October 9, 1963. The questions, the two letters, and a list of the advertisements have been placed in the record. A modification of §1.105(j) (1) was agreed upon, to permit the sponsor of a prescription drug to develop a program of advertising to publicize information on side-effects or contraindications involving fatalities or serious injury as an alternative to preclearance of individual adver tisements. Counsel for the objectors have concluded that these clarifications of the regulations satisfy the objections to § 1.105 (e), (f), (g), (i), and (j), and the objections were withdrawn. Counsel maintains the objections to paragraph (h), and requests 30 days for briefing the objection. Counsel for the Food and Drug Administration reserves the right to produce evidence on this objection after the brief is presented. Section 1.105 (j) (1) (28 F.R. 9837) is revised to read as follows: (j) (1) No advertisement concerning a particular prescription drug may be disseminated without prior approval by the Food and Drug Administration if: (1) The sponsor or the Food and Drug Administration has received information that has not been widely publicized in medical literature that the use of the drug may cause fatalities or serious damage; (ii) The Commissioner (or in his absence the officer acting as Commissioner), after evaluating the reliability of such information, has notified the sponsor that the information must be a part of the advertisements for the drug; and (iii) The sponsor has failed within a reasonable time as specified in such notification to present to the Food and Drug Administration a program, adequate in light of the nature of the information, for assuring that such information will be publicized promptly and adequately to the medical profession in subsequent advertisements. If the Commissioner finds that the program presented is not being followed, he will notify the sponsor that prior approval of all advertisements for the particular drug will be required. Nothing in this paragraph is to be construed as limiting the Commissioner's or the Secretary's rights, as authorized by law, to issue publicity, to suspend any new-drug application, to decertify any antibiotic, or to recommend any regulatory action. Now, therefore, under the authority provided in sections 502 (n) and 701 (a) and (e) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 352 (n), 371 (a), (e); 52 Stat. 1050, 1051, as amended 76 Stat. 790, 791, 792; 1055, as amended 70 Stat. 919, 74 Stat. 380), and delegated to the Commissioner of Food and Drugs by the Secretary of Health, Education, and Welfare (25 F.R. 8625), the regula tions in 1.105 (e), (f), (g), (i), and (j) (2), (3), and (4), published in the Federal Register on June 20, 1963 (28 F.R. 6376-6377) and the revision of 81.105 (J) (1) included in this order are hereby made effective 90 days after the publication of this order. Counsel for the objectors to paragraph (h) may, within 30 days from the publication of this order, file a brief in support of objections, and a further order will be made either giving notice of a hearing on the objections or acting on the objections without the necessity for a hearing. (Secs. 502 (e), (n), 701 (a), (e), 52 Stat. 1050, 1051, as amended 76 Stat. 790, 791, 792; 1055, as amended 70 Stat. 919, 74 Stat. 399; 21 U.S.C. 852 (e), (n), 371 (a), (e)). Dated: October 10, 1963. GEO. P. LARRICK, Commissioner of Food and Drugs. [Published in the Federal Register Nov. 16, 1963] TITLE 21-FOOD AND DRUGS CHAPTER I-FOOD AND DRUG ADMINISTRATION, DepartmeNT OF HEALTH, EDUCATION, AND WELFARE PART 1-REGULATION FOR THE ENFORCEMENT OF THE FEDERAL Food, Drug, AND 2 СОВМЕТІС Аст Regulations Relative to Prescription-Drug Advertisements; Extension of Time for Filing Briefs With Reference to § 1.105(h) On request of counsel for the objectors, the time for the filing of briefs in relation to the proposed amendment to 1.105 (h) in the above-identified action is extended to December 14, 1963. (Secs. 502 (e), (n), 701 (a), (e), 52 Stat. 1050, 1051, as amended 76 Stat. 790, 791, 792; 1055, as amended 70 Stat. 919, 74 Stat. 399; 21 U.S.C. 352 (e), (n), 371 (a), (e)). Dated: November 13, 1963. JOHN L. HARVEY, Deputy Commissioner of Food and Drugs. [Published in the Federal Register Dec. 17, 1963] TITLE 21-FOOD AND DRUGS CHAPTER I-FOOD AND Drug Administration, DepARTMENT OF HEALTH, PART 1-REGULATION FOR THE ENFORCEMENT OF THE FEDERAL FOOD, Drug, and Regulations Relative to Prescription-Drug Advertisements; Extension of Time for Filing Briefs With Reference to 1.105 (h) · On request of counsel for the objectors, the time for the filing of briefs in relation to the amendment to §1.105 (h) in the above-identified action is extended to December 30, 1963. (Secs. 502 (e), (n), 701 (a), (e), 52 Stat. 1050, 1051, as amended 76 Stat. 790, 791, 792; 1055, as amended 70 Stat. 919, 74 Stat. 399; 21 U.S.C. 352 (e), (n), 371 (a), (e)). Dated: December 13, 1963. JOHN L. HARVEY, Deputy Commissioner of Food and Drugs. [For release in a.m. papers Jan. 18, 1964] U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, The Food and Drug Administration has completed the publication of its regulations controlling prescription drug advertising. Regulations issued last October became fully effective January 13. They spell out the manner in which information must be presented in prescription drug labels and advertisements, so as to insure a balanced presentation of the facts regarding the drug advertised. Effective in 90 days is a regulation published January 10 with regard to the supporting data which will be required for advertisements of "old drugs." As originally proposed, this regulation would have required that advertisement for old drugs, as well as for new drugs, be supported by "substantial evidence" that the drugs would have the effectiveness advertised. Substantial evidence of effectiveness is defined in the Kefauver-Harris Drug Amendments to mean evidence obtained through adequate and well-controlled scientific investigations. The point was made by the drug industry that some old drugs, long in use in medical practice, had substantial clinical experience to support their claims, although they have not been subjected to the kind of controlled clinical investigations that are needed to support the claims for new drugs. Under the revised regulation, FDA will accept adequately documented clinical experience to support the advertising claims for old drugs. Industry objections have been withdrawn. The revised regulation will become effective in 90 days. As revised, the regulations permit the advertising of these old drugs for uses "for which there exists substantial clinical experience, adequately documented in medical literature or by other data (to be supplied to the FDA, if requested), on the basis of which it can fairly and responsibly be concluded by qualified experts that the drug is safe and effective for such uses." The regulations require prescription drug advertisements to present information concerning side effects and contraindications for uses recommended or suggested in the ads and for any other use or uses for which the dosage form adver tised is commonly prescribed. There must be a fair balance between the desir able and any undesirable effects of the drug. DRUG SAFETY [Published in the Federal Register of Jan. 10, 1964] TITLE 21-FOODS AND DRUGS CHAPTER I-FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH, 135 PART 1-REGULATIONS FOR THE EXFORCEMENT OF THE FEDERAL FOOD, Drug, and COSMETIC ACT PRESCRIPTION DRUG ADVERTISEMENTS The Commissioner of Food and Drugs, on October 15, 1963 (28 F.R. 10993), issued an order placing into effect the regulations in § 1.105 (e), (f), (g), (i), and (j) with respect to prescription-drug advertising. This order allowed counsel for the objectors thirty days within which to file a brief in support of objections to paragraph (h). The time for filing this brief was extended to and including December 30, 1963. Further consideration of paragraph (h), with counsel for the objectors, has developed a revision on the basis of which the objections have been withdrawn. The revision applies to § 1.105 (f) and (h). Section 1.105(f), as previously published in the FEDERAL REGISTER of June 20, 1963 (28 F.R. 6376), and made effective in the FEDERAL REGISTER of October 15, 1963, is hereby withdrawn and is revised to read as follows, and § 1.105 (h) (28 F.R. 6376) is also revised to read as follows: §1.105 Prescription-drug advertisements. (f) (1) An advertisement for a prescription drug covered by a new-drug application approved after October 10, 1962, or any approved supplement thereto, shall not recommend nor suggest any use that is not in the labeling accepted in the approved new-drug application or such supplement. The advertisement shall' present information from the approved new-drug application labeling concerning those side effects and contraindications that are pertinent with respect to the uses recommended or suggested in the advertisement and any other use or uses for which the dosage form advertised is commonly prescribed. (2) If a prescription drug was covered by a new-drug application or a supplement thereto that became effective prior to October 10, 1962, an advertisement may recommend or suggest: (1) Uses contained in the labeling accepted in such new-drug application and any effective or approved supplement thereto. (ii) Additional uses contained in labeling in commercial use on October 9, 1962, to the extent that such uses did not cause the drug to be an unapproved "new drug" as "new drug" was defined in section 201 (p) of the act as then in force and to the extent that such uses would be permitted were the drug subject to paragraph (h) of this section. (iii) Additional uses contained in labeling in current commercial use to the extent that such uses do not cause the drug to be an unapproved "new drug," as defined in section 201 (p) of the act, as amended. The advertisement shall present information from such labeling concerning those side effects and contraindications that are pertinent with respect to the uses recommended or suggested in the advertisement and for any other use or uses for which the dosage form advertised is commonly prescribed. (h) In the case of an advertisement for a prescription drug other than drug the labeling of which causes it to be an unapproved "new drug" and other than drugs covered by paragraphs (f) and (g) of this section, an advertisement may recommend and suggest the drug only for those uses contained in the labeling thereof: (1) For which the drug is generally recognized as safe and effective among experts qualified by scientific training and experience to evaluate the safety and effectiveness of drugs; or (2) For which there exists substantial evidence of safety and effectiveness consisting of adequate and well-controlled investigations, including clinical inrestigations, by experts qualified by scientific training and experience to evaluate the safety and effectiveness of the drug involved, on the basis of which it can fairly and responsibly be concluded by such experts that the drug is safe and effective for such uses; or (3) For which there exists substantial clinical experience, adequately documented in medical literature or by other data (to be supplied to the Food and Drug Administration, if requested), on the basis of which it can fairly and repsonsibly be concluded by qualified experts that the drug is safe and effective for such uses; or (4) For which safety is supported under any of the preceding clauses in subparagraphs (1), (2), and (3) of this paragraph and effectiveness is supported under any other of such clauses. The advertisement shall present information concerning those side effects and contradictions that are pertinent with respect to the uses recommended or suggested in the advertisement and for any other use or uses for which the dosage form advertised is commonly prescribed. Now, therefore, under the authority provided in sections 502(n) and 701(a) and (e) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 352(n), 371 (a), (e); 52 Stat. 1050, 1051, as amended 76 Stat. 790, 791, 792; 1055, as amended 70 Stat. 919, 74 Stat. 380), and delegated to the Commissioner of Food and Drugs by the Secretary of Health, Education, and Welfare (25 F.R. 8625), the regulations in 1.105 (f) and (h) included in this order are hereby made effective 90 days after the publication of this order in the FEDERAL REGISTER. (Secs. 502 (e), (n), 701 (a), (e), 52 Stat. 1050, 1051, as amended 76 Stat. 790, 791, 792; 1055, as amended 70 Stat. 919, 74 Stat. 399; 21 U.S.C. 352(e), (n), 871 (a), (e)) Dated: January 2, 1964. JOHN L. HARVEY, Deputy Commissioner of Food and Drugs. Mr. LARRICK. 5. Beginning on October 10, 1962, the date of passage of the new law, we initiated the recordkeeping and reporting of clinical and other experience requirements for new drugs in letters approving applications. This requirement was established by regulation published on June 20, 1963. This provision was included in the Federal Register publication of that date covering new drugs which I have already submitted for the record. 6. On February 28, 1964, we announced new proposals to require the establishment of records and routine reporting for all new drugs and antibiotics that have been approved since 1938. A part of this proposal will require the drug industry to make a review of clinical experience and promotional practices with respect to approved drugs. Then it will advise us whether the labeling and advertising actually in use is in harmony with labeling in the approved new drug application and whether this labeling is supported by the clinical experience reported to or obtained by the drug manufacturers. This will accomplish a twofold purpose. It will bring us up to date on recordkeeping and reporting, and it will provide the base for reevaluation of the safety of drugs we have approved and for enforcement of the new "effectiveness" requirements which take effect on October 10, 1964. The 1962 law allowed a 2-year lag period for proof of effectiveness for new drugs that were approved and on the market when the law was passed. I submit for the record the press release and proposed regulations pertaining to that requirement. Mr. FOUNTAIN. If there is no objection, that regulation will be inserted in the record.1 (The above-mentioned material follows:) The final regulations, which were published in the Federal Register on May 27, 1964, and an explanatory press release are also included. DRUG SAFETY [For immediate release Feb. 28, 1964] 137 U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, The Food and Drug Administration today announced its proposed regulations requiring a comprehensive review of the effectiveness of all drugs cleared for human use under the new drug and antibiotic certification provisions of the Federal Food, Drug, and Cosmetic Act. The review applies to all drugs cleared between passage of the Act in 1938 and June 20, 1963. Drugs approved since June 20, 1963, are already subject to periodic reporting and review requirements under the Kefauver-Harris Drug Amendments of 1962. The proposal would require manufacturers to notify FDA whether previously cleared drugs are now on the market and how they are labeled and promoted. It would require manufacturers to show that clinical experience with a drug justifies the labeling allowed in the new drug application or antibiotic submission or any changes that have been made in the labeling. It would also assure that promotion accords with appropriate labeling. The proposed review of clinical experience, drug labeling, and promotion will provide the basis for applying provisions of the Kefauver-Harris Drug Amendments of 1962 which become effective October 10, 1964. These provide for the relabeling or removing from the market of drugs cleared under the 1938 Act unless there is substantial evidence that the drug is effective for the purposes claimed. Prior to the Kefauver-Harris Drug Amendments of 1962 FDA did not have the authority to prevent the marketing of a safe new drug solely on the grounds it had not been shown to be efficacious. The proposal was published in the Federal Register Friday, February 28, 1964. Interested persons have 30 days to file written comments with the Hearing Clerk, Department of Health, Education, and Welfare, Room 5440, 330 Independence Avenue SW., Washington, D.C., 20201. Under the proposed regulations, firms whose new drug or antibiotic applications are deemed approved would have 30 days from the date of publication of the final regulation to report to FDA whether the drug was marketed, whether it is currently being marketed, and if marketing was discontinued the date and reason for this. The firms would have 90 days from the date of publication of the final regulation in which to submit the following: 1. A copy of the label on the package of the drug and of the package insert or brochure bearing directions or information for use. 2. A report of any changes from the cleared labeling with an explanation and the data supporting the changes. 3. A statement as to whether the labeling fairly reflects the clinical experience reported to or otherwise received by the firm. 4. Copies of representative promotional labeling and advertising and a statement as to whether they accord with the cleared labeling. 5. A report on any differences between currently used promotional material and the cleared labeling with an explanation and the data supporting the changes. 6. A supplement to the application proposing changes in labeling claims for effectiveness or disclosing side effects, warnings or contraindications if indicated by clinical experience. 7. Information about any mixup in the composition or labeling of the drug, any deterioration of the drug or failure to meet its specifications, and any information not disclosed in the drug's labeling about side effects, injuries, toxicity, or sensitivity reactions. 8. All reports would be sent to the Secretary, Department of Health, Education, and Welfare, for the Commissioner of Food and Drugs, in envelopes marked "New Drug (or Antibiotic) Report" and hearing the new drug application number or antibiotic account number. Failure to make the reports or to report the discontinuance of marketing may result in withdrawing approval of applications after giving applicants opportunity for a hearing. Notice of such hearings would be published in the Federal Register to furnish any person who would be adversely affected an opportunity to participate in a hearing. |