Page images
PDF
EPUB

fore, it has a social use. For clarification of the record, I am assuming you do not mean to say they have any constructive social uses.

Dr. GODDARD. I hope my remark would not be interpreted that it did; no. I tried to say that it is a social phenomenon that we have to contend with. It is a bad one.

Senator NELSON. I knew you intended to say that, and I did not want to leave the record open to an incorrect interpretation.

Dr. GODDARD. There are those who disagree.

Mr. GORDON. I have one more question. This is a quote from someone else's statement which we will hear next week:

Recent figures of FDA inspections, for example, do little to encourage optimism in this regard. The agency made 3,651 inspections of drug plants in 1966. Impressive as that figure may seem, it is 150 inspections less than the 1965 figure and 34 less than the number for 1964. I do not recite these figures to criticize the FDA, Mr. Chairman. Their inspections, of necessity, are becoming more complex and time consuming and FDA personnel shortages are persistent. Nevertheless, fewer inspections are being made, not more. It seems to me, therefore, it would be imprudent to rely heavily or solely on this mechanism as the method of assuring drug quality.

The import of this whole thing is that you cannot rely on the FDA, but rather you have to rely on the reputation and fame of the manufacturer to insure good quality drugs. Since you are here, I think it might be a good idea for you to comment on this.

Dr. GODDARD. We are taking steps to make certain that you can rely on the FDA. We are going to have two different approaches. One is carrying out more selective kinds of inspections. Working with Booz, Allen and Hamilton, we are identifying the critical areas of an inspection, those parts of the inspection that most frequently reveal flaws in the system. So our inspectors will do more partial inspections, but more target kinds of inspections.

Secondly, we are going to select 300 pharmaceutical firms next year for special attention, and add 300 more pharmaceutical firms for special attention the next year. That second year, we will have 600 of the 900 that produce prescriptions under very close surveillance, and the third year, all 900.

Now, let us not misunderstand what I am saying to mean that this will provide complete assurance of quality of drugs. It will not. Most of the responsibility still is and probably belongs on the manufacturer who enters commerce and produces these drugs. Concomitantly, we are operating and will be expanding the National Center for Drug Analysis, where we hope to get up to the analysis of several hundred thousand samples of drugs purchased at the retail level. Thus we will be able to act as a further step in the manufacturer's own quality control program with respect to those features that can be seen in the laboratory.

Now, I would like to make the point that companies, large and small, require surveillance. You look at the recall list and it is not uniquely the property of the small company. Companies constantly make this claim, "Our drugs are better, higher quality, they are guaranteed," these kinds of things. I would like to see the evidence that their drugs are therapeutically more effective than small companies. They point to some isolated episodes that have occurred. We know these, too, and we have taken steps to correct them, such as the

sugarcoated tetracycline episode several years ago.

Mr. GORDON. That was a big company, too, was it not?

Dr. GODDARD. That involved a large company, yes. So, yes, they are making the claim, but their making the claim does not make the fact so, is my point.

Mr. GORDON. But it is not so. Is that right?

Dr. GODDARD. Our job literally is to assure the physician: “Doctor, you can prescribe any drugs in the marketplace with the assurance that it will do the job that you had in mind when you selected it." Once that is done, we will have taken a great step.

Mr. GORDON. I have no further questions.

Senator NELSON. We had testimony at an earlier date from a pharmacologist. It was on the question that you have just commented on that I did not intend to raise at this hearing with you. It was on the question of whether, if a drug meets USP standards, the presumption can be made that all drugs which meet that standard are equivalent. The testimony that we have in the record is that there are only about a dozen cases where this did not turn out to be true. The testimony was that for almost all of the thousands of drugs on the market, if they met USP standards, they are equivalent in their therapeutic value and effectiveness.

Do you agree with that position?
Dr. GODDARD. I think that is a fair statement.
Senator NELSON. This was the statement of Dr. Miller of USP.

Dr. GODDARD. I think Dr. Miller's point is well taken. However, I say there is enough concern at the present time about the question of therapeutic equivalency that we are undertaking the testing of about 40 or 50 of the most frequently prescribed drugs that are available as both generic and brand-name drugs to determine biological availability, if you will, blood levels, which indicate that the drug has been absorbed. You can get some direct measurement in humans.

Now, if we find that after 20, 30, 40 of these drugs have been tested that equivalency is present, I think we have reason to feel reassured that this is true across the board.

Now, you see, there are also exceptions, in these systems. A man working on a given piece of equipment in any firm can fail to provide the proper maintenance or can make a slight change; for example, the tab letting pressure could be changed. This could influence thé availability of a drug when ingested.

Senator NELSON. Well, it probably would not meet USP standards. It would not dissolve at the proper rate.

Dr. GODDARD. Right. But you see, there would not be any knowledge of that. This means a feedback into the production in terms of the quality program may have to be made. But generally, I agree with Dr. Miller.

Senator NELSON. We are talking about the heart of a persistent argument that goes on in the industry and the medical profession.

Dr. GODDARD. This is why, Senator, I have said, show me your evidence. The large companies that make this claim consistently, and I would like to see their evidence. They have not produced it yet, other than these 12 isolated episodes that you have been talking about.

Senator NELSON. This is the problem about which there is so much confusion. It seems to me that what the industry is really arguing is that the exceptions that we find once in a thousand times prove the rule that there is not an equivalency among drugs that meet USP standards, when really it is the other way around. The exception just tests the rule. Once in a while the clinical and pharmacological knowledge about a drug is not sufficient at first to set foolproof standards. When more is known, modified standards are developed which incorporate the new knowledge. But this is an exceptional case.

So is it not really true that so far as we know, if drugs meets USP standards those drugs are equivalent therapeutically and you have to prove that they are not? As you know, we had this case recently of prednisone reported on in the Medical Letter. They tested 22 prednisones and accumulated scientific expertise around the country, and on this basis flatly stated that the present differential in price from 59 cents to $17.90 to the pharmacist is not warranted by differences in quality. This has never to this date been refuted by anybody in the industry.

Dr. GODDARD. We are trying to extend that to the drugs most frequently prescribed, those in the 200 most frequently prescribed list that are available by generic as well as by trade name. We are going to conduct that kind of test on human volunteers, you see, through Georgetown, with a contract there, through Public Health Service programs, and perhaps Veterans' Administration programs.

Now, let me point out to support what I have said, every instance that has come up, we and others have moved in on it, have studied it in depth, and it has resulted in a change in the standards. That is necessary. That is a role we must play and the scientific community engages in these kinds of studies to try to understand why the finished product of tetracycline, for example, was not performing at that point in time. When we understand it, then the standard can be changed. But it would seem to me that your point that the exception proves the rule is a valid one. The drugs are therapeutically equivalent until proven otherwise. But we do feel a burden to carry out further testing and get this thing wrapped up. We are going to improve the good manufacturing practices, too, Senator, which will also contribute to the improved quality of drugs.

Senator NELSON. You are going to what?

Dr. GODDARD. Improve what we call the good manufacturing practices, the requirements that manufacturers must meet.

Senator NELSON. You are going to increase the standard; is that what you are saying?

Dr. GODDARD. Yes, in effect.

Senator NELSON. You referred to testing 200 of the most frequently used drugs.

Dr. GODDARD. No, selecting from the 200 most frequently prescribed drugs those that are available in a generic name form. If it is a unique source, there is no point in checking, because of the unique source. Many of these drugs, by the way, came through the NDA procedure originally, so we have the information on clinical effectiveness already in hand.

Mr. GROSSMAN. Dr. Goddard, may I ask you, is then the purpose of the study they are conducting to corroborate the position you now hold as to equivalency?

Dr. ĠODDARD. Yes; to lay to rest these

Mr. GROSSMAN. This is really important in these hearings; you realize that?

Dr. GODDARD. Yes.

Mr. GROSSMAN. I just want to understand, what is your position as of right now!

Dr. GODDARD. Our position is drugs generally are equivalent. These cases are the exceptions rather than the rule. I have not seen any evidence that I have asked for from the large companies to show me that this is not the case, other than on an exception basis.

Mr. GROSSMAN. So this study will hopefully-
Dr. GODDARD. Lay this to rest.
Mr. GROSSMAN. When do you assume the study will be completed?
Dr. GODDARD. It will take about 16 months to complete.
Mr. GROSSMAN. This is the same amount of time as the compendium.
Dr. GODDARD. Yes; but for different reasons.
Mr. GROSSMAN. Thank you.

Mr. GORDON. Commissioner, Dr. Solomon Garb, a rather well known pharmacologist at the University of Missouri, testified before our committee that a doctor has to assume, in order to practice medicine, that, when he prescribes any drug, it will be therapeutically effective.

Dr. GODDARD. That is correct.
Mr. GORDON. Otherwise, you cannot prescribe

Dr. GODDARD. And we think that is our job, to be able to say: "Doctor, you can make that assumption and it is a safe one."

Mr. GORDON. They have been making it, have they not?

Dr. GODDARD. Yes; they have been, or there would not be as many companies in the marketplace as there are.

Senator NELSON. I do not have any further questions at the moment. There are, as per your first appearance, some other matters we will want to explore later and I assume we may bring that up with your staff and set another date for a hearing on some other problems we would like to discuss with you.

Dr. GODDARD. Fine.

Senator NELSON. We appreciate your testifying this morning. You have made a fine contribution.

Dr. GODDARD. Thank you.
(The prepared statement of Dr. Goddard follows:)

STATEMENT OF DR. JAMES L. GODDARD, COMMISSIONER, FOOD AND DRUG

ADMINISTRATION

Mr. Chairman: It is a pleasure for me to again appear before this distinguished Subcommittee. As you have requested, I will amplify my previous recommendation to this Subcommittee that a Compendium of prescription drugs should be published by the United States. I will also direct my testimony to an issue which has engendered considerable controversy since my last appearance before this Subcomittee. Thus, as you have also requested, I will attempt to clarify my position on marihuana.

As you know, vital information concerning all prescription drugs is presently disseminated via the “package insert.” A condensation and compilation of “package inserts” into a readily readable compendium distributed without cost to the physicians, pharmacies, hospitals, etc., would be a significant step forward in educating the health professions to the safe and effective use of therapeutic agents. It could also relieve the drug industry from the burden of printing the voluminous “package inserts” as such a compendium could appropriately replace this type of labeling.

The content of "package insert" type of labeling is initially approved by FDA during the new drug clearance procedure and is constantly reviewed by our medi. cal staff to insure that the labeling is consistent with current knowledge. Often the “package insert” is the only source of such necessary data on medicines which are prescribed daily.

Unfortunately this information seldom reaches the physician-it remains on the local pharmacist's shelves. Proper utilization of this information is further hampered by the present format of the “package inserts." They are printed in fine type and are extremely lengthy. Adidtionally, it is impossible to determine whether a particular insert is the most up-to-date version, thus the physician may prescribe a drug without full knowledge of recent discoveries that are important to proper use of the product.

Although this full disclosure labeling provides an excellent library of drug information for each pharmacy which might be used to advantage by the prescribing physician, it is essential in our view to develop a mechanism that makes it more available to and more useable by the practicing physician.

The “package insert” only has to accompany the drug package from which the prescription drug is dispensed. The drug labeling would hardly be meaningful to the patient and, indeed, could be detrimental.

The legal basis for an insert is founded in regulations promulgated pursuant to Section 502(f) (1) of the Federal Food, Drug, and Cosmetic Act which requires the labeling of all drugs to bear "adequate directions for use."

These regulations provide that the prescription drug label must bear: the statement “Caution: Federal Law prohibits dispensing without prescription"; the recommended or usual dosage; the route of administration if not for oral use; the name of all inactive ingredients (with some exceptions) if not for oral use; and an identifying code number from which it is possible to determine the complete manufacturing history of the drug. These label requirements are obviously most essential for proper usage and in order to monitor recalls. The concept of a compendium should in no way abrogate such label information. Additionally, the regulations require :

"Labeling on or within the package from which the drug is to be dispensed bears adequate information for its use, including indications, effects, dosages, routes, methods, and frequency and duration of administration, and any relevant hazards, contraindications, side effects, and precautions under which practitioners licensed by law to administer the drug can use the drug safely and for the purposes for which it is intended, including all purposes for which it is advertised or represented; and

"If the article is subject to (the new drug, antibiotic and insulin provisions) of the act, the labeling bearing such information is the labeling authorized by the approved new-drug application or required as a condition for the certification or the exemption from certification requirements applicable to preparations of insulin or antibiotic drugs: Provided, however, That the information required by (the above paragraph) may be omitted from the dispensing package if, but only if, the article is a drug for which directions, hazards, warnings, and use information are commonly known to practitioners

licensed by law to administer the drug. The information required by this regulation is appropriate and useful. I do not believe that anyone would say that the physician is not entitled to such labeling. Instead, the busy physician relies on promotional literature in medical journals and publications such as the Physician's Desk Reference (PDR). As you know, we have instituted several regulatory actions against drugs because of their advertisements, and we are presently requesting four drug firms to issue “Dear Doctor" remedial letters in order to correct PDR monographs. We are also engaged in revising our advertising regulations issued pursuant to the Kefauver-Harris Amendments.

This type of surveillance of advertising coupled with our administrative action will, I believe, substantially increase the quality of such promotions. Nevertheless, advertising will remain advertising.

The information contained in package inserts is essential to counter-balance the claims made in many drug promotions. Unfortunately, the inserts are not accomplishing this function. Primarily, this is because it is not directed to the physician himself. Further, it is not in an easily readable form because of its length, and, of course, there is no index to package inserts or coordination with other drugs. Obviously, the “package stuffer" is just not an available reference

« PreviousContinue »