Addendum to Testimony Regarding Technical Drafting Issues Relating to H.R. 3074, Lopid Patent Term Extension and Fairness Act of 1987 like Mr. Chairman, before concluding my remarks, I would also to address concerns which may be raised today regarding the language of H.R. 3074. Specifically, I understand there may be some question as to the possibility that the provisions of my bill may be applicable to more than one drug. In response to such concern, let me state unequivocally that the intent of H.R. 3074 is to provide legislative redress in the form of a five year statutory patent extension one, and only one, drug: Lopid. If further assurance for is needed to ensure that only this one drug is covered by the provisons of H.R. 3074, I would be amenable to discussing any appropriate redrafting that would satisfy you and the other members of this Subcommittee. In this regard, I would suggest that language could easily such as reference to the date of the FDA letter of NDA approval for Lopid - to meet such concerns. Moreover, I want to assure the committee that I am ready and willing to address this or any other technical drafting issue that may be identified today. Mr. KASTENMEIER. We thank our colleague for a brief butMr. DERRICK. Well, you know, Bob, I serve on the Rules Committee, and I appreciate brevity. I hope the Committee does, too. Mr. KASTENMEIER. We know how it is when we appear before the Rules Committee. I just have really one question I would like to ask of you, and we will have opportunities to ask other questions of other witnesses. Do you, therefore, consider that H.R. 3074 is really a private bill rather than a public law? Mr. DERRICK. Yes. As I understand it, it would be under the provisions to preserve justice and fairness in the application of the public laws when, as I said in my testimony, something slips through the hole. That would be the case, yes. Mr. KASTENMEIER. Does anyone else have any questions of our colleague? Mr. MOORHEAD. I just want to make a comment that we really welcome you here to this Committee. Many of us appear before you, and you do not get over here to visit us very often. We very much appreciate the courtesy that you give us, and we try to return the same to you. Mr. DERRICK. Well, it is a little different sitting on this end of the room. Thank you, Carlos. Thank you very much. Mr. KASTENMEIER. Does any other member of the Committee have any questions for Congressman Derrick? If not, we thank you very much. Mr. DERRICK. Thank you very much. Mr. CROCKETT. I have no questions, Mr. Chairman. I would like to associate myself with Mr. Derrick's comments primarily because this company was formerly a constituent in my congressional district. Mr. DERRICK. They did not go to my district from your district, I hope, did they? [Laughter.] Mr. CROCKETT. Thank you, Mr. Chairman. Mr. KASTENMEIER. Judge Crockett's loss is your gain. Mr. DERRICK. Thank you. Thank you, Mr. Crockett. All of you have a nice weekend. Mr. KASTENMEIER. Now the Chair would like to call a panel of witnesses, two witnesses, representing the Administration. They are Dr. Frank Young, Commissioner of the Food and Drug Administration, and Rene Tegtmeyer, Assistant Commissioner for Patents from the Patent and Trademark Office, U.S. Department of Commerce. We are delighted to have them both. They are both very knowledgeable people who have the utmost respect of the communities that they regulate or serve, as well as the Congress. I am also informed that accompanying Dr. Young is Mr. Scarlett, counsel for FDA. He, too, will be part of the panel. First, I would like to call on Dr. Young. You may proceed as you wish, Doctor. TESTIMONY OF FRANK E. YOUNG, M.D., PH.D., COMMISSIONER, FOOD AND DRUG ADMINISTRATION, ACCOMPANIED BY THOMAS SCARLETT, ASSOCIATE GENERAL COUNSEL, FOOD AND DRUG DIVISION; AND HON. RENE D. TEGTMEYER, ASSISTANT COMMISSIONER FOR PATENTS, PATENT AND TRADEMARK OFFICE, U.S. DEPARTMENT OF COMMERCE Dr. YOUNG. Thank you very much, Mr. Chairman. I greatly appreciate the opportunity to be here today to provide your Subcommittee with any information that I can in your consideration of H.R. 3074, the Lopid Patent Term Extension and Fairness Act of 1987. As I understand it, the purpose of the legislation is to extend the patent which claims the new drug product called Lopid, a lipid-regulating agent, if the Food and Drug Administration approves this drug for a second indication. As you know, the drug was originally approved for marketing in 1981 for a narrow indication. In our public health regulatory mission in the case of new drugs, we are responsible for reviewing whether an applicant for marketing approval has established the safety and effectiveness of the drug for its intended use. In making this determination, we do not consider economic factors or matters relating to the patent laws. I am particularly pleased to have my colleague from the Patent and Trademark Office here today to address that segment. Although we supported the enactment of the 1984 patent extension law for drugs on the grounds that it would foster innovation in the pharmaceutical industry, we have no position on the merits of individual patent relief based on possible adverse financial consequences caused by that 1984 law. I would like to, therefore, just briefly summarize the regulatory history and then answer any questions that I can for you. The new drug application for Lopid was submitted to FDA in November 1980 and was approved in December 1981. The initial application was for the use of Lopid for lowering blood cholesterol and triglycerides. In our review of the clinical studies, we concluded that our general requirements for demonstrating an effect in reducing triglycerides were met, but they did not meet all of the requirements for lowering cholesterol. Thus, the primary indication FDA allowed in the physician's package insert labeling was for lowering serum triglycerides rather than for lowering serum cholesterol, although a very restricted indication for lowering serum cholesterol was permitted. It was the FDA policy to require all sponsors who sought cholesterol-lowering claims to conduct post-approval studies, primarily to obtain additional information on safety. I have reviewed the correspondence between FDA and Warner-Lambert and have noted that the company was requested to-and I quote from a September letter "conduct an appropriate Phase IV study of certain aspects of effectiveness and long-term safety of gemfibrozil" in the approvable letter. In this particular case, we were concerned because Lopid is chemically related to another drug that was found to have excess mortality in the World Health Organization clinical trial, and also because the indicators for the effect on the cardiovascular system are indirect and primarily looking at the lowering of triglycerides and the lowering of cholesterol itself. Mr. KASTENMEIER. Dr. Young, it might be a good point to interrupt, since there was reference first in the presentation to Phase IV testing. To an uneducated panel could you indicate to us what Phase IV testing is and what implications it has generally? Dr. YOUNG. Surely. I appreciate your asking this. I have learned in my three years in Washington that there is a lot of jargon, and I frequently do not explain the language that we use. I am delighted to do so. I will go back right to the beginning, if I could, to put it in perspective. Drugs are developed through the analysis first of laboratory and animal experiments before human experimentation begins. At the onset of human experimentation, the sponsor files with FDA an application for an investigational new drug. One then goes through a number of phases, not necessarily in sequence but usually in sequence. They are Phase I, in which the drug is given to between 40 to 80 patients, and one looks at primarily factors that influence safety; Phase II where one enlarges the number of patients that are under study, usually a hundred to two hundred patients, and begins to look at effectiveness in addition to safety and concentrates on the dose used. After that, we recommend a conference with FDA to determine the best ways to move towards Phase III studies, which verify the clinical findings. After the verification studies, the company usually spends a few more months putting together a rather large application. It can amount to as much as 100,000 pages. In fact, a recent application that was submitted for AZT or Retrovir was 20 linear feet. That application is submitted as a new drug application to FDA. FDA then reviews the application, usually taking approximately 24 months. In this year, there were two drugs that we did approve in less than a year, but that is infrequent. Then in many instances, for a variety of different reasons, we require a Phase IV study. This may deal with small issues that are of concern to FDA. They also may focus on some safety and effectiveness issues as well. I went back and read the correspondence in my attempt to construct what this Phase IV study meant to the general Phase IV studies, and I will come to that in a moment. But the idea is to provide additional information that is important for the understanding of the claims of that particular drug in some instances, the enlarging of claims of that drug in some instances, focusing on long-term safety concerns, particularly if the drug is going to be used throughout one's life. In this particular case, when I looked at the letters back and forth, I noted that in the earliest letter, the one on September 21st that I quoted from, there was a recommendation that the drug-I will get the letter for you, if I may. The focus was on an additional study dealing with the safety and effectiveness of certain aspects of that particular drug. Then in the reply to that letter, that request for the study was acknowledged by the company and then acknowledged back in a letter from Marion Finkle that was dated December 21st. In that one, the oper ative paragraph was, "We also refer to your communications of October 8, 27, 29 and November 9." Parenthetically, they dealt mostly with labeling. "And in your October 8, 1981, letter, you stated that Phase IV studies that we requested as condition for approval had been undertaken." It was that dialogue back and forth that I referred to. So there are a variety of reasons for Phase IV studies, and in this case it seemed to be both for safety and for efficacy, and there was a reference to the Finnish study that was designed to provide these answers. I should possibly provide one bit of clarification that is of interest in lipid-lowering drugs. One always looks for, wherever possible, an effect on the patient. So if a study provides information on morbidity-that is, changes that affect the health of an individual-or mortality, leading to changes which would influence death of patients, you can certainly say that a drug is clearly effective. In all of the lipid-lowering drugs, there is a problem because you can see triglycerides going down, serum cholesterol going down, but then to make that leap into the effect on patients usually requires a larger study. In more contemporary terms, you see that controversy being played out in the case of TPA as the Agency is trying to act now on the Advisory Committee's recommendations to it. The concern was the drug dissolves the clot, but does that have any effect on the patient? So the concern is here that cholesterol might go down, triglycerides might go down; what effect does that have on morbidity and mortality? The Agency clearly approved it for the narrow claim and asked for the safety and effectiveness Phase IV study as part of its further evaluation process. I am sorry. That was a longer answer, but it was a very perceptive question that you asked. I should have had that information for you. Mr. KASTENMEIER. Well, I appreciate the response because I think we need to understand what we are talking about when we discuss a Phase IV study in terms of the sequence of events and what an applicant goes through and the reasons for it. You have given a very good answer. Please continue, Doctor. Dr. YOUNG. Surely. The manufacturer of Lopid has conducted such a Phase IV study. In this instance, the study, which was proposed by the manufacturer, was designed to look at both coronary artery disease as well as excess mortality. It comes right to the center of the question that you raised. The drug might not only have some effect in lowering chemical parameters in the body, but also it may affect the wellbeing of a patient. That is the bottom line that one looks for. As a physician, you are not just looking for chemical changes but changes that will affect the well-being of a patient. It is our understanding that the data have been assembled, and we expect to receive it shortly for our detailed review. In your letter of invitation, you expressed a special interest in how many patents would be affected by the proposed legislation. In the tabulation that we maintain on post-marketing studies, we list |