one. But in terms of our requirements for animal studies, that is one of the principles of that Code and was followed up in the Helsinki Agreement. Mr. LUNGREN. So that is a recognized limitation on the ability of scientists or entrepreneurs, or however you want to define them, in terms of their own experimentation? Dr. Tocus. This is an ethic in terms of science and research in developing substances to be given to humans for the first time. Mr. LUNGREN. And that is the foundation upon which the FDA comes up with the procedures that require animal experimentation before human experimentation? Or a part of the ethical foundation? Dr. Tocus. I couldn't say that is "the," but I would certainly say that it is consistent with the ethics of doing experimentation in humans, yes. Mr. LUNGREN. I guess I would address this question to the panel because I think it is part of the criticism that this bill may engender. Have you had complaints from small researchers that your requirements are so expensive and extensive that they prohibit development by anybody but large pharmaceutical companies? Dr. Tocus. We have had that complaint over the years. That small pharmaceutical companies may come in, they have come in, they explain they don't have the resources and they would like exemptions. We explain that since their product will be on the market and will be available to the entire United States population, and that the safeguards built in by the Food, Drug, and Cosmetic Act must apply. Their size is not material in the scientific development of a drug. Mr. LUNGREN. So you have had that complaint before. Mr. LUNGREN. And you try and at least Dr. Tocus. We sympathize with them. We refer them very often to larger pharmaceutical companies who may be interested and have the resources. We refer them to other organizations that may have resources to fund studies that need to be done if they can't. But there is no exemption. Mr. LUNGREN. What I am trying to do is figure out which complaints against the bill are specifically focused on the bill and which complaints are generic; that is, to the way things are occurring with respect to the FDA, which, if I get a sense of that I can find what response we can make in the bill, if it is endemic to the bill, and what we cannot do. Can you tell me whether there is any waiver for a university medical center, a university psychological department, that allows them to do drug tests on humans without an IND? Dr. Tocus. If the substance is an investigational new drug substance under our regulations, that is, as I explained, it is not marketed, does not have an approved NDA, it is entering interstate commerce, and it has no IND, there is no exemption. The requirements are uniform. Dr. Houk. Mr. Lungren, pardon me. Mr. LUNGREN. Yes. Dr. Houk. There is not even an exemption for the Federal Government. Mr. LUNGREN. Pardon me? Dr. Houk. There is not even an exemption for the Federal Government. Mr. LUNGREN. Geez, that is one we missed along the way I guess. [Laughter.] OK. Thank you very much. Thank you, Mr. Chairman. Mr. HUGHES. Let me just follow up, if I might, just on that point once again dealing with what would be caught by existing law; who would have to, in fact, register. If I were a private researcher, a physician, working with a couple other physicians and I developed an analog that I want to test. I don't want to distribute or market in interstate commerce, but I want to test on some patients. What is required of me by Federal law presently? Dr. Tocus. You must demonstrate that the substance that you want to test is chemically within certain limits in terms of purity. You must demonstrate, with results of animal toxicity studies, that the doses that you want to give to humans are reasonably safe by the route that you want to give them. Mr. HUGHES. I have to establish that to the Food and Drug Administration? Dr. Tocus. Yes. But you really should want to establish that to yourself. Because if you are a physician and you are going to expose your patients, you must certainly have some scientific data which demonstrates satisfactorily Mr. HUGHES. Would I fall within one of these two exceptions? Mr. HUGHES. Would I fall within one of these two exceptions: an exemption for investigational use within the meaning of section 505 of the Federal Food, Drug, and Cosmetic Act Dr. Tocus. Yes, sir. If you submitted an IND application to the Food and Drug Administration, then you would be exempt. Mr. HUGHES. Or a new drug application? Dr. Tocus. Well, a new drug application is way down the line. That is after we have got all the studies completed. Mr. HUGHES. But I would fall within the exemption, section 505? Dr. Tocus. Yes. If you submit an IND to the Food and Drug Administration. Mr. HUGHES. And I would be required to? Dr. Tocus. That is my understanding. Mr. HUGHES. Before I could conduct that kind of research, I would be required to file an application with the Food and Drug Administration? Dr. Tocus. That is my understanding. Mr. HUGHES. There is a number of other areas that we have to get into, and that is another vote. So I hate to ask you to remain for a little bit, but I am going to recess for another 10 minutes. [Recess.] Mr. HUGHES. The subcommittee will come to order. I know, Dr. Houk, you have a plane to catch. We can just take your area, then perhaps excuse you, then I will get back to this other area. I understand that the proposed rescission of that million dollars that your center has for its research in these analogs has been re jected and that money will be spent for your center. Am I correct in that? Dr. Houk. Yes, sir, you are, Mr. Chairman. Mr. HUGHES. I see. Is that adequate resources given the dimension of the problem? Dr. Houk. We have designed a program using that million dollars to initiate something and, if I may, I would like to describe what we know now and how we are going to go about using the million dollars this year to learn more. In California we know that, as you said in your opening statement, there are hundreds of people involved-there are at least 10 who have definite Parkinson's disease or Parkinson-like things, and dozens more who have symptoms like that. We have 287 people who have been definitely exposed who are being followed in a longterm follow-up. In Florida, there is at least one person who has known Parkinson's and several suspected cases. In South Florida it appears that the MPTP analog is present both by itself, as a contaminant of what is labeled as heroin, and as a contaminant of what is labeled as cocaine. Also based on the description of the kinds of drugs in use it appears that we have a similar problem in Detroit and also the State of Texas. And I think to say that the problem is limited to those areas does not meet with fact. We certainly think that it is beyond that. What we intend to do in addition to following-up to learn more about this-and as Dr. Hawks says, the administration and HHS certainly support our efforts, to try to stop this and to deal with what is already out there, are the following kinds of actions. As Senator Chiles mentioned, one of the major things is going to be an educational program in the very low levels of the schools. And this is not going to be textbooks. We are trying to figure out ways now that we can use the video tapes that you have now if we can resolve the privacy issues. If the kids see the results of taking these drugs this is the best thing. We have experience in smoking and a few other things, that indicates more impact if they actually see the damages rather than being told about them or the elusive idea of death. In addition, we are going to establish a surveillance system with the forensic pathologists in the country to assist them when they have deaths or overdoses of unknown kinds, to determine whether or not it was a "designer drug" rather than some unknown cause. We will set up a surveillance system with the neurologists in the large cities of the country specifically looking for young people with Parkinson-like disease. In addition, where we have some reason to suspect potential problems we will try to set up some focus where people can send anonymously samples of their street drugs and the drugs that they have to be analyzed. And they can get that report back on an anonymous basis with a number, but in addition to that, it will give us a handle of where these "designer drugs" are located throughout the country and in these particular cities. And last, but equally important, is to develop some standards for safety for the Drug Enforcement Administration inspectors who raid the clandestine laboratories and are involved with other ac tivities that might result with dangerous contacts with these drugs. Because there is pretty good evidence that a very small amount of this entering the body inadvertently through the skin or just inadvertently taken in by someone who didn't intentionally do it can produce the same kinds of health problems which the drug abusers experience. We put very high priority on trying to solve this problem, getting information out to the people in Florida and California, a large distribution to the medical community, but more importantly, to the drug-abusing community-the streets, the clinics-of what they can expect if they handle or their hands on some of these products. I would urge since we are going to be dealing a lot with youngsters that we try to get rid of the term "designer drugs." Designer refers to "Calvin Klein" jeans, designer shoes-generally good things, as does "recreational." We need some other term that has the connotation that it is a bad substance. Mr. HUGHES. Do you have a suggestion? Dr. Houk. I think "controlled substances analog" is a very good one. Mr. HUGHES. I see. It sounds like you have a number of initiatives underway to deal with the controlled substances analog problem. Have there been any research programs cancelled, any initiatives cancelled, for lack of resources? Dr. Houk. We have been involved in this since 1983 using our own funds under other authorities, principally section 301(a) of the Public Health Service Act. We have not had sufficient moneys to do as much as we want to. There has been nothing cancelled. We would not use this money that is coming to us that Senator Chiles was instrumental in getting into the Senate appropriations for basic research on Parkinson's disease as it relates to this drug. We think that these moneys are for the purposes of trying to prevent the spread of these drugs among young people and to other people, and there should be other moneys to do the basic scientific medical research on Parkinson's. Mr. HUGHES. Thank you, Doctor. We appreciate your testimony. And you are excused so that you can catch your plane. Thank you so much. Let me, if I might, Dr. Hawks, just take you back to the central question of the breadth of the statute and whether or not it is going to catch unwittingly people who are conducting bona fide research. Any suggestions on how we can clarify it any more than we have in the proposed bills to make intent very clear? Dr. HAWKS. Well, let us say we have discussed that point among ourselves as well as with some of our grantees and contractors who work in this area, and without getting into what I would consider fairly cumbersome descriptive language of the kinds of situations that they would be concerned about, I am not sure we can do a great deal better than what is in there now. At least I haven't heard suggestions and I haven't been able to come up with much better ones on my own. It does say that we don't want to inhibit-in the bill-legitimate scientific research, and that is defined primarily by whether someone has an IND or an NDA application or whether they are using it for something other than human purposes. One could think of words such as establishing credentials for people who might not yet have an IND and who have been doing research on certain kinds of compounds or for certain kinds of purposes, but you very quickly get into the kinds of things that people would bring up if they were taken to court to prove their innocence, or from the other side, to provide their lack of innocence. It almost seems like those kinds of subtleties are going to have to be worked out when this bill starts being used for enforcement and from interpretations from the courts and in the policy that results from that. I don't have any immediate suggestions for changes in the wording. I think Dr. Tocus has a comment to make on that, if he would. Mr. HUGHES. When an analog is being investigated pursuant to an investigative process, they still are required to apply for registry with the Food and Drug Administration? Dr. HAWKS. If it is not intended for human use, there is no reason to. I mean, if there is not going to be human experimentation. Mr. HUGHES. If it is not intended for human use. Dr. Tocus. Mr. Chairman. Mr. HUGHES. Is that the only exception? Dr. Tocus. An application can be made to the Food and Drug Administration at any time along the development of the drug. They don't have to wait until they intend to give it to humans. Someone interested in developing a drug can make an application at the time they first synthesize it and carry that along. It is our belief that the Food, Drug, and Cosmetic Act is the best and quickest way to see a drug that has useful therapeutic uses gets to the market. We see that studies have proper controls. One of the things that we look at is the design of the studies to make sure that there is useful scientific information that is going to come out, that people aren't put at risk with the drugs that have no basis in scientific fact. Actually, the Food, Drug, and Cosmetic Act is the mechanism by which drugs can quickly come to market. One of the greatest rewards of working at the Food and Drug Administration is seeing a good drug get through and get out to the American people. That is what we want. If it has useful activity, we work with the scientists. But we make sure that it is on a scientific basis. Mr. HUGHES. OK. I don't have any further questions. The gentleman from California. Mr. LUNGREN. No, I have no questions. Mr. HUGHES. Well, thank you very much, Doctors. We appreciate your testimony. You have been very helpful to us today, and we appreciate that very much. Mr. HUGHES. Our last witnesses will appear as a panel. Our panel consists of: Mr. James N. Hall, the executive director of the Up Front Drug Information Center, Miami, FL, a member of the Florida cocaine task force set up by Governor Bob Graham and a member of NIDA's community epidemiology work group. Robert T. Angarola, a lawyer with the firm of Hyman, Phelps & McNamara, a professional corporation, here in Washington. Mr. |