stantial advertising efforts. Advertising in medical journals is clearly the best means of bringing to the physicians' attention an important new drug or a new use of an old drug or the continued availability of a long recognized drug for long recognized uses. In a highly competitive market, it would be folly for a manufacturer to fail to use this means of creating and stimulating medical interest in his products.

We deplore "overselling" and "extravagant claims." We recognize that intense competition such as exists in our industry can lead to excess. But we think that there are and have been controls that prevent and have prevented excess. In addition to governmental control by the FDA and the FTC, the editors and publishers of the medical journals exercise control. Attached hereto1 is a document entitled "Principles Governing Advertising in the AMA Scientific Publications." This sets forth the procedures through which drug advertising must pass. I submit that it is effectively designed to guard against the publication of any questionable advertisement. I believe that all responsible journals follow similar procedures. I know of no case in which any responsible editor has yielded to any pressure from an advertiser to permit an advertisement that had not satisfied the requirements.

The doctors exercise control by their response, sometimes favorable, sometimes critical, to advertising. The manufacturer knows that his most priceless asset is the confidence of the doctors in his integrity. Such confidence is built up by years of professional experience with the manufacturer's products and with the accuracy, objectivity and completeness of the information supplied by the manufacturer. No responsible manufacturer is willing to endanger this confidence by "overselling" or "persuasion and pressure” or “extravagant claims" or concealment of possible adverse effects. Every manufacturer knows that the truth will always catch up, and that in the long run, extravagant claims are bound to hurt the man who makes them.

I recognize that in some cases an advertisement or a series of advertisements has been criticized with justification. Exceptions to general standards of conduct will always occur. However stringent are the controls-both governmental and nongovernmental-there will always be some advertising to which criticism is directed. This is particularly true in the case of drug advertising. As we have pointed out in this and other connections, there is and always will be substantial difference of eminently qualified opinion as to the merits of particular pharmaceutical products. Doctors often seem to be congenitally decisive and absolute in expressing their opinions. We have seen the sharpest kind of debate on the basic question of whether or not a particular drug should even be available to the physician, or whether an available drug should be used for a certain medical problem, and we can expect such debates to continue. How very natural it is, therefore, that such debates flourish on the merits of the medical claims made in advertisements. I do not for a moment urge that such debate be curtailed even if that were possible. What I do urge is that the existence of such debate not be made the basis for attack on advertising in general. Too often evidence of difference of opinion has become confused with the charge of excessive promotion.

The pharmaceutical industry in the United States operates, and wants to continue to operate within the framework of the private enterprise system, subject to such governmental controls as are necessary in the public interest. No producer under our system can exist, much less grow, unless he sells his product. He cannot sell his product unless he advertises it. Dishonesty and misrepresentation have no place in any advertising, least of all in drug advertising. We think that in spite of isolated cases that have been subjected to criticism, phar maceutical advertising in this country has been as straightforward and honest as it has been vigorous. Under the new Federal drug law amendments, each advertisement will have to include more information even though the inclusion of certain information under such law may itself lead to confusion and more de bate. Each advertisement as it is expanded will be more expensive. But unless the competitive vigor of the industry collapses, I anticipate that the manufac turers will continue to remind the medical profession of their products in the most effective way they can. The brakes on the enthusiasm of the seller will continue to be applied by the editors of the medical journals, by the physicians and by the manufacturers themselves who know that they can never retain the confidence of the medical profession unless their advertising adheres to the

1 Not reprinted in this volume since the pamphlet will be published in pt. 6, relating to testimony by the American Medical Association.

highest standards of honesty and taste. In this way the person with his reputation at stake, the manufacturer, and the person best qualified to judge what message he wishes to extract from an advertisement, the practicing physician will be able to keep to a wholesome minimum the allegations of overpromotion and yet hold a permissible maximum of therapeutic suggestiveness for modern drug therapy.

Sincerely yours,

EXHIBIT 259

AUSTIN SMITH, M.D., President.

LABELING CLAIMS: INTERNAL MEMORANDUM FROM A FOOD AND DRUG ADMINISTRATION MEDICAL REVIEWER CRITICIZING “LAXITY" BY THE AGENCY AND "IGNORING" OF ITS REQUESTS FOR RE-LABELING

On page 2230, Senator Ernest Gruening read from an internal memorandum of the Food and Drug Administration as regards alleged excesses in labeling claims. There follow additional excerpts on this and related subjects from the memorandum. It had been prepared by Irving L. Cooperstein, M.D., for presentation at a medical officers staff meeting, February 6, 1963. The memorandum was 10 pages long and dealt almost entirely with the specific subject of its title, Summary of Some Problems Encountered With Labeling of Corticotropin and Corticosteroids. Only those excerpts which are of a more general nature are reprinted herein (since most of the contents were highly technical as to this particular category of drugs).

SUMMARY OF SOME PROBLEMS ENCOUNTERED WITH LABELING OF CORTICOTROPIN

AND CORTICOSTEROIDS

INTRODUCTION

"Actually, the package insert or direction circular is a scientific document. More physicians should read it!" (Editorial, Ann. Int. Med., 50, 829, 1959) This editorial was written by a physician in the pharmaceutical industry.

Enthusiasm

Time

The graph represents how enthusiasm for a new preparation frequently alters with time (the dotted line has been known to occur).

Labeling is an official term under the law and does include package inserts, brochures and literature mailed to physicians. Under the amended act, labeling should provide for effective as well as safe use of a drug. False or misleading claims should be deleted. Advertising of prescription drugs is subject to FDA surveillance.

EVALUATION

The preceding represents just a few examples of the problems with these anti-inflammatory steroids. There have been obstacles to this type of report. I had hoped to list the number of NDA's containing each steroid, but it would not be accurate. For example, Lederle has 12 approved NDA's for triancinolene; chemical indexing has placed only 6 on the list I requested. Two corticotropins

88-311 0-64-pt. 5——————7

were not on their list. No notation has been made of the preparations firms have voluntarily withdrawn.

Essential in any type of medical evaluation by the nonexpert is the library. Our facilities are inadequate, there is no room for the journals required to ade quately survey the literature. The more recent symposia or surveys are not accessible. They are on reserve at the National Library and one-half a day is consumed traveling there and back. There should be no such geographical separation from medical sources. The reference file in the library gives one a false sense of security since only articles which are contained in journals received by our library are scanned. If the article does not include the name of a drug it more than likely won't be filed. For example, important articles and discussions on the adverse effects of topical steroids for ophthalmic use were not on file.

The immediate problem is to cease the laxity the FDA and industry has maintained about the scientific caliber of labeling of these preparations. It is impossible for one or several physicians to operate in the hit or miss fashion this division has done in the past. The time consumed over labeling of one firm's product is considerable. A firm will ignore your requests and the only response may occur when an inspection is made. Then the long tedious negotiations over changes begins, as the firm is reluctant to have mediocre claims for a mediocre product. It is common practice for firms to send nonmedical and even nonscientific personnel to discuss medical matters. Little is accomplished, since they are the equivalent of the detail men some of us encountered in practice. Some firms merely ignore requests we initiate because they don't want to submit anything like a supplement. Promises have been made over the phone with no attempt to fulfill them.

With such an important group of drugs and the numbers involved (e.g., Upjohn has 14 different preparations for ophthalmic use; Merck has 8), there has to be another solution. One approach may be to supply minimal standards of labeling for each drug or groups of drugs, which would represent an official position by the FDA. (Some firms that are willing to alter labeling would like us to write it for them.) There standards may be in the form of the FDA (without its inaccuracies) and compiled by outside authorities. Special problems such as promotion of combination drugs, and the ophthalmic preparations would require panels or study sections.

Any satisfaction that HEW has with the evaluation made of the safety and effectiveness of these agents at the NIH has to be dampened by the use made of this information by the FDA in the past. A nonconformist once stated that "happiness is promoted by the association of people with similar ideas and interests."

EXHIBIT 260

DRUG LABELING: VIEWS OF ANOTHER MEDICAL OFFICER, FOOD AND DRUG ADMINISTRATION, ON A COMPANY'S ALLEGED OBSTRUCTIVE TACTICS IN RE-LABELING A DRUG

On page 2230, Senator Gruening referred to an internal memorandum of the Food and Drug Administration with regard to the problem of securing adequate labeling of drugs. For the purpose of completeness of the record, identifying names (not cited during the hearing) are included by direction of the chairman. There follows the text of this memorandum.

JANUARY 10, 1962.

To: W. H. Kessenich, M.D., Director, Bureau of Medicine. From: David S. Davis, M.D., Medical Officer, Division of New Drugs. Subject: Recommendations for Relabeling of Triacetyloleandomycin, NDA's 10551, 11117, 11310, 11348, 11500, 11587, 11588, 11658, 11631, 12841, 12473. At our last meeting with representatives of Chas. Pfizer and Co., Inc., January 2, 1962, copies of a memorandum containing our recommendations for relabeling of products containing triacetyloleandomycin were given to Mr. A. C. Von Oehsen and the other Pfizer representatives. The memorandum contained 11 recommendations. One week earlier, in a similar meeting, the firm was apprised of the first three recommendations contained in the memorandum issued subs quently, referred to above.

On January 4, 1962, Mr. Von Oehsen phoned me and assured me that the firm had incorporated all of our recommendations in their latest revision of the labeling, which, at our meeting of January 2, 1962, we had been assured we would receive no later than January 8, 1962. Mr. Von Oehsen called me again January 8th and told me the revised labeling had been mailed January 5th. I received this material January 9th in an envelope postmarked January 8, 1962. My review of this latest labeling reveals that our basic recommendations-the first three referred to above-have been completely disregarded:

1. The firm continues to make recommendations for the management of acne and chronic pyodermas;

2. Prophylactic uses continue to be recommended;

3. Whereas we have recommended beginning of monitoring no later than the 10th day of continuous therapy, the firm continues to recommend monitoring of the liver profile on the 14th day.

It is readily apparent that this latest "relabeling" is a continued illustration of the Pfizer firm's bad faith in their negotiations with us on this matter. It is my conclusion that further attempts at negotiation by the Bureau of Medicine in this regard would be unwarranted, fruitless, and degrading. I recommend that this matter be transmitted to the Commissioner for further action at once. More than 3 months ago, Wyeth Laboratories furnished us with proposed revised labeling which contained all of the basic recommendations which we agree to be appropriate. At all times, during this period, and most recently, in a communication dated December 29, 1961, Wyeth has demonstrated their complete willingness to relabel triacetyloleandomycin products which they market in accordance with our recommendations. Accordingly, I recommend favorable action in the Wyeth proposals at once.

DAVID S. DAVIS, M.D.

EXHIBIT 261

A 1962 LETTER FROM WINTHROP LABORATORIES WHICH HAD NOT BEEN ACKNOWLEDGED FOR A YEAR: FOLLOW UP COMMENTS BY FOOD AND DRUG ADMINISTRATION

On page 2230, Theodore Klumpp, M.D., referred to a letter from Winthrop Laboratories which had not been acknowledged by the Food and Drug Administration. There follows an explanatory letter received from Commissioner of Food and Drugs, George P. Larrick.

JULY 31, 1963.

DEAR SENATOR HUMPHREY: This is in reply to your letter of June 20 transmitting a copy of the transcript of the hearings held by your subcommittee on June 19, 1963. You request our comments on the testimony of Dr. Klumpp appearing on pages 327-9 relating to an unanswered letter from Winthrop Laboratories dated May 31, 1962, to the Food and Drug Administration.

We looked into the matter and found the letter was received and considered. However, the question which Winthrop Laboratories raised was one which at that time was under consideration by the Executive Committee of the U.S. Pharmacopeia, and accordingly a substantive response was delayed pending resolution of the matter by that committee. In our discussions with representatives of Winthrop Laboratories after the letter of May 31, 1962, had been received, we pointed out to the firm's representatives that the question raised was being considered by the Executive Committee of the U.S. Pharmacopeia.

During the lengthy period the committee had the question under consideration, Winthrop's letter of May 31 was filed without having been acknowledged. We have now acknowledged Winthrop Laboratories' letter and a copy of our letter is enclosed.

Sincerely yours,

Enclosure: Ltr. to Winthrop Labs.

GEO. P. LARRICK, Commissioner of Food and Drugs.

Dr. THEODORE KLUMPP,

(Enclosure)

President, Winthrop Laboratories,

New York, N.Y.

JULY 30, 1963.

DEAR MR. KLUMPP: It came as a surprise to us to learn that we had not answered your letter of May 31, 1962. The first information we had to this effect was your testimony before the Senate Subcommittee on Reorganization and International Organizations on June 19.

We looked into the matter and found that your letter had been filed without acknowledgement after we learned that the Executive Committee of the U.S. Pharmacopeia was considering the same matter. We are looking into the situation now.

Needless to say, we regret our failure to acknowledge your letter.

Sincerely yours,

GEO. P. LARRICK, Commissioner of Food and Drugs.

Senator GRUENING. Our next witness is Dr. Burney. We welcome a distinguished public servant here, who has had a long and outstanding career in the U.S. Public Health Service as Surgeon General. We are glad to see you back in Washington.

Would you go ahead as the other witnesses have and take the high spots in your testimony. Your biography and full statement will be in the record. I suspect very shortly the bell will ring and we will be called over to hear the President's message on civil rights.

STATEMENT OF DR. LEROY E. BURNEY, VICE PRESIDENT FOR HEALTH SCIENCES, TEMPLE UNIVERSITY, REPRESENTING THE GREATER PHILADELPHIA COMMITTEE ON MEDICAL-PHARMA. CEUTICAL SCIENCES

Dr. BURNEY. Thank you, sir.

EXHIBIT 262

LEROY BURNEY, M.D.: BIOGRAPHICAL SUMMARY

There follows a summary, as prepared by the U.S. Public Health Service in 1959, on the professional career of Dr. Leroy Burney.

BIOGRAPHICAL SKETCH

LEROY E. BURNEY, M.D., SURGEON GENERAL, PUBLIC HEALTH SERVICE, DEPART MENT OF HEALTH, EDUCATION, AND WELFARE

September 4, 1959.

Dr. Leroy E. Burney, a native of Burney, Ind., was appointed Surgeon General of the Public Health Service by President Dwight D. Eisenhower on August 3, 1956.

Surgeon General Burney, who is the eighth person to hold that office, has spent his entire professional career in public health activities. He was commissioned in the Regular Corps of the Public Health Service in 1932. From 1945 to 1954 on detail from the Service, he was Secretary and State Health Commissioner. Indiana State Board of Health. At the time of his appointment as Surgeon Gen eral, Dr. Burney was Assistant Surgeon General and Deputy Chief of the Serv ice's Bureau of State Services.

Surgeon General Burney established the first mobile venereal disease clinic service in Brunswick, Ga., in 1937, inaugurating a type of service which became