduced. The Act also contains a number of other provisions designed to increase the efficiency of the FDA in regulating drugs. 33 86 Stat. 559, 92nd Cong., 2d sess.; Aug. 16, 1972. CAPSULE LEGISLATIVE HISTORY OF THE FEDERAL FOOD, DRUG, AND COSMETIC ACT I. The Food and Drug Act of 1906 (S.88) P.L. 59-384; June 30, 1906. Senate Report No. 59-8 (Comm. on Manufacturers). House Report No. 59-2118 (Comm. on Interstate and Foreign Commerce). Conference Report No. 59-5056. Feb. 21: considered and passed Senate. June 23: considered and passed House, amended. II. The Sherley Amendment of 1912 (H.R. 11877) Aug 19: considered and passed House. III. The Federal Food, Drug, and Cosmetic Act of 1938 (S. 5) P.L. 75-717; June 25, 1938. Senate Report No. 75-91 (Comm. on Commerce). Senate Report No. 75-152 (amended report). House Report No. 75-2139; supplemental report, pt. II (Comm. on Interstate and Foreign Commerce). Conference Report No. 75-2716. Mar. 9: considered and passed Senate. June 1: considered and passed House, amended. IV. Insulin and Antibiotic Certification Amendments P.L. 77-366; Dec. 22, 1941 (H.R. 6251). House Report No. 77-1542 (Comm. on Interstate and Foreign Commerce). Dec. 18: considered and passed House. Dec. 19: considered and passed Senate. P.L. 79-139; July 6, 1945 (H.R. 3266). House Report No. 79-702 (Comm. on Interstate and Foreign Commerce). Senate Report No. 79-410 (Comm. on Commerce). June 19: considered and passed House. P.L. 80-16; Mar. 10, 1947 (H.R. 2045). House Report No. 80-75 (Comm. on Interstate and Foreign Commerce). Senate Report No. 80-45 (S. 445) (Comm. on Interstate and Foreign Commerce). Mar. 3: considered and passed House. Mar. 5: considered and passed Senate, in lieu of S. 445. P.L. 81-164; July 13, 1949 (H.R. 3151). House Report No. 81-499 (Comm. on Interstate and Foreign Commerce). Senate Report No. 81-600 (Comm. on Labor and Public Welfare). May 16: considered and passed House. July 6: considered and passed Senate. P.L. 87-781; Oct. 10, 1962 (S. 1552). Senate Report No. 87-1744 (Comm. on the Judiciary). House Report No. 87-2464 (H.R. 11581); supplemental report, pt. II (Comm. on Interstate and Foreign Commerce). Conference Report No. 87-2526. Aug. 23: considered and passed Senate. Sept. 27: considered and passed House, amended, in lieu of Oct. 3: Senate agreed to conference report. V. Regulatory Amendments of 1948 (H.R. 4071) P.L. 80-749; June 24, 1948. House Report No. 80-807 (Comm. on Interstate and Foreign Commerce). Senate Report No. 80-1221 (Comm. on Interstate and Foreign Commerce). Conference Report No. 80-2400. Jan. 13: considered and passed House. June 15: considered and passed Senate, amended. VII. The Durham-Humphrey Amendment of 1951 (H.R. 3298) House Report No. 82-700 (Comm. on Interstate and Foreign Commerce). Senate Report No. 82-946 (Comm. on Labor and Public Welfare). Aug. 1: considered and passed House. Oct. 15: considered and passed Senate, amended. Oct. 17: House agreed to Senate amendments. VIII. Factory Inspection Amendments of 1953 (H.R. 5740) P.L. 83-217; Aug. 7, 1953. House Report No. 83-708 (Comm. on Interstate and Foreign Commerce). Senate Report No. 83-712 (Comm. on Labor and Public Welfare). Aug. 3: considered and passed Senate, amended. |