Mr. MEADER. Are you aware of any activity on the part of the Federal Trade Commission to stop such abuses?

Dr. DOWLING. No, sir; I am not.

Mr. MEADER. You are aware that they do have a responsibility under the statute in this field?

Dr. DOWLING. I am.

Mr. MEADER. But so far as you know, the Federal Trades Commission has taken no action, at least that has come to your attention, to police misleading advertising to physicians of ethical drugs? Dr. DOWLING. As far as I know.

Mr. BLATNIK. Any further questions?

Mr. MEADER. I would like to ask one more question. In your recommendations, it seems to me you start out by recommending, first, the industry exercise self-restraint; second, perhaps a code of ethics of some kind on advertising of ethical drugs be established, either by the industry or perhaps by some governmental agency; third, that the industry be exempted from antitrust laws so that it can suppress any misleading advertising by individual drug companies; and then as a last resort that the Government police this advertising, which, of course, already is written into the statute. I mean the Federal Trade Commission has that authority. But you believe that that authority should be exercised not by the Federal Trade Commission, but by the Food and Drug Administration. Am I correctly summarizing your recommendations?

Dr. DOWLING. Yes.

Mr. MEADER. That is all.

Mr. BLATNIK. Thank you very much, Dr. Dowling, for your very helpful and enlightening statement.

Our next witness is Dr. Albert H. Holland, Jr., Head, Medical Department, Food and Drug Administration.

Good morning, Doctor. We welcome you to the committee and appreciate your assistance here in previous conferences in this field. Doctor, you have a prepared statement?

Dr. HOLLAND. I do.

Mr. BLATNIK. Do you have any preliminary statement you wish to make or shall we proceed with the reading of this?

Dr. HOLLAND. I will proceed with this.

Mr. MEADER. Why don't we have a little biographical sketch?

Mr. BLATNIK. The doctor is well known and has testified before. Make a brief statement, Doctor, how long you have been in your present capacity, and submit any additional material for the record. STATEMENT OF DR. ALBERT H. HOLLAND, JR., MEDICAL DIRECTOR OF THE FOOD AND DRUG ADMINISTRATION

Dr. HOLLAND. I joined the Food and Drug Administration as its Medical Director March 31, 1954, and served in that capacity to date. I received my medical education at New York University College of Medicine at New York City and my hospital training in New York Post-Graduate Hospital and Medical School, and Memorial Hospital for Cancer and Allied Diseases. I was then inducted into the service and assigned to the Manhattan Engineering District in Oak Ridge, Tenn., where I stayed on in a civilian capacity with the Atomic Energy Commission for a total of over 4 years.

I then left the Atomic Energy Commission and joined the Armour Laboratories in the pharmaceutical industry in Chicago, and was with that firm for 4 years as its medical director before coming to the Food and Drug Administration.

Mr. BLATNIK. Doctor, please proceed with the reading of your

statement.

Dr. HOLLAND. Thank you.

Mr. Chairman and members of the committee, my name is Dr. Albert H. Holland, Jr. I am the Medical Director of the Bureau of Medicine, Food and Drug Administration, Department of Health, Education, and Wefare.

The Food and Drug Administration is charged with the sobering responsibility of administering and enforcing the provisions of the Federal Food, Drug, and Cosmetic Act and the general regulations pertaining thereto. This legislation was originally enacted by the Congress in 1906 and was comprehensively revised in 1938. It provides broad and essential protection to the American people, to the consumer, with respect to foods, drugs, devices, and cosmetics. Concurrently it tends to safeguard the honest manufacturers and distributors from some of the abuses and inroads of the dishonest and the irresponsible. Of signal import is the continuing protection the statute affords to both physician and patient alike in the field of drugs. Both have justly come to rely on the safety and reliability, as well as in most instances, the efficacy of our American drug supply. Without doubt one of the most significant provisions of the law is that pertaining to new drugs; that is, section 505. The group of drugs currently of interest to this subcommittee, the so-called tranquilizers, are considered to be new drugs under the law and are, therefore, subject to its special requirements. To the best of my knowledge, all of the new tranquilizers now distributed in interstate commerce for prescription use have been shown to be safe for use under the conditions suggested in their labeling, through compliance with these new-drug requirements.

Specifically, section 505 provides that no person shall introduce or deliver for introduction into interstate commerce any new drug unless an application is effective with respect to such drug. In order to obtain an effective new-drug application the applicant must furnish the Secretary (1) full reports of investigations which have been made to show whether or not the drug is safe for use; (2) a full list of the articles used as components of such drugs; (3) a full statement of the composition of such drugs; (4) a full description of the methods used in and the facilities and controls used for the manufacture, processing, and packing of such drug; (5) such samples of the drug and its components as the Secretary may require; and (6) specimens of the labeling proposed to be used for such drug. This information in proper form constitutes a new-drug application which any person has the right to submit to the Secretary for review. The Food and Drug Administration acting for the Secretary must take appropriate action and respond within 60 days or the application becomes automatically effective as provided for in the statute.

Apart from the consideration of inherent safety of the drug under the proposed conditions of use, the labeling assumes primary importance to the physician and to his patient. It, obviously, is inseparably linked to safety for it is only through truthful, informative

labeling that the physician becomes aware of the usefulness, the limitations, and the potential side effects and contraindications to its use. Labeling is defined in the act as any printed, written, or graphic material which accompanies the product. This includes the information on the actual label of the immediate container; the information on the carton, if one is used; perhaps of greatest import, the information contained in a package insert or other official brochure referred to on the label as literature available to physicians on request; and generally any promotional literature which reaches the physician or consumer in possession of the drug. For new drugs, the labeling on the retail package and the official brochure are subject to detailed review, sometimes sentence by sentence and even word by word, by our New Drug Branch. I should like to emphasize here that while administrative and legal considerations are inevitably involved in this work, primarily we are dealing in a highly complex area of medical science and technology, therefore, our relationship with a new drug applicant is preponderantly at the scientific level.

It is the policy of the Food and Drug Administration, publicly expressed by both Commissioner George P. Larrick and myself, that it is the manufacturer's or distributor's responsibility to assure himself that his promotional and educational literature to physicians, so-called direct mail, conforms to and stays within the terms and limitations of his effective new-drug application. The official brochure of the product establishes an unmistakably clear pattern for the firm to follow. Of course any new-drug application can always be amended to extend its scope when and as additional and acceptable scientific work justifies it. At that time the official brochure must also be revised to reflect the changes and to convey the information to the medical profession.

This statute, the Federal Food, Drug, and Cosmetic Act, is a permissive statute, but does provide penalties and remedies for violators. Only when an individual or firm transgresses the requirements of the law does it become necessary to resort to various means of enforcement. The same principle applies to new drug literature. We do not and cannot require the prior approval or review of all medical literature to physicians about new drugs. We do, however, make every attempt to fairly enforce the provisions of the new drug section of the law, including those relating to professional literature. If, as occasionally happens, a firm makes statements which exceed the terms of their new-drug application, then we immediately seek to correct the situation. This can be accomplished in several ways. First, we seek to achieve a maximum degree of voluntary compliance as recommended by the Citizens Advisory Committee of 1955 by inviting the firm's attention to the statements in question and requesting the firm to present supporting data as a supplemental application or to immediately delete the offensive statements. Second, in instances of flagrant disregard for the requirements of the law or the truth, the firm is given the opportunity for formal hearing to show cause why their new-drug application should not be suspended, which would, in effect, prohibit distribution and sale of the product. Finally, when there is a clear and imminent danger to the public health as a result of violative acts, the administration can immediately proceed with multiple seizures of the product, criminal prosecution, and if indicated, issue appropriate public warning. It should be noted, how

ever, this is not a legal limitation nor, indeed, a partial one in all cases. This, Mr. Chairman, constitutes a brief presentation of the authority and control of new drugs as provided by law and regulations under the Federal Food, Drug, and Cosmetic Act. I shall be happy to attempt to answer any questions which you or the members of the committee may wish to ask.

Mr. BLATNIK. Thank you, Dr. Holland.

Mr. Plapinger.

Mr. PLAPINGER. Dr. Holland, does the FDA, on these new drug applications, routinely request from the drug firms making the application evidence of negative reports, whether published or unpublished?

Dr. HOLLAND. Yes, and the law provides that the firm must present full reports. They do not have the privilege of selection and presenting only those which are favorable and deleting those which are unfavorable.

Mr. PLAPINGER. Now in connection with the promotion of tranquilizers, are you aware of or have there been excesses in the promotional literature?

Dr. HOLLAND. There are a few instances, Mr. Plapinger, where we have taken action where we felt that statements were being made by the firm which exceeded the terms or provisions of their new-drug application.

Mr. PLAPINGER. Can you generally comment on the type of excess that has been indulged in?

Dr. HOLLAND. Yes. I should like to point out first, as I said in my testimony, we do not and cannot review or grant prior approval to all of the direct mail to physicians in this country. However, when we find a piece which we believe to be in violation of a new-drug application, either because we perused this material ourselves or have it directed to our attention, we then take appropriate action. One instance which I can recall, a statement was made by a firm which we did not believe was justified for any medication. When this advertising material was presented to me and members of my staff reviewed it, we immediately wrote that firm. The letter went out the same day. The medical director of the firm responded by telephone call the next morning and, as I recall it now, was in my office on the following day.

We discussed the subject, gave him our views, with which he was in general agreement. He was able to go back to his firm and stop, as of that time, any future use of the statement.

Mr. PLAPINGER. Meanwhile this was material that had already been forwarded to the profession?

Dr. HOLLAND. Yes, it had gone out in at least one mailing, I know of, and had been included in some journal advertising.

Mr. PLAPINGER. Was there any retraction or just a revision of the advertising that was requested?

Dr. HOLLAND. In this instance we did not require a retraction. In another instance with which I am familiar, a firm was quite blatant and, in fact, in our judgment misleading, as well, in their claims, which far exceeded the terms of their effective application. In that instance we thought that the violation was serious enough to serve them with notice for a formal hearing to show cause why their application should not be suspended. They immediately responded be

cause a suspended application puts the firm out of interstate commerce, unless it chooses to do so in complete violation of the law. They responded immediately. We had several meetings during a period of a week or 10 days, with representatives of the firm, the firm's counsel, and members of our staff and our general counsel's office. In that instance we caused this firm to write letter to about 150,000 physicians, to every physician that had ever been on their mailing list, on any of the mailing lists they had ever used, saying it had been called to their attention by the Food and Drug Administration that the claims that were made were not in accord with their effective new-drug application, and that they, therefore, were enclosing a revised official brochure which set forth the only legitimate claims which were recognized at that time under the new-drug procedure.

Mr. PLAPINGER. This type of excess, is this peculiar to tranquilizers or have you had any other instances involving other drugs?

Dr. HOLLAND. Yes, we have, Counsel, primarily in instances where statements were made in advertising material for which we felt that there was either questionable or no support. I must say that in my short tenure with the Administration, I have no knowledge or I have yet to come across an instance when such a problem was called to the attention of the firm that the firm did not change voluntarily and immediately.

Mr. PLAPINGER. There has been some previous testimony-I believe Dr. Dowling made some allusion to the rash of new drugs on the market. How has this reflected itself in your workload? It is your office that processes the new-drug applications?

Dr. HOLLAND. Yes, it is, sir. In my office, our New-Drug Branch, of which Dr. Ralph Smith is the Chief, the initial new-drug applications, original new-drug applications, as we call them, processed in fiscal year 1957 was 530; in 1956, it was 520; in 1955, it was 606. If I may jump back then to 1950, there were 618; in 1945, there were 213. In addition to the processing of these original new-drug applications, we also are charged with the responsibility of processing supplements or amendments to applications which are in effect. Such amendments may provide for a new dosage form or a different dosage level or a different medical indication for use.

In 1957 we processed some 3,322 supplements; in 1956, there were 4,613; in 1955, there were 4,552; and in 1954 there were 1,197.

Mr. PLAPINGER. You mentioned in your statement that unless action is taken on this new-drug application within 60 days the application becomes automatically effective.

Dr. HOLLAND. Yes.

Mr. PLAPINGER. Are you able to process this volume of work within the statutory time limit?

Dr. HOLLAND. With very few exceptions, Mr. Plapinger. Our staff has processed this tremendous load within the statutory time provided, but only at the cost of great personal sacrifice on their part. There was a time not too long ago in the Bureau of Medicine when the group in our New-Drug Branch was spending something in the neighborhood of a hundred hours of unpaid overtime a week in order to keep ahead of this workload.