FDA Reform in Congress: Interview with Peter Barton Hutt

Legislation to change the U.S. Food and Drug Administration has now been introduced in both houses of Congress. This legislation might become law, and interested parties need to make themselves heard now, as Congress must act quickly on these bills, or it will be too late for this year. Those who are not aware of the issues involved could miss the chance to have a say in decisions affecting them.

For one view on these issues, AIDS TREATMENT NEWS interviewed Peter Barton Hutt, who is widely recognized as one of the world's leading experts on FDA law. Mr. Hutt has practiced regulatory law for the past 35 years, and served as general counsel of the FDA between 1971 and 1975. He is now in private practice at the Washington D.C. law firm of Covington and Burling, and also teaches a course in food and drug law at Harvard Law School.

We told Mr. Hutt that we were especially interested in the earlier stages of the drug development process, as well as in the current legislation.

AIDS TREATMENT NEWS: Some people are saying that the rapid approval of protease inhibitors shows that FDA reform legislation is not needed, that any problems have already been fixed. What else should these people be aware of?

Hutt: The rapid approval of a number of new drugs shows that where FDA wishes to do so, it can place its resources and can improve the system. The difficulty is that those cases represent ad hoc decisions under a great deal of pressure at one particular point in time, and do not represent a systematic change in FDA procedures and policies. One cannot conclude that these improvements will apply for a longer time to a wider group of therapies.

The drug approval process cannot be viewed in isolation. It is part of an extraordinary lengthy discovery, research, and development process that now takes more than a decade. Only 20 years ago, the process from drug discovery to approval averaged approximately six to at most eight years. Today it is in the area of 15 to 16 years. The time required has roughly doubled during the last two decades.

What has happened is that the FDA has become more stringent overall in its requirements. While the time for APPROVAL has remained the same or diminished slightly, the time for research and development has escalated dramatically, making it take even longer for important new products to reach the marketplace. Therefore, in looking at legislation, one must focus on all aspects of this process, not only on the final decision of approval or disapproval.

ATN: Where in the earlier phases do you think major time savings can and should be made?

Hutt: They must be made in every stage. The first stage is preclinical testing. FDA has requirements that must be met before any drug can be put into a human. These have been relatively stringent and relatively inflexible. If they are made less stringent and more flexible, human trials could start more rapidly.

Second, one must look at the requirements FDA has imposed for submission of an IND application. [Note: An IND -- Investigational New Drug -- application must be approved by the FDA before a new drug can be tested in humans.] If you compare the size and content of an IND in the United States and in Europe, you will see that the one in the United States can be six or eight feet thick, and the one in Europe is six or eight inches. That difference represents an enormous investment of time, resources, and of course money. In Europe you can investigate more drugs than in the United States, because the investment required is less.

Third, when you look at the requirements for monitoring and record keeping, and adverse reaction reporting, in Europe vs. the United States, you understand why more and more clinical trials are being conducted abroad. You can do much more for less money, more quickly and more efficiently, abroad than you can in the United States. The consequence is that some investigational drugs which are available abroad cannot be used for any form of expanded access or compassionate use in this country.

ATN: The cost of new AIDS drugs is now a major issue. Could we reduce drug prices by cutting the cost of development?

Hutt: Time is money. The amount of resources needed to investigate and ultimately bring to approval a new drug depends on time, and also on the complexity of the requirements imposed. Regulatory requirements therefore directly decide the ultimate price of a drug.

ATN: Someone described the current "Good Laboratory Practice" regulations as 40 tons of cure imposed because of isolated instances of abuse.

Hutt: One company submitted fraudulent data on its testing of pesticides and other products. As a result, FDA imposed, in the late 1970s, stringent Good Laboratory Practice record keeping requirements that are enormously costly and burdensome.

Every bit of this contributes to cost and time. The difficulty is that, if you take any one of these issues in isolation, you can find some justification for it. In isolation, you can say, "That only costs so much more." But if you put them all together -- and consider that they have been added one on top of the other for the last 40 years -- you begin to understand the enormous impact.

ATN: How do the bills in Congress now address these problems? [Note: The bills referred to in the following discussion are S. 1477, introduced by Senator Nancy Kassebaum, Republican, Kansas, on December 13, 1995, and H.R. 3199, introduced in the House by Congressman Richard Burr, Republican, North Carolina, on March 29, 1996.]

Hutt: These bills are remarkably close in philosophy and intent. They are written with different words and phrases, but that should not be interpreted as meaning a fundamentally or structurally different approach. They are very similar.

ATN: We reported to our readers when a draft of the Kassebaum bill became available (see AIDS TREATMENT NEWS #235, November 17, 1995) that this bill focuses on procedures to hold the FDA accountable for its performance, rather than on mandating or micromanaging specific decisions.

Hutt: The same concept occurs in the House bill. That is why I said they are similar in concept. Both bills realized that you cannot focus on just one part of the total discovery, research, development, and approval process. You have to deal with every aspect of that or you will not make a difference.

Each bill has its strength and weaknesses. Let me mention one difference which is important, and may be misunderstood.

The Senate bill contains a provision, a strongly worded statement of philosophy, which says that any patient, through a physician, has the right to request an investigational drug for expanded access treatment use, and any company has the right to provide that. The company does not have an obligation to provide it, but they have the right to do so. That statement does not occur in the House bill, but the House bill clearly provides, without saying it, that the same is true.

My personal preference would be to include this explicitly in the legislation. But it is erroneous to think that the House does not agree with expanded access because it did not include this specific language. I would certainly support an explicit provision of that kind, which gives a flavor, tone, or mandate that otherwise might not be clearly understood.

ATN: But it does not create a new legal right?

Hutt: It is legally unenforceable in both bills, but it is nonetheless a very powerful statement of intent.

ATN: But you think that patient advocates might want to make it clear to Congress that they want the Kassebaum version to prevail in the final legislation?

Hutt: Yes. I believe interested people should make clear to the House that they consider immediately incorporating it into the next version of the bill.

ATN: And they could copy the language right out of the Kassebaum bill?

Hutt: Yes. The language in the Kassebaum bill to my knowledge has not been substantially opposed by anyone -- not by patient groups, not by the industry, not by consumer advocates, not by anyone. It may have been omitted from the House bill only because nobody lobbied the House on it.

Hutt: There is another important provision in the Senate bill that your readers should be aware of, and come to their own decision. Under current FDA regulations, for a drug treatment IND and for all medical devices, a company is permitted to charge for an investigational product. They can charge for the manufacture of the drug, for the cost of research and development, and for the cost of handling. Under the Senate bill, the cost of research and development was deleted.

The first question is, what does that mean? Will the FDA have to delete the cost of research and development from the treatment IND and medical device regulations? I do not believe that is what is intended, but the meaning is quite unclear. The second question is why was that provision deleted, who deleted it, and what was the intent of the Committee? That is unclear to me as well.

If in fact it means that companies would be completely prohibited from taking into account their research and development costs in charging for investigational products, it seems to me highly probably that far fewer companies would be willing to make investigational products available. They would be lucky to break even. Considering the time and effort it takes them to provide expanded access, it would undoubtedly not be worth their effort. In my judgment, this change would substantially reduce the number of investigational products available for expanded assess. People should consider this issue, and whatever their views are, make them known to both the Senate and the House. There is no comparable provision in the House bill.

ATN: What is the timetable for this FDA legislation?

Hutt: The timetable in Congress is tight. There are relatively few legislative days left in Congress this session. Senator Dole, on the campaign trail, did commit to bring this bill to the floor in the Senate, so it is likely that will happen.

ATN: Is Kennedy likely to oppose the bill, or not?

Hutt: The position of Senator Kennedy remains unclear. He voted against the bill in the Senate markup, but three Democrats voted for it. There are attempts to achieve compromise to make it less likely that he will oppose it. It is entirely uncertain what his ultimate position will be.

ATN: Is Kennedy concerned about allowing pharmaceutical companies to talk about off label uses of drugs?

Hutt: That provision was deleted from the Senate bill in the markup, because the Committee could not reach a consensus on exactly what it should say. There are efforts now to reach a compromise and put that provision back into the bill.

ATN: What are Kennedy's main objections at this point?

Hutt: That is a very long story. It appears that every time one of his objections is met, he comes up with a new objection on a different provision. There is some concern that there is an endless list that would gut the entire legislation if it were met.

ATN: Do you think the FDA wants to conduct a war of attrition against the bill through Senator Kennedy?

Hutt: In one syllable, yes. This is not a surprising strategy. The FDA is totally opposed to the entire legislation. There is nothing in the bill that is acceptable to FDA. It will do whatever it can to delay the bill or defeat it.

ATN: What can individuals and organizations do to get their views heard and considered on these issues, at this late time?

Hutt: People should work through their organized groups, which are singularly the most effective way of making their views known, as well as getting in touch with their own personal representatives in the Senate and the House. Working through organized groups that are in Washington, and can monitor the progress and the changes that are made, is always the most effective way to proceed.