had his pharmacy staff member and others; Mr. Oddis represented the American Society of Hospital Pharmacists; I represented the American Pharmaceutical Association; we had AMA at the executive vice president level, the general counsel, the director of their law division. Mr. GORDON. Who was the general counsel at that time? Dr. APPLE. Mr. Stetler was the person who participated in most of these meetings in 1963. Mr. GORDON. And he was at that time in favor of the formulary system? Dr. APPLE. I cannot answer that. Mr. GORDON. At least he represented the AMA. Dr. APPLE. He represented the AMA, and the statement that was finally worked out during these conferences was subsequently ratified by the boards of the four organizations, including the AMA Board of Trustees. We have a copy of that statement appended to the record here of our testimony. Mr. GORDON. Do I understand correctly that Mr. Stetler now is opposing the formulary system? Dr. APPLE. I have no knowledge of this. Mr. GORDON. I was just wondering. Dr. APPLE. We think the formulary concept can be extended through communities with the cooperation of the medical and pharmaceutical professions and with the same beneficial effects. For lack of a better title, we refer to this as a community formulary. The antisubstitution laws would not pose any serious impediment and, in fact, would assure effective functioning of the community formulary. The local medical and pharmaceutical societies would establish a pharmacy and therapeutics committee to develop a list of drugs to be utilized. This listing then would be circulated to all physicians and pharmacists in the area. Information included would be the scientific name of the drug and the acceptable suppliers chosen on the basis of the collective experience of the panel, literature reports, comparative product costs, therapy rationale in much the same manner as is now done in hospitals. When the prescriber wrote his prescription order, he would merely signify that he wished the pharmacist to use the "formulary equivalent," or he could prescribe by established name with the direction that a formulary-accepted product be utilized. If the pharmacist dispensed a product other than that listed in the formulary, he would, of course, have violated the antisubstitution law, just as if he had used one brand in place of another. Under this system, the physician would know that he was not receiving an "unknown" product of dubious quality. Several pharmaceutical groups have indicated an interest in "testing" this concept in a number of States, and we plan to lend our every assistance to these efforts. We think that effective development of such a system would be consonant with the hallowed principles of medical and pharmaceutical practice and serve the public interest. Much has been made of the need for pharmacists to know why two drug products may be different. But, if the pharmacist is going to be able to use this knowledge for the benefit of society, he must have the factual information on how the drug products do in fact differ. Until now, this information has not been available. All accredited hospitals must have pharmacy and therapeutics committees. The purpose of these committees is to constantly improve the quality of drug therapy. A byproduct of their activity is to keep the hospital pharmacy's inventory to the minimum by eliminating needless duplications, not by reducing the useful therapeutic agents available to the prescriber. Another byproduct is purchasing an acceptable quality drug product at the lowest possible cost. We believe that physicians and pharmacists can effectively introduce some of these same benefits for patients outside the hospital by developing a community formulary system. Seven years ago a discussion started on how more complete and reliable information on prescription drug products could be made available and disseminated to the prescribing and dispensing professions. In 1960, we filed statements with the Department of Health, Education, and Welfare outlining our interest and making specific suggestions. It was our position then that the increase of information on the package or package insert would not effectively provide the prescriber with the desired information. As we pointed out, the prescriber seldom sees the product or its packaged content. Moreover, we also pointed out that the package insert constitutes an inefficient and ineffective means of promptly communicating current information to pharmacists. As an alternative to the proposals offered by the Food and Drug Administration at that time, we recommended a nine-point program involving the cooperative efforts of FDA, the pharmaceutical industry, and the health professions immediately involved. Copies of our 1960 statements are attached. Since 1960, we have had discussions with FDA and members of the pharmaceutical industry on this subject. For example, we have pointed out that when there are supplements to, or modifications in, the package insert, there may be a considerable timelag before the information reaches the physician or the pharmacist. These practitioners have no obvious way of knowing if the package insert they have in their possession at a given moment is the most recent one approved by FDA. In 1964, APhA considered publishing a compilation of the latest approved labeling for the 500 most frequently prescribed drugs. We were forced to abandon the project because at that time FDA was unable to provide us with the information we required. Currently, we are participating in the discussions of the National Academy of Sciences/National Research Council on the possible alternatives for the current package insert system. Based on our experience the past 7 years, we can underscore the growing importance of a better means of communicating specific drug product information to the medical and pharmaceutical professions. This need is not limited to prescription legend drugs. It extends to drug products available and utilized in self-medication. We believe that our association is making real progress in meeting this need. Three months ago, we published a "Handbook of Nonprescription Drugs"-the first such comprehensive reference in the world. It has been well received by physicians and pharmacists, and before the year ends we will be reprinting it for the third time. APhA is still hopeful that the need for information on prescription legend drugs can be met promptly through the voluntary, cooperative efforts of the professions concerned and the pharmaceutical industry. We can assure the manufacturers and FDA that any soundly conceived effort will have our assistance. In conclusion, we recognize that the health and life of people today increasingly depend upon drugs. For 115 years, the American Pharmaceutical Association has supported constructive steps-and initiated several-to improve the Nation's drug supply and, Mr. Gordon, as a matter of fact, just late this month our Academy of Pharmaceutical Sciences is sponsoring a program here in Washington, and the entire symposium is devoted to the subject of development of safer and more effective drugs. I would be glad to supply the committee copies of the program and abstracts for its files. Mr. GORDON. Thank you very much. We do appreciate that. Dr. APPLE. As I have indicated, we have supported constructive steps and initiated several, to improve the Nation's drug supply and the professional services involved in making drugs available to patients. This will continue to be one of our major objectives. Thank you. (The attachments to Dr. Apple's statement follow :) AMERICAN PHARMACEUTICAL ASSOCIATION, Re notice of proposal to amend labeling requirements (21 CFR 1, 130) dated Department of Health, Education, and Welfare, Washington, D.C. DEAR SIR: The following statement is submitted in response to the opportunity afforded by the Commissioner of Food & Drugs for interested persons to express their views on the proposed labeling regulations. Realizing that others will comment upon those phases of the proposed regulations of immediate interest to them, our remarks will be confined to matters directly affecting the American Pharmaceutical Association, the profession of pharmacy, and the efforts of pharmacists to discharge their professional responsibilities as drug and therapeutic device consultants to prescribers and as community custodians of drugs and such devices. We are in complete agreement with the intent of the proposed amendments which are advanced in the interest of providing more complete information relevant to the professional use of any article bearing a prescription legend or otherwise limited to order of particular practitioners. Our Association has repeatedly advocated increased disclosure of product information in order that pharmacists may serve more proficiently in their capacity as consultants to prescribers of all prescription legend articles. To meet the demand for reliable information, individual pharmacists have, among other things, attempted to maintain product reference libraries and to develop extensive product reference brochure files within pharmacies. At their own expense, in order to be of service to prescribers, some pharmacists have even attempted to publish and distribute product information gleaned from a variety of reference sources. For the guidance of every practitioner licensed by law to administer prescription legend articles, complete product information concerning use, dosage, cautions, and contraindications should be readily available. For these reasons, we believe in the principle, embodied in the proposed regulations; that is, of disseminating additional product information. However, we seriously question the practicality of certain aspects of the mechanism proposed for achieving our mutual purpose—the availability of complete product information for prescribers. SECTION 1.106 (b) (3) The information required by this subsection is designed for communication to, and use by, practitioners licensed by law to administer prescription legend drugs. However, in the usual course of employing such a drug, the prescriber creates a prescription which in turn is communicated to the pharmacist. Therefore, the prescriber does not see either the product or its packaged contents. It is the pharmacist who has physical possession of the product, its container or wrapper, and any written, printed, or graphic material accompanying such an article. Consequently, there is no basis for believing that by increasing the volume of literature included in every prescription drug container, communication of information to prescribers will thereby be facilitated. A pharmacist with numerous packages of a particular drug in stock will have numerous copies of the same literature, which will seldom or never be seen by the prescriber. Moreover, as supplementary information develops, each existing product container and enclosures would be incomplete, inaccurate, or otherwise deficient under the proposed regulations. A realistic appraisal of product expense for initial packaging, shipping, and storage in relation to the degree of product information communicated to prescribers which might be achieved by the proposed procedures will reveal the impracticality of this particular mechanism. This significant expense ultimately would have to be passed on to the patient, thereby increasing the cost of his medication, with little hope of achieving the desired purpose of the proposed regulations. Furthermore, the existence of extensive professional information within each product package increases the risk of this information passing into hands of the laity. Obviously, this might easily result in untoward consequences. It must be remembered that the purpose of exempting drugs, subject to the requirements of Section 503(b)(1) of the Act, from Section 502(f) (1) is to preclude the use of dangerous prescription legend drugs except under the direct supervision of a practitioner licensed by law to administer such drugs. As an alternative to the proposals contained in this subsection, we recommend a cooperative arrangement, involving the Food and Drug Administration, the pharmaceutical industry, and the health professions immediately involved, through which the following procedures would be effected: 1. Every manufacturer would be charged with the responsibility of preparing, for each product subject to the regulations, a complete "official brochure" containing full professional information. 2. The "official brochure" would be in accordance with the new regulations proposed by the Food and Drug Administration. 3. A non-governmental, non-profit agency approved for that purpose by the Food and Drug Administration, the United States Pharmacopeia Revision Committee, and the Committee on National Formulary would serve as the coordinator and distributor of each "official brochure." 4. The "official brochure" design would be uniform in format and conform to specifications developed by the agency referred to in paragraph 3 with the advice of the United States Pharmacopeia Revision Committee and the Committee on National Formulary. 5. All production, publication, and distribution costs for each "official brochure" would be borne by the respective manufacturer. 6. The agency referred to in paragraph 3 would promptly distribute each "official brochure" to every pharmacy in the United States. 7. Pharmacists would be advised that the availability of these brochures is as essential for the proper information of the medical and pharmacal professions with regard to the drugs involved as is the case with the latest editions of the United States Pharmacopeia and the National Formulary. By state board ruling or by state law the availability of the resulting compilation of "official brochures" could be made a part of the standard prescription equipment of every pharmacy. 8. Additional copies of each "official brochure" would be made available for distribution to pharmacies so that any practitioner licensed to administer the drug described in an "official brochure" could obtain the desired information or a copy of the "official brochure" from a pharmacy as well as from the agency referred to in paragraph 3, or from the manufacturer of the drug. 9. It would be expected that accredited institutions engaged in preparing persons to practice any of the professions in the health science group would also be supplied with copies of the "official brochure." A unique feature of this proposal is the added benefit of having the "official brochure" information locally available to the practitioner through every pharmacy although supplies of the drug may not be at hand. Furthermore, the "official brochure" information could thereby be available to the practitioner even before the manufacturer begins the initial marketing and distribution of his product. If, as we trust, our suggestion meets with favor, we will be pleased to cooperate with the Food and Drug Administration, the United States Pharmacopeia, the National Formulary and the pharmaceutical industry in order to make this essential distribution of information on each product subject to the regulations effective. SECTION 1.106 (b) (4) This proposed regulation would require that full information accompany all labeling "that furnishes or purports to furnish information for use or which prescribes, recommends, or suggests a dosage" for use. Some modification is needed. It is our belief that journal advertisements and promotional literature sent directly to professional personnel should be clearly differentiated from "labeling." Because of inclusiveness usually associated with the term "labeling," we fear that without modification unreasonably long, involved, and extensive advertising copy could be required for otherwise simple advertisements. Under the proposed regulation, serious questions arise about possible significant curtailment in the degree of advertising in professional and scientific journals. We believe such advertising curtailment will adversely affect the continued publication of professional journals, the principle purpose of which is the dissemination of scientific, technical, and research information irrespective of products advertised. The sale of advertising space in professional journals helps in large measure to defray the costs of these essential publications. It is our opinion that the purposes intended by the proposed regulations would be achieved through an arrangement by which all advertisements would contain a precautionary statement referring the reader to the "official brochure" for additional necessary information and indicating its availability from (a) any pharmacy, (b) the non-governmental, non-profit agency approved for that purpose by the Food and Drug Administration, the United States Pharmacopeia Revision Committee, and the Committee on National Formulary, or (c) the manufacturer of the drug. By employing the mechanism we have just suggested, the purposes of the proposed regulations would be achieved without placing unreasonable burdens upon advertising copy and interfering with the publication of essential professional journals and the dissemination of scientific information. SECTION 1.106 (C) (3) AND (d) (3) Because our comments, opinions, and suggestions pertaining to these sections parallel those stated in relation to Section 1.106 (b) (3), in the interest of conserving your time, we will not repeat them. SECTION 1.106 (C) (4) AND (d) (4) Because our comments, opinions, and suggestions pertaining to these sections parallel those stated in relation to Section 1.106 (b) (4), in the interest of conserving your time, we will not repeat them. The American Pharmaceutical Association, its facilities, and its entire personnel, are ready to assist the Food and Drug Administration in effecting the objectives we have outlined. We also respectfully request that our Association be given the opportunity to participate in any future hearings which may be held to resolve differences of opinion over the proposed regulations which have been expressed by interested persons. Sincerely, WILLIAM S. APPLE, Secretary. t |