That is a very honest answer.

Dr. GOLDBERG. That is a part of the democratic framework.
Mr. LARRICK. That's right.

Dr. GOLDBERG. The Division of Pharmacology is outside the Bureau of Medicine, yet I understand it has an integral part in evaluating the test data that are being acted upon by the Bureau of Medicine. Do you find the arrangement satisfactory? Do you find that the Bureau of Medicine gets as much service and the kind of service that it would like from the Division of Pharmacology as if it had pharmacologists in its own shop?

Mr. LARRICK. I think we are going through some growing pains, Dr. Goldberg. I think the exchange between the Bureau of Medicine and the Division of Pharmacology has been very excellent. Mr. Rankin, who is my immediate assistant, has been spending half or more of his time trying to help with the growth of these groups during this period, which is both a formative as well as a trying period. I am convinced that the evolution of this process is going along rather well. Dr. GOLDBERG. Do you feel it is a satisfactory working relationship? Mr. LARRICK. I think there is a satisfactory working relationship. I think that there are many things that we can and will improve. Considering the tremendous extra burden we have had because of our bigger job, I think very splendid progress has been made, particularly with so many new people.

Mr. GRAY. Relevant to the last point made by Dr. Goldberg, I am interested in getting back to this decisionmaking process. I would like to know the extent to which the pharmacologist participates in the actual decision that is made with regard to the approval of an application.

I know that as a matter of course the pharmacologist is consulted by the medical officer in charge, and an opinion is rendered. But is the Bureau of Medicine then in position to ignore the opinion of the pharmacologist if they so choose, or are they more or less bound to abide by his opinion?

Mr. LARRICK. This answer is one at which I have arrived after extensive consultation and discussion with people in science in whom I have great confidence. The Bureau of Medicine gives full weight, credence, and consideration to all of the views of the Division of Pharmacology. But the Bureau of Medicine as an institutional group, not any one man, but as an institutional group, has reviewed all of this scientific data. In the final analysis the decision of whether or not the drug is suitable for administration to man is a medical decision. And the Medical Bureau, just as the physician in a hospital, is the one which makes that scientific decision.

The only recourse, where there is serious difference of opinion, would be to bring the question to the office of the Commissioner. Then perhaps we would go to outside experts for some more advice.

But basically the question of whether or not the drug should be administered to people is a decision to be made by persons who are licensed to treat people.

Mr. GRAY. Certainly the opinion of the pharmacologist based upon the animal data submitted is relevant to that decision.

Mr. LARRICK. Should have great weight and contributes very heavily to that decision. I am sure that it does.

Mr. GRAY. It perhaps would be helpful, Mr. Larrick, again from the standpoint of an understanding of this institutional decisionmaking process you have referred to, if you would explain exactly how the Bureau of Medicine is organized. I understand there was a reorganization about a year or a year and a half ago, which was, I suppose, in anticipation of perhaps the drug amendments of 1962. I think this might throw some light on this decisionmaking process. Mr. LARRICK. There is the Office of the Commissioner. Under this are the bureaus. One of the bureaus of the Food and Drug Administration is the Bureau of Medicine. And that Bureau of Medicine was subdivided at the time to which you refer into a Division of Medical Review, a Division of New Drugs, a Division of Research and Reference, and a Division of Veterinary Medicine.

Mr. GRAY. Could you explain what each of these divisions is supposed to do in arriving at these decisions?

Mr. LARRICK. The Division of Medical Review basically and originally was set up to deal with the problems that arise from old drugs. They review, for example, the great mass of factory inspections, samples that come in from the field, proprietary remedies, old prescription drugs, and the whole gamut of medicines that come into headquarters with the question or recommendation from the field that some criminal prosecution, injunction, or seizure be undertaken. Originally the latter work was their primary function.

I think the title "Division of New Drugs" is in itself pretty explanatory. They deal, in this reorganization, with new antibiotic drugs, they deal with the status of new drugs. And because the Kefauver-Harris bill broke new drugs down into the investigative stage and the clinical use stage, we have a group that deals with the drug in its investigational drug stage.

We have another group

Mr. GRAY. Was that not a separate division?

Mr. LARRICK. No. Those are units of the New Drug Division; not a separate divison.

You asked me to break down the Division of New Drugs, and that is what I was doing. Let me start again.

There is a Division of Medical Review. I explained what it does. The Division of New Drugs handles new drugs and investigational drugs.

There is a Division of Research and Reference. That is the group that deals with the reports we get in from all the veterans hospitals, Public Health Service hospitals, and private hospitals. They perform the library function for the whole Bureau of Medicine, but they do much more than that because they comb the literature of the world to hunt for these adverse drug reactions that we have talked so much about.

There is, finally, a Division of Veterinary Medicine, and the title of that division is self-explanatory.

Mr. GRAY. Let's go back to the Division of New Drugs and go into the reorganization of the Division of New Drugs and the various branches that have been established and their functions.

Mr. LARRICK. There is the Director and the Assistant Director, who superintend the entire operation in the new drug area. Under

them is the Antibiotic Drug Branch. That I believe is self-explanatory. They had a big new job handed to them because 21 new antibiotics which had not previously been subject to certification were put under certification by the Kefauver-Harris bill, and they had to pass on the question of efficacy which they did not have to pass on previously.

The New Drug Status Branch has a number of responsibilities, the principal function of which is to produce uniformity in the Food and Drug Administration about what is and what is not a new drug. We are dealing there with a statutory definition using words of craft. And the industry writes in with great frequency and says: I have a drug to be composed of this, this, and this, and it will have this claim on it, and so on; is it a new drug? We set up this branch to pass on that question and try to bring about consistency in our answers.

The Investigational Drug Branch is a new group with which you are very familiar. They deal with drugs at the time that they reach the clinical testing stage.

Controls Evaluation Branch: Each new drug application has a section in it that deals with the controls. If it is a spinal anesthetic, you have to have a control there that will run bacteriological tests to make sure that you are not shooting living bacteria into the spinal column. You have to have a very specialized control that will deal with pyrogens. Those are substances that cause an elevation in temperature. You have to have very, very meticulous chemical controls. The right methods of analysis must be used. The right size sample must be taken. Drug Control Evaluation is a highly skilled, specialized branch of pharmaceutical chemistry. We have a special group of people who are not only trained in this branch of pharmaceutical chemistry but who have had vast experience inspecting pharmaceutical houses and know that aspect of the operation as well. They pass on that phase of the application.

We have a Surveillance Branch which is responsible for keeping track of the new drug after it is on the market. That task is blowing up like a balloon with surveillance dealing not only with the drugs that we are currently passing under the new regulation we told you about, but going back and picking up this whole problem from 1938 to date, taking on all the brochures that are put out from all the pharmaceutical houses in the country and moving on into the advertising and whatnot.

I would anticipate that because of these new jobs we will have some further reorganization to do and some further breaking down as the workload, size, and character begins to emerge.

The Medical Evaluation Branch, which is the final unit in the New Drug Division, I think is self-explanatory. It has to do with the evaluation of the therapeutic capabilities of the drug in relation to the claims that are made.

Would you wish to have a very simple chart that says this for the record?

Mr. FOUNTAIN. If there is no objection, that will be included in the record.

(The chart referred to follows:)

1 Dr. Joseph F. Sadusk, Jr., became Medical Director on Apr. 1, 1964, and Dr. Smith returned to his position as Director of the New Drug Division.

Mr. GRAY. This Surveillance Branch you mentioned appears to have a pretty big job cut out for it. How many people do you have in that Surveillance Branch?

Mr. RANKIN. We have approximately 10 people in that Branch, as I recall. Is that correct?

Dr. SMITH. Approximately.

Mr. LARRICK. I do want to make clear that we are currently restudying the relationship between this Branch and the Division of Medical Review. As the old drugs disappear and more and more of the drugs are in the new drug area, there probably will be some adjustments to make.

Mr. GRAY. I don't want to dwell too long on this, Mr. Larrick.

A couple of more points: You mentioned that you take these pharmacologists, physicians, chemists, and so on, and you give them special training which equips them to make recommendations concerning the safety of drugs for the good of society and so on.

What kind of special training do you give these people?

Mr. LARRICK. I think Dr. Ralph Smith can comment on the special training.

Dr. SMITH. I can, Mr. Gray. When a new man comes in, he is given close supervision by his supervisors or the men who have been carrying on the work over the past few years. He is gradually given more and more responsibility and receives his training more or less by the preceptor system.

Of course there are certain courses to which he is exposed that are given to large numbers of new Food and Drug employees which make them familiar with the Food and Drug procedures, Food and Drug laws, and so forth.

But the important part of his training is on a preceptor basis. Mr. GRAY. I am sure that all of your medical officers are M.D.'s. Dr. SMITH. That is right.

Mr. GRAY. What portion of them are specialists as opposed to general practitioners?

Dr. SMITH. I am sorry I don't have the absolute numbers. A considerable number are certified by a specialty board or do have a specialty.

Mr. LARRICK. We would be happy to supply that for the record and complete the record.

Dr. SMITH. There are some in internal medicine, some in obstetrics, and gynocology, and so forth.

Mr. FOUNTAIN. It would be interesting to have that for the record. (The information referred to follows:)

You asked that we supply the percentage of our medical officers who are specialists. We now have a total of 85 medical officers in the Bureau of Medicine but this question appears to relate specifically to the Division of New Drugs so we have developed statistics reflecting the percentage of specialists in that unit:

Division of New Drugs (May 4, 1964)

Total medical officers____.

51

Medical officers who are board certified or board eligible specialists-----Medical officers whose specialty is pharmacology (for which there is no board certification)_

39

4

Total specialists--

43

Percentage of medical officers who are specialists-.

84