Mr. FOUNTAIN. I don't think anybody can argue with that. Mr. LARRICK. I know that. They are always in a state of flux. At about this time, Mr. Chairman, some of us became concerned about our new drug process and I asked the Secretary of the Department to have independent scientific people select a committee of the best scientists they could find from outside to come into Food and Drug and take a cross-section of the new drug files as they were being handled, and to evaluate the total scientific effort of the Food and Drug Administration, as of this time. Now, these people included Dr. Miller, who is professor of medicine, University of Chicago; Dr. Dingle, professor of preventive medicine, Western Reserve; Dr. Maxwell Finland, associate professor of medicine at Harvard; Dr. Colin M. MacLeod, professor of medicine, New York University; Dr. Karl Meyer, who is from the University of California Medical Center; Dr. John R. Paul, professor of preventive medicine, Yale; Dr. Schmidt, professor of pharmacology, University of Pennsylvania; and Dr. Spink, professor of medicine, University of Minnesota. These men came into Food and Drug and took new drug applications at random and went through them step by step and they did make some suggestions for improvement. But we were not unmindful of the changing problem that we had in this whole area. With your permission, I would like to include the names of those people and their recommendations in the record. Mr. FOUNTAIN. You mean their recommendations concerning the improvement of your operating procedures? Mr. LARRICK. Right. Mr. FOUNTAIN. You are referring to the report of the Special Committee, Advisory, to the Secretary of Health, Education, and Welfare, to review the policies, procedures, and decisions of the New Drug Branch, Food and Drug Administration? Mr. LARRICK. That is correct. I was only suggesting for the purpose of not putting too much in the record, that the part on page 1 that lists the members of the Committee and their connections and on pages 2 and 3 that list the recommendations, and the following page that gives the members of the Committee. Mr. FOUNTAIN. If there is no objection, those portions of the report and any other portions which the committee may subsequently decide ought to be in the record will become a part of the record. (The document follows:) EXHIBIT 25-REPORT OF SPECIAL COMMITTEE ADVISORY TO THE SECRETARY OF HEALTH, EDUCATION, AND WELFARE TO REVIEW THE POLICIES, PROCEDURES, AND DECISIONS OF THE DIVISION OF ANTIBIOTICS AND THE NEW DRUG BRANCH OF THE FOOD AND DRUG ADMINISTRATION (a) Mission. This Committee was appointed in June 1960 by the president of the National Academy of Sciences at the request of the Secretary of Health, Education, and Welfare. It was asked to review the policies and procedures used by the Food and Drug Administration in reaching decisions concerning the acceptance and certification of new drugs, including antibiotics, and the scientific soundness of the decisions made in recent years. The Committee was also invited to present such recommendations as it might consider desirable for the protection of the public health through the functions of the FDA. (b) Procedure.-The Committee met on June 28 to plan its activities and again on September 8 to discuss its findings and formulate its recommendations. In both meetings it had the assistance of representatives of the Secretary's Office and the FDA, who cooperated by providing pertinent information and answering questions arising from the study. The necessary legal steps were taken to permit members unrestricted access to the FDA files. In addition, an extensive file of documents concerning the law and regulations, policies and procedures, staffing and organization, and other pertinent matters was forwarded to each member for background and reference. (A list of these documents is appended.) It was at once apparent that the Committee could not hope in any reasonable period to examine all, or even a large proportion, of the thousands of voluminous applications for certifiable antibiotic preparations and new drugs processed under the Federal Food, Drug, and Cosmetic Act in recent years. It was therefore decided that the members would select for detailed study a limited number of preparations which they considered to be of especial significance. In all, 29 applications were reviewed, covering 3 preparations of certifiable antibiotics, 14 of antibiotics classed as new drugs, and 12 of other new drugs. (c) Conclusions.-While the proportion of decisions studied was necessarily small, the Committee believes its sampling to be sufficiently representative, particularly of preparations which have been the subject of some controversy, to provide a reasonable basis for conclusions as to the performance of the FDA staff in protecting the public health. Taking into account the limitations of the FDA's authority, funds, and scientific personnel, the Committee found the decisions it reviewed acceptable, despite certain deficiencies in the quality and quantity of the data upon which they were based. It found no evidence of disregard for the public health, and noted that appropriate action had been taken when hazards were established by subsequent clinical experience. Nevertheless, the Committee concluded that certain weaknesses inherent in the existing law and current staffing and budgetary support hamper the FDA in its task of protecting the public health. Accordingly, it has addressed its recommendations primarily to the correction of these defects. The increasing rate at which medical research is expanding and new and powerful drugs are being developed is multiplying the number of potential hazards to be controlled. Therefore, the Committee believes it essential that these recommendations be acted upon with the least possible delay. (d) Recommendations.— 1. The FDA should be given statutory authority to require proof of the efficacy, as well as the safety, of all new drugs. Treatment of a patient with an ineffective drug in place of an effective one may jeopardize his recovery. This is true even though the drug may not be intrinsically harmful, and even though the specific condition for which the drug is given may not be ordinarily regarded as life-threatening. 2. The FDA should be given statutory authority to require manufacturers of new drugs to maintain records and submit reports of clinical experience and other relevant data, not only before but after the drug is released for sale, as requested by the Commissioner in his proposed Factory Inspection and Drug Amendments of 1960. Any evaluation of a new drug is subject to revision in the light of broader experience, and the FDA must be in a position to advise the profession and warn the public promptly whenever new hazards are revealed. 3. The FDA should be given statutory authority to apply certification procedures to all antimicrobial agents used in the prophylaxis and treatment of infectious diseases. The Committee sees no reason for limiting certification to those antibiotic preparations which happen to have come on the market prior to 1950, and further believes that all agents employed for equally serious conditions should be subject to equivalent measures of control. 4. The Committee recognizes the importance to the public health of insuring that all drugs are prepared under the highest standards of quality control. It therefore endorses the Commissioner's proposals in the Factory Inspection and Drug Amendments of 1960 to clarify and strengthen existing inspection authority, and to require that all drugs be manufactured and packaged under adequate controls. 5. The Committee believes that the information supplied to physicians concerning drugs should be not only accurate, but also complete, and that the date of such information is essential to its proper evaluation. It therefore endorses the proposed amendments to present labeling requirements published by the Commissioner in the Federal Register for July 22, 1960. 6. The Committee considers that the advertising of pharmaceuticals requires more careful regulation than that of products unrelated to the prevention and cure of disease. It therefore recommends that careful study be given to the problem of coordinating the supervision of labeling, promotional material, and other advertising of drugs, now divided among several agencies of the Government, and to means of insuring that all information concerning drugs conveyed to the profession and the public by whatever media be in conformity with scientific fact. 7. When a decision has been reached concerning an application, a statement should be prepared and incorporated in the file summarizing the conclusions, the names and opinions of those involved, and such other data as may be necessary to provide a concise record of the basis for the decision. This should be of great assistance in the administrative review of current actions and in the scientific review of the files in relation to subsequent applications, as well as when the advice of consultants is sought. 8. The staff members responsible for processing applications should be supported to the utmost in their efforts to obtain submission of truly dependable scientific information on the efficacy and safety of the products. The data initially submitted by the manufacturer are not always of sufficient quality and quantity to permit a sound decision as to the merits of the product. 9. The FDA should be strongly supported in its effort to maintain a research program of high quality on the methodology and standardization of drug testing and related areas of basic science. This is important not only to improve the methods available for carrying out its responsibilities to the public, but also as an aid in recruiting and retaining competent scientists on the staff. 10. The Committee urges the Commissioner to seek such authorization as may be necessary to establish an advisory organization of scientific and technical experts as a recognized resource for advice on criteria, procedures, and policies for the execution of the responsibilities of the FDA. 11. It is recognized that these various recommendations cannot be carried out without expanded resources, both of funds and of personnel. The Committee also considers that the present resources of the FDA are less than adequate to meet existing responsibilities. It therefore urges that the FDA be granted the authority and funds required to employ and retain larger numbers of highly qualified personnel and to support their activities, and endorses the recommendations made to this end by the Citizens' Advisory Committee in 1955. Approved September 27, 1960. MEMBERS OF COMMITTEE Dr. C. Phillip Miller, Chairman, professor of medicine, University of Chicago Dr. Maxwell Finland, associate professor of medicine, Harvard Medical School. Dr. Karl F. Meyer, director emeritus, George Williams Hooper Foundation, University of California Medical Center, San Francisco. Dr. John R. Paul, professor of preventive medicine, Yale Univerisity School of Medicine. Dr. Carl F. Schmidt, professor of pharmacology, University of Pennsylvania School of Medicine. Dr. Wesley W. Spink, professor of medicine, University of Minnesota Medical School. BACKGROUND MATERIAL FURNISHED BY FDA TO MEMBERS OF SPECIAL COMMITTEE 1. Material for NRC Committee-Certification of Antibiotics, June 20, 1960: A. Federal Food, Drug, and Cosmetic Act (exhibit A). B. Organization, Division of Antibiotics (exhibit B). C. Organization, Antibiotics Branch, Bureau of Medicine (exhibit C). E. Antibiotics Regulation, vol. II (exhibit E). F. Operations of the Division of Antibiotics (exhibit F). G. Research in the Division of Antibiotics (exhibit G). H. Reprints of various publications (exhibit H). 37-272-64-pt. 2-19 I. Curriculum Vitae of Dr. Welch (exhibit J). 2. Types of decisions involved in establishing antibiotic regulations, June 23, 1960. (Certifiable Antibiotics only.) 3. Memorandum, background information for the NAS Committee, June 22, 1960, from Dr. W. H. Kessenich, Medical Director, Bureau of Medicine, with attachments: A. Federal Food, Drug, and Cosmetic Act. B. General regulations for the enforcement of the Federal Food, Drug, and Cosmetic Act. C. New Drug Regulations (encl. 2). D. New Drug Application Form (encl. 3). E. Statement of George P. Larrick (encl. 4). F. Organization chart of FDA and Bureau of Medicine (encl. 5). 4. Memorandum, background information for the NAS Committee from Bureau of Medicine, June 28, 1960. 5. New drug applications handled during period January 1958 to March 1960. 6. Staffing pattern, FDA, July 1, 1960. 7. Report of Citizens' Advisory Committee on FDA, dated June 1955. 8. Pamphlet, "Protecting Consumers of Food, Drugs, Cosmetics," dated October 15, 1959. 9. Report of Panel on Food Additives, dated May 9, 1960. 10. "Factory Inspection and Drug Amendments of 1960," press release dated July 1, 1960, bill and amendment. COMMENTS BY THE SECRETARY OF HEALTH, EDUCATION, AND WELFARE, ARTHUR S. FLEMMING, ON THE RECOMMENDATIONS OF THE SPECIAL ADVISORY COMMITTEE TO REVIEW THE POLICIES, PROCEDURES, AND DECISIONS OF THE DIVISION OF ANTIBIOTICS AND THE NEW DRUG BRANCH OF THE FOOD AND DRUG ADMINISTRATION Recommendation 1 Comments. I concur in this recommendation that FDA be given statutory authority to require proof of the efficacy, as well as the safety, of all new drugs. There are now two significant concepts on the basis of which the Food and Drug Administration does, in fact, require a demonstration of the efficacy of new drugs before applications are cleared; namely, (1) when the drug is offered for the treatment of a life-threatening disease, and (2) when the drug may have a definite potentiality to do harm where we have to measure the good the drug does against its possible hazards. But I agree that the new drug procedures are not adequate to insure the efficacy of drugs which are essentially innocuous. Commissioner George P. Larrick, testified before the Senate Subcommittee on Antitrust and Monopoly on June 3, 1960, as follows: "We would endorse a proposal that the new drug section of the Food, Drug, and Cosmetic Act require a showing of efficacy as well as a showing of safety." Recommendation 2 Comments. I concur in this recommendation that the Food and Drug Administration be given statutory authority to require manufacturers of drugs to maintain records and submit reports of clinical experience, particularly after the drug is released for sale. Senate bill 3815 introduced in the 86th Congress, 2d session. specifically provides for such recordkeeping and reporting. The Department of Health, Education, and Welfare submitted this bill as a proposal to Congress to strengthen the Federal Food, Drug, and Cosmetic Act. Recommendation 3 Comments. I concur in this recommendation that FDA be given statutory authority to apply certification procedures to all antimicrobial agents. The present law now provides for certification for products composed wholly or partly of any kind of penicillin, streptomycin, chlortetracycline, chloramphenicol, or bacitracin, or any derivative thereof. Recommendation 3 would extend mandatory certifications procedures to all antimicrobial agents whether produced by living microorganism or by any other means. Recommendation 4 Comments.-I concur in this recommendation that the inspection authority be strengthened to require that all drugs be manufactured and packaged under adequate controls. S. 3815, proposed by the Department of Health, Education, and Welfare, specifically provides that drugs be produced under adequate controls and manufacturing, processing, packaging, and storing, or be deemed to be adulterated within the meaning of the act. Recommendation 5 Comments.-I concur in this recommendation that the information supplied to physicians concerning drugs be accurate and complete. The proposed revisions in the regulations under section 502 (f) (1) as published in the Federal Register for July 22, 1960, will aid-as far as the Food, Drug, and Cosmetic Act will permit-in the control of false and misleading promotion of new drugs to the medical profession. Recommendation 6 Comments.-The issue reflected in this recommendation is an important one. I am asking that a careful study be made of the organizational problems involved and, when this study has been completed, I will make recommendations to the President. Recommendation 7 Comments. I concur in this recommendation that a concise record be prepared for the file summarizing the basis on which the decision is made to permit a new drug application to become effective. I have asked Commissioner Larrick to submit proposals to me as to what needs to be done to carry out this recommendation. Recommendation 8 Comments. I concur in this recommendation that the staff members respon. sible for processing new drug applications be supported fully in their insistence that they receive complete and dependable scientific data to support new drug applications. This Department is aware of its enormous responsibility in the clearance of new drugs and antibiotics, and it recognizes the importance of and need for comprehensive, competent scientific data, and information on the safety and efficacy of new drugs. I shall continue to insist upon the fullest submission of safety and efficacy data necessary for intelligent study and evaluation of new drug applications. Recommendation Comments.-I concur in this recommendation that FDA should have a sound research program on methodolgy and drug testing. Such a research program is an essential part of the Food and Drug Administration's effort to improve its enforcement operations. We recently increased our work in this area and plan to broaden it still further. Recommendation 10 Comments. I concur in this recommendation that the Commissioner of Food and Drugs seek authority to establish an advisory organization of scientific and technical experts. The complexity of present day new drugs and the constant flow of progress and new developments in the drug field makes it essential that the Food and Drug Administration have for its guidance the most competent scientific resources available in the United States. I have asked Commissioner Larrick to make appropriate proposals to me for the implementation of this recommendation. Recommendation 11 Comments. I concur in this recommendation that FDA needs expanded resources support. Without adequate resources of both funds and personnel the great responsibilities imposed upon the Food and Drug Administration cannot be met. I anticipate increased recognition of this fact. Mr. FOUNTAIN. In your testimony yesterday, Mr. Larrick, you stated that FDA obtained the opinions of a number of experts in the treatment of gout, to determine whether the benefits to be derived from Flexin outweighed its dangers, and whether it should therefore remain on the market. I wonder if you would tell the committee just how the FDA went about selecting these experts. |