these animals to small amounts of widespread or widely used chemicals, comparable to human exposures to the same chemicals. The toxicologic effects which will be looked for will include, but will not be limited to, cancer, deformities, and genetic mutations. The importance of such studies lies in the fact that many chemicals occur quite commonly in our food, water, and air in small or trace amounts and we need to determine the risk to health that may be associated with their occurrence.

Since the problems of toxicologic effect are not unique to any one Federal agency, and since the Center contains much highly sophisticated scientific equipment that will be of value in other types of study, it is planned to make other agencies welcome to use such facilities as may be available from time to time. FDA will be responsible for its administration but FDA will be advised by a multi-agency Policy Board that will approve all projects undertaken at the Center, basing such approval upon priorities of national need.

It is anticipated that each Agency having work performed at the center will, or at least may, have a resident agent or staff maintaining liaison with the work being performed on its behalf.

16. What arrangements have you made to ensure that the interests of consumer, occupational, and environmental groups are adequately represented-legally and scientifically in the formal stages prior to FDA decision-making? How many of the several FDĂ Advisory Committees include such consumer group members?

A. Almost all FDA regulatory decisions are published for comment in the Federal Register prior to promulgation for effect. The high frequency of comment from organized groups speaking for consumers, for environmental protection, and for various special interests indicates that this is an effective means of communication with organized groups of this kind and with individuals who have chosen to be spokesmen for these interests. In addition to the written comments, FDA's top officials meet on request with representatives of these groups. Recent examples: 1. A meeting FDA's Associate Commissioner for Compliance and Director, Bureau of Drugs, held with representatives of the Center for Law and Social Policy on the Final Order entitled "Institutional Committee Review of Clinical Investigations of New Drugs in Human Beings.” (Orginally referred to as "Peer Group Committee Review.")

2. A meeting Commissioner Edwards, Associate Commissioner Fine and Assistant General Counsel Goodrich held with the five law students comprising LABEL, Inc., on their petition to promulgate a regulation requiring declaration of mandatory ingredients on standardized foods.

Existing Food and Drug Administration public advisory committees are of a scientific and technical nature, dealing with a particular class or aspect of foods, drugs, or with a particular medical or veterinary science, and are staffed with academic, medical, and veterinary people. We have no committees operating at present which are structured to include consumer, occupational, or environmental representation.

The Poison Prevention Packaging Technical Advisory Committee established under the Poison Prevention Packaging Act of 1970, P.L. 91-601, will include representation from consumer and public affairs groups. The nominations for this committee were recently approved by the Secretary and the committee met for the first time in May.

We are also about to request the Secretary's approval for the establishment of a National Advisory Drug Council to advise the Commissioner on policy matters of national significance. The Council will include membership from consumer, education, and public affairs groups.

17. The April 2, 1971 issue of Science contains an article entitled, "Food and Drug Administration: Is Protecting Lives the Priority?" (Copy enclosed) Since this raises a number of questions of FDA procedures in general, we would appreciate your opinion of the charges. If any of the allegations are false, describe how they are inaccurate and inform me of your choice of action in this situation.

A. Generally, the Science article represents a considerable distortion of the events discussed and, of course, includes a great deal of information obtained by the author from sources outside this agency and persons other than Mr. Blatt. Since essentially all of the information Mr. Blatt provided to Mr. Robert J. Bazell has been taken so far out of the context of the conversation with him, it is neither desirable nor possible to rebut each of his allegations. Mr. Bazell was apparently unwilling to accept the basic concept that the "problem" of which FDA became aware in mid-December 1970 was not the ultimate problem with

which FDA is now dealing (microbiological contamination associated with the Abbott screw-cap closure).

The Science article states at one point that Dr. Duma, the senior author of the article "Septicemia from Intravenous Infusions" ultimately published in the New England Journal of Medicine on February 4, 1971, advised FDA of this problem in July 1970, yet at another point states that FDA learned of the problem in January 1971. To the best of our knowledge, our initial awareness of Dr. Duma's findings came on December 10, 1970, in a conversation between Dr. John Bennett, CDC, and Mr. Robert C. Swanson, Office of Associate Commissioner for Compliance, FDA. In fact, the original draft of Dr. Duma's paper was dated August 7, 1970. The first time FDA saw Dr. Duma's drafts was approximately December 17, 1970. Review by CDC and FDA resulted in the conclusion that the paper, as a scientific document, served no purpose other than as an indicator for additional followup. This was undertaken by CDC in a study at the University of Virginia Medical Hospital at Charlottesville in February, 1971.

The chronology of the entire sequence of events is relatively clear. Basically, however, the realization that a problem might exist with the product was reported to FDA by CDC on March 1, 1971. Prior to that, both FDA and CDC believed the problem was one of hospital technique and the possible design_weakness of the intravenous administration sets. Even on March 1, CDC and FDA had no basis on which to reach a conclusion. On March 2, Bureau of Drugs, FDA, advised the Regional Food and Drug Director in Chicago of the possible problem and suggested he discuss this matter with Abbott Laboratories at a previously scheduled meeting in Chicago on March 3, 1971.

Subsequent to that date, Abbott Laboratories, which had been advised of CDC's findings, requested a meeting at CDC. On Tuesday, March 9, Dr. Dennis Maki, CDC, called and said that Abbott had requested a meeting on the latest aspects of the problem. Dr. Maki requested that FDA representatives be present. It was not until Wednesday afternoon, March 10, that CDC advised the FDA representatives of the details of their findings, and not until March 11, that CDC gave FDA (simultaneously with Abbott Laboratories) an indication of their projected actions. Upon receipt of additional data, including information concerning production capabilities of other manufacturers, FDA requested Abbott to recall its stocks.

WASHINGTON, D.C., January 11, 1972.

Hon. ABRAHAM RIBICOFF,
Senate Office Building,

Washington, D.C.

DEAR SENATOR RIBICOFF: Enclosed are my comments on the FDA's response to questions about "Chemicals and the Future of Man." I believe that a serious problem exists in the food and drug regulatory authority. I do not believe that it is possible for the FDA to operate on the premise that anything should be allowed in the food supply until it is proven to be unsafe. Such a premise lowers the protection of the consumer of food below an acceptable level.

It appears to me that the recommendations made by Dr. Epstein during the hearings were sound and need to be implemented. I have commented in some detail on those that FDA responded to in the enclosure to this letter. However, I think it is quite important that we establish a screening system that will separate out chemicals which have potential dangers from those that do not indicate potential dangers. I think that those chemicals which are potentially dangerous must be subjected to rigorous study and used only under the most compelling conditions requiring their use.

Concerning the question of efficacy, I believe that chemicals should also be divided into two groups. I believe that a group of chemicals should be identified which serve no useful purpose in the preparation, marketing, distribution of food. These chemicals should not be used in the food supply. Conversely, I believe that there are chemicals that are essential for use in the food supply, but all of them must be subjected to the rigorous testing program outlined above. It appears to me that the chemical environment in this society is posing significant problems of health to the society. It is unclear just how widespread that problem may be. It is important at this time to adopt a policy of caution in an effort to undo whatever damage may have already been done and to eliminate the possibility of future damage. The fact that science is limited should not be used to justify the excessive use of chemicals. Rather it should be a warning to cause us to move ahead cautiously in the use of chemicals.

I have enclosed a copy of a law journal article which adresses the subject of chemicals in the environment and relies heavily on the very wise policy decision embodied in the Delaney Amendment to the Food and Drug Law. I hope that these comments will be useful to you.

Sincerely yours,

P. M. NEAL, (For James S. Turner).

COMMENTS ON FDA FOOD SAFETY TESTING

1. The FDA states "the Commissioner will be 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." This guideline is an imperfect one. The NAS-NRC has articulated a concept known as "toxicological insignificance." This concept is currently a matter of serious debate in the scientific community.

Specifically, the NAS-NRC seems to argue that traces of cancer-causing chemicals can be safely included in food products. Contrary to this position, the National Cancer Institute has argued that there can be no safe level of a carcinogen in food. The committee of NCI experts that argued against the concept of "toxicological insignificance" specifically singled out the NAS-NRC publication on this subject as being flawed and not worthy of implementation. That the FDA should rely on NAS-NRC guidelines in view of this controversy is disturbing. The fact that the FDA has indicated dose levels at which it will institute certain types of toxicological testing makes the FDA position on carcinogenic testing even more disturbing.

2. The point of all mutagenicity and teratogenicity testing is to divide up chemicals into three separate categories-those which are clearly safe, those which are clearly unsafe, and those about which there is a question.

The usefulness of any kind of required test is in fact as a screen: exactly the FDA indicated present capability. Chemicals should be run through the screen in order to separate out those which do present a hazard. Then those that do not present a hazard can move ahead without any hindrance. Those that do present a potential hazard could at that point then be subjected to the more sophisticated types of testing now being developed. At least there should be an indexing of these chemicals by using the currently available screening type tests.

The problem with the FDA answer to number two is that it is still trying to and a definitive basis for human safety. This is not a real possibility as everyone in the field knows. The argument then boils down to this question: if we cannot have definitive safety, how do we proceed? Do we include those items which are potentially hazardous in the food supply or do we proceed to use only those which presently appear to present no hazard?

The current food safety issue presents a basic policy question. Shall the use of chemicals in the food supply and the environment be encouraged or discouraged by public policy? That question must be answered before FDA regulatory methods can be evaluated. Once that question is answered, one of two courses of action must be followed. If public policy becomes the encouragement of the use of chemicals in the environment, then the procedure that is followed by the FDA presently should be continued. However, if the policy decision is to discourage the use of chemicals, then we should begin a new method.

That method would consist of: (1) screening all chemicals so that those that present any potential hazard are set in one category and those that present no potential hazard are set in another category. (2) Only those chemicals which present no potential hazard shall be placed in the environment and in the food supply without any further action. (3) Those that do present some potential hazard shall have to undergo further testing in order to determine the nature of the hazard. Unfortunately, the argument that it is difficult to present a definitive basis for human safety is used now to discourage vigorous testing. It should in the future be used as a warning against the uninhibited use of chemicals in the environment. In short, a new standard for the use of chemicals must be created. Specifically, it must be made clear that no chemical shall be included in the food supply or in the environment unless it performs some useful purpose. At the same time that purpose must outweigh any potential risks associated with use of the chemical.

While there is some considerable diversity of opinion about how to predict the mutagenicity of a chemical, there is not very much disagreement that chemicals are related to genetic defects. Scientists know that some chemicals cause damage but they do not know which chemicals cause which damage. In this situation, given the limitations of science, we must decide whether to proceed in ignorance or to use caution. We do know, however, that there is a serious potential problem related to our actions if we do not act with caution. Are the benefits of chemicals worth it?

The FDA guidelines which have been made available to interested parties in industry and the academic community should, if not already, be made available to the general public as well.

3. The FDA adverse drug reaction reporting program does not work very effectively. Most of the adverse reaction reports are sent directly to the manufacturers of the drugs. The manufacturers then immediately screen these reports. The companies have a decided bias in their screening to try to show that their drug was not in fact the cause of whatever the adverse reaction is. As a result histories are prepared of the individual patients at the time the incident is reported that tend to give weight to those factors which suggest that the drug did not in fact cause the adverse reaction. The adverse reaction report system operating in this manner must not be allowed to continue to distort the reports received from physicians.

The need is for more than just the detailed, technical aspects of reporting to be looked into. The FDA must work out some kind of reporting system which is easily monitored by the public. This means that in every way every time that an individual has an incident occur which can be related to a drug reaction, this information must be made known to others than merely the FDA and the drug company. It is possible to do this in a number of ways. One would be to require a publishing, not necessarily by name, of all the events surrounding a particular, reported reaction in such a way that it can be looked at by others. Even more

basic than that, many of the drug reaction reports do not ever reach the FDA and this also must be clarified in some way.

4. It is important to point out under four that the toxicological data are not released but a summary of the toxicological data is released. The data in summary form are of little value to a scientist in making an appropriate evaluation.

For example, in the area of radiation used as a food additive, the summaries of the data misled even the FDA. However, when the FDA was able to collect all of the data, after having its curiosity aroused by suggestions published outside the agency, it was able to discover that the tests themselves did not establish safety. The point is that summaries of the toxicological data are not in fact of much use. Furthermore, a careful reading of the exemptions that the FDA claims for itself will reveal that the FDA believes that whenever it is not required to release a document, it is justified in withholding it. It is this very policy which lies at the heart of the FDA's information problems.

The Freedom of Information Act divides data into three categories: data which cannot be released under any circumstances, data which must be released under all circumstances, and data which is within the discretionary judgment of the FDA. Much of the data which people now seek from the FDA is in the discretionary area and the FDA chooses not to release this material. It chooses not to release this for public policy reasons which reflect a position favorable to the industries that present the data to the FDA. It is in this area that the FDA is most suspect.

"kinds of material which are exempt from mandatory disclosure . . . respecting Food and Drug Administration regulatory activities: trade secrets or commercial or confidential information (Notice the subtle change. The Food and Drug Act which this prohibition is based on only prohibits the release of "any method or process which as a trade secret is entitled to protection.") voluntarily revealed in requests for opinions and related records indicating that a person, firm or product is or is not in compliance with the law; records relating to factory inspections, sample collections, seafood inspection, and other examinations and investigations by the Food and Drug Administration; investigational new drug files; new drug applications and master files, other than final printed labeling; report and records relating to individual adverse drug reaction(s) data in support of petitions relating to pesticide chemicals, food standards, food additives, and color additives, and master files relating thereto; files relating to certification of insulin, antibiotics, and color additives, and master files relating thereto; notices of hearings issued to individuals and firms under 21 USC 335 and records related thereto; records relating to regultory activities of the Food and Drug Administration.

Note: Certain documents in some of the above files may be available upon request indentifying the particular documents.

In addition, the underlined portion of the 32 FR 11443 cannot possibly be considered to be adequate. The crucial problem here is that toxicological information should not be considered to be commercial property. When it is considered as commercial property, unnecessary financial and scientific costs result. Each company must at great cost reproduce the toxicological information on each chemical that it desires to market. As a result accumulated scientific data are kept locked away in FDA and company files.

This toxicological information is not of any great marketing value as a spur to marketing. It is only of value because it keeps others from proceeding to market on the basis of what is found by this toxicological information. FDA protection of information should not exceed that which is protected by law. Toxicological information is not necessarily a trade secret and it is not covered by patent protection.

5. An academician, if he receives his support from a company, is responding to a vested interest in the same way as would a commercial laboratory. That is the exact point of the proposal made by Dr. Epstein. In that proposal, the company wishing to market the chemical would approach the FDA and say "we have a chemical we would like to have tested." The FDA would then turn around as a buffer and seek a third party tester. The third party tester could be an academician, it could be an independent laboratory. It could be one of any number of various kinds of laboratories. Apparently there are about 15,000 facilities in this country available to do testing of this kind.

The point is that the company would pay the money to the FDA and the FDA would pay the money to the third party tester. Thereby no academician or company laboratory or independent laboratory would be directly dependent upon a company for its money. In addition, the FDA would inspect the laboratories to