(2) Because of its toxicity or other potentiality for harmful effect, or the method of its use, or the collateral measures necessary to its use, it is not generally recognized among experts qualified by scientific training and experience to evaluate its safety, as safe and efficacious for use except by or under the supervision of a practitioner licensed by law.

The language we propose in the stead of that of the bill is taken from the present regulations under section 502 (f) of the Food, Drug, and Cosmetic Act. It would create a positive legislative standard for determining which drugs must be sold only upon prescription and which drugs when prescribed can only be refilled with additional authority from the prescriber.

The standard is similar to that proposed by H. R. 3298, but instead of granting authority to the Food and Drug Administration to determine the facts and create a list of drugs, this change would leave the question properly open to ultimate determination by courts. Some of the examples brought before this committee of similar products of different manufacturers, one bearing a "Caution" legend and the other adequate directions, result from honest differences of opinion among real experts in the field. We are not opposed to a resolution of these differences, but we feel an impartial court should make the decision and make it without the prejudice of prior administrative hearings and determinations of fact. Administrator Ewing with delightful candor told this committee that as now drafted it is conceivable that some future Administrator might decide to put aspirin on the list of drugs for limited refill.

I would like to interpolate here and use one illustration from an administrative ruling in 1945 by the Food and Drug Administration, to the effect that no eardrop preparations, no matter how harmless and innocuous they might be, could be sold except on prescription, because it was possible that they would mask the symptoms of a serious condition; that an earache might be a symptom of a mastoid condition.

Now, you can see how that philosophy can be extended on down very quickly to aspirin. Aspirin is a pain killer, and as such it may well mask the symptoms of some serious disease. And yet, unless we are going to live in front of an X-ray machine and in a hospital, we have got to be a little bit more courageous about some of these symptoms. I am not suggesting that any serious symptoms should be overlooked, but there certainly is a large field for proper self-medication.

As we visualize it, the committee thus has two routes by which it can separate those drugs that are dangerous and should be limited in distribution, from the harmless ones which can be sold across the counter or refilled at will by the druggist.

The one approach-that of the bill as now drafted-would give vast powers to the Food and Drug Administration, involve lengthy hearings and appeals. The other the one we propose as an alternate would set the same standard. The responsibility for meeting this standard, however, would be placed where it belongs, on the manufacturer. The druggist would need only follow the simple guide of the labels. And you will remember that those exhibits that you have had placed before you consist of two classes of drugs: those that say "Caution-To be dispensed only by or on the prescription of a physician," and the others, which have directions. Each witness, as he went through them, was clear in his mind. He understands

exactly what he can do with those. Where it says "Caution-To be dispensed only by or on the prescription of a physician," that can be sold only upon a prescription, and the other can be sold freely across the counter. The druggist will have a complete guide. He will have his list upon the shelves of his drug store. That list will be constantly up to date because drugs are constantly changing, and you can only depend upon the label. A list would be very stale a week after it has been issued.

If this provision is adopted, henceforth any druggist can tell instantly by a glance at his drug shelves whether the product bears the restrictive clause. If it does, he may not refill a prescription for this drug without authority from the doctor. If the product does not bear such restrictive legend, the druggist is at liberty to refill prescriptions for it at will. Such a guidepost is simple, positive, and constantly up to date.

We submit that when an aggravating problem such as this prescription-refill problem can be solved in a fashion acceptable to most elements of pharmacy, that this course should be followed over a method that has the vigorous opposition of the majority of pharmacists.

The third change that we propose is to delete lines 15 through 25 on page 3, and lines 1 through 20 on page 4. There is a typographical error in our prepared statement. It reads "1 through 20," and it should read "1 through 14 on page 4."

The material stricken here is that covering the requirements for hearings and court review. If Congress enacts a standard for separation of dangerous from harmless drugs, there will be no necessity for costly hearings, determinations of facts, and appeals. It will also dispose of the question of the propriety of a review, de novo, in the circuit court of appeals.

After this brief and, we hope, clear statement of the views of the American Drug Manufacturers Association, we would like to discuss one or two phases of the hearings about which there appears to be some uncertainty.

Mr. Warnack, Mr. Waller, and again Commissioner Larrick, brought in numerous exhibits where different manufacturers had labeled the same drug, one with a "caution" legend and the other with directions for over-the-counter sale. Each witness said this showed the high state of confusion in retail drug circles. Not one of the witnesses, however, was at all in doubt as to how a druggist is required to sell such products.

May I use the illustration of looking down a street at traffic lights. You see a red one, and you see two green ones, and you see another red one, and you see another red one, and another green one. You might say that is confusing, and yet we know exactly what we must do at each corner. Where it is green we can go, and where it is red we have to stop; and the same thing is true with these labels. They are not confusing at all as to what the druggist may do in selling them. He is horribly confused, and the purpose of this bill is to get rid of that confusion, on what he can refill. There is the confusion, and it is real confusion. He certainly needs the relief that this committee should give him, because he doesn't know whether he can refill anything. The public shouldn't be deprived of proper medicines because of that confusion in the law.

If the drug has a caution legend on it, the druggist knows he may not lawfully sell it without a prescription. So far, 112 druggists have been convicted because they willfully violated the law and sold prescription drugs across the counter.

Now, that really is a tribute to the druggists rather than a condemnation of them; when you consider there are 50,000 druggists in the country, and only 112 of them have been violating the law or been convicted of it, that is a pretty small number. You are not going to have perfect compliance with the law at any time, and of that we are all very much aware.

Far from being confusing, the situation is crystal clear. What is confused is not what drugs can be sold without prescription, but what prescription can be refilled without first getting the physician's approval. The examples shown this committee do not bear upon this problem at all. If H. R. 3298 is adopted, with the revisions we propose, it will clarify the doubt as to refillability of prescriptions.

Some witnesses, in particular Mr. Warnack and Mr. Waller, stated flatly that caution-legend items are on some relatively harmless drugs because the manufacturer is trying to escape his responsibility by making such statements. They are talking about the law and the regulations as they were prior to the change in the regulations in 1946. From 1939 to 1946, the regulations of the Food, Drug, and Cosmetic Act allowed a manufacturer to choose, without any rules other than his own choice, whether he wished to sell his drugs across the counter or whether he wished to put a prescription legend on them and confine them to a physician's use. În 1946 the regulations were changed. From that time to date there are only two classes of drugs. Under the law, if adequate regulations can be written for a drug for lay use, the law says that they must be written, and it it misbranded if you don't write them. If, on the other hand, its toxic potentialities are such that it can only safely and efficaciously be administered under a physician's supervision, then it must bear the caution legend and it must be sold only on prescription; and under the standard we propose here, that type of prescription would require the physician's authorization before it could be refilled.

The exhibits that were brought in had a number of drugs that are slightly confusing unless you understand how the chemical manufacturer operates. These are preparations, two of them put out by Merck & Co. and two put out by Mallinckrodt. Both are large chemical manufacturers. They make raw materials. They sell them mostly to manufacturers of pharmaceuticals and to druggists; and in the case of the sales to the druggist they are for the purpose of use in compounding prescriptions. It is much like going out and buying the material for a suit. You buy the goods, but you don't expect to have the buttons sewn onto it and the buttonholes worked into it. If you want a suit, you buy a suit, but if you buy the materials you buy the materials.

These are raw materials. However, any druggist that wants to sell those across the counter, like calcium carbonate, can buy, and they do buy, from so-called label houses, prepared labels. These come in a roll, and they have a rack of these prepared labels, in the prescription pharmacy. The pharmacist just tears off a label and puts it on the 2-ounce package and sells it. It has the directions on it.

There is nothing in the law that prevents the sale of a harmless preparation like this across the counter, if it has adequate directions. The law doesn't care who puts those directions on, whether the original manufacturer or the pharmacist. But, essentially, these are raw materials for preparing prescriptions in the drugstore, and they are not designed for over-the-counter sale.

Some of the labels that were brought in are stale labels. By that I mean that they are products that were manufactured prior to the 1946 change. That is bound to be true in any drugstore we go in. The labels are changing constantly. It is almost impossible to have entirely fresh labels in your drugstore all of the time.

Here is a very good example that has been brought in. It is Heptuna, brought out by Roerig. It is exactly the same product, put out by the same manufacturer. It may seem very strange that one of them has a caution legend and the other has adequate directions. The explanation for it is, it is a preparation containing folic acid, and the one under the caution legend was manufactured and distributed at a time when the Food and Drug Administration did not have, nor did the manufacturers have, enough experience with folic acid to say that it was safe for use except under a caution legend and under a physician's guidance. The other is put out after the evidence accumulated and it no longer needed to be so restricted and could be sold across the counter.

Now, those are not in contradistinction to each other. They show the progress in drug development that is going on all of the time. That is another reason why a list is a poor approach to this division, because the list is going to be constantly out of date. The label on the package that is put out day by day is the only up-to-date guide that you can possibly get.

There are and maybe always will be some very honest and legitimate differences of opinion among medical, pharmacological and legal experts, as to whether a drug should be limited to prescription. These differences will become increasingly lessened, however, when the Food and Drug becomes more active in this field. For example, if I may speak for a moment on behalf of the Upjohn Co., alone, Commissioner Larrick has one product of the Upjohn Co. in his list of exhibits. It is dehydrocholic acid. Mr. Larrick thinks it should have a prescription limitation. The Upjohn medical staff felt that under the mandate of law, directions could be written for overcounter sales. This is definitely a border case. As is our customary practice in such cases, we will yield to the views of Food and Drug and change. We will even go further. We will change as often as their opinion may change. And without any reflection at all on the. Food and Drug Administration, but just to illustrate the way these things do change, we have numerous examples, as has every manufacturer and as has the Food and Drug Administration, of changes back and forth across the counter as to opinions when a drug should be sold under a caution legend and when it should not.

For many years the Food and Drug Administration required that all parenteral preparations under this law should be sold only under a caution legend, and you couldn't put any directions on the package. Well, that caused so much trouble in medical circles where they needed the guidance of these inserts and detailed discussions of the drug, its indications and use, that they changed the regulations and

now you are prohibited from putting a caution legend on a parenteral preparation, and you must include adequate directions. That is perfectly logical, but it shows the change. You can't keep drugs static, because science marches on and things keep changing all of the time.

Again, in closing, we urge that a legislative standard be created to classify the drugs that may be refilled without limit. Such a standard earnestly enforced will clear up this problem.

H. R. 3298 presents but one question of major importance. That question is: What prescriptions may the druggist refill without further authority from the physician. There is a collateral problem concerning oral or written prescriptions, and we think it would be appropriate for the manufacturers not to comment on this. It is a problem which the pharmacist is qualified to discuss, and it has been discussed at great length. It isn't a problem that would affect us and we would prefer not to talk about that.

There are just one or two remarks, if I may have the permission of the Chairman, in regard to Mr. Larrick's testimony, that I would like to try to tie into our proposal. Mr. Larrick in his testimony used as illustrative of the attitude of the Food and Drug Administration a series of dangerous drugs, and they are all dangerous drugs; and he said, and Administrator Ewing ahead of him said, that this was the real concern of the Food and Drug Administration. It is the real concern of the pharmaceutical manufacturer. But those drugs are all on the "caution" legend now. You don't need any list to get them there. All you need is this law, properly amended to allow the druggist to refill all prescriptions for products that don't bear the caution legend, without the authority of the doctor.

Now, the one area in which we have some dispute with the Food and Drug Administration, an honest difference of opinion, is in this word "efficacy." We have proposed the word "efficacy" in adopting the language of the present regulations, but we are frank to say that we are very nervous and apprehensive about its ultimate effect. If it is included in the draft as we propose it, we think that the committee report, in the interest of keeping the thing straight, should include the statement of Mr. Larrick on page 7 where he said:

Opposition has been expressed to this bill on the ground that the Government is empowered to determine whether or not a drug is efficacious for its intended use. The language of the bill does not justify this conclusion.

The bill does not authorize the Administrator to determine the efficacy of a drug. It authorizes him to hold a hearing where the evidence of the best informed experts in the country would be received. On the basis of this testimony he would then determine not whether the drug is efficacious, but whether or not a layman can use the drug effectively without the diagnosis or supervision of a physician.

When Mr. Larrick said that the principal reason that they wanted a list was because of the disagreement with some of the drug-industry lawyers, he wasn't talking about the dangerous and toxic drugs, because there isn't any substantial difference or any difference at all in opinion between the lawyers of the industry and the Administration in this regard. There certainly is no difference of opinion in the actions of the industry and that is the real standard: What does the industry do, and how do they label the products; not what their lawyers may think is the standard. Lawyers are always talking up and down both sides of the street.