the FDA aware of the discovery of researchers at Massachusetts General Hospital linking DES to a rare form of vaginal cancer? (See "Adenocarcinoma of the Vagina: Association of Maternal Stilbestrol Therapy with Tumor Appearance in Young Women," The New England Journal of Medicine, 284 (16): 878881, 1971). Is the FDA aware of the study that showed as little as 7/100th of a microgram of DES caused cancer in 50 percent of the mice tested? (See "Mammary Tumors and Mammary-Gland Development in Hybrid Mice Treated with DEŠ for Varying Periods," Journal of the National Cancer Institute, 25: 10231039, November 1960) Or the research, "Canine Ovarian Tumors Following Stilbestrol Administration," Australian Journal of Experimental Biology and Medical Science, 37: 549-566, 1959) Or Survey of Compounds Which Have Been Tested for Carcinogenic Activity, Supplement 2, US Department of Health, Education and Welfare, 1969? Or the studies that showed development of breast cancer, fibroid tumors, and excessive menstrual bleeding in women, sterility and impotence in men and retardation of growth in children? (See "Possible Cancer Hazards Presented by Feeding DES to Cattle," Symposium on Medicated Feeds, New York, Medical Encyclopedia, p. 118, 1956? With such a large amount of research linking DES to cancer both in animals and humans, why has the FDA refused to declare this drug unsafe? You state you are not aware that the "FDA knowingly allowed three major producers of medications and sweeteners containing cyclamates to continue shipping and selling the chemical after being advised that such shipments would be illegal." My original question was "is it true, as numerous reports have stated, that although cyclamates were banned effective July 1, 1970, the FDA knowingly allowed three major producers of table sweeteners containing cyclamates to continue shipping and selling the banned chemical?" I did not state in my original question that the companies were advised such shipments were illegal. Two, as director of the Office of Compliance, do you still deny knowledge of “FDA documents showing three major producers of cyclamate-containing table sweeteners continued shipping the products until August 14, 1970?" As director of the Office of Compliance, do you still deny knowledge of the FDA documents showing "Abbott told the FDA last November it intended to sell rather than destroy its stock of Sucaryl?" I would also like to point out I originally did not ask you if you had any information "concerning a letter of November 1970" as you stated in your letter. My original question was "is it true that Abbott labs notified the FDA in November 1970 that they would continue to sell rather than destroy its stock of Sucaryl?" You have a definite habit of twisting my questions around to ask for something I did not ask for. Finally, did Dr. Charles Edwards, FDA Commissioner, have knowledge of these documents or of Abbott's notification to the FDA? Awaiting your reply to the questions. PAUL ZAGORSKI, (Underlining in the quoted material is printed in italic.) Associate Editor. JULY 28, 1971. THOMAS BROWN, Director, Office of Compliance, Food and Drug Administration, DEAR MR. BROWN: On June 21, 1971, I sent you a letter in reply to your letter of May 11, 1971. My letter raised questions concerning your refusal to release the filth tolerances, the 30 year wait before some of the tolerances were made public, and an apparent contradiction between FDA's standard on tolerances or guidelines and the actual wording of the Food and Drug Act. We have never received a reply to this inquiry. On July 2, 1971, I sent a second letter raising questions that evolved from my doing research on the FDA. These questions involved hazardous Vitamin C tablets, nitrite levels in meats, research on the carcinogenic potentialities of nitrites, the number of people killed by eating excessive amounts of nitrites, the number of people injured by cosmetics every year, numerous questions on the drug diethylstilbestrol (DSF), violations of the cyclamate ban, and the FDA's stand on (probably "effective" drugs. The registered letter was received by your office July 6, yet we still have received no reply even though these points are relevant to the public's health and I clearly indicated the information would be used in an article on the FDA. Could you please at least inform us when we can obtain this information? Since the July 2 letter, Mr. Stewart Wands, Executive Vice President, American Spice Trade Association, complained about the briefcase item and pointed out that the limits for spices and herbs applied only to the testing of imported spices and herbs. He included the article by Mr. Weems Clevenger, "A Venture in the Spice Trade." After reading the article, there are still some questions. One, has the FDA ever checked the industry inspectors or inspections to verify their analysis? The article states "District officials made it clear to the importers that no lowering of standards for purity would be considered and that new procedures would be formulated to provide continued surveillance of the spice industry.' Two, doesn't this contradict your news release that you have made new limits for spices and herbs or are the limits given to the newspapers the old limits? Three, what is the "continued survellance" you are going to use? Four, what testing procedures are used by the FDA to verify the wholesome nature of the spices and herbs during and after processing? Five, does the FDA ever test these products as they appear on the retailers' shelves? May I have the lot numbers of the Prince Parmesan and Prince Ramano cheeses recalled because of contamination by BMC and FH6? Is it true the FDA has only one man to investigate drug tests? Looking forward to hearing from you in the near future. Cordially yours, PAUL ZAGORSKI. Associate Editor. GROCERY MANUFACTURERS OF AMERICA, INC., Hon. ABRAHAM A. RIBICoff, DEAR SENATOR RIBICOFF: Your letter of June 24, 1971, requested GMA's comments on six subjects. Our intitial reply, dated July 27, 1971, responded to three of those subjects and included GMA's support for an orderly review of the GRAS list and recommended that two others-sodium nitrate and animal drugsbe referred to the American Meat Institute and the Animal Health Institute, respectively. We are prepared at this time to comment on the remaining three topics of "chemical screening," third party testing, and publication of scientific protocols in the Federal Register. These subjects are interrelated in that each involves suggested techniques for improving food ingredients safety testing. GMA supports the timely review by the scientific community, by regulatory agencies, and by Congress of procedures to ensure the safety of food ingredients. Knowing full well that today's tests will be outdated by tomorrow's experiments, we urge that food safety testing decisions be made by the scientific community at large. CHEMICAL SCREENING "Chemical screening" is a term which we understand to mean the battery of relatively short-term tests for mutagenicity, teratogenicity, and reproductive pathology conducted in animal systems for safety evaluation. While useful as a form of shorthand, "chemical screening" does not convey full understanding of safety evaluation. Safety evaluation of food ingredients is a continuing process and occupies many well-trained scientists in the laboratories of food companies, academia and independent organizations. The commitment of the food industry to the meaningful evaluation of new food additives is demonstrated by these continued efforts, not only involving established procedures but also including newer testing procedures. The knowledge of the scientific community as it relates to foods and their toxicological safety has expanded greatly in the last decade. Many proponents of new food additives now conduct teratological and reproductive tests in animals. GMA endorses the application of this new knowledge to new food additives. Our single caveat is that new testing procedures not be required until their utility in identifying potential hazards associated with food additives has been established and accepted by the scientific community. For example, there is no agreement at this time as to the significance of mutagenesis observed in in vivo or in vitro test systems. The lack of consensus is due in large part to the relatively new status of this area of toxicology. This conflict will be resolved only by additional testing of a variety of compounds. The detection of mutagenesis in a test system is not prima facie evidence that the compound is a mutagen in man since not all compounds with mutagenic potential in test systems are necessarily mutagens in man. Before new tests are required, Congress or the delegated agency should consult with a significant segment of the scientific community to assure that the proposed procedures are scientifically accepted and meaningful for new food additives. THIRD PARTY TESTING We understand third party testing to mean a system outlined in your letter as follows: The (third party testing) plan advocated in hearing testimony seeks to establish within the FDA a chemical testing referral board, which has the authority to advertise for contract bids from the chemical industry to commercial laboratories. This would establish an industry-supported, but inde pendent, system monitoring our present reliance on the industry's own efforts. Briefly, the advocates of third party testing suggest that industry scientists are biased and cannot be relied upon to bring forward reliable research. In turn, it is claimed that consulting laboratories, since they are bound to the sponsor by financial ties, are also biased. We reject these false premises. This unsubstantiated charge is not an indictment against industry but against the scientific community at large. The solution offered to correct the alleged problem is inappropriate and not in the best interest of the American public. Today, consulting laboratories are selected on the basis of their competence to perform needed research at a fair cost. If manadtory third party testing were required, the authority to select the most competent laboratory-the single most important decision-would be delegated to someone unfamiliar with all the details. The balancing of in-house capabilities with the judicious use of consulting laboratories has effected the safety evaluation of a host of important food ingredients. The decision to utilize an outside consulting laboratory is based on an assessment of in-house testing capabilities and current work levels. Trained scientists and technicians working in industry are as competent and professional as their colleagues working in other settings, and many of our members have invested heavily in research capabilities. It has been suggested that FDA needs better communication with industry on protocols, data, interpretation, etc. The suggestion does not give due recognition to the joint planning and the fact that many, although not all, current studies are agreed to after consultation with FDA scientists. Protocols and intermediate test results are available to the regulatory agencies in most cases simply for the asking. When a food additive petition is filed, all of the test results must be shared with the government. None of the data can be withheld. This permits the government to arrive at a judgment as to the safety of a food additive totally independent of the interpretation and conclusions of the sponsor. Dialogue between the sponsor and the consulting laboratory is an essential feature to assure competent results. It is unreasonable to expect that a government "baffle" designed to assure impartiality can faithfully transmit industry's thinking to a third party. The Food Additives Amendment clearly obligates the sponsor to define safety. The corporate scientist's primary mission is concentrated on the compilation and interpretation of required data on limited numbers of specific compounds. It would be unreasonable to assume that a scientist within the regulatory agency with his diverse responsibilities could focus as much time and attention to a few compounds. Finally, the grocery industry is not interested in simply passing minimum regulatory goals. Our dedication to superior quality assurance programs is a basic industry tenet. In the competitive grocery business, corporate/brand images are achieved by repeated favorable consumer experiences. The stewardship of corporate integrity, brand images, and consumer trust means that companies are rarely satisfied simply to meet minimum regulatory requirements. To excell in quality assurance is to guarantee a corporate future. PUBLICATION OF PROTOCOLS Heretofore, the Commissioner has been guided by the principles and procedures for the safety of food additives stated in current publications of the National Academy of Sciences/National Research Council. Proponents suggested that FDA publication in the Federal Register could provide more formal direction to the food chemical industry as to exactly what testing is currently required by FDA for approval of new food additives and could minimize testing delays. While this recommendation may sound plausible, it may prove nearly impossible to develop recommendations which are applicable to all compounds. To anticipate each of the variables in a prescribed protocol appears to be an impossible task. For example, testing would vary depending upon (a) the expected intake level, (b) the uniqueness of the compound, (c) its metabolic fate, (d) degree of absorption, (e) interaction with other food additives or drugs, (f) test results to date, etc. The current practice which has proven successful-that of conversations between industry and FDA scientists-should be continued and perhaps expanded. These conferences permit testing programs to be tailored to the particularities of each compound. There are advantages in scientific publications which summarize current thinking on the advantages of various testing, such as the report of the Advisory Committee on Protocols for Safety Evaluations: Panel on Reproduction Report on Reproduction Studies in the Safety Evaluation of Food Additives and Pesticide Residues (Toxicology & Applied Pharmacology, 16, 264, 1970). Such FDAsponsored documents are very helpful and permit scientific debate on highly technical questions. To codify in the Federal Register technical issues which continue to change as new information is gathered is to disregard all experience from the past. Both the issues of third party testing and the publication of protocols presume that toxicological testing is a set procedure. A predesigned, required protocol implies that there is a maximum and minimum test program. As a result, there may be too little testing or too much, based not on the accumulated evidence but on what is defined by the regulatory agency. If we could anticipate the future, there would be little need for safety testing. We need flexibility, not rigidity, to assure food additive safety. GMA appreciates the opportunity to respond to these issues. Sincerely, GEORGE W. Koсн, President. |