Re S. 2628, psychotoxic drug control of 1964. Hon. LISTER HILL, KAY-FRIES CHEMICALS, INC., New York, N. Y., May 4, 1964. Chairman, Committee on Labor and Public Welfare, SIR: We are quite concerned at what we believe is an unintended inaccuracy in part of the definition for "psychotoxic drug" in S. 2628. We refer to section 3(a) of that bill and specifically to the amendment of section 201 of the Federal Food, Drug, and Cosmetic Act designated as (v)(1)(A). The part of the definition which we question states: "(v) The term 'psychotoxic drug' means (1) any drug which contains any quantity of (A) barbituric acid or any of the salts of barbituric acid;". Barbituric acid is a chemical name which describes a specific chemical structure. Salts of barbituric acid are such compounds as sodium barbiturate or ammonium barbiturate and also defines a specific chemical structure. They are not "barbiturates" as the term is commonly or popularly used to describe a class of hypnotic drugs. These hypnotic drugs, known as barbiturates, have the same general structure but have additional chemical groups attached and technically are called substituted barbituric acids. The seventh edition of 1960 of the "Merck Index" lists under use for barbituric acid: "Mfg. Plastics, pharmaceuticals." (It is used in the manufacture of pharmaceuticals other than barbiturates notwithstanding the similarity in name.) In addition, the same "Merck Index" has a note under the description of Barbituric acid as follows: "Unsubstituted Barbituric acid has no hypnotic properties." Ammonium barbiturate is not listed in the "Merck Index," which is not surprising since it has only been used as an experimental chemical in industries other than the pharmaceutical. Neither is sodium barbiturate listed. This is also not surprising since to the best of our knowledge, its main use is in connection with the aircraft industry. To the best of our knowledge, ammonium and sodium barbiturate as direct salts of barbituric acid should show no hypnotic effect, and neither of these, nor barbituric acid, are used as pharmaceuticals. Our interest arises from the fact that Kay-Fries manufactures barbituric acid and sodium barbiturate and, upon occasion, have also manufactured ammonium barbiturate. We manufacture these compounds only for use as intermediates or building blocks in the synthesis of other chemical products. It would appear that if S. 2628 were enacted in its present form, we literally would be unable to manufacture and sell these compounds for their present industrial uses. In addition, our customers, industrial users, including those in defense industries, could not use these materials since they are obviously not pharmaceutical manufacturers. We do not believe that this is the intention of the bill. We believe that the purposes of the bill will be adequately and completely satisfied by the changing of (1) (A), line 16, 17, page 3 to read: (1) any drug which contains any quantity of (A) a substituted barbituric acid or any of the salts of a substituted barbituric acid;". We would appreciate greatly your consideration of these comments. Of course we would be glad to have a representative come down for an informal discussion with your committee staff if you should feel that this is necessary. We also would request that if further action is needed on our part, that we be given an opportunity to testify if hearings should be called on S. 2628. Thank you very much for your consideration. Very truly yours, H. Kent VanDERHOEF, Vice President. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, Mr. ROBERT W. BARCLAY, Committee on Labor and Public Welfare, DEAR MR. BARCLAY: Thank you for your letter of May 8, 1964, requesting that we comment on a letter sent to Senator Hill by Mr. Vanderhoef of Kay-Fries Chemicals, Inc., concerning the definition of psychotoxic drug in S. 2628. Mr. Vanderhoef's letter accurately quotes the seventh edition of 1960 of the "Merck Index" with respect to unsubstituted bartituric acid having no hypnotic properties. The problem here is that unsubstituted barbituric acid can be changed from a substance which does not have hypnotic properties to one which does by relatively simple chemical manipulation using basic equipment. Thus amending the definition as suggested would create a serious loophole in the consumer health protection afforded by the proposed legislation. If manufacturers of basic unsubstituted barbituric acid were not required to register with the Department of Health, Education, and Welfare, keep records as to production and distribution, and comply with the other requirements of the bill it would be relatively simple for bootleggers to obtain this substance and convert it to a drug which would be subject to the restrictions of the law but as a practical matter would be beyond its reach because the drug would already be in illegal channels of commerce. In view of the foregoing we would be opposed to the change in definition recommended by Mr. Vanderhoef. We do not see any provision in S. 2628 which should lead Mr. Vanderhoef to conclude that passage of the bill would make his firm "unable to manufacture and sell these compounds [salts of unsubstituted barbituric acid] for their present industrial uses." If we can give you further information please feel free to contact us. W. B. RANKIN, Re S. 2628, psychotoxic drug control of 1964. KAY-FRIES CHEMICALS, INC., Chairman, Committee on Labor and Public Welfare, SIR: In connection with the definition of psychotoxic drugs in S. 2628, we would like to comment on Mr. W. B. Rankin's (Assistant Commissioner for Planning, Department of Health, Education, and Welfare) letter of July & addressed to Mr. Barclay of your staff on the Committee for Labor and Public Welfare. This letter comments upon my previous letter to you dated May 4, 1964. Mr. Rankin states that "unsubstituted barbituric acid can be changed from a substance which does not have hypnotic properties to one which does by relatively simple chemical manipulation using basic equipment." He is correct in his statement that the unsubstituted acid theoretically can be changed to a substituted barbituric acid. Indeed, many chemicals can be changed to a substituted barbiturate by "relatively simple chemical manipulation." As a case in point, it is perfectly conceivable and chemically practical that vinegar (a dilute solution of acetic acid) could be converted to the cyano derivative then hydrolyzed and substituted, reacted with urea, and one would obtain an hypnotle, substituted barbiturate. These are all simple chemical steps though there are several of them. However, anyone who could do the manipulation from unsubstituted barbituric acid to substituted barbituric acid could easily run these same steps. Are we then to call vinegar a psychotoxic drug? To the best of our knowledge, unsubstituted barbituric acid or its salts have never been used to make substituted barbiturates; i.e., those having hypnotic properties, in any commercial quantities. Because of the chemistry involved, it would be an uneconomical synthesis. As a matter of fact, the commercial synthesis for the substituted barbiturates involve intermediates which are both simpler and easier to use. If, indeed, bootleggers are to make the barbiturates, it is difficult to believe that they would not be knowledgeable enough to use more economical and more easily obtainable material. Mr. Rankin says that he does not see any reason why we would be unable to manufacture and sell the unsubstituted barbituric acid and its salts for their present industrial uses if this bill were passed. As I read S. 2628, section 4(Q) (3) the possession itself of unsupstituted barbituric acid or its salts by our customers would be a violation since they are not presumably registered as pharmaceutical manufacturers and are not wholesale pharmacists or hospitals or physicians, etc. For these customers to have these materials in their possession, they would not only have to register but would be required to keep records of accountability of a type which would be quite impractical for their kinds of operation. The unsubstituted barbituric acid and its salts which we sell are used for defense purposes as well as in the space program in propellant compositions. While much of this work is obviously confidential, these materials have been mentioned in this connection; see U.S. patent 2,973,256, dated February 28, 1961, and U.S. patent 2,988,435, dated June 13, 1961. These patents are assigned to the Standard Oil Co. of Indiana, a company that is not a pharmaceutical manufacturer to the best of our knowledge. There are also other industrial uses though we are limited in discussing them because in doing so we would be breaking confidence with out customers. Since (1) the method of choice of synthesis for substituted barbiturates would not be through unsubstituted barbituric acid or its saits, and (2) the uses for unsubstituted acid and its salts are completely out of the field of hypnotic drugs, we believe that the definition of psychotoxic drugs in S. 2628 should be modified as suggested in our letter of May 4, 1964. We thank you for your consideration and we respectfully request that this letter and our letter of May 4 be put in the record on the Senate committee hearings for S. 2628. If additional information is needed or desired, we will be most happy to cooperate. Very truly yours, H. KENT VANDERHOEF, Vice President. DEPARTMENT OF HEALTH, EDUCATION, AND WElfare, Mr. ROBERT W. BARCLAY, FOOD AND DRUG ADMINISTRATION, Committee on Labor and Public Welfare, DEAR MR. BARCLAY: This replies to your request for our comment on a letter dated August 3, 1964, from Kay-Fries Chemicals, Inc., New York, N.Y., to Senator Lister Hill, with regard to S. 2628, "The Psychotoxic Drug Control Act of 1964." There is nothing in S. 2628 which would affect chemical firms who are shipping or receiving unsubstituted barbituric acid for industrial, nondrug purposes. The bill would define a psychotoxic drug as being, among other things, "any drug which contains any quantity of (A) barbituric acid or any of the salts of barbituric acid ***" The basic Food, Drug and Cosmetic Act, which this bill would amend, classifies as a drug a substance intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and articles intended for use as components of drugs (other portions of the drug definition are not germane at this point). Thus, if Kay-Fries Chemicals, Inc., prepares unsubstituted barbituric acid, or one of its salts for industrial, nondrug purposes, does not label or represent the product for drug use, and ships it in good faith to another firm for industrial nondrug purposes, the chemical would not be a drug within the meaning of the Food, Drug, and Cosmetic Act and would not be subject to the present controls of that act, or the controls proposed by S. 2628. This applies not only to suppliers of the chemical, such as Kay-Fries Chemicals, Inc., but also to customers who employ barbituric acid for nondrug purposes. As indicated in our letter of July 8, 1964, we recommend against deletion of barbituric acid from the definition of psychotoxic drug in S. 2628. Historically, barbituric acid was the basic raw material from which barbiturates were first manufactured and more recently a patent has been granted which covers a process of producing barbiturate intermediates from barbituric acid. There would be added safeguards, we believe, to having any barbituric acid intended for drug purposes, classified as a psychotoxic drug. Sincerely yours, W. B. RANKIN, Assistant Commissioner for Planning. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE, Hon. RALPH YARBOROUGH, FOOD AND DRUG ADMINISTRATION, Washington, D.C. DEAR SENATOR YARBOROUGH: Thank you for your letter of August 3, 1964, asking for our views on testimony which was presented with regard to S. 2628 after I finished testifying. While we are in accord with the American Medical Association's view that education and State activity are important in dealing with the psychotoxic drug problem, our experience indicates that these alone are not an answer to the probfem. An adequate handling of the problem will, in our judgment, also require additional Federal efforts along the lines proposed in S. 2628. In the absence of a mandatory nationwide record keeping program which permits audit of the manufacture and distribution of psychotoxic drugs to detect points of diversion, we believe that effective control will be many years in coming if it ever arrives. The enclosed staff memorandum gives our specific comments on the changes suggested in S. 2628 by representatives of the two pharmaceutical associations. With regard to the views of the pharmacists that they should not be required to keep records unless physicians are subjected to the same requirement: We have had to bring many legal actions against retail pharmacists because they diverted psychotoxic drugs into illicit channels. During the same period of time, we have also had to bring actions against a few physicians. Because the physician has been relatively a very small factor in the diversion of the drugs, we were prepared to and do endorse S. 2628 as drafted (without requiring physicians to keep the records specified in the bill). However, we would have no policy objection to amendment of the bill to cover doctors as well as others who handle psychotoxic drugs, if in the committee's wisdom, such amendment is advisable. We appreciate the opportunity to submit these views to the subcommittee. Sincerely yours, GEO. P. LARRICK, Commissioner of Food and Drugs. FOOD AND DRUG ADMINISTRATION COMMENTS ON TESTIMONY ON S. 2628 Representatives of the American Pharmaceutical Association recommended four amendments to S. 2628, which are discussed below. 1. The association requested that "pharmaceutical, medical, and dental practitioners, pharmacies, hospitals, and other establishments currently governed by State law" be exempted from the recordkeeping and inspection requirements of the bill. It suggested new language for inclusion in section 511(d) (3). It is not the purpose of S. 2628 to duplicate effective work by the States. It is the purpose of the bill to provide effective controls over psychotoxic drugs which have not been provided in many States. Pharmacists have been a major point of diversion of psychotoxic drugs from legal channels. There is no valid basis for creating a loophole by exempting them or their pharmacies from the recordkeeping and inspection requirements. (Medical and dental practitioners are already exempted under the bill.) 2. The association requested that the proposed section 511(a)(4) be amended to include pharmacists (as persons entitled to manufacture, compound, or process psychotoxic drugs). Pharmacists are already included as individuals entitled to manufacture, compound, and process psychotoxic drugs by the proposed section 511 (a) (7); thus, the suggested amendment would be surplusage. 3. The association suggested that the possession clause (the proposed section 511(e)) be amended by inserting the words "in reasonable quantities labeled in conformance with this act," in the appropriate place. We would have no objection to inclusion of this provision in the bill. We should point out that the provision would classify as a violation the possession of a psychotoxic drug, properly obtained, which had been transferred by a patient from the prescription vial to the purse. Of course it would not be our purpose to refer such a technical violation to the courts. 4. The association recommended that section 9 be amended by adding "nor shall anything in this act be construed as enlarging, reducing, or otherwise altering professional rights and privileges conferred by State law." It is one purpose of the bill to place certain specific responsibilities upon pharmacists who deal in psychotoxic drugs whether or not the responsibilities are imposed by State law. The effect of the proposed amendment could be to nullify this requirement in many areas. In view of the demonstrated need for adequate controls of the handling of psychotoxic drugs by pharmacists, we must oppose the suggested amendment. Section 9 of the bill as it now stands has adequate safeguards of the rights of the States to limit the handling of psychotoxic drugs to a greater degree than would Federal law, if they so desire. There is nothing in S. 2628 (which among other things would authorize proper inspection of prescription files by duly constituted Government authority) that would infringe upon the "physician-patient-pharmacist" relationship, referred to by the association. The inspection authority proposed by this bill is a limited authority to accomplish a demonstrated need. Representatives of the National Association of Retail Druggists also testified in opposition to granting the Federal drug inspector authority to inspect prescription files. The association recommended an amendment on line 12, page 9, of the bill to exempt pharmacies. For the reasons stated earlier with regard to testimony of the American Pharmaceutical Association, we recommend against the adoption of the amendment proposed by the National Association of Retail Druggists. Senator THOMAS J. DODD, Washington, D.C. AMERICAN HOSPITAL ASSOCIATION, WASHINGTON SERVICE BUREAU, DEAR SENATOR DODD: The American Hospital Association wishes to comment upon S. 2628 which you have introduced. The proposed legislation, to be known as the Psychotoxic Drug Control Act of 1964, contains provisions which could significantly affect the Nation's hospitals. This association numbers among its members the vast majority of the country's hospitals which contain more than 90 percent of all general hospital beds. It is a voluntary organization dedicated to improving hospital care for all the people. We are pleased to note that section 511(a) exempts "pharmacies, hospitals, clinics and public health agencies, which maintain establishments in conformance with any applicable local laws regulating the practice of pharmacy and medicine and which are regularly engaged in dispensing prescription drugs ***." Hence, it would be no violation for hospital pharmacies to manufacture, compound, or process any psychotoxic drug. But in section 511 (d) (1), elaborate recordkeeping is required even of those establishments exempt under section 511(a). A hospital would be expected to keep accurate records of all stocks of psychotoxic drugs, data regarding their manufacture, compounding, and processing, records of how such drugs were acquired and disposed of, from and to whom. Of course, hospitals prepare these records already. Retaining some of them for 3 years and in any special form, though, could prove to be a hardship to many institutions. It is, in our estimation, unnecessary, cumbersome, and expensive. Most hospitals retain their patients' medical record charts for many years, some even indefinitely. Each order or prescription for a psychotoxic drug, for example, would be written in the chart and the notation of its administration by the nursing staff would also be recorded. The pharmacy, however, might very well want to destroy its patient order files in less than 3 years because they would serve little good as long as the definitive prescription information is in the patients' chart. The slips tend to clutter up the pharmacy's files. The records of purchases of drugs and inventory records could be retained for 3 years without undue hardship and usually are kept for a considerable time. |