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.

it

Dr. HOLLAND. If the advertising is distributed in such a way that 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

never had to resort to this in my experience because as soon as a firm is confronted with such a formal notice, they immediately see the handwriting on the wall and with good legal advice, they are quite willing indeed to mend their ways.

We do not review all of the new drug literature and advertising and journal ads. We do review the basic piece which is referred to as the official brochure. In that document is set forth all of the essential information which the physician needs at least initially to safely, and we hope effectively, use the drug.

This is a crystallization, if you will, of the views of the many investigators who have worked with this drug and whose data is submitted as part of that firm's new drug application. And while I regret that I cannot submit it as a matter for the record, I would like to invite your attention to a new drug application, some eight volumes of this, which we brought along for exhibit purposes. This represents one new-drug application. It happens to be on one of the tranquilizers, which has been under discussion before this committee on occasion. This is supporting data which the firm furnished the Government and which was reviewed by our staff before this drug was marketed. Now the reports from investigators in there will differ because investigators differ. Their experiences will differ. They have used different dose levels; they have selected their patients differently. A whole variety, a whole host of factors come into play.

The official brochure attempts to crystallize the essential data from the experience of the expert investigators who have worked with the product and reduced to writing in an acceptable form to us, such that it is available either as a package insert to accompany each bottle or package of the drug or must be available to any physician who writes in for literature on request. They may send him other material, other information, but this official brochure must be furnished along with anything else. It is mandatory that this information be available to physicians in response to literature available upon request.

Mr. MEADER. You don't have any similar body of information with respect to old drugs, as I understand it?

Dr. HOLLAND. No, sir. Those that were exempted from the new drug procedure under the grandfather clause of the 1938 act, we do not have this kind of information available in such an integrated form. Of course, a wealth of information is available in the medical literature.

Mr. MEADER. Is it only those grandfather drugs that are regarded as old drugs? Does a new drug application continue indefinitely or is there a period when a new drug becomes an old drug?

Dr. HOLLAND. There is such a time when we de-new drug-a new drug, if you will. This is not a very well defined period or interval, Mr. Meader, but, rather, is tied to the basic definition of a new drug in the law, and a new drug is defined as any drug, the safety of which is not generally recognized by experts qualified by scientific experience and training to make such judgment as being generally safe for use.

Now, when a drug has been in commerce, been widely used by the medical profession and an abundance of papers appear about its use in the medical literature and the profession generally and, in particular, the experts in the profession say, "Oh, yes, this is now a

standard drug," this is a time at which we will entertain at least a request to take this drug off the new-drug list.

Now, at long as it remains a new drug, any firms that market the drug in interstate commerce must have an effective application on file with the Secretary. As soon as the drug is no longer declared to be a new drug, then any firm in the drug business, in the legitimate drug business, can pick up this drug-other than for patent problems can pick up this drug and use it in any usual dosage form or in many combinations, or what have you, at will. The Government effectively loses much of its control of drugs when they are taken off the new-drug status.

Mr. MEADER. You spoke about the possibility of your exercising policing powers with respect to direct-mail advertising. This may be a silly question, but I think it has been suggested by previous witnesses, that sometimes even with respect to ethical drugs, other forms of advertising-radio and television-are used to induce the patient to request the physician to prescribe this drug. Do you bother at all with any representations made through television and radio or any other way that representations may be made?

Dr. HOLLAND. I don't believe that we have found this to be a very significant problem to date. This is a problem of general education, in my judgment. A great deal has appeared in the lay medical press which is very worthwhile, indeed. I recall very well, despite the chagrin of some of my medical colleagues, what I think was, nevertheless, a very beneficial effect of an article which appeared in the Reader's Digest back in 1944 teaching a woman or essentially pointing out some of the techniques of self-breast examination. This article brought many women with tumors of the breast to physicians' offices that otherwise would have perhaps delayed considerably longer in getting there.

We would not, of course, condone any high-pressured or intense lay advertising campaign, something along the lines of "Go see your doctor and get this tranquilizer," or "Go see your doctor and get some penicillin," or "Go see your doctor and get some cortisone." I think the firm, of course, would be risking their own reputation very considerably, because they would immediately be going beyond their ethical channels of distribution and promotion. They would no longer be in the ethical field then; they would be resorting to proprietary advertising.

Mr. MEADER. You would have authority through your various sanctions to stop that kind of thing?

Dr. HOLLAND. If this were a new drug, I believe we would; certainly, sir.

Mr. MEADER. And if it was an old drug, you would have authority, but your sanctions would not be quite as effective; is that correct?

Dr. HOLLAND. I think that is right; and then, of course, we have some friends in the Federal Trade Commission who would be very much interested in this situation, too.

Mr. MEADER. That gets down to my next question. I am gathering the impression that there isn't much in the field of representation of ethical drugs that you don't have authority to police. Is there a limit to your jurisdiction? Is there a place where the Federal Trade Commission takes over and you have no authority, or do you both have authority in the same field?