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routinely request from the drug firms making the application evidence of negative reports, whether published or unpublished?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 a 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.

Mr. PLAPINGER. Incidentally, how many people do you have in your New-Drug Branch? How many professionals?

Dr. HOLLAND. We have positions for 8 physicians and 9 chemists. Unfortunately, even though those are budgeted positions, we are unable to fill a significant portion of those jobs.

Mr. PLAPINGER. What do you mean by a significant portion?

Dr. HOLLAND. Well, in the chemist field we are more fortuante. We now have 8 out of 9 chemists on the job today. When it comes to physicians, however-and we are talking about a highly trained specialized type of physician-one who has had considerable experience in one of the basic sciences, preferably pharmacology, biochemistry, or physiology, in addition to his medical training, we have 3 full-time physicians out of 8. Because we were running so far behind, because we have so much difficulty in recruiting this kind of personnel, we have had to resort to employment of some half-time physicians. We went to some friends of ours at George Washington University and told them of our plight and they were able to select for us some young men who were just finishing either 3, 4, or 5 years of residency training, able and competent people, who were slated to go into private practice, but who until their practice got well established would be able to devote half time to processing new drug applications for us. We now have 4 such people with us, which, in effect, is 2 more full-time people. So out of our 8 budgeted positions for NewDrug Division, we have but 5 filled and 2 of those represent 4 half-time

men.

(See appendix, exhibit 13, p. 226, for additional statement of Dr. Holland.)

Mr. PLAPINGER. Now, you referred to the difficulty of getting people to fill these positions. Is that because of the unique background or experience that is required for the position or are there also other factors involved in your inability to recruit personnel?

Dr. HOLLAND. I think it is both. Certainly the kind of background that we would prefer and that we believe the public is entitled to and in a sense the industry is entitled to if these men are to sit in judgment on the Nation's supply of new drugs demands people of the highest caliber, ability, and training.

In addition to that, we, of course, are beset with the usual difficulties of Government salary scales, and particularly is this acute with competent physicians.

Mr. PLAPINGER. What is the salary scale for your eight physicians? Dr. HOLLAND. The Chief of the Branch is a GS-15, and the other members of the Branch are 14's or lower.

Mr. PLAPINGER. You have mentioned that you have difficulty in obtaining people at these salary levels. Do you have difficulty in retaining them, also? What is the turnover in the New Drug Branch?

Dr. HOLLAND. I can't give you an exact figure over a prolonged period of time, but I can give you some specific instances. Just short of a year ago we lost one of our most valuable and experienced people, a man mentioned in prior testimony by Dr. Kline. That was Dr. Ernest Q. King. Dr. King left us and transferred to the Veterans' Administration, who offered him something close to $3,000 more a year, which in terms of retirement and things that he wanted to do in life, got to be pretty important. In addition to his actual increased income on an annual basis, this also represented some

thing in the neighborhood of $100 a month additional in retirement for himself and his family. One certainly cannot-stand in a man's way under those circumstances. You should almost urge him to take the job. Without urging he did.

Mr. PLAPINGER. What was Dr. King's position with the Branch? Dr. HOLLAND. Dr. King was, other than Dr. Smith, the senior member of the New Drug Branch. He reported to Dr. Smith, as Chief of the Branch.

Mr. PLAPINGER. It seems to me that when Commissioner Larrick was up here last year, he was accompanied by another gentleman who was Deputy Director.

Dr. HOLLAND. That was Dr. Farrago, my assistant at the time. Dr. Farrago has since returned to the Abbott Laboratories and back to the pharmaceutical industry in Chicago. That job is not yet filled.

Mr. PLAPINGER. That job has been vacant since when, Doctor? Dr. HOLLAND. This job has been vacant since last August. We made a selection of an individual, however, and pending final approval, I hope to be able to announce it shortly.

Mr. PLAPINGER. Would you rather not discuss whether that would be from within the agency or from outside of the agency?

Dr. HOLLAND. I think for the moment, sir, I would appreciate the privilge of not answering that, if I may.

Mr. PLAPINGER. The Government Operations Committee gives you the equivalent of the fifth amendment.

Dr. HOLLAND. May I take it with immunity?

Mr. PLAPINGER. Even with impunity.

I haven't anything further.

Mr. BLATNIK. Mr. Meader.

Mr. MEADER. Dr. Holland, I am not clear where the responsibility of the Food and Drug Administration ends and the responsibility of the Federal Trade Commission begins with respect to preventing misrepresentation by pharmaceutical houses to the medical profession with respect to ethical drugs. Could you mark out that line of jurisdiction, if there is one, or if there is overlapping, would you describe the nature of it?

Dr. HOLLAND. I will attempt, sir, to perhaps a little further delineate the area that I believe falls directly within the scope of the Food and Drug Administration responsibility, but I don't feel that I am quite competent to comment on what the Federal Trade Commission's responsibilities are, as such.

In the field of new drugs, which you understand is only part of the prescription drug field; there are many drugs that are on prescription which are no longer considered as new drugs, but for reasons of public safety are restricted to dispensing by prescription. New drugs, however, as defined in the law and the regulations

Mr. MEADER. Before you leave that, do we call those old drugs? Dr. HOLLAND. We loosely call them old drugs. I think officially they are known as nonnew drugs.

Mr. Meader. Does the Food and Drug Admiinstration have any responsibility whatever with respect to the so-called old drugs? Dr. HOLLAND. Oh, yes; in terms of prescription dispensing. Mr. MEADER. I mean with respect to the advertising.

Dr. HOLLAND. If the advertising is distributed in such a way that it may be considered labeling; in other words, if it is written, printed

or graphic material which accompanies the product, in those instances and there have been some court cases which would perhaps permit this kind of a technical interpretation, though we have not been enthusiastic in enforcing it from that point of view-in those instances where the written, printed, or graphic material finally arrives at a common point, where in the physician's possession he also has the drug, plus this descriptive material, then it may be considered as labeling.

Mr. MEADER. Then is there any difference between the new and old drugs with respect to the scope of jurisdiction of the Food and Drug Administration?

Dr. HOLLAND. In this respect, sir, that with the new drugs, as they are processed through this new drug procedure, members of our staff have not only the opportunity but the responsibility of going over the labeling information, all of the labeling information, including the official brochure, in the greatest detail, and on this score the burden of proof in the new drug procedure rests with the applicant. He must demonstrate safety to our satisfaction, whereas this is not true with a prescription drug which is no longer considered to be a new drug. If we chose to then take action on an old drug, the burden of proof would be on the Government, and this is quite another matter in the courtroom.

Mr. MEADER. It is merely the procedure for enforcement, rather than the scope of your authority, then, which differs with respect to new and old drugs?

Dr. HOLLAND. Yes, sir.

Mr. MEADER. Proceed, then, with the relationship between your responsibility and that of the Federal Trade Commission.

Dr. HOLLAND. There are some circumstances where direct mail on new drugs might be considered as labeling. We have not set out to make any cases of this nature because to date we have had what, in my judgment, is a satisfactory degree-not a perfect degree, but a satisfactory degree of voluntary compliance on the part of the responsible segments of industry in correcting or changing or modifying questionable advertising practices in those instances where they came to our attention, and we in turn called them to their attention.

It is conceivable that each journal ad, under some circumstances, could be identified as labeling. Again we have not undertaken to make such a tenuous case, but, rather, have preferred the approach of going directly to the firm where unacceptable statements were involved. By and large, however, due to the construction of the law which enables this new drug procedure, and due to our limited staff and facilities, as well, and I think perhaps to some recognition of the responsibility of the pharmaceutical industry in this country to do some of its own policing and to assume the responsibility for statements made in the names of their own firms and in the names of their own products, we have not been anxious to get into this field on a legal basis, in terms of bringing actions against firms for violations.

Our first action which we would bring, if this were a new drug, from a legal point of view, would be, as I have indicated, to offer the firm an opportunity for formal hearing to show cause why their application should not be suspended. As long as a drug is a new drug, this is a very potent tool in the hands of the Government. In effect, it is a license, and with suspension of a license, they are in great difficulty. We have