SPEAKERS CONTENTS INSERTS
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PLEASE NOTE: The following transcript is a portion of the official hearing record of the Committee on Government Reform. Additional material pertinent to this transcript may be found on the web site of the committee at [http://www.house.gov/reform]. Complete hearing records are available for review at the committee offices and also may be purchased at the U.S. Government Printing Office.
HOW ACCURATE IS THE FDA'S MONITORING OF SUPPLEMENTS LIKE EPHEDRA?
HOUSE OF REPRESENTATIVES
ONE HUNDRED SIXTH CONGRESS
Page 2 PREV PAGE TOP OF DOCMAY 27, 1999
Serial No. 10660
Printed for the use of the Committee on Government Reform
Available via the World Wide Web: http://www.house.gov/reform
COMMITTEE ON GOVERNMENT REFORM
DAN BURTON, Indiana, Chairman
BENJAMIN A. GILMAN, New York
CONSTANCE A. MORELLA, Maryland
CHRISTOPHER SHAYS, Connecticut
ILEANA ROS-LEHTINEN, Florida
JOHN M. MCHUGH, New York
STEPHEN HORN, California
JOHN L. MICA, Florida
THOMAS M. DAVIS, Virginia
DAVID M. MCINTOSH, Indiana
MARK E. SOUDER, Indiana
JOE SCARBOROUGH, Florida
STEVEN C. LATOURETTE, Ohio
MARSHALL ''MARK'' SANFORD, South Carolina
BOB BARR, Georgia
DAN MILLER, Florida
Page 3 PREV PAGE TOP OF DOCASA HUTCHINSON, Arkansas
LEE TERRY, Nebraska
JUDY BIGGERT, Illinois
GREG WALDEN, Oregon
DOUG OSE, California
PAUL RYAN, Wisconsin
JOHN T. DOOLITTLE, California
HELEN CHENOWETH, Idaho
HENRY A. WAXMAN, California
TOM LANTOS, California
ROBERT E. WISE, Jr., West Virginia
MAJOR R. OWENS, New York
EDOLPHUS TOWNS, New York
PAUL E. KANJORSKI, Pennsylvania
PATSY T. MINK, Hawaii
CAROLYN B. MALONEY, New York
ELEANOR HOLMES NORTON, Washington, DC
CHAKA FATTAH, Pennsylvania
ELIJAH E. CUMMINGS, Maryland
DENNIS J. KUCINICH, Ohio
ROD R. BLAGOJEVICH, Illinois
DANNY K. DAVIS, Illinois
JOHN F. TIERNEY, Massachusetts
JIM TURNER, Texas
THOMAS H. ALLEN, Maine
Page 4 PREV PAGE TOP OF DOCHAROLD E. FORD, Jr., Tennessee
JANICE D. SCHAKOWSKY, Illinois
BERNARD SANDERS, Vermont (Independent)
KEVIN BINGER, Staff Director
DANIEL R. MOLL, Deputy Staff Director
DAVID A. KASS, Deputy Counsel and Parliamentarian
CARLA J. MARTIN, Chief Clerk
PHIL SCHILIRO, Minority Staff Director
C O N T E N T S
Hearing held on May 27, 1999
Levitt, Joseph A., Director, Center for Food Safety and Applied Nutrition, Food and Drug Administration
Soller, R. William, Ph.D., senior vice president and director of scientific and technical affairs, Consumer Health Care Products Association; Theodore M. Farber, Ph.D., principal, Toxachemica, International; Daniel B. Mowrey, Ph.D., president, American Phytotherapy Research Laboratory; Annette Dickinson, Ph.D., vice president for scientific and regulatory affairs, Council for Responsible Nutrition; Karen Schlendorf; Barbara Michal, H.E.A.T.; and Raymond Woosley, Ph.D., professor of pharmacology and medicine, Georgetown University
Letters, statements, etc., submitted for the record by:
Dickinson, Annette, Ph.D., vice president for scientific and regulatory affairs, Council for Responsible Nutrition, prepared statement of
Page 5 PREV PAGE TOP OF DOCFarber, Theodore M., Ph.D., principal, Toxachemica, International, prepared statement of
Levitt, Joseph A., Director, Center for Food Safety and Applied Nutrition, Food and Drug Administration, prepared statement of
Michal, Barbara, H.E.A.T., prepared statement of
Mowrey, Daniel B., Ph.D., president, American Phytotherapy Research Laboratory, prepared statement of
Schlendorf, Karen, prepared statement of
Soller, R. William, Ph.D., senior vice president and director of scientific and technical affairs, Consumer Health Care Products Association, prepared statement of
Waxman, Hon. Henry A., a Representative in Congress from the State of California, summaries of complaints
Woosley, Raymond, Ph.D., professor of pharmacology and medicine, Georgetown University, prepared statement of
HOW ACCURATE IS THE FDA'S MONITORING OF SUPPLEMENTS LIKE EPHEDRA?
THURSDAY, MAY 27, 1999
House of Representatives,
Committee on Government Reform,
The committee met, pursuant to notice, at 1:30 p.m., in room 2154, Rayburn House Office Building, Hon. Dan Burton (chairman of the committee) presiding.
Present: Representatives Burton, Morella, Horn, Waxman, Norton, Cummings, Kucinich, Tierney, Schakowsky.
Staff present: Kevin Binger, staff director; Daniel Moll, deputy staff director; Beth Clay, professional staff member; David Kass, deputy counsel and parliamentarian; Mark Corallo, director of communications; Corinne Zaccagnini, system administrator; Carla Martin, chief clerk; Lisa Smith-Arafune, deputy chief clerk; Phil Schiliro, minority staff director; Phil Barnett, minority chief counsel; Kristin Amerling, Cherri Branson, Sarah Despres, and Michael Yang, minority counsels; Karen Lightfoot and Denise Wilson, minority professional staff members; Ellen Rayner, minority chief clerk; Earley Green, minority staff assistant; and Barbara Wentworth, minority research assistant.
Page 6 PREV PAGE TOP OF DOC Mr. BURTON. The committee will come to order.
I want to apologize for a lot of Members not being here. We had a rule on the floor that went down just a short time ago, and there is a conference going on with a large number of our members expressing their discontent with some of the things that have happened; and I don't know if you have ever been in a food fight, but those things happen from time to time, and I decided to extract myself from that and come up here to be at the meeting. I don't know what the Democrats are doing, but we have two fine Democrat Representatives here so
Mr. KUCINICH. We are in a supplement fight.
Mr. BURTON. We are getting ready to go on a break back in our districts.
The Chair sees a quorum and a quorum being present, the Committee on Government Reform will come to order. I ask unanimous consent that all Members' and witnesses' opening statements be included in the record, and without objection, so ordered.
We are here today to continue our dialog with the Food & Drug Administration on their regulation of dietary supplements. Today's hearing will focus on the need for a better system to monitor adverse events with dietary supplements.
The Food & Drug Administration is responsible for tracking adverse events for different products, prescription drugs, over-the-counter drugs, infant formula, dietary supplements, and even veterinary medicines.
So what is an adverse event? Clearly, if someone takes a drug or dietary supplement and dies from it, that is a very serious adverse event. If you take a product and suffer a stroke as a result of a heart attack, that is a serious adverse event. If you take a product and develop a skin rash, that is an adverse event, but not necessarily a serious event.
An adverse event can be one or more of a range of things. Why does the Food & Drug Administration have monitoring systems? These are early warning systems to protect the public if food or a drug unexpectedly starts hurting people. The Food & Drug Administration has the authority to seize products which pose a public health risk, or the FDA can propose regulations to limit the way in which a product is used.
Page 7 PREV PAGE TOP OF DOC Obviously, it is very important that the FDA has an accurate and effective system. People's lives may depend on it. Companies' reputations are at stake. Sometimes millions or billions of dollars of investments can be affected. So it is very important that the FDA does a good job in this area.
Today, we are going to talk about the adverse events monitoring systems for dietary supplements. We have been looking at this system for a while now, and there appears to be some very serious problems.
I think that the FDA will concede that this system has some shortcomings. The point of today's hearing is not to say that we should not have an early warning system. The point of the hearing is that we need to have an accurate system and that the facts need to be checked and good information needs to be provided to the American people. The FDA uses this monitoring system to develop regulations. If you want to have good regulations, you have to have good information.
Through our review, we have identified six problem areas: causality not established. There is no analysis of possible causal relationships between products and adverse reactions for dietary supplements. The FDA does not followup to make sure that an adverse event is actually caused by a dietary supplement.
Ironically, this is done for veterinary drugs. For instance, if a dog takes a medicine and a dog has a heart attack and dies, the FDA evaluates this report to see if the death was related to the drug or not. Because they followed up on the veterinary reports, the FDA was able to determine that in 1997, of 3,000 adverse event reports to the center for veterinary medicine, only 1 percent were definitely associated with a product, 31 percent were probably associated, 45 percent possibly were associated, 12 percent were definitely not related to the product, and 11 percent lacked adequate information to determine association.
With people and dietary supplements events, the FDA has not done this analysis. They cannot provide this type of information. If the FDA does this for animals, why not for people? On the FDA website, two deaths are attributed to ephedra, 15 to ephedrine, and 12 to ma huang.
Page 8 PREV PAGE TOP OF DOC I have further information on two such cases. This case states that one death attributed to ephedra was actually attributable to hypothermia, the other is the death of a woman who had been using an ephedra supplement. She died after driving her automobile the wrong way on a one-way street and struck a pole going 90 miles an hour. Her blood alcohol limit was .212, more than twice the legally intoxicated limit in most States. Are these two cases really ephedra deaths?
No. 2, no classification of seriousness of event. The website lists over 2,000 adverse events, but there is no evaluation of whether these are mild events, moderate events, or serious events. The impression the FDA gives, especially in the press, is that all of these events are serious events.
According to information provided to the committee by the FDA, of 600 events received, 60 percent were not serious events. Additionally, it is unclear on the website what actually should be reported as an event.
On the prescription drug reporting site, a detailed explanation is given of what an adverse event is. However, the dietary supplement site is vague and lists an adverse event as an illness or injury associated with the use of dietary supplements.
Are there dual definitions for adverse events? This is a very important issue because the FDA frequently quotes the numbers of adverse events in dietary supplements and uses these numbers as a means of developing policy.
I understand my colleagues on the Science Committee have requested a General Accounting Office evaluation of the FDA's use of this monitoring system in the development of policy regarding ephedra. The report is expected to be released in the coming months, and we look forward to utilizing this report in our investigation.
Three, time lag for Freedom of Information Act requests. If someone outside the FDA wants more information on an adverse event, they have to file a Freedom of Information Act request. This process is so slow that sometimes it takes over a year.
Page 9 PREV PAGE TOP OF DOC Can you imagine being a manufacturer of a supplement and the FDA's website states that someone died after taking your product, and the FDA will not provide you information about the report for over a year? Think about that. You could go out of business because they erroneously put something on a website about an adverse reaction to a product that you produce and they are wrong, and you can't get that corrected for over a year while your product is on the market. You can bankrupt a business when the FDA is wrong. That can't be correct.
One case recently reported in the press was a manufacturer who had 14 events and one death reported on the FDA website for their product, and the FDA told the manufacturer they were too busy to respond to his concerns. They are still waiting after 11 months for the FDA to provide information on these events.
Another requester has still not received information after 1 year. The industry wants to work with the FDA, but how is the industry supposed to be responsive when the FDA will not give them any information?
Is the FDA's response to the pharmaceutical industry the same on prescription drugs or to manufacturers of infant formula and other food products?
Fourth, timely updates to the FDA website. The current website has not been updated since October 1998. This is over 6 months. If the public is looking to this website for information on adverse events and dietary supplements, they are not well served by a system that is not current, that is out of date.
No. 5, brand and corporate name identification without confirmation. The FDA identifies products and companies on the website. Is it appropriate to do so, especially since they did not determine if the product actually caused the event or whether the product was actually consumed by the patient?
So you list something on the website that has not yet been documented or proven, and you put that company in jeopardy without proper information and proper confirmation.
Page 10 PREV PAGE TOP OF DOC No. 6, incorrect information not purged. Sometimes the FDA makes mistakes. Companies may find their name or product listed as having caused an adverse event when they do not make a product which contains the ingredients listed.
If the FDA went back and fixed mistakes, there would be no problem, but they don't. The FDA commissioner alluded to this problem in response to questions at our March 25 hearing. They told us that it is a monumental task to have the FDA make any changes to a report, so if they make a mistake, it is a monumental task for them to correct the mistake.
Is it a responsible act to leave misinformation about a company on a government website with a small footnote stating the corrected information? With the increased use of dietary supplements by Americans and with concerns about adulterated products, drug interactions and the need to identify public health concerns, an accurate and effective reporting system for dietary supplements should be a high priority for the Food & Drug Administration.
Now, let's talk about ephedra, as an example. In January, the FDA published its priority list for 1999 activities. Resolving the proposed rule on ephedra was listed at the top of the Center for Food and Applied Nutritionals' list for dietary supplements.
Ephedra has been a very controversial supplement. It has been used for thousands of years in traditional Chinese medicine for asthma. Approximately 15 billion servings of ephedra supplements were used last year in hundreds of products.
The plant version of ephedra is used as a dietary supplement. The synthetic version is used in over-the-counter medicines like Sudafed and Primatine Mist. Sometimes it has been abused.
In the past, there have been a few unscrupulous companies that marketed illicit street drugs containing high doses of ephedrine. We applaud the FDA for stopping these companies. We also applaud the respectable supplement manufacturers who worked with the government to stop this criminal activity.
Page 11 PREV PAGE TOP OF DOC We will hear today from two mothers whose sons died after taking products containing large amounts of ephedrine. Our sympathies are with them and their families.
Let me make it very clear that no one in Congress has fought harder against drug trafficking than I and many of my colleagues. We have sponsored legislation to give the death penalty to drug pushers. It is my understanding that these products are now off the market, the ones that we are talking about.
If they are not, the FDA clearly has the authority to seize them. This hearing is about whether the FDA is doing a good job in tracking adverse events; are they giving the public and the medical community reliable information.
On the one hand, if a supplement is causing harm, it should be removed from the marketplace. On the other hand, if the FDA is giving the public erroneous information, then potentially good products that help people could be removed from the market and many companies could be in jeopardy. What we need is good information so the American people can make good decisions, and the Congress as well.
This hearing is not about deciding whether the current proposed rule on ephedra is the correct stand or not. It is about finding effective solutions for the obvious problem of an ineffective system so the FDA can fulfill its mandate of protecting the public. With the passage of the Dietary Supplement Health and Education Act, the onus is on the FDA to determine safety of a product, and if it is not safe to remove it from the marketplace.
Some have said that the FDA would like to use a tragedy caused by a few unscrupulous manufacturers to change how we regulate an entire industry, retract the Dietary Supplement Health and Education Act and regulate dietary supplements as drugs, not foods. I hope that is not the case. That is not the right way to make policy.
We are pleased that Dr. Joseph Levitt, Director of the Center for Food Safety and Applied Nutrition at the Food & Drug Administration will be addressing us on the development of the special nutritional adverse events monitoring system. He will detail how this system functions and how it compares to other monitoring systems within the FDA and other HHS organizations.
Page 12 PREV PAGE TOP OF DOC I have been told by my staff that Mr. Levitt and staff from the FDA plan on leaving after the first panel is finished. I would request, Doctor, that you stay to hear the other witnesses and be available to answer questions that may arise as a result of the other testimony.
Mr. Levitt, I appreciate that you are here today, but these people represent the public that both you and I serve. I really think if it is at all possible that it is valuable for you to stay and hear what they have to say, especially considering that we have two mothers who have lost their sons to adverse events.
We will hold the record open until June 10 to allow written submissions to the record. I will wait until the second panel comes to the table to introduce them. But before I introduce our first panel, I would like to recognize our ranking minority member, Mr. Waxman, for his opening statement.
[NOTE.The submissions referred to may be found at the end of the hearing.]
Mr. WAXMAN. Mr. Chairman, today's hearing raises important questions about the regulation of dietary supplements. The Food & Drug Administration [FDA] is supposed to ensure the safety and effectiveness of an enormous range of health products, including supplements. To do so, it is essential that manufacturers report deaths and other adverse events to the FDA. This is the rule that applies in the case of drugs and medical devices.
But the public will be surprised to learn that manufacturing of dietary supplements are exempt from the most basic public health protection. When Congress enacted the Dietary Supplement Health and Education Act of 1994, we severely limited FDA's authority over supplements. FDA may not approve supplements before they are marketed and FDA is held to the very high threshold of demonstrating a ''significant or unreasonable risk of illness or injury before it can remove an unsafe supplement from the market.''
Page 13 PREV PAGE TOP OF DOC This is a higher threshold than FDA has for dealing with foods, drugs, or medical devices. This means it is up to the supplement industry to ensure that the products that they are making are safe. But here, too, we have restricted the FDA.
We require all drug and medical device companies to report any adverse events they learn of which are associated with their products, but not dietary supplement companies. Instead, we rely on them on a wholly voluntary system of reporting.
This system is not adequate to protect public health. There are many unavoidable problems with a voluntary reporting system, not least of which is the possibility that manufacturers become aware of problems with products and choose not to share that information with the FDA.
I am interested in learning from today's witnesses how reliable the current system has been and how the system can be strengthened.
I want to commend the chairman for his balanced approach in putting this hearing together. He has graciously and appropriately agreed to allow three witnesses that we have requested to testify. As a result, we are going to have witnesses here today who can tell both sides of the story, including witnesses who have lost family members because of ephedra products.
I look forward to hearing their stories and to learning from their firsthand experience about the need for a strong monitoring system, especially for dietary supplements that do not have to undergo any premarketing testing for safety.
Let me make a final comment about FDA's regulation of ephedra. Ephedra is practically a molecular twin to methamphetamine, or speed. The DEA already has restricted its availability. And, in response to hundreds of adverse events related to ephedra supplements, including several deaths, the FDA proposed to limit the amount of ephedra permitted in supplement doses and to require labeling to fully inform consumers about their risks.
This seems to me sensible. Despite the industry's claims, there is no ephedra ban. No one is going to burst into your home to take away your ephedra. Instead, the regulation appears to contain minimal, common sense health safeguards.
Page 14 PREV PAGE TOP OF DOC There is a lot of misinformation about ephedra. That is why I found Dr. Tim Johnson's comments this morning on Good Morning America to be so helpful, and I would like to play his comments for the committee. I think he cuts through a lot of false claims and provides a balanced analysis.
[Video tape played.]
Mr. WAXMAN. I hope that we can approach this issue with the same kind of objectivity that Dr. Johnson displayed in his presentation. I welcome our witnesses, and I look forward to their testimony. I hope that out of this hearing we will get information that will help us do our jobs better.
Thank you, very much, Mr. Chairman.
Mr. BURTON. Did you have an opening comment?
Mr. KUCINICH. Just for a minute.
Mr. BURTON. Let me yield to Congresswoman Morella.
Mrs. MORELLA. I want to thank you for calling for this hearing because I look forward to hearing about the adverse event reporting system. But I was just reminded of the fact that recently I had a group of school students who came in and I took them on the floor of House.
I showed them where the Speaker stands; and during the Q and A one of them said, You have a speaker, but do you have a listener? So I am going to be a listener today, and I hope to learn a great deal. Thank you.
Mr. BURTON. That is refreshing.
Mr. KUCINICH. Thank you very much, Mr. Burton. I want to thank you, Mr. Burton, for your continuing efforts to provide a balanced public presentation of the possibilities of alternatives of health care in this country.
Page 15 PREV PAGE TOP OF DOC I think that all of us appreciate the opportunity to look at not only the challenges which face health care but also the possibilities of new approaches that people might use in order to expand their own health and to improve the quality of their lives.
I support your endeavors in looking at alternative medicine, and I know that the concerns that are expressed today about the use of supplements are concerns that ought to be taken with a great deal of seriousness.
It is my view that while food supplements can provide many useful opportunities for people to have better health, I think we are starting to gather a lot of information that would suggest that some degree of professional supervision may be helpful in order to protect the health of the consumer.
Not every consumer has the kind of background that would enable them to be safe in the consumption of some of these products. On the other hand, I don't think that products ought to be withheld from the market simply because they are not approved by the FDA.
Now, this is a very difficult matter that we face, and I know that the testimony will help to resolve some of it, at least for the moment. So I thank you again, Mr. Chairman. Thank you, Mr. Waxman, for your leadership on this issue.
Mr. BURTON. Do other Members wish to be heard?
Mr. CUMMINGS. Mr. Chairman, thank you very much. I join with my colleagues in expressing appreciation to you for this hearing.
Whenever I go to the health food stores, the place is packed with people trying to improve their health, trying to deal with health problems, and so this hearing is quite appropriate.
The Food & Drug Administration is the governing body charged with the responsibility of regulating the production, distribution, and consumption of prescription and over-the-counter drugs. In keeping with its general purpose, it seems only natural that the FDA has an adequate system of monitoring the adverse effects of dietary supplement products that are not FDA regulated, specifically those like ephedra.
Page 16 PREV PAGE TOP OF DOC The need for a careful examination and assessment of the Food & Drug Administration's AER reporting system, particularly in the way of stimulus-like drugs, like ephedra, is evidenced by not only the 38 deaths and the several hundred voluntarily reported cases of adverse events caused by ephedra or synthesized versions, but also in the history of the Federal action involving ephedra, which dates back as early as 1983.
In addition, after giving consideration to the fact that in 1998 the DEA noted an increased relationship between synthesized ephedra and the street drug methamphetamine, it becomes obvious that the nature of this stimulant is one that necessitates mandatory monitoring and reporting of its adverse effects.
I am interested to hear Mr. Levitt's testimony concerning the AER system and how the FDA seeks to modify the process toward making it a more efficient and effective means of monitoring ephedra and other dietary supplements which might have adverse effects to the public. Thank you very much.
Mr. BURTON. I thank the gentleman.
Are there further Members that want to be heard? If not, Mr. Levitt would you come forward.
Mr. BURTON. We welcome your opening statement, Mr. Levitt.
STATEMENT OF JOSEPH A. LEVITT, DIRECTOR, CENTER FOR FOOD SAFETY AND APPLIED NUTRITION, FOOD AND DRUG ADMINISTRATION
Mr. LEVITT. Thank you, Mr. Chairman and members of the committee. My name is Joseph A. Levitt. I am Director of the FAA Center for Food Safety and Applied Nutrition, often referred to as CFSAN.
Page 17 PREV PAGE TOP OF DOC Joining me today at the table is Janice F. Oliver, my Deputy Director in the center, and on my right, Dr. Elizabeth A. Yetley, who is Director of the Office of Special Nutritions within our center and it is their office that we regulate dietary supplements.
I am pleased to be here today to discuss FDA's adverse event reporting systems generally, and specifically CFSAN's adverse event monitoring system, referred to by the initials SN/AEMS, which stands for special nutritionals adverse event monitoring system, and this includes dietary supplements.
Mr. Chairman, if I may respond to your request that you made in your statement about my staying at the hearing, while I had not planned to, at your request I will be glad to with the one request that I be allowed a 2-minute break between panels in order to rearrange my schedule.
Mr. BURTON. That is fine.
Mr. LEVITT. Let me begin by saying that we are here today to focus on FDA's adverse event reporting system for dietary supplements. As Dr. Henney stated when she testified before this committee on March 25, 1999, the intent of the Dietary Supplement Health and Education Act [DSHEA], was to provide consumers with broad access to dietary supplements while at the same time to assure the safety and proper labeling of those products.
The adverse event monitoring system for dietary supplements is a critical part of FDA's ability to meet the consumer protection provisions of the law. We believe the current system serves as a valuable source of information to signaland we will be hearing that word a lot todayto signal potential hazards associated with the use of dietary supplements.
However, we agree with what you said, Mr. Chairman, in your opening. We believe there are both enhancements and refinements to the current system that need to occur.
As we move ahead, we want to learn from our experience to date, including our experience with ephedra-containing products, which I know that the committee is particularly interested in. We welcome this opportunity to continue a dialog with the committee on this important issue and how we approach this task.
Page 18 PREV PAGE TOP OF DOC Mr. Chairman, if I may just divert for one moment with your indulgence, since this is my first time for appearing before your committee as a principal witness, let me just share for a moment some of the overall themes that I have tried to bring to the center in the leadership position that I have been at for a little over a year now.
One thing that people are very curious about when somebody takes a new job, is what does that person really stand for? What values does that person bring to the job? And I have over here a poster on my right which stands in our lobby. It is a little faded because it has been there for a year, but it lays out five major values that I have tried to stress in the year that I have been at CFSAN and which I think are very applicable here today.
No. 1 is public health and safety. We are a public health and safety agency and that needs to be our highest priority. Clearly you are recognizing that, and that is the subject of today's hearing.
No. 2 is respect. I think it is very important that we at FDA and in government as public servants show respect for all of those on the outside that we deal with, be they from industry, health professionals, or consumers; and I think Dr. Henney tried to signal that also in her testimony here earlier this spring.
I also think that it is important that we show respect for the law. I am a lawyer. I think in our case the law provides both tools for us to get our job done as well as boundaries that we must live within. As a lawyer I have particular sensitivity to that.
No. 3 is integrity. In all that we do, what FDA needs to stand for more than anything else is we are a group that is independent and able to provide objective assessments for the public. That is the groundwork on which our credibility is based, and that is paramount.
Four is dedication. I have worked at FDA for over 20 years, and I think if there is probably one word that characterizes our work force more than anything else, it is dedication. We have a hard-working, dedicated staff that does its best on behalf of the public.
Page 19 PREV PAGE TOP OF DOC Finally, it is not just dedication to anything; it is a dedication to excellenceexcellence in science, excellence in regulatory policy, excellence in communication. You spell those out as you can see and it spells out pride.
I have tried to bring a sense and culture of CFSAN pride to all of the work that we do; and I have found that in the first year that I have been there, it has been a very valuable galvanizing force to say this is what we stand for. Thank you.
Moving back to dietary supplements, I would like to summarize my written testimony by highlighting three main points.
First, there are inherent strengths, but also inherent limitations in all spontaneous reporting systems, be they for drugs, biologics devices, or dietary supplements.
The major utility of a surveillance system based on spontaneous reports is to generate signals of potential health problems. These signals warrant and demand further investigation and must be evaluated in the context of other information which may include one or all of the following: controlled clinical trials, scientific literature, market and consumer surveys and product analysis.
There are also significant limitations. The major limitations to consider when assessing spontaneously reported information is underreporting of adverse events, report quality, adverse event recognition or attribution, reporting biases that are inherent and estimation of population exposure.
Notwithstanding these very relevant limitations, postmarketing surveillance based upon spontaneous report data has been a very powerful tool for detecting adverse event signals.
Second, within the FDA the most developed system for adverse event reporting is a system used for prescription drugs. This system, however, has had over three decades to mature and benefits from a number of tools not available to dietary supplements, for example, premarket testing a data base, mandatory reporting by manufacturers, and access to market exposure data, sometimes referred to as denominator data.
Page 20 PREV PAGE TOP OF DOC Moreover, even in its current state, the agency continues to incorporate enhancements into the prescription drug reporting system and to fine-tune it as necessary. By contrast, the agency's reporting system for dietary supplements was developed only recently in 1993. And so comparatively speaking, it is still in its infancy.
This means we are still in the process of developing the infrastructure, the resource base, and the overall framework of this adverse event monitoring system. We recognize that there are many challenges that we face with the current system and we intend to address each area that will make the system stronger.
The fiscal year 2000 budget request which is now before the Congress includes $2.5 million to enhance the adverse event monitoring system within the foods program. Most of these funds would buttress reporting system for dietary supplements as these products provide the largest share of the center's adverse event reports.
If these funds are provided, we would hire several additional clinical staff to review the adverse event reports, and we would develop a system to integrate adverse event reporting and to modernize it for our entire center programs.
This system would also be compatible with other adverse event systems within the agency. We are also now in the process of assessing our longer-term needs as we develop the budget for 2001.
Third and most importantly, notwithstanding its degree of development, the dietary supplement adverse event monitoring system is capable of and has surfaced important safety issues for the benefit of the American public. This includes identifying a serious manufacturing product in samples of raw material labeled ''plantain'' that contained digitalis, and more recently identifying the basis for removing from the market products contain gamma butyrolactone or GBL.
It is critical that FDA be able to move rapidly to protect consumers when significant safety problems arise, and I believe there is general acceptance of that principle.
Page 21 PREV PAGE TOP OF DOC In closing, Mr. Chairman, I would like to place in context today's subject of adverse event reporting for dietary supplements as it relates to our commitment to develop this calendar year an overall strategy for achieving effective regulation of dietary supplements under the law.
As part of our ongoing consultation with stakeholders, the agency has scheduled two public meetings to solicit comments that will assist CFSAN in developing a strategy and this will include, certainly, input on adverse event reporting for dietary supplements.
The first meeting is coming up soon, July 8 in Washington, DC. The second is on July 20 in Oakland, CA. I will personally chair each of these two meetings. I would encourage interested persons to attend one of these sessions.
It is not necessary to attend both, as we are essentially repeating the same meeting on the West Coast so as to save stakeholders the time and expense of traveling East. For those who cannot attend, comments may be submitted in writing to the public document.
We look forward to input on development of an overall strategy for dietary supplements. Developing the solid blueprint for implementing the DSHEA is essential. This will ensure that the implementation is guided by a framework that will both protect consumers and enable them to make informed choices by using dietary supplements to improve their health.
Thank you, Mr. Chairman. I would be happy to respond to questions you may have. I also note I am getting a note passed to me that I have misspoken. The two public meetings, one is in June. It is on June 8. The second is on July 20. I am sorry if my eyes skipped down.
Thank you very much for your attention. I will be happy, with my colleagues, to try to answer questions.
Mr. BURTON. Thank you, Mr. Levitt, and thank you for that correction.
[The prepared statement of Mr. Levitt follows:]
Page 22 PREV PAGE TOP OF DOC INSERT OFFSET FOLIOS 1 TO 36 HERE
[The official committee record contains additional material here.]
Mr. BURTON. Why is it that the FDA evaluation reports determine the causality in veterinary medicine for animals but not the dietary supplement for humans?
Mr. LEVITT. I think the question is addressing how we evaluate the strength of the reports. That is really what you are talking about. In your statement you listed two main things. One is seriousness and one is what you referred to as causality. I would like to think of that as attribution or how strong is the association.
Inherently, with any passive reporting system, whether it is veterinary drugs or human drugs, there are going to be limitations in terms of how much information is available to us, both in terms of how much is available and what other activities are present, whether it is other therapies, other medical conditions, special populations. All of those have to be evaluated together.
I think it is, however, a misconception that that is not part of the system as we have it because inherently when our medical staffwe view reports, that is a very important part of what they look at.
One thing that I have, I think, gleaned from, as I have looked more into this recently, is an important lesson from what has happened is that we need to have greater transparency and understanding of the process that we have. And one thing that we will be undertaking will be to describe better what processes that we do use and also how can we refine those processes.
Now, if I can addto help us do that, we have set up a working group under the auspices of our food advisory committee to address, specifically, adverse event reporting; and this has broad membership of health professionals as well as industry. And this group is just getting going so the timing is very good.
Page 23 PREV PAGE TOP OF DOC They have two charges which have already been written out. I think after this hearing we will go back and decide if we need to broaden or refine the charge because the timing is too good not to take advantage of that. But the charges are twofold.
No. 1, to identify medical toxicological and communication principles or guidance that could assist industry in establishing and implementing a system to solicit, collect, evaluate, and report potential safety concerns associated with product purity and consumer complaints and reports of illness or injury. So the first charge is what are things that the industry should be looking at to do better.
The second is directed to FDA. Based on your knowledge or experience in other food safety or food science arenas, could you please suggest mechanisms for FDA to share post market surveillance information with consumers, the dietary supplements industry, the medical community, and other surveillance system.
So as I said, this group is being assembled right now and I think that we should take advantage of what is learned today and feed that back in so we can have recommendations.
Mr. BURTON. I glean from your answer that you are going to be doing that in the future, and in the past you haven't.
Mr. LEVITT. What I am trying to say is that in the past, that has been more a part of the process of internal evaluation, and it has been obvious to outsiders because it hasn't been designated to 1, 2, 3, 4.
But when I talk to the reviewers and ask them how do you evaluate the reports, one of the most important elements that they look at is how strong or how weak is the association with it. And I think we need to clarify that.
For example, when we later talk about ephedra, there are large numbers of reports that are often reported, saying FDA has so many reports, and that is so. However, FDA within the internal analysis breaks those down much more and tries to look at that.
Page 24 PREV PAGE TOP OF DOC So we need to spell out where and how we do it so it is better understood. And if we are not doing it as well as we should, we should improve that, too.
Mr. BURTON. Thank you. One of the things that concerns meand I mentioned it in my opening statementis that things are posted on your website and they may or may not be accurate. The information that you have on there may be a conclusion that is reached, but it takes a year or more for that to be clarified or removed. During that time the company that may be the ''victim'' or the person who suffers from this, may not be able to get that clarified, and it may hurt the sale of their product at the marketplace. During that time many companies have had difficulty getting the FDA to respond to them to clear up these misunderstandings.
I know that my time has expired, and I will talk more about this in a second round. One of the things that concern meI take Slim Fast. I know I look thin, strong, healthy and everythingwhy is it that nobody is smiling at that?
In any event, if you look at the website that you have, you show approximately 22 problems that are created by Slim Fast that may or may not be accurate and probably hasn't hurt because people still continue to use it, but could hurt a product like that in the marketplace.
And during the time that a company is trying to explain to the people that buy it, who might be scared to death after reading something like this on the website, they have no recourse because you are not having a dialog with them and getting it cleared up.
So what's the answer to that?
Mr. LEVITT. I think the answer to that is that we at the FDA need to have a greater sensitivity to the manufacturers in this whole process. We have focused primarily on our internal work. The reports come in. We try to look at them, and making time and resources available for getting the reports FOI purged and ready to submit has taken a back seat.
Page 25 PREV PAGE TOP OF DOC Earlier this year, when that was brought to my attention, we have allocated funds this year but we are terribly behind and it will take us some time to catch up.
But if I were to paint a picture of the way that I would like to see it, we need to have a system so that as with other product centers, if you look around within FDA, reports come in; they go through the normal purging for names and identifiers of health professionals and patients if they are there, and they are sent to manufacturers because the manufacturers have an important role to play, not just in knowing what is there but in helping and investigating what is going on with this product. And that's something we have to try and fix.
Mr. BURTON. I want to go ahead and yield to Mr. Waxman, but let me just say that I think that's something I would like to work with you on, and I think the committee would like to work with you to make sure that businesses who may have been hurt by misinformation that has been put on the website or public, into the public domain, have quicker access to the FDA so they can clarify those things so they don't suffer.
If a product is bad, it should be off the market. We don't want it to hurt the people. But at the same time in the free enterprise system, we want to make sure that businesses don't suffer either because of erroneous information put on the website that they can't get off, and work with you to clarify those things.
Mr. LEVITT. Yes, thank you. And we need to be working more closely with companies on their followup.
Mr. BURTON. OK.
Mr. LEVITT. So that we can have a stronger system.
Mr. WAXMAN. Thank you very much, Mr. Chairman. One of the most fundamental safeguards of public health is adverse event reporting. An adverse event is a death or serious disease or injury that's linked to the use of a drug, a medical device, or a dietary supplement. Adverse event reporting is required of some product manufacturers but not of manufacturers of dietary supplements.
Page 26 PREV PAGE TOP OF DOC Can you explain why adverse event reporting is so important to protecting the public health?
Mr. LEVITT. Well, with any product, even those that have premarket testing and review, once the product gets onto the market, it is exposed to many more people, many different kinds of people, people that are taking different kinds of medications, have different medical conditions, and any premarket system is not going to be able to pick up rare events, interactions or other things that control trials cannot do.
When you have a system such as here, where there is no premarket, that is even more important because that is the way that we can pick up signals that there may be a problem with the product. And so we need it as a critical feature to signal us, hey, there may be a problem with this product; FDA, you need to look into it; you need to work with the company and say maybe we need to do something to improve things.
Mr. WAXMAN. If a drug is on the market, and it has already gone through an approval process where FDA assures the safety and efficacy of that drug, is the manufacturer of the drug required to report adverse impacts from the use of the drug?
Mr. LEVITT. In the context of prescription drugs, yes, manufacturers are required to report to FDA all adverse events that they receive associated with their product. They have to report on a more urgent basis those that are serious and unexpected, meaning not on the product label; and later on, more routine reports. But, yes, they are required to submit those.
Mr. WAXMAN. How about medical devices such as x-ray machines or artificial joints; does the law require the manufacturer of medical devices to report adverse events?
Mr. LEVITT. Yes. Medical device manufacturers are required to report. The definitions are a little different, but by and large, it is an attempt to require the submission of important serious adverse events to the FDA.
Page 27 PREV PAGE TOP OF DOC Mr. WAXMAN. Now dietary supplements, however, are governed under different rules. Can you tell us whether manufacturers are required to inform FDA if they learn about an adverse event report?
Mr. LEVITT. There is no requirement that manufacturers make those submissions to us.
Mr. WAXMAN. This, as you pointed out, is like a double whammy. With other products, you have to assure the safety and in many cases the efficacy before the product can be sold. Dietary supplements can go right on the market without any scrutiny by FDA in advance. But even manufacturers of those products that had to be preapproved before they could be marketed are required to report when there is an adverse event. But dietary supplement manufacturers are not required to report an adverse event to you. They are, however, encouraged to do it voluntarily; isn't that true?
Mr. LEVITT. That is correct, as are health professionals. We probably need to strengthen our outreach there to get as many high-quality significant reports as health professionals are coming across, as well as to the industry.
Mr. WAXMAN. Well, it seems to me this puts a good manufacturer at a disadvantage because it makes it impossible for a consumer to know which products have been manufactured responsibly and which products have not. Would you agree?
Mr. LEVITT. That is correct.
Mr. WAXMAN. Now, under the Dietary Supplement Health and Education Act, we have a voluntary system of reporting adverse events. This means that if a dietary supplement manufacturer learns of a problem associated with its product, there is no obligation to report the problem to the FDA. Are you aware of any situations of manufacturers not reporting problems about its product to the FDA?
Mr. LEVITT. We don't have direct evidence, information, on that one way or the other. Also, unlike the other systems, manufacturers are not required to register with the FDA.
Page 28 PREV PAGE TOP OF DOC Mr. WAXMAN. If they don't tell you, you don't know?
Mr. LEVITT. That's correct.
Mr. WAXMAN. Well, let me tell you and everybody else here that my staff is doing some research on this issue, and they talked to the people in the State of Texas where they found that there were manufacturers and distributors who had received a large number of complaints about their products.
In fact, I have for the record a list of some of these adverse impacts from the use of the products. One company received over 150 complaints of side effects, including complaints of high blood pressure, kidney problems, difficulty in breathing. Another company received complaints that their product had been linked to at least one heart attack and one case of seizures. Many of these complaints even came directly from doctors' offices, where the doctor learned about what was happening to the patient and called the manufacturer and said, ''You better know that your product is causing these distressing events.''
While many of these complaints went to the manufacturer, we found out from the Texas Department of Health that the companies didn't share these complaints with the public or the Texas Department of Health until they were compelled to do so by a court.
And I would like to ask unanimous consent to put in the record at least a summary of some of these complaints I doubt you ever heard about these complaints unless you found out about them after the court case. But the manufacturers weren't rushing to report voluntarily what they, in my view, should have been required to report under the law, if the law had been drafted the way it should have been.
Mr. BURTON. Would the gentleman allow us to put a sampling of those along with the number that you have?
Mr. WAXMAN. Mr. Chairman, I ask unanimous consent that they be put in the record at the discretion of the chairman. You can go through them and determine whatever is appropriate to get the point across.
Page 29 PREV PAGE TOP OF DOC Mr. BURTON. Very well.
[The information referred to follows:]
INSERT OFFSET FOLIOS 38 TO 55 HERE
[The official committee record contains additional material here.]
Mr. WAXMAN. One of the arguments we sometimes hear is adverse event reporting is not needed because dietary supplements are always safe. I want to ask you about that. FDA has received about 1,000 adverse event reports relating to ephedra. About how many of those reports are classified as serious?
Mr. LEVITT. Of thewe have received overall about, I believe the number is about 1,000 reports altogether. The number, total number that is serious, I am goingI am going to give an estimate and then provide for the record something that is more detailed. But my impression, it is in the vicinity of 30 to 40 percent. I could be wrong on that but that is the impression I have from talkingit is a large enough number that it isthat it is of concern to us. It is not by any means all of the reports.
Mr. WAXMAN. My last question to you is: Is it not correct that of those reports, 45 were of deaths?
Mr. LEVITT. There are a number of reports of deaths in there. I don't know if that is the exact number but we could certainly check on that, too.
Mr. WAXMAN. Thank you very much.
Thank you, Mr. Chairman.
Mr. BURTON. I think that we might ask Dr. Henney at some point to sit down with us and discuss some of the issues that have been raised by Mr. Waxman after this meeting to see if something can't be done to clarify some of these issues.
We would certainly like to look into that and talk to her about that.
Page 30 PREV PAGE TOP OF DOC Mr. LEVITT. I thinkI don't know what the right process is but I would hope there is also a process for FDA to obtain access to the adverse event reports if there are safety issues there that we need to know about.
Mr. BURTON. There is a definition of serious side effects for prescription drugs, is there not?
Mr. LEVITT. Yes.
Mr. BURTON. Did you have questions? I am sorry. Ms. Schakowsky.
Ms. SCHAKOWSKY. Yes.
Mr. BURTON. Let me yield to Ms. Schakowsky and I will get back to my questions in just a moment. I am sorry.
Ms. SCHAKOWSKY. Thank you, Mr. Chairman. I don't mind waiting for you.
I wanted to continue the line of questioning that Mr. Waxman was beginning.
You had said that there were 30 to 40 percent that were serious. Actually, we heardand we also heard that there were about 45 deaths. But what is considered serious? Could you tell us what kind of events are considered serious?
Mr. LEVITT. Yes. The general issues that we would consider serious are as follows, and I think I will just read them to be sure that I get this exactly right.
No. 1 is when the outcome is death, is life-threatening, it requires hospitalization or prolongs hospitalization, causes disability, congenital abnormality or requires intervention to prevent permanent impairment or damage. Those are the general criteria under the MedWatch program.
In addition, within our program, we would add on the following, which says that other medical events that may not be immediately life-threatening but which require intervention to prevent one of the serious medical conditions, meaning one of the MedWatch outcomes I just said, would also be considered medically serious.
Page 31 PREV PAGE TOP OF DOC So it wouldboth something where we have reached the outcome as well as something that could lead to it. And we consider all of those to be serious under, if you will, the general categorization of dangerous, critical or alarming.
Coming back just to a point earlier, this is not something that we have been as transparent to the outside world as we should be, and that is something that we will be addressing so that it is clear to everybody. It also is worth noting that in the recently revised regulations for prescription drugs, the definitions are very consistent.
Ms. SCHAKOWSKY. Just to clarify, then, in my own mind, you are saying that while these serious eventthese reports are not requiredthat of the thousand reports, you think probably about 30 to 40 percent are serious. You have read what serious is. I think anyone listening to that would agree that's very serious; and it seems to me that your expression of concern is certainly warranted and that is shared by members of this committee as well and may require some further action. I think it almost certainly would.
FDA has issued warnings to consumers about a number of other supplements besides ephedra, and I want to mention a couple of those. The FDA recently issued a warning about products containing GBL and asked companies to recall the product. According to the FDA press release, GBL is related to 55 adverse events. Can you talk a little bit about what those adverse events were and how serious they were?
Mr. LEVITT. Yes. Well, the GBL is a product that converts itself in the body to a drug referred to as GHB, which is a well-known sedative and not an approved product on the marketplace.
We had, of those 55 events, they all were consistent with each other as being quick after taking the product. About 20 of those were associated with somebody who actually was unconscious, sometimes into a coma. There was also one event that was reported in the context of a death.
Page 32 PREV PAGE TOP OF DOC In that setting, it was clear, I think, thatto everybody looking at it, we had a clear pattern.
Going back, Mr. Chairman, to your question about causality or attribution, we had a very strong association; we had a known product; we had exactly the same kind of result that would be anticipated from what we know of that product, and we said that product needs to come off the market.
Ms. SCHAKOWSKY. In this instance, it was one death?
Mr. LEVITT. One death reported. One report was based on a death, yes.
Ms. SCHAKOWSKY. In 1998, the FDA issued a warning about 5 HTP, which is found in supplements promoted to treat insomnia, depression, obesity, and for children with attention deficit disorder. According to the FDA press release, 5 HTP contained impurities that are similar to the impurities that were found in L-tryptophan, which was banned because it was so dangerous.
Do you remember how many adverse events were associated with L-tryptophan?
Mr. LEVITT. I am going to ask Dr. Yetley to see how her memory is since that's prior to my involvement.
Dr. YETLEY. That particular issue was one that was related to a report that came out of the Mayo Clinic in which they had analyzed those products on the marketplace and had found the presence of an impurity. As soon as they had raised that issue to our attention, we had our chemist work with the Mayo chemist. They developed a method, they developed a standard method, for it. We met with the industry, shared our information on how to test their products for this particular contaminant.
It is my understanding that the industry has worked hard to look at their products and to assess them. So that was not particularly an issue that came up from the adverse event system but was one in which we were trying to prevent adverse events because we had information about a contaminant.
Page 33 PREV PAGE TOP OF DOC Mr. LEVITT. If I could just add, I am not sure Dr. Yetley heard the question properly. She reacted to something that happened within the last year or so. If you are reactingquestioning about L-tryptophan which was in the late eighties, there were a number of reports associated with that.
Do you recall the number?
Dr. YETLEY. L-tryptophan is a related but somewhat different product than the 5-hydroxy L-tryptophan.
This was a concern that was raised through the reports of adverse events. We had a number of serious injuries and illnesses. We worked with the manufacturers. They did voluntarily recall those products from the marketplace. We did issue warnings, and there was some research done and we have never clearly resolved whether or not those injuries were due to a contaminant, were due to the product itself or to some interaction within the product, but there was a fairly quick action on the part of the agency and a response by the industry in response to those adverse events.
Mr. LEVITT. Right. There was a sizable number, were there not?
Dr. YETLEY. It was a sizable number. I don't remember the exact number.
Ms. SCHAKOWSKY. If I could just make one more comment. It seems to me then, given these examples, that adverse event reporting can help to resolve these dangers and that we have some good examples of that being the case?
Mr. LEVITT. Yes, absolutely. And that was one of the points I tried to highlight earlier, but thank you for reinforcing that.
Mr. BURTON. Before I yield to Mr. Horn, let me just say that it is my understanding that L-tryptophan, it was because of an adulteration of the product that you had a problem; it was not the L-tryptophan itself?
Page 34 PREV PAGE TOP OF DOC Dr. YETLEY. It is not clear. The research that was done did not clarify that completely.
Mr. BURTON. But once you worked with the industry and they cleaned up the L-tryptophan to take out the other adulterated products, was it no longer a problem?
Dr. YETLEY. I believe the marketing of that particular product was pretty much limited or restricted to a great degree.
Mr. BURTON. Well, it is still being marketed and used, though, is it not?
Dr. YETLEY. I don't know the current use, but it was not used for quite a long time after that particular period.
Mr. BURTON. It was my understanding that it was because of the adulteration, but we will look into that.
Mr. HORN. Thank you very much, Mr. Chairman. I am sorry I have missed some of the previous presentation.
Let me give you an example apparently that occurred on the website. The FDA reported that a 27-year-old female had nausea, passed out, suffered liver damage as a result of taking Slim NRG Plus, a product containing ephedra. However, the woman had also taken Nyquil and two glasses of wine. A drug screening showed she had also consumed acetaminophen, nicotine and three other drugs.
I guess the question is: What does the FDA do to make sure that the adverse events that it is reporting on its website are actually related to the dietary supplement being listed on the website?
Mr. LEVITT. OK. Thank you for raising that. I got to address only part of that point earlier in response to the chairman's question.
Page 35 PREV PAGE TOP OF DOC Let us take a moment on the website itself, because I think the website is misunderstood for what it is intended to be. Maybe based on what it is, we need to make changes also, but the website is nothing more than a table of contents of reports submitted to FDA.
We got all of these reports. We need to kind of keep track of them, and a system was worked out with just a minimal amount of information which basically is the product, the company, the nature of the reaction reported, and I guess the ingredient. It is just a line listing, and when you see it it is just one line across the page. That is taken verbatim from the report that comes in, even before there is an evaluation done.
That originally, as I have come to understand it, was the center's way, if you will, of cataloging what came in and then following through and doing a more detailed review.
What has happened over time is there were so many requests for that information, and actually under the revised FOI statute for electronic availability we are actually charged with putting up on the web frequently requested documents, and people are asking for this all the time so it was put up on the web.
From FDA's point of view, it was always understood to simply be a table of contents of what was submitted. The problem, I believe, that we have come up to is not so much that, although maybe there are some issues there, too, but the juxtaposition of what the chairman raised about putting that up now and not being able to make the underlying report available to the manufacturer for very long periods of time. So that is the only thing that is up there.
What is done in other centers is that the initial line listing is up there; but the report is up there, too. And so the manufacturer has access to everything and you have, if you will, a full record.
As I testified earlier, and maybe before you were able to be here, we are seriously behind in our purging, what is called purging, or making those documents publicly available because we have to go through each one and take out any identifying information.
Page 36 PREV PAGE TOP OF DOC I have authorized funds for a contract to bring us up to speed; but the way it ought to be running, which is the way we will try, resources permitting, to do, is we have got to get all the information available to the manufacturers and up there so that there is a complete and full record and people are not misunderstanding, misusing or hurt by what was originally a table of contents of something that comes in.
Mr. HORN. Well, shouldn't FDA have a disclaimer as to the possible inaccuracies? For example, when they put it up here and say the Slim NRG Plus bit and the fact is they didn't know the woman had taken Nyquil and the two glasses of wine and the five additional drugsand it seems to me somewhere either the authors are at fault in some medical journal and they should have noted that and have a drug screen and so forth, or at least a patient history.
And it seems to me when somebody tunes in to a government-sponsored website they think this is certainly truth, except for the IRS. But actually I would think the FDA, with its scientific reputation, would want to put a disclaimer on any case it puts up there, that you don't know what else this person had that led to the particular conclusion of that little point in time of a case.
Mr. LEVITT. You are right. In fact, that is at least one thing that we have been doing. It appears at the beginning of the website. I have heard a recent suggestion that maybe somehow it ought to appear
Mr. HORN. On every case.
Mr. LEVITT [continuing]. On every page, but here there is half a dozen disclaimers. But the one that you are referring to says ''There is no certainty that a reported adverse event can be attributed to a particular product or ingredient.'' The available information may not be complete enough to make this determination. So we have tried to make that disclaimer, and maybe we need to tie it closer to the other information so there is no confusion.
Page 37 PREV PAGE TOP OF DOC Mr. HORN. If a person is taking numerous drugs and supplements and possibly even alcohol, isn't it reasonable to assume that the medical condition could have been caused by any of those things?
Mr. LEVITT. Yes.
Mr. HORN. One last question here. If a person takes two different dietary supplements and has a serious problem and the FDA only reports that the problem was related to one of those supplements, couldn't the FDA wind up banning or regulating the wrong substance?
Mr. LEVITT. Again, that report you are referring to is simply the ingredient listed by the person sending in the report. It does not reflect FDA's judgment in any manner about whether it is serious, whether it is actually attributed to that ingredient or not.
As I said, it is a line listing of everything that has come in. That's why I said it needs to be joined with the fuller document so that all that information is clearly available and people are not misled that just because somebody reported it, it is necessarily associated and or serious.
At the same time, a lot of them are and it would be of benefit to have the information out there.
Mr. HORN. If there are two different supplements, as we postulated there, it seems as though FDA doesn't try to narrow down the cause of the illness; and the end result of that not being done is that the FDA could wind up banning one substance and it is the wrong substance.
Which would really be the most dangerous, to leave that on or to test it or what, as to which substance might really have been the problem?
Mr. LEVITT. Again, it would belet me take a moment on this. It would be very unusual for us to make a conclusion about whether a product, say, ought to be on the market or not based on a single report. What we are trying to do is actually quite the opposite. Each report needs to be looked at and followed up on, but then we need to be looking at the reports in the aggregate to say, No. 1, is there a pattern here? Is there a consistency?
Page 38 PREV PAGE TOP OF DOC So I think the system does have that correction already within it, subject, as I said, we need better transparency if that's not well understood.
Mr. HORN. Thank you.
Thank you, Mr. Chairman.
Mr. BURTON. Thank you, Mr. Horn.
Ms. Norton, did you have any questions?
Ms. NORTON. No questions.
Mr. BURTON. Let me ask just a couple of questions.
Go ahead, Henry, and I will finish up. I will yield to you now.
Mr. WAXMAN. Mr. Levitt, if I couldjust so I understand this problem of what is on the website, what do you put on the website, a complaint from a consumer that you haven't checked out? Is that it?
Mr. LEVITT. Every report that comes in, the first step is to simply make a line entry into, if you will, the inbox that says, all right, this is a report. We will assign it a number. We will put on that listing whatever the report says.
Mr. WAXMAN. I think it is a valid complaint if a consumer reports a problem with a product, and it turns out that it may not have been that product at all that caused the problem, but the FDA has posted the complaint on the website.
On the other hand, I think people who have a problem with a product and they are sophisticated enough to go to the website and pull down the information that is there should have some information, even though you may not have reached a complete conclusion.
Now, I gather you have a problem in cleaning up your website because you don't have the resources to do it. How about putting a disclaimer that these are reports that FDA has received but cannot verify? After all, you know, the manufacturers for dietary supplements have a disclaimer on their products saying they make the following claim, but FDA has not approved this claim and so there is a disclaimer that the claim may not be true.
Page 39 PREV PAGE TOP OF DOC That could be a subject for further discussion, but there is a disclaimer. Why can't you make a disclaimer and continue to post reports so people can get that information?
Mr. LEVITT. We do have that disclaimer.
Mr. WAXMAN. You do have that disclaimer?
Mr. LEVITT. That's up there. The question that has been raised is whether or not thatthat disclaimer automatically comes up when consumers, you know, go into the data base or it is somehow at the beginning somehow, so we can look at that. But the disclaimer is there.
Mr. WAXMAN. Does the disclaimer say something like there is no certainty that a reported adverse event can be attributed to a particular product or ingredient? The available information may not be complete enough to make this determination?
Mr. LEVITT. Yes, that's correct.
Mr. WAXMAN. That's your disclaimer?
Mr. LEVITT. Right. And that's up there and that's available, and there are a half dozen other disclaimers along with it.
Mr. WAXMAN. Look, in the ideal world we want you to get to the bottom of the information, put on the website information that's useful for consumers to know but that's accurate. I think that's asking a lot of you because you don't have the staff resourcesI know from my experience when I was chairman of the Health and Environment Subcommittee that oversaw legislatively and otherwise FDA. But maybe we should talk further about this issue because it seems to me again that we want the information, even if it is not complete and accurate and full information, to be available to people. We want full disclaimers of that information.
We want you to clean up that website as quickly as possible, and if we are going to ask you to do that then we ought to provide you the funds to do it, among all the other things we want you to do.
Page 40 PREV PAGE TOP OF DOC Mr. LEVITT. Thank you for recognizing that.
Mr. BURTON. You will find this interesting, but Henry and I agree on this.
Let me just say that it seems to me that it would not be a great deal of additional work, for instance on the Slim Fast issue, which I used earlier. You have got four pages of allegations related to Slim Fast that scared me to death when I read it. I thought, my gosh, I must be missing something because I haven't had any migraines or kidney infections or gall stones or dizziness. So if you could just put out at the side of each one of these allegations, or whatever you want to call them, please see disclaimer, please see explanation at the beginning of the website or something so that people can realize that this might be an isolated case that might be related to something else that they were taking at the same time, I think that would really be helpful.
It shouldn't take a lot of additional work just to put that asterisk out there or some kind of a notation to see the disclaimer.
Mr. LEVITT. We will look into that straightaway.
Mr. BURTON. OK. I want to get back to the issue of companies that are listed on your website as having an adverse event. A lot of times those reports come from doctors, as I understand it.
Mr. LEVITT. Uh-huh.
Mr. BURTON. The companies that may be the subject of the criticism, or adverse event, don't even know about them. They file a Freedom of Information Act request after they find out about them, and they have to wait for a year many times before they really know what the problem is; and that can cause, as I said before, a lot of economic problems as well as other problems.
They have complained to us about that because they have to wait because of the Freedom of Information Act requirements.
Page 41 PREV PAGE TOP OF DOC Now, did I understand you to say that you have an avenue, other than the Freedom of Information Act, to get that information to these companies so that they can work with you to clear up a problem if it does exist?
Mr. LEVITT. No. I wasyou did not understand exactly what I meant to say anyway. What I meant to say was what we need to doand I said I have allocated some funds to get this done but we are still behind, so that those reports, when they come in are promptly made so they can be made publicly available to the public at large but also certainly to the manufacturer. It is the same preparation process we have to go through, because somebody has to go through every page of the records and be sure that any individual names are not on there.
Mr. BURTON. No, I understand that. But a number of the companies that have contacted us have said, yes, we would like to work with the FDA if these kinds of complaints are made.
Mr. LEVITT. Right.
Mr. BURTON. We would like to get on with it as quickly as possible and clear it up if there is a problem, but because of the Freedom of Information Act and because it takes so long we can't and it does cause problems.
So if there is some way to streamline that, I think it would be helpful to the companies and make people look with a different attitude toward you and the FDA.
Mr. LEVITT. OK. Well, thank you. What we tried to do was to have people on staff do it ''when they had time.'' And what happened was they never had time. So we did take that suggestion and said, all right, we will hire an outside contractor.
We are in the process of training that contractor and being sure that there is somebody dedicated to that task. As I said, it will take us some time to catch up; but, you know, we need to find and have the resources so that is available, because, I mean, the industry complaints, as Mr. Waxman said on this, are correct. They need to have the information, too, and they need to be part of the solution here.
Page 42 PREV PAGE TOP OF DOC Mr. BURTON. If you could give us some kind of a report after you get this contractor trained and up to speed on how long a company can anticipate having to wait, it would be helpful to just give a general idea, we would sure appreciate that.
Mr. LEVITT. OK. We would be happy to do that.
Mr. BURTON. We discussed the fact that there were some fly-by-night companies making some dangerous products containing ephedra. The number of milligrams that were in the product were excessive, and I think we are going to probably hear from one of the parents who lost their son or daughter because of that.
What did the FDA do when they found out about that?
Mr. LEVITT. Well, I mean, FDA had a really massive effort trying to deal with all of the reports and questions that came in about ephedra.
Mr. BURTON. OK. But when you found out that there was a company that was loading up products with ephedra so that kids could get an artificial high or whatever, it happened to be way above the norm, did you move and were you successful in getting those products off the market?
Mr. LEVITT. That was a little before my time so I am going to let Dr. Yetley try to answer that question.
Mr. BURTON. Did you get them off the market?
Dr. YETLEY. I assume you are referring to the so-called street drug alternatives.
We did indicatewe put out warning, first of all, so there was public warning, and then we transferred authorityor responsibility for those to our drug center, and they have dealt with those as unauthorized drugs and taken appropriate compliance action.
Mr. BURTON. And they have been removed?
Dr. YETLEY. Yes.
Page 43 PREV PAGE TOP OF DOC Mr. BURTON. OK. Let me ask you two more quick questions here; and then I would like to, unless another Member has additional questions, hear from the second panel and get back to you.
Mr. WAXMAN. Mr. Chairman.
Mr. BURTON. I am just about finished.
Mr. WAXMAN. Go ahead and finish. I was just going to ask for a unanimous consent.
Mr. BURTON. Sure. Did the legitimate companies that make products, including ephedra, work with you to solve that problem?
Mr. LEVITT. My understanding is there were a number of meetings with representatives from the supplement industry in an effort to try and figure out what can we do to fix this problem. Again, since Dr. Yetley was there, I will let her elaborate if we can.
Mr. BURTON. Can you tell us about the cooperation you received from these companies? Were they cooperative? Were they trying to help to make sure that illegitimate users of ephedra were getting those products off the market?
Dr. YETLEY. We did get good support from the major trade associations, and they did publicly support the agency for dealing with these as drugs.
Mr. BURTON. Did you get that kind of support from the supplement industry as well?
Dr. YETLEY. That's the industry I am referring to, yes.
Mr. BURTON. Thank you very much. I don't have any other questions.
Mr. WAXMAN. Mr. Chairman, is it true that some of these products are still being sold over the Internet? I have one product called X tablets, an herbal Ecstasy alternative. Do you know, in fact, whether some of these products are still available for sale over the Internet?
Page 44 PREV PAGE TOP OF DOC Mr. LEVITT. Given that, under law, companies make market products without telling the FDA, that is entirely possible. I don't personally have information on it one way or the other. I will ask if anybody else does.
Mr. WAXMAN. I gather there's another place where you are shortchanged in resources and that's the enforcement area.
Mr. LEVITT. Yes.
Mr. WAXMAN. So I shouldn't be surprised if there are products that are being sold?
Mr. LEVITT. It would be entirely possible.
Mr. WAXMAN. I would hope that you would be able to respond to further questions we might have in writing for the record.
Mr. LEVITT. We would be more than happy to.
Mr. WAXMAN. I will ask the chairman for a unanimous consent at the appropriate time so that we can include those in the record.
Mr. HORN [presiding]. Well, without objection.
Mr. WAXMAN. You are the chairman?
Mr. HORN. I am the chairman.
Mr. WAXMAN. Thank you, Mr. Chairman.
Mr. HORN. Without objection, they will be put at this point in the record. Go ahead if you would like to continue questioning.
Mr. WAXMAN. No, no. I want the ability to ask them questions to respond for the record after the hearing.
Mr. HORN. Right. If you want some more time, why, take it.
Mr. WAXMAN. No.
Mr. HORN. Let me ask just a few closing questions here. In reviewing the adverse events website for dietary supplement, it appears that there hasn't been an update since October 1998. Now, that's 7 to 8 months ago. I am just curious, how frequently is the website updated?
Page 45 PREV PAGE TOP OF DOC Mr. LEVITT. OK. Again, this really is a resource-dependent issue, and what we have tried to do is to focus our attention first on, if you will, the substantive review of the reports and to do the public availability afterwards. In retrospect, we may have gone too far in one direction on that.
We update it, I think, as available. Is there a specific
Mr. HORN. Why don't you speak in the microphone.
Mr. LEVITT. OK. The goal had been to update it every quarter, quarterly, but we have not been able to keep up with that.
Mr. HORN. Suppose there is a change in that particular item you picked 2 or 3 months before and there is a correction somewhere in a journal or whatever it is, do you try to include those updates?
Mr. LEVITT. OK. Again, the website, as I tried to explain before, I think, is, greatly misunderstood. It is a line listing of reports submitted to the agency, nothing more.
Mr. HORN. Now those reports come from various doctors?
Mr. LEVITT. They come from doctors. They could come from consumers. They come from companies. They come from poison control centers, from States, from whatever source we receive from anyone.
Mr. HORN. So there is no peer review on this?
Mr. LEVITT. No. These are with any spontaneous reporting system. The idea is that if you, whoever you are, a doctor or consumer, feel that you have seen a problem with something, there should be a place that you can send that to; and then it is the responsibility of the recipients, in this case FDA, to go through and do a more detailed analysis of what that entails.
That goes to a lot of the issues we have talked about earlier; but I guess I just want to repeat it again, the website has a whole series of disclaimers. It is not intended to provide an FDA analysis or validation of the information that was reported. It is simply a line listing. It is like a table of contents, of reports, that have been submitted. So somebody looking at it could get an idea of what kinds of products people are writing in about, the kinds of things they are raising, but by no means would it be proper to reach any conclusions from that website on, ah, there is a problem with this product. That would be grossly incorrect.
Page 46 PREV PAGE TOP OF DOC Mr. HORN. One last question. How many adverse effects would you estimate have been filed on dietary supplements in the last 7 months? Do you have any feel for those data?
Mr. LEVITT. It has been running about 500 per year.
Mr. HORN. I see. OK. Thank you very much, Mr. Chairman.
Mr. LEVITT. Thank you.
Mr. BURTON [presiding]. I want to thank you, Mr. Levitt.
Let me say this about that. 500 complaints per year? Do you know how many millions of people take these dietary supplements? I think I take a million myself.
Let me thank you. I really appreciate your testimony. Please stick around for a little bit because we might have another question or two for you. I really appreciate your cooperation. Thank you.
We would like to now hear from a public panel. Dr. William Soller of Consumer Health Care Products Association will discuss elements and effective adverse events monitoring system. Dr. Soller has extensive experience with nonprescription drugs and dietary supplements and will offer viable solutions for the problems that have been identified today.
Dr. Theodore Farber is a pharmacologist and a board-certified toxicologist with FDA and EPA experience. He will review the FDA's handling of ephedra adverse events. He conducted an extensive evaluation of the published adverse events on ephedra.
And Dr. Daniel Mowrey is the president of the American Phytotherapy Research Laboratory. He will present testimony on the use of ephedra throughout its history. He will also discuss the level of scientific research in ephedra and what we know through scientific evaluation on usage, serving size, side effects, and adverse events.
Also Dr. Annette Dickinson of the Council of Responsible Nutrition is joining us again to offer advice on how to develop a good monitoring system.
Page 47 PREV PAGE TOP OF DOC Mrs. Karen Schlendorf is the mother of a young man who, while on spring break in 1996, took Ultimate Xphoria and died.
Ms. Barbara Michal is the founder of H.E.A.T., Halt Ephedrine Abuse Today, a nonprofit organization whose mission is to increase public awareness about the dangers of ephedrine and its related drugs, and to promote the prevention of abuse of ephedrine and its related drugs.
And Dr. Raymond Woosley, a professor of pharmacology and medicine at Georgetown University, will testify about the importance of good adverse events monitoring.
So let me just ask Dr. Soller, Dr. Farber, Dr. Mowrey, Dr. Dickinson, Mrs. Schlendorf, Mrs. Michal, and Dr. Woosley to please stand because this is important. Please raise your right hands.
Mr. BURTON. Let me start with Dr. Soller, and if you could give us an opening statement we would like to, if it is possible, restrict your opening statements to 5 minutes, and then we will get into questions.
I want to apologize for not having more of our members here, but as I expressed before we started, we had some problems here at the beginning of the day and some of the Members are still in that conference and others probably have departed. Please proceed.
STATEMENTS OF R. WILLIAM SOLLER, PH.D., SENIOR VICE PRESIDENT AND DIRECTOR OF SCIENTIFIC AND TECHNICAL AFFAIRS, CONSUMER HEALTH CARE PRODUCTS ASSOCIATION; THEODORE M. FARBER, PH.D., PRINCIPAL, TOXACHEMICA, INTERNATIONAL; DANIEL B. MOWREY, PH.D., PRESIDENT, AMERICAN PHYTOTHERAPY RESEARCH LABORATORY; ANNETTE DICKINSON, PH.D., VICE PRESIDENT FOR SCIENTIFIC AND REGULATORY AFFAIRS, COUNCIL FOR RESPONSIBLE NUTRITION; KAREN SCHLENDORF; BARBARA MICHAL, H.E.A.T.; AND RAYMOND WOOSLEY, PH.D., PROFESSOR OF PHARMACOLOGY AND MEDICINE, GEORGETOWN UNIVERSITY
Page 48 PREV PAGE TOP OF DOC Mr. SOLLER. Thank you. Good afternoon. I am Dr. Bill Soller, senior vice president and director of science and technology for the Consumer Health Care Products Association [CHPA].
Thank you, Mr. Chairman, members of the committee, for the opportunity to address you on a matter of fundamental importance to the dietary supplement industry, adverse experience reporting.
Founded in 1881, CHPA represents producers of quality nonprescription medicines and dietary supplements, including over 200 member companies across the manufacturing, distribution, supply and service sectors of the self-care industry.
I have had 20 years' experience in the self-care industry, having held scientific regulatory and product development executive positions in consumer health care product companies manufacturing both OTC medicines and dietary supplements and have been with the association since 1985, holding similar responsibilities.
On many occasions in my career, I have personally compiled, analyzed, and reported AERs to FDA on self-care products.
By way of background, let's keep in mind that the vast majority of dietary supplements have a very wide margin of safety. Let's also not forget that there is general agreement that the current sourcing mechanisms for AERs, FDA's MedWatch, SN/AEMS, the consumer hotlines, as well as mechanisms that are maintained by the Consumer Product Safety Commission, U.S. Pharmacopeia, the American Association of Poison Control Centers, the National Institute of Drug Abuse and Centers for Disease Control are adequate signal generators of potential problems with consumer products, though systems integration is needed.
And let's not also forget the bigger picture. Ephedra may be the example today, but we must all take a direct interest in ensuring that in the future the right infrastructure and policies are in place at CFSAN to enable it to handle efficiently, expeditiously, and fairly any and all AERs on dietary supplements.
Page 49 PREV PAGE TOP OF DOC Therefore, we recommend the following.
As part of Dr. Jane Henney's initial directives as FDA Commissioner, FDA studied prescription drug approvals pre- and post-PDUFA, issuing a report just this month, which calls for an overhaul of the prescription drug AER program, including adoption of a systems approach to FDA's management of AERs. We support this total quality management approach for CFSAN as well.
Second, we support renewed emphasis within CFSAN on FDA's long-standing overarching safety policy. The policy states for warnings that they must be scientifically documented, clinically significant, and important to the safe and effective use of the product by the consumer. And the significant importance of this policy is that it focuses us on scientific documentation.
Without rigorous critical evaluation of how AER data are collected, analyzed and reported, it is literally impossible to determine their significance.
Third, the controversy surrounding ephedra is clouded by the nature of the data collection and analysis by the agency. This is not unexpected, especially where AERs may be difficult to interpret due to their nature, severity, source, and affected organ systems.
In controversial situations, a refined, integrated system with documented policies and procedures is vital to help ensure that the details of such situations are as accurately documented and professionally handled as possible.
Therefore, we could then concentrate on the science, not the administration, of the process.
In summary then, we recommend that CFSAN prepare a written plan for and adopt a systems approach to managing AERs on dietary supplements, grounded in its current safety policy.
CFSAN should keep current written protocols for CFSAN personnel handling AERs to expedite accurate data collection, including a detailed decision tree for use by those whose responsibility it is to filter serious and nonserious reports and route those reports for expeditious followup.
Page 50 PREV PAGE TOP OF DOC Third, CFSAN needs a policy and procedures for timely sharing of serious AERs with affected companies in order to help facilitate adequate followup and so address incompleteness and inaccuracies in AER reports. Affected companies are inherently motivated to ensure complete, accurate information on AERs.
Four, specific CFSAN training manuals and procedures should be established to ensure quality collection, analysis, and reporting of AERs.
Five, CFSAN should undertake a review of the core competency of the personnel who would operate different facets of an adequate AER system on dietary supplements.
Six, a reengineering of the public process to AER reports for dietary supplements is needed. AERs should be available to the public in a timely fashion when, A, FDA has communicated with the affected company identified in the AER and; B, is prepared to provide publicly a complete file of the report omitting confidential information, not just a table of contents.
Seven, public input is needed in the development of policies and procedures to be used in CFSAN's systems approach to AER management.
And the time is right for these steps. We want consumers to use safe and beneficial dietary supplements for health promotion and health maintenance. Consumer confidence in these products is essential to their usage, and recognizing that the vast majority of dietary supplements are safe and beneficial, a strong systems approach to AER management for dietary supplements is nevertheless needed to ensure that those few dietary supplements that may have safety questions are fairly and expeditiously addressed in order to help maintain consumer confidence.
Hence, we urge this committee to take an interest in the recommendations we have set forth concerning CFSAN's management of AERs for dietary supplements.
We are pleased to hear that Mr. Levitt would use the $2.5 million budget request to upgrade CFSAN's AER system. However, we recommend that the committee consider a specific inquiry to FDA asking for a detailed resource allocation plan for adopting a documented systems approach to AER management.
Page 51 PREV PAGE TOP OF DOC Thank you, Mr. Chairman, members of the committee.
Mr. BURTON. We would like to have your requests and recommendations in writing, if you have those, and we will look at them ourselves and also submit them to Mr. Levitt and to FDA.
Mr. SOLLER. Yes, sir. We provided them prior to the meeting to counsel.
Mr. BURTON. OK. Fine. Thank you. I haven't had a chance to read them yet, but I will.
[The prepared statement of Mr. Soller follows:]
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[The official committee record contains additional material here.]
Mr. BURTON. Dr. Farber.
Mr. FARBER. Thank you, Mr. Chairman.
I am Dr. Theodore Farber. I am
Mr. BURTON. Can we get you to pull the mic a little closer?
Mr. FARBER. Sure.
Mr. BURTON. Thank you.
Mr. FARBER. I am Dr. Theodore Farber. I am president of ToxaChemica, International, which is a consulting toxicology firm located in Rockville, MD.
Before founding this company, I was in government service at the Food and Drug Administration for over 19 years, serving in many senior science positions.
I then served 4 additional years at the Environmental Protection Agency, as a member of the Senior Executive Service. I was director of the health effects division in the pesticide program at EPA and supervised and developed the science policy for the largest group of regulatory toxicologists in the world.
Page 52 PREV PAGE TOP OF DOC I am board certified in toxicology for the last 20 years, and I believe I enjoy an international reputation in my discipline.
Mr. Chairman, if there is only one thing that I could say to the committee, it would be that I have looked at every report in the Food and Drug's AER reporting system in the docket, and I can confirm my belief that dietary supplements containing ephedra, when used according to the label, are safe and effective and have been used for millions of people here in America.
Food and Drug's current system does not provide valid information to the FDA, the public, and the industry about safety of dietary supplements. Instead, because of the way in which AERs are currently handled at Food and Drug, the AER lacks standardized methodology, and this leads to inconsistent applied science from one case to the other.
It causes public confusion over whether an adverse effect was professionally assessed and actually connected with the product mentioned and whether it is simply mentioned as one of the many potential causes, including preexisting conditions and natural causes in other products that may have caused or produced a negative reaction; and it is wasteful of the agency's resources to pursue whole categories of products, branding them as unsafe when the agency might better focus its attention on specific products that are irresponsibly manufactured and marketed.
This is a summary of how Food and Drug's AER system works. Reports from any source concerning the dietary supplement product are received by Food and Drug. They are collected and filed within this AER system. The vast majority of reports, particularly for any product that is the subject of an FDA press release, comes to Food and Drug through a hotline, a number that Food and Drug publicizes. These reports are, almost without exception, anecdotal reports from lay persons who heard about or allege to have had an experience, an adverse effect.
These reports are useless from a scientific perspective, as they typically lack one or more pieces of information critical to scientific analysis, including product identity and ingredients, product dose, frequency and duration, and medical records describing the adverse effects in accurate medical terms.
Page 53 PREV PAGE TOP OF DOC FDA's system does not take into account whether or how publicity affects the reporting rate and I have with meand it is in my written testimonycharts showing that most of the reports FDA has received were as a result of FDA press releases and followup TV programs stating that ephedrine products are dangerous and have killed people. These press releases and TV shows encourage the public to call an FDA hotline to report any problems.
I would like to make one final point. The AER files supporting this proposed rule were in such a disarray when the rule was first published that Food and Drug was required to take unprecedented steps of closing the rulemaking to fix the AER files. Even after this process was completed, I found that the vast majority of AERs for these products, almost 85 percent of these events FDA had publicized as associated with ephedra products, were informationally worthless.
Further, FDA has placed in the docket for that proposed rule a clear statement of its policy on AERs, which acknowledges the scientific fact that unevaluated AERs are inherently unreliable and, therefore, should not be used to establish product risk.
Nonetheless, as Food and Drug has implicitly stated in black and white in the proposed rule, FDA relied on just 13 AERs to establish proposed serving limits for these products, which conservative estimates show that there have been billions of these servings sold that have been consumed by millions of consumers.
FDA even admitted in writing in the proposed rule that the agency had not scientifically evaluated these 13 AERs to determine whether there was any connection to product consumption in the 13 reported events. In fact, the treating physician in 1 of the 13 cases stated that there was no such connection.
Therefore, Food and Drug was almost forced to admit in writing in the proposed rule that the agency's proposed serving limits may have no public health benefit.
Mr. Chairman and members of the committee, I thank you for the opportunity to address you today, and I would be more than happy to answer any questions.
Page 54 PREV PAGE TOP OF DOC Mr. BURTON. Thank you, Dr. Farber.
[The prepared statement of Mr. Farber follows:]
INSERT OFFSET FOLIOS 66 TO 76 HERE
[The official committee record contains additional material here.]
Mr. BURTON. Dr. Mowrey.
Dr. MOWREY. Mr. Chairman, members of the committee, thank you for inviting me here today.
My name is Dr. Daniel Mowrey. I own a company called American Phytotherapy Research Laboratory near Salt Lake City, UT, where our main activity is to investigate the medicinal properties of plant materials, their safety and efficacy.
For the past several years, I have been involved in the investigation of ma huang, its perhaps medicinal properties, its health benefits, its historical uses and so forth.
I have authored a book on the subject called Thermogenesis: Fat Management Related. I think you have a copy there. It deals with the historical background relating the advent, if you will, of ma huang and ephedrine into the weight loss category and what scientific support there is for that. I think I list about 1,400 references in there to detail how that has all come about.
I was asked to testify today about the historical use of ephedrine on ma huang. In doing that, I thought it was fairly impossible to know how long people have benefited from ma huang. However, some time ago I read where ephedra plants were found in a grave alongside the remains of a Neanderthal man dating back about 20,000 years.
This seemed like a good starting point to begin a historical discussion of ma huang, but I must admit to some degree of hesitation in citing this ancient case. It might just wind up in some AER. I can see the headlines now, Killer Herb Has Been Killing People for 20,000 Years.
Page 55 PREV PAGE TOP OF DOC Anyway, back to my point. This case of, this Neanderthal case, I think demonstrates mankind's long association with ma huang. Chinese and other Asian texts show that ma huang has been traditionally used in herbal medicine for at least 5,000 years.
Now, in traditional Chinese medicine, the twigs of this rather scraggly looking ma huang plant were broken up or pulverized and brewed up as a tea. They didn't have capsules in those days, in the ancient days, but they did have a lot of teas.
Several ounces could be used in one serving, and a serving could be taken several times a day. It was served as a tonic; or it was concentrated to be used in the treatment of colds, fevers, and other debilitating conditions.
All in all, I think it was a highly prized herb, used throughout Asia; and it still is to this day, for these traditional systems have not changed much in the way that they use medicinal plants.
By the way, seldom was ma huang used by itself. It was most often combined with a variety of other plants that moderated its effectiveness and its action in the body; and I think that that particular property of ma huang is evident in the way that it is used in modern therapy in weight loss.
Now, although ephedra is normally associated with traditional Chinese medicine, it does grow in the United States, at least related species can be found here. As a matter of fact, early American settlers in Utah, where I reside, brewed up a beverage known as Mormon tea or Brigham tea. It was a favorite beverage and it was used by pioneers to combat exhaustion and fatigue, and often as a primary source of energy or food, since the conditions in the early pioneer days in Utah were not very good.
Brigham Young was said to enjoy an occasional cup of this namesake tea, although I don't think we have any evidence that any of his 20-some-odd wives did that.
The point to all of this is to show that throughout recorded history, in cultures around the world, ephedra has been considered just another herb to be routinely used by human beings. It was never singled out as an exception to standard herbal lore, but fit quite naturally in the traditional medical and nutritional systems.
Page 56 PREV PAGE TOP OF DOC While great reservations are found in traditional medicine about the use of plants, such as magic mushrooms, mandrake, jimpson weed, foxglove, rawolfia and other pyschoactive and cardiovascular plants, no record exists anywhere to suggest that similar concerns were ever directed toward ephedra.
So in recent years, ephedra has become a favorite herb of millions of Americans as a tool for safe and effective weight management. We have identified the active constituents, synthesized them, and these products, or the ephedra-related products, have been widely used throughout modern countries, civilized countries, if you will, not just Third World countries, but actually throughout Europe.
In fact, ephedrine-based weight loss products are the most popular weight management product in Europe and is rapidly becoming so in America.
Given the fact that obesity itself is more prevalent than ever before and that more people are dying of obesity-related disorders than ever before, the notorious syndrome X, the use of ephedra as a dietary supplement may be just the thing that we have been looking for.
Given its centuries-long reputation as a perfectly safe and useful herb, we have to ask the question, why all of a sudden is there this concern over ephedra's safety?
I can see two reasons for that. One is just flat out abuse. The second, I think, is an AER system that has failed us by creating misinformation rather than giving us the truth. The two reasons are intertwined.
The AER thing has been addressed. I just would like to say something about the area of abuse. While I sympathize with people who have lost members of their family to taking substances containing ma huang, whether that was the active constituent or not, I think that we are in a situation where we need better labeling for these things.
I don't think we are in a position where we should get rid of thethrow the baby out with the bath water, as it were.
Page 57 PREV PAGE TOP OF DOC We need to use the tool the way that it can be used safely, to help the millions who need it, at the same time devising labeling requirements and other regulations that reduce the risk of abuse. I thank you very much for allowing me to speak today.
Mr. BURTON. Thank you very much, Dr. Mowrey.
[The prepared statement of Dr. Mowrey follows:]
INSERT OFFSET FOLIOS 77 TO 102 HERE
[The official committee record contains additional material here.]
Mr. BURTON. Dr. Dickinson, it is nice seeing you again.
Dr. DICKINSON. Thank you very much, Mr. Chairman.
The Council for Responsible Nutrition is a trade association of dietary supplement manufacturers representing some hundred member companies who are deeply committed to producing safe and quality products.
We are proud of the safety record of dietary supplement products overall, but we recognize that there is a need for an adverse reaction reporting system because any product, including preapproved products, can result in unexpected effects when taken by millions of people in the general population.
Therefore, the adverse reaction reporting system is a very important signal to us where there may be some errors in product manufacture or some other issues that are causing consumers to be harmed, and it is a valuable indication of that need for action.
We share the concerns expressed by the chairman in your opening remarks regarding the need for FDA resources to handle these systems appropriately, the need for prompt reporting of adverse reactions on the public system.
We question the appropriateness of listing the company name and the product name as part of the table of contents. Mr. Levitt was referring to the publicly available website. The AER system is a table of contents of the system, and I would like to suggest an alternative to the kind of listing that we see on the current system.
Page 58 PREV PAGE TOP OF DOC We also share the chairman's concern about the need to correct errors that may creep into initial listings; and, actually, our new proposal may address some of that concern.
There is an overwhelming need to evaluate the strength of the association, both in terms of the seriousness of the reactions and the nature of the causality of the product taken and the effects seen.
I would like to spend just a couple of minutes describing what may be a very useful new way of approaching the development of this system.
In our statement that we submitted prior to this hearing, we suggested that there might be a three-step system that could be adopted for making these reports publicly available.
First of all, as soon as FDA receives the report, we believe it should immediately become available on the public system, that is, on the website. We would suggest, however, that that initial posting perhaps should only include a description of the generic nature of the product involved and a description of the ingredients of that product, if that is available, and the nature of the symptoms that are observed in the adverse reaction.
We see no reason, no compelling reason, why the name of the company and the name of the product should be part of this very first initial product listing which is only an indication that a report has been received and has not been at this point evaluated in any way.
Therefore, we would suggest that FDA consider having a separate part of its reporting system that is reserved for the initial reports where there would only be generic information about the reaction.
We agree with Mr. Levitt that the priority is that as soon as FDA receives these reports, they should immediately purge them of personal information that is not releasable, so they may be released in a very prompt fashion.
We also believe that the FDA should immediately share those reports with the manufacturer or, in the case where the manufacturer has not been identified, with trade associations representing the industry so they may work with FDA to provide more complete information about the nature of the product, about the nature of its expected effects, and also assist in investigating the particular adverse reaction report.
Page 59 PREV PAGE TOP OF DOC Therefore, we would suggest that as soon as FDA has conducted the second phase of the investigation, that is, has shared the report with the manufacturer and has done some analysis of the likely causality involved in the report, that it be moved from this initial report section, which is a summary form into one of two more permanent report sections.
One of those two sections would be reserved for adverse reactions that the FDA has, in fact, determined are likely to be related to the product itself. And in that case it may be appropriate to include in that listing the name of the product and the name of the company after the company has been notified of that.
We think that there should be a third section of these reports which will be reserved for reports which are determined definitely not to be related to the product taken or about which there is insufficient information available to make a determination.
Therefore, we would end up with a three-part reporting system, an initial part which is a summary, a second part which is essentially the ones that are either not related to the product or about which there is not sufficient information, and then a third part which would really be the core of the permanent record and would be the basis for FDA's future analysis of any action to be taken which would be limited to those reports that have been evaluated and where there is sufficient evidence to believe that the report, the adverse event is, in fact, related to the product.
We think that this would improve the ability of FDA and the industry and other health professionals to use these adverse event reports in a productive way to address questions that need addressing as promptly as possible.
Thank you very much.
Mr. BURTON. Thank you, Dr. Dickinson.
[The prepared statement of Dr. Dickinson follows:]
INSERT OFFSET FOLIOS 103 TO 108 HERE
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Mr. BURTON. Ms. Schlendorf, we appreciate you being here, both you and Ms. Michal; and we are very sorry about the experiences you have had.
Ms. SCHLENDORF. Thank you.
Mr. Chairman, members of the committee, my name is Karen Schlendorf. To me Peter Schlendorf is not an adverse event but my youngest child who, like too many others, suffered from the fatal effect of a herbal supplement which contained ephedrine.
I believe that I am speaking for so many people who can no longer speak for themselves, Kristopher Michal, Rosanna Porras, to mention a few; but let me tell you about Pete Schlendorf.
As a mother, it is very difficult to put into words the depth of my feelings for my youngest son. Pete was the joy of my life. From the day he was born, Pete was someone very special. He made me smile every day, and I thanked God that I had been blessed with such a wonderful gift.
My three children meant the world to me; and as a full-time mother, I enjoyed every minute that I spent with them. On the day that I began my job as a high school guidance counselor, Pete, who was then 10, picked a bouquet of flowers from our garden for me.
I had always given the children a small gift on the first day of school and told them how proud of them I was, and now he was doing the same thing for me. He was always a kind and thoughtful person who made people glad that they knew him. He brightened a room every time he entered it.
He was always the center of attention, not because he asked for it, but because it seemed to come to him naturally. Pete was bright and funny, athletic and talented and a leader among his peers. I was proud of his accomplishments and prouder still of the man he was becoming.
Page 61 PREV PAGE TOP OF DOC Then one day the unthinkable happened. He died. Pete had gone to Florida on spring break with some of his friends. On a cold and overcast day, they decided to explore some of the shops along the beach. All week they had seen ads and banners promoting herbal supplements of all kinds. They went into one of the shops and decided to try one.
It is all natural, safe, harmless. The store clerk said that she and her friends took 10, 12 of them all the time, made them feel great and gave them lots of energy. So the boys tried them.
Pete took somewhere between four and eight pills and almost immediately began to feel strange. His heart rate was faster, he felt tingly, hot all over and had a pounding headache. He took a shower, but it didn't help.
He told the other boys to go out, and he would lie down for a while; and when he felt better, he would join them later. The last time his friends saw him alive, he was sitting on the edge of a bed reading the label on the box. What had he taken? What was wrong? What should he do? There was no help on that box.
It took weeks, months for us to understand what happened to our beautiful, wonderful, healthy son. At least now we know the facts. But I don't know that we will ever really understand. Pete died because a company cared much more about profits than about lives. Pete died because he had an unfortunate chance encounter with Ultimate Xphoria.
The manufacturers of this product have admitted to us their irresponsibility and their callousness. They have admitted that they are not sure how many or which additional herbs were in each batch.
They claim not to know where the ma huang came from, which part of the plant was used, the time of year it was harvested, or how strong the concentration was. They didn't know, or perhaps they didn't care; but my son died because Ultimate Xphoria was improperly manufactured and irresponsibly marketed toward young people.
Page 62 PREV PAGE TOP OF DOC A number of ingredients in this product posed a risk to Pete or any other healthy individual. Combined, they caused an insurmountable risk of harm. I know that there is a great deal of information in publications and on the Internet that disputes these truths. I have read them myself. But this is the truth.
I have a copy of Pete's autopsy, something no mother should ever have to see; and it shows beyond a shadow of the doubt that the only thing in Pete's system was the ingredient in this product. He had been on spring break with his friends, but there was no evidence of any drug or alcohol or anything else except the lethal herbal supplement that he bought over the counter in a little shop on the beach.
Ephedrine is a drug. It has been known as a drug for over 5,000 years. No amount of legislation will make it a food. Proponents of ephedrine-containing supplements like to say that the Chinese have used it for centuries. They have, through practitioners who prescribe it as part of their traditional medicine, not for weight loss, not for energy boosts.
Scientists have agreed on what ephedrine does. It dilates bronchial muscles, contracts nasal mucosa, raises blood pressure, acts as a cardiac stimulator. Although there may be some disagreement as to a safe limit of ephedrine, I do not dispute that in proper hands, ephedra can be appropriate and safe.
However, the Dietary Supplement Health and Education Act of 1994 has allowed irresponsible persons to contaminate the marketplace with false claims and dangerous marketing. I doubt that it was the intention of this governmental body to allow people like those who caused my son's death to get rich at the expense of America's youth.
I fully understand that there are many people and certainly many manufacturers making millions of dollars from these products who don't want to hear any of this, but I would hope that my government would want to hear this.
Filing an adverse event report was our vehicle to the truth, and I did this in honor of my son, Peter Charles Schlendorf.
Page 63 PREV PAGE TOP OF DOC Mr. BURTON. Thank you very much. That was a very touching statement.
[The prepared statement of Ms. Schlendorf follows:]
INSERT OFFSET FOLIOS 109 TO 110 HERE
[The official committee record contains additional material here.]
Mr. BURTON. Ms. Michal.
Ms. MICHAL. Mr. Chairman and members of the committee, my name is Barbara Michal of Novi, MI, founder of the nonprofit National Coalition Halt Ephedrine Abuse Today. I am here today at my own personal expense, and I am deeply grateful for you allowing me to testify today.
My keen interest in the ephedrine regulation issue came about through a parent's deepest terror, the death of a child. On March 14, 1997, ephedrine killed my 24-year-old son Kristopher.
Since that time, I have been researching ephedrine; and I am appalled at how much information is available as to the serious dangers of this powerful cardiovascular and central nervous system stimulant and equally appalled at the lack of strict regulation of this drug.
Some members of the dietary supplement industry with their huge profits and their powerful lobbyists have mounted a concerted campaign to discredit the work of the FDA in gathering adverse event reports and in promulgating proposed ephedrine controls rules. Their motivation is to protect their profits, not the safety of the citizens of the United States.
Mainstream drug companies not only welcome adverse event reports, they have physicians and pharmacologists on staff to review and evaluate each adverse event report. With prescription and mainstream over-the-counter drugs, physicians and other health-care practitioners know to report adverse events to the FDA.
Page 64 PREV PAGE TOP OF DOC However, the unregulated dietary supplement industry is another story all together. There is no industry-wide adverse event reporting procedure. Product labels generally do not carry 800 numbers for consumer use in reporting adverse events.
In general, the public is unaware that the FDA wants to receive adverse event reports on dietary supplements, and I strongly doubt that the dietary supplement manufacturers have physicians and pharmacologists on staff to evaluate what adverse event reports they do receive.
The industry disputes the validity of the data base of the FDA, yet they are not required to submit reports to it. Now they come to you complaining that the FDA adverse event reporting system is seriously deficient, the data base is suspect and the FDA has not used sound scientific studies upon which to base their proposed ephedrine control rules.
I respectfully ask whether the dietary supplement industry has submitted even one peer-reviewed, sound scientific study to prove the safety of their ephedrine-laced products in humans. They are bashing the science and data of the FDA because they have nothing of substance to support their position.
They also use the Chicken Little argument, the sky is falling. They claim that strict regulation of ephedrine will destroy the dietary supplement industry. This argument is preposterous on its face. Some dietary supplement manufacturers have recognized the serious dangers and potential liability of this amphetamine analog and have already removed it from their products; and those products are selling quite well, thank you.
My organization, Halt Ephedrine Abuse Today, is conducting a survey of ephedrine use on the Internet. As of April 30, 1999, with 227 people reporting, 48 percent report addiction.
Of those reporting using dietary supplement products as opposed to synthetic ephedrine products, 28 percent, over one-fourth report addiction. Among other adverse reactions, we have had reports of psychosis, stroke, cardiac arrythmia, kidney damage, nerve damage, heart attack, and death.
Page 65 PREV PAGE TOP OF DOC Contrary to the staffing problems with the FDA not being able to followup on these reports, I have spoken personally with many of these people after they have contacted me through the Internet. We have received an additional 85 responses since the end of April. They have not yet been collated.
This report is not scientific. It has not been reviewed by a licensed medical professional. It is purely the voices of American citizens detailing the adverse event reactions and injuries they have experienced. And this is just the tip of the iceberg.
My organization is hearing only from people with Internet access and who are actively seeking information on ephedrine; and of those, very few have reported their experiences to the FDA, and some even say, I didn't know I should.
Comparatively, the FDA already has in place a centralized reporting system where both private citizens and health-care professionals can report adverse reactions. If the industry has a problem with the reporting system and data collected, they should be working directly with the FDA to suggest improvements, which I have heard today they are doing, which I am very pleased with.
They should not be bringing their crusade to Congress in an effort to tar and feather the FDA without being sure that they provide constructive input as to how to fix the alleged deficiencies.
Regarding the industry's argument that the FDA has no legitimate science upon which to base their proposed ephedrine control rules, I respectfully refer the committee to the bibliography at the end of the June 2, 1997, proposed rules as published in the Federal Register.
Along with my written statement that I submitted, I included a bibliography of medical journal articles that I have collected. The proof is out there. The fire storm the industry is trying to ignite against the FDA serves only as smoke and mirrors to divert the focus from the real issue: Is ephedrine a threat to the health of the citizens of the United States? Yes.
Page 66 PREV PAGE TOP OF DOC Is the industry taking responsibility for seeking out and collecting adverse event reports to learn the truth? No. Does ephedrine need to be strictly regulated? Yes.
I sincerely thank you for this opportunity to be heard. The playing field in this controversy is far from level. We ephedrine victims and our families don't have millions of dollars in corporate profits to spend. We don't have powerful lobbyists with political connections. We don't have paid professionals whose job it is to be aware of and attend every hearing and committee meeting.
We are members of the general public; and we have a voice, too.
Thank you, Mr. Chairman and members of the committee, for hearing that voice.
Mr. BURTON. Well, thank you, Ms. Michal. We appreciate your comments.
[The prepared statement of Ms. Michal follows:]
INSERT OFFSET FOLIOS 111 TO 139 HERE
[The official committee record contains additional material here.]
Mr. BURTON. Mr. Woosley.
Dr. WOOSLEY. Good afternoon, Chairman Burton and members of the committee. I am actually a physician; I am a pharmacologist and physician.
Mr. BURTON. Excuse me, Dr. Woosley.
Dr. WOOSLEY. No problem. It gave me a chance to emphasize the fact that I am a physician.
I have to say I am moved and even shaken to follow the previous two witnesses. I reviewed the FDA reports of their children's deaths, and I have to tell you it was difficult then, and it is more difficult now. I read those cases ofas they described, young children unknowingly taking poisons.
Page 67 PREV PAGE TOP OF DOC I have helped the FDA analyze these cases, and that is one of the reasons that I am here today. I have helped them analyze these and many other cases, and I would like to tell you that there is nothing wrong with that process. It can be made better, but it doesn't make mistakes.
Since 1977, I have conducted clinical research and basic research on the mechanisms of the adverse effects of drugs in humans. In over 250 scientific publications, I have examined the toxic effects of prescription and nonprescription drugs, mainly on the heart.
My research has identified the mechanisms responsible for the potentially lethal cardiotoxic effects of several drugs, including Seldane, a widely prescribed antihistamine recently removed from the market.
I mention my background because it is this experience upon which I base my conclusions and the recommendations to you today. You have asked this panel to address a very serious question, and I don't appreciate the levity that some have introduced; it really seems inappropriate.
This question has major consequences for the health and welfare of many citizens in our Nation. You have heard testimony from others that there are major weaknesses in the FDA's voluntary reporting system; and I also have criticized it in the past, but usually for what it has not done, not for what it has done. Some have tried to cast doubt on the data that comes from the FDA's surveillance system. Please don't allow them to confuse you on this issue.
In 1994, I was asked by the attorney general of the State of Texas and the Center for Food Safety and Applied Nutrition at the FDA to review 88, and later another 147, cases. These were cases of suspected toxic reactions of ephedrine-containing products. I have enclosed a copy of my initial report to the FDA for the record.
As you will see, in 1994 I concluded that there were reports of chest pain, heart attack, stroke, seizures, cardiac arrest, sudden death, two that we have heard today, some of these people in the prime of their lives. I concluded that these reactions are perfectly consistent with what one would expect to see from excessive dosage or extreme sensitivity to ephedrine.
Page 68 PREV PAGE TOP OF DOC In August 1996, I served as a member of the FDA Food Advisory Committee to review all of the scientific evidence that had been accumulated by the FDA. The FDA has done due diligence. They have had a processperhaps it hasn't been made known to everyone, but they have seriously investigated this issue. There was full agreement by this committee that the 800 cases submitted to the FDA were absolute proof of the harm associated with dietary supplements containing ephedra.
I and others have constructively proposed improvements to the FDA's current voluntary reporting system because it has inadequate staff. It often requires months to years before identifying an adverse event associated with a drug or a devise. The system is plagued by underreporting, incomplete reports, and inadequate staff for analysis of those reports. However, no credible argument has ever been made that the system makes errors in detection. It is a blunt instrument, but an essential one, that is capable of identifying frequent, serious problems, especially when they are closely associated with exposure to a product, as in this case.
In 4 years, over 800 reports of adverse events associated with over 100 different ephedrine-containing products were received at the FDA, 100 different, not just a few rebel products, 100 different products. The FDA has estimated that less than 1 percent of serious adverse drug reactions ever get reported. Therefore, the actual number of reactions to ephedra is far greater than the number that they have on record.
I have absolutely no doubt of the validity of the harm detected by the FDA scientists. In the past, the adverse drug reactions detected by the systems have been routinely confirmed by regulatory scientists in other countries that have used a wide range of different methodologies. An important part of the FDA system is the confirmatory process applied in the analysis of these, often less than adequate, reports. For example, because we know that ephedrine increases the blood pressure and heart rate in animals and in people, the profile of adverse events that you would predict to occur would be arrhythmias, stroke, cardiac arrest, and sudden death. These are exactly the kind of reactions I reviewed in those reports.
Page 69 PREV PAGE TOP OF DOC Additional confirmation is obtained by comparing the patterns of reactions to those seen with drugs that have similar pharmacologic action, such as amphetamine and methamphetamine. These have been the exact same kind of events reported with ephedrine.
Additional evidence for the reliability of the association is seen in the fact that 26 percent of the 800 reports included documentation that the adverse events subsided when the product was withdrawn. Further, in 4 percent of the cases, the exact same symptoms recurred when they reinstituted the therapy or the drug was again administered.
In summary, the FDA's spontaneous reporting system accurately detected and confirmed the harm that results from compounds containing ephedra. The public must be protected from the proven harm of these products.
Because of the biologic variability in the way people respond to these products and the fact that many people don't know that they have conditions which predispose them to the products harmful effects, such as coronary artery disease, it is impossible to identify a safe dose of these products.
I sincerely request that you give your strong support to the FDA's efforts and affirm their authority to take even stronger action and remove every one of these products from the marketplace.
When my 7-year-old son grows up and goes to Florida on spring break, don't let these products kill him.
Mr. BURTON. Thank you, Dr. Woosley.
[The prepared statement of Dr. Woosley follows:]
INSERT OFFSET FOLIOS 140 TO 143 HERE
[The official committee record contains additional material here.]
Mr. BURTON. I have a granddaughter and a grandson, and I share your concern about their exposure to things that could harm them.
Page 70 PREV PAGE TOP OF DOC Let me ask you a question. You reviewed the reports on the two young people who died. By any chance in those reports did you notice how much ephedra they had taken?
Dr. WOOSLEY. We tried to estimate that based on their labelled content, but in the FDA hearings it became very clear that you can't. FDA scientists collected those products that were being marketed then and measured their ephedra content. The content of ephedra and ephedrine-like alkaloids varied from 1 milligram to 100 milligrams, even though they were labeled to contain on average about 12 milligrams. We have no way of knowing how much these two young people took. The other aspect of it is it really doesn't matter how much it was, any amount could have been lethal.
Mr. BURTON. It is of concern. I take Sudafed and my wife takes a product that she uses for her asthma.
Dr. WOOSLEY. But that is not ephedrine. That is Sudafed. That is a much weaker compound. It is a totally different drug.
Mr. BURTON. All right. We will get back to that. That may be a layman's understanding.
Dr. WOOSLEY. This is a potent, toxic drug.
Mr. BURTON. What I would like to understand, when your son was in Florida and he took this, as I understand it, that particular product was advertised as giving people some kind of a feeling of euphoria?
Ms. SCHLENDORF. Yes, a feeling of euphoria or an energy boost or 100 other things.
Mr. BURTON. Right.
Ms. SCHLENDORF. It was also stressed that it was perfectly safe and harmless. Pete took at least four pills, could have taken as many as eight. His friends said they thought he took four. We were trying to account for all of them, so there could have been a couple more than four, but they didn't think that they were taking anything dangerous.
Page 71 PREV PAGE TOP OF DOC And what came out in our investigation of the pills and of the company, the company didn't know how much ephedra was in the product; and one box could have varied greatly to the next. We don't know how much he took.
Mr. BURTON. And I don't like to get into too much of the detail because it is not comfortable for everybody, but the autopsy that was performed, I presume, did it indicate in any way how much of this product or this substance was in his system?
Dr. WOOSLEY. I don't remember in this specific case, but I recall in several of the cases there was analytical data indicating the quantity in the body.
The problem with all of that is, it doesn't really matter how much is in the body or even in the pills. There are people who are exquisitely sensitive. He may have been such a person.
In the hearings, I argued long and hard but failed to win the argument that there is no safe dose of ephedrine as a dietary supplement because there is no way you can give it to a large number of people without hurting an exquisitely sensitive person, for example someone who didn't know that they have high blood pressure.
Mr. BURTON. There are some products that I might buy over the counter which are perfectly legal and very safe for healthy people to take that might cause hives or severe problems for other people in my family, so that may not be unique to ephedrine.
Let me ask Dr. Farber about this. Doctor, Dr. Woosley has indicated that there is no safe amount of ephedra that can be taken, and you seem to have some expertise in this area. Can I have your opinion on that.
Mr. FARBER. Yes. I can't agree with Dr. Woosley. It is almost contrary to what every pharmacologist or toxicologist knows. Over 400 years ago, the father of modern toxicology said that the poisoning is in the dose and so forth.
And for a pharmacologist to say that there is no level of a material that is safe is mind boggling to me. There is a safe level of ephedra alkaloids; and the products of the responsible companies in this industry which do have proper labeling presents a product to millions of individuals that can be taken safely every day, and, in fact, billions of servings have been taken by people over the years.
Page 72 PREV PAGE TOP OF DOC This would, indeed, make this product safer than peanuts and shellfish and chocolate and strawberries and aspirin and wine; and I could go on and on and on in regards to products that we all use with the concept that we are using it safely, that, in fact, has produced a higher incidence of reactions in the public than these products.
Mr. BURTON. Do you have a comment, Dr. Mowrey?
Dr. MOWREY. In the ephedrine hearings that took place in 1995 and 1996, I believe those were the years that Dr. Woosley was a part of, questions came up about what is the history of toxicology with ephedrine hydrochloride prescribed at a dose of 150 milligrams per day, which is over twice as much as what we are saying isis established in the research on ephedrine or ma huang currently in use.
Somebody said there isn't any. I can't remember who that individual was, but the point was that with all of the millions and millions of doses of that ephedrine hydrochloride that have been administered, such as in Primatine, which does contain ephedrine, there is virtually a total lack of this kind of toxicology that we are discussing here today.
And so the idea of a disconnect was suggested. There is some kind of a difference between the alkaloids present in ma huang and those in ephedrine; and it was an open question at that time.
Since then there has been research published to demonstrate the pharmacokinetics of ephedrine in ma huang is virtually identical to the pharmacokinetics of ephedrine hydrochloride. I think we have settled that issue at least temporarily in view of maybe we need more research along those lines, but I think that question has been addressed and the initial response is that they are fairly identical in their reactions in the body.
Mr. FARBER. Mr. Burton, could I make another comment?
Mr. BURTON. Sure. Go ahead.
Mr. FARBER. Dr. Mowrey brings up an important point in regards to Primatine and some of the products that are offered to millions of Americans in over-the-counter preparations. Primatine contains ephedrine, and the labeling allows for a dose level as high as 150 milligrams a day.
Page 73 PREV PAGE TOP OF DOC With the dietary supplements that we are talking about right now put out by responsible companies, the labeling suggests that there be no more than an exposure of 100 milligrams of ephedrine alkaloids, not necessarily ephedrine, but ephedra alkaloids; and some of those alkaloids are weaker, in fact, than ephedrine.
But it is interesting to note that people out there are taking Primatine at 150 milligrams a dayand at one time several years ago it was as high as 300taking 150 milligrams a day and having ubiquitous contact with caffeine in coffee, in tea, in chocolate, in cola beverages; and there are no significant number of AERs being reported or in the files of the Food & Drug Administration. Doesn't that raise some questions? Thank you.
Mr. BURTON. Dr. Soller, has there ever been any analysis as to what is a safe amount of ephedrine and what is an excessive amount of ephedrine? Obviously Ms. Schlendorf's and Ms. Michal's sons took amounts that were excessive and did end up in their demise.
How do we know what is a safe amount, and what do we tell the American people?
Mr. SOLLER. Thank you. It is always difficult to try and be objective when you areand deal with the science when you are dealing with tragic stories; and of course, we very much reach out to the parents, knowing that we have children as well.
And so with that and attempting now to step back and think objectively and what we know about the science, there has been a review of ephedrine through the OTC review that began in 1972 and subsequent reviews as well; and as a bronchodilator, ephedrine is used both as an inhalation form and an oral tablet.
Inhalation it will be about 5.5 milligrams per inhalation and then wait about 5 minutes and take another dose. And for the tablet, a total of a 25 milligram dose taken on a 4-hourly basis.
Page 74 PREV PAGE TOP OF DOC Now, information that has been sent in to FDA in reviewing this particular issue looked at the drug abuse warning network and found that ephedrine is fairly low on the list in terms of potential for abuse, that is, reports of an abuse situation to an emergency room setting.
And that is not particularly unusual in the OTC field because it is at the issue of a low potential for abuse, not absence of abuse. But what was backed up in that particular data-set for ephedrine was a 15-year cohort of AERs reported to companies finding that in a period where about a billion OTC tablets were sold, there were 171 adverse experiences and 3 of those were serious reports. There were no deaths.
So there appears to be a different situation on that OTC side than on this other side, and I would just like to make one or two more comments that kind of rounds out a view in terms of what I have heard here.
That is that the main issue here is for CFSAN to focus in on the safety of dietary supplements, and I would agree with Dr. Woosley that we have basically a system in effect at FDA which can be refined.
And even on the drug side, Jane Henney knows that there needs to be refinement by CDER, and we would suggest that same systems approach be put through all centers, including CFSAN, and that we do not get into the kinds of situations where we are arguing the administration of AERs but we are looking at the science and carefully documenting. That is very important to do.
The other aspect is that GMPs are very important to the industry, and we have commented to FDA and urged that GMPs be adopted into regulation that would be somewhat different than food GMPs, not quite as high as drug GMPs for appropriate technical reasons we need not get into.
But that is very important because it would raise the issue of identity and concentration within the particular dietary supplement and would very much help, as you would get reports from the field that would talk about unknown amounts.
Page 75 PREV PAGE TOP OF DOC And if a company doesn't know what is in their particular product from an identity standpoint, it is our belief that raising the level of awareness on GMPs, allowing FDA to have that standard of inspection, would help the field and some of the occurrences that we have heard about today.
Mr. BURTON. Thank you. Ms. Schakowsky.
Ms. SCHAKOWSKY. Thank you, Mr. Chairman. Since we are talking today about accurate reporting, I just wanted to elaborate a bit. We are talking about 500 voluntarily made adverse event reports on dietary supplements. That was Mr. Levitt's comment.
But I asked him later privately, and he said that is a tiny number of adverse events, that is how many were reported under this voluntary system, that is all there were. When I said 1 percent, he seemed to indicate that was more like it.
So I think it would be a mistake for us to conclude that there are not any adverse events larger than 500. But I wanted to also ask Dr. Farber in the interest of accurate reporting, Dr. Farber, do you have or have you had any kind of a financial relationship with a dietary supplement manufacturer of an ephedra product?
Mr. FARBER. I have been retained by the law firm of Hyman, Phelps & McNamara that represents several diverse companies in the dietary supplement industry.
Ms. SCHAKOWSKY. And you said that AERs are useless. That was your testimony.
Mr. FARBER. No, I really didn't.
Ms. SCHAKOWSKY. No, I wrote that down. You said AERs are useless.
Mr. FARBER. In this particular instance, they are close to worthless. I could show you some further information in regards my analysis on these AERs. I have personally spent, and my associate, over 700 hours examining every one of the AERs in the public docket. If you are interested, I can show you the analysis.
Page 76 PREV PAGE TOP OF DOC Ms. SCHAKOWSKY. What I am interested in is the AERs that were filed by Ms. Schlendorf regarding her son Peter. Is that worthless?
Mr. FARBER. No. No. I didn't say that. I said that when you look at the whole situation, there is very little that isthat you are able to interpret. Now, I have looked at the Schlendorf file, and I have looked at the autopsy report. I feel very sad for Mrs. Schlendorf in regards to this situation, but regrettably this young man took an illicit street drug, masquerading, perhaps, as a dietary supplement, and regrettably lost his life.
I don't condone the marketing of this product. Neither do the people that I have been working with or the industry that I have been trying to help. They are appalled that these products have been allowed to remain in the marketplace.
The Food & Drug Administration, indeed, had the powers under DSHEA to remove these products before Peter bought the product. They did not take the action that they were permitted by DSHEA to take against these things.
Ms. SCHAKOWSKY. I thought that you testified that it is safer than peanuts.
Mr. FARBER. I said when the products of the responsible industry companies are taken according to the labeled instruction on the product that they are safe and they are effective. That is not to sayI am not saying that abuse potential doesn't exist with ephedra. It does.
But I knowand it has been recently establishedI think you are familiar with the Physicians' Desk Reference. I think almost every American has looked at this book to check on side effects of drugs. There is a new PDR on herbal remedies. That PDR says that ephedra is safe at levels up to 300 milligrams a day.
Now, the responsible members of this industry are recommending that their labeling state not to take any more than 100 milligrams a day.
Page 77 PREV PAGE TOP OF DOC Ms. SCHAKOWSKY. Thank you, Doctor. I would like to let Dr. Woosley respond to a number of things that were said here today. Go ahead, Dr. Woosley.
Dr. WOOSLEY. Thank you for that opportunity. I think it is very important to point out that the PDR and the PDR for herbals is simply a compilation of materials submitted by manufacturers. It has absolutely no other special credibility.
I would also defend myself as a pharmacologist in my statement that ephedrine has no safe effective dose as a dietary supplement. You can give 25 milligrams, 50 milligrams, 75 milligrams of ephedrine to everybody in this room and no one will ever feel anything more than a rapid heart rate and a headache and maybe trivial side effects.
But if you give it to millions the way that it is happening today, you get hundreds, or tens at least, of people dying like the ones that we heard about today, even at the low dose that is currently being recommended with no, absolutely no, proven benefit other than a high.
Do we want to recommend products be out there that can kill when there is no proven benefit?
Ms. SCHAKOWSKY. Could I go on for a minute. Just to underscore that, I am looking at some of the marketing of this product on the Internet.
Psychedelic Shrooms. Take a psychedelic magic carpet ride with the greatest pill on earth. Contains ephedra, sinac, whatever that is.
Then we have got each capsule contains 800 milligrams of ma huang extract; dosage orally, one to two capsules on an empty stomach 30 to 40 minutes before activity. Do not exceed recommended dosage.
We have got Midnight Ecstacy, Herbal Coke, Turbo Charge, all being advertised right now on the Internet.
Dr. Tim Johnson said on the tape this morning that he felt that ephedra should be acknowledged as a drug and therefore should be regulated as a drug, and I would like to hear the doctors' comments on whether or not they agree with that.
Page 78 PREV PAGE TOP OF DOC Mr. FARBER. Clearly the products that you have discussedand I can go on and name many, many more like Brain Wash, Cloud 9, Ultimate Xphoria, Love Potion 69 and so on and so forththey have all been taken out of the market at least by action of the Food & Drug Administration.
These products are winding up on the Internet, and the Food & Drug Administration has to work out some game plan to take action against these products. They are illicit street drugs; they are not dietary supplements.
Ms. SCHAKOWSKY. Should ephedra be regulated, as Dr. Tim Johnson said, as a drug?
Mr. FARBER. No, I don't believe so. If these dietary supplements are used according to the labeland the labeling on these products are almost identical to the labeling on Primatinethey can be used safely and effectively by the public without having to turn them into prescription items.
Ms. SCHAKOWSKY. And what is a safe dose?
Mr. FARBER. A safe dose would be 25 milligrams a day four times a day, not exceeding more than a 100 milligrams per day of ephedra alkaloids. The literature indicates that 25 milligrams per kilo four times a day is a safe dose even in the presence of caffeine. And you can go back into the literature.
Ephedrine had been derived from ephedra 75 years ago by K.K. Chen who became the scientific director of the Eli Lilly Laboratories. It has been extensively studied. We do know its pharmacology and what its side effects and toxicity is.
It is not a substitute for methamphetamine. For somebody to say it has the potency of methamphetamine and it has the capability of producing highs like amphetamine is wrong.
The DEA has acknowledged that it is not a substitute methamphetamine, and the United Nations has indicated that this material is not a drug or a substance that has any particular high level of drug abuse potential, and that has been as late as March of this year.
Page 79 PREV PAGE TOP OF DOC In fact, there is a letter to Congressman Farr from the State Department declaring that ephedra is considered by the United Nations to be not a significant drug of abuse.
Ms. SCHAKOWSKY. Mr. Chairman, I wanted to ask that the accompanying materials to Ms. Michal's statement also be put into the record; and she seems really anxious, so say something.
Mr. BURTON. Without objection. Ms. Michal.
Ms. MICHAL. Thank you very much.
As far as the addiction and abuse and the effect of ephedrine mimicking amphetamine, it is an amphetamine analog. It is molecularly similar to amphetamine. It has been proven in studies by Dr. Paul Wellman at the head of the department of psychology at Texas A&M University that it affects dopamine in the brain exactly the same way cocaine and amphetamine do.
I mentioned that I was getting these reports from people over the Internet. I have just two comments that I would like to share with you as far as ephedra not mimicking amphetamine or giving them the same feeling.
I have a 40-year-old female from California reported that she was addicted to speed. She is a recovering drug addict. She took a product called Power Trim, two pills as per the label, took it once and she said, I knew right away it is the same stuff that I took when I was addicted to methamphetamine.
I have another one that basically said the same kind of thing. She was a former drug addict addicted to metha female, 24 from Oklahoma, and she took two pills, took it once of Advantage A.M. 300, and it was the same reaction: this is the same stuff that I was addicted to before, and I can't take it again.
Ephedrine is an amphetamine analog. I have a 48 percent addiction report rate, dosage run-ups to incredible levels.
Ms. SCHAKOWSKY. Mr. Levitt, is it true that those are illegal on the Internet? Are those drugs that I was referring to that are being marketed on the Internet, are they, in fact, illegal according to the FDA, which is what Dr. Farber said that those are illegal?
Page 80 PREV PAGE TOP OF DOC Mr. BURTON. We might ask him to return to the table after we conclude with this panel.
Ms. SCHAKOWSKY. I'm sorry.
Mr. BURTON. That is fine.
Let me just end up by asking one or two more questions. I want to make a comment. Dr. Woosley, you said that the food supplement industry did that PDR, but as I understand it from my staff, that PDR is based on the German government's commission and monograph. Is that correct?
Dr. WOOSLEY. There is something called the German Commission Monographs that is a translation of the monographs on herbal preparations.
Mr. BURTON. Is that the one to which you were referring?
Dr. WOOSLEY. No, that is a different document. The PDR for dietary supplements is a separate book and it isMedical Economics markets these products.
Mr. BURTON. As I understand it, the industry took their PDR from the German government's?
Dr. WOOSLEY. They may have taken parts of it, but it is a form of advertising. It is not a scientifically rigorous document.
Mr. FARBER. Mr. Chairman, if I could make a comment.
Mr. BURTON. Dr. Farber.
Mr. FARBER. I have extensively used the German Commission E monograph, not AufDeutsch, but the English translation, and clearly ephedrine is recognized as a useful herb and recognized to be safe at dose levels considerably higher than 100 milligrams per day. The West German government has set up this commission, and it is heavily dependent upon the opinions found in these monographs.
Mr. BURTON. Let me ask Dr. Mowrey one more question. Dr. Dickinson, because we have not asked you a whole bunch of questions does not mean that we don't value your contribution.
Page 81 PREV PAGE TOP OF DOC Dr. Mowrey, can you give us any information about ephedra and how it works on fat metabolism?
Dr. MOWREY. This is a fairly new application for ma huang. It has its historical roots in the science of thermogenesis, and in particular in the discovery that brown adipose tissue in human beings is truly capable of significant thermogenesis in terms of its ability to help the body in its efforts to control weight.
Ephedrine turns out to be the only safe and effective molecule that we know of today to really activate this process in the body via sympathetic mediation. The process is under the control of the sympathetic nervous system, and we stimulate that with ephedrine.
There is plenty of research to support the contention that it is a safe and effective treatment for obesity in human beings. Like I say, it is the most popular treatment throughout Europe. Ephedrine/caffeine combinations there account for 80 percent of the weight loss market, and considerable research has been generated by Arn Astrup and a group in Denmark to demonstrate the efficacy and safety of this particular combination.
Granted, there are mild adverse events that occur, as we have been mentioning here, but serious adverse events are not seen in that research. That research, the subjects of course are screened so they don't have cardiovascular complications coming into the research. Labels are designed to help screen out people from taking the product that might be susceptible to that kind of an accident.
In the United States the Harvard group led by Patty Dailey with Lawrence Lanceburg on the team established the safety and efficacy of long-term treatment of human beings with an ephedrine, caffeine, and aspirin combination. That was published in the International Journal of Obesity in 1993.
Since the publication of that document, there has been a dramatic increase in interest in this particular mechanism for weight control. I think that it represents right now perhaps the boldest and the best program that we have for controlling weight because it seems to address the underlying physiology of the problem.
Page 82 PREV PAGE TOP OF DOC In fact, most of the genetic research going on right now with leptin and other genetic mutations all seem to have as a common pathway metabolism in adipose tissue, in particular brown adipose tissue.
So it's a very strong thrust for the medical profession right now to be involved in doing this, and it is, I suppose, what has led the dietary supplement industry into producing products that contain those substances.
Mr. BURTON. OK. Well, let me just say to all of you how much I appreciate your time and your patience.
Once again, our condolences to both of you. We will certainly take into consideration everything that you two have said, as well as Dr. Woosley. We sure have heard a diverse group of opinions here. So thank you very much.
We would like to have Mr. Levitt return to the table just for a couple of seconds. Mr. Levitt, thank you for being patient and sticking with us for a little bit here.
I think what I would do is I will initially yield to Ms. Schakowsky, and then I just have a couple of questions for you, Mr. Levitt, esquire.
Ms. SCHAKOWSKY. Thank you so much, Mr. Chairman. I really appreciate this opportunity.
Let me ask you directly then what I had mentioned before. The 500 voluntarily made adverse events reports represent, in your view, what percent or how much of the total adverse events that occur with dietary supplements?
Mr. LEVITT. Well, we believe with all regulated products that the reports that get submitted is a tiny percentage of what is really out there, because people don't necessarily either make the connection themselves or even if they make the connection think that eithereither don't know where to report it to or don't know how to or aren't sure what is going to become of it.
Page 83 PREV PAGE TOP OF DOC So we estimate, even in the pharmaceutical area, that reporting is in the neighborhood of 1 percent of what really is out there.
Ms. SCHAKOWSKY. So would it be accurate then to conclude, because there are so few reported cases then, that there are, therefore, so few problems out there?
Mr. LEVITT. Well, I think it is hard to say that. What I think it is important to say is that the point of the adverse event reporting system, and I appreciate the chance to emphasize this, is to signal a potential problem. And even with under reporting, which is accepted in all of these systems, the chances are high that somebody is going to report it and then FDA has a chance to see it and check other data bases, other existing information, check the literature and, see, yes, do we think this signal is right.
So there is definitely under reporting, as there are with all of those. What we hope is reported is, if you will, an illustrative example and we can pick from even under reported important signals that can identify safety problems.
Ms. SCHAKOWSKY. Thank you so much for that.
I also wanted to clarify whether or not these drugs that contain ephedra, that are advertised over the Internet, are theyis that illegal to purchase them and to offer them for sale?
Mr. LEVITT. OK. The rule on that is that if these products arecontain what we would consider a drug claim, that makes them subject to the drug rules. Now what you have there is we have had to go back and say are thereby the kind of title that they give the product, by the kind of statements, if they are really essentially marketing it as an alternative to street drugs, that we will consider that a drug and in this case, since we know they don't have pre-market approval as an approved drug, then they would be illegal.
But the fact that they are illegal doesn't mean that it is easy to chase down. Things market over the Internet. FDA can try to do something. It is very simple for somebody to change their website, alter their name a little bit, and it is very much a difficult process to chase these people down.
Page 84 PREV PAGE TOP OF DOC Ms. SCHAKOWSKY. So it is a subjective conclusion on what they are claiming to be? I mean, energetic sensations, waves of sensual pleasure, gentle tingling sensations, states of nirvana, is this illegal?
Mr. LEVITT. The actual analysis of those is done by a different part of the FDA so I am not expert in the specifics, but that is the general point. The general point is howif in the jargon that is used, if what they are really saying is that this is an alternative street drug, it is used for recreational purposes, it is not identified for weight loss or for something that is a normal mainstream use, then that would make it a drug claim and not lawfully marketable.
Ms. SCHAKOWSKY. Thank you.
Mr. BURTON. Thank you, Ms. Schakowsky.
Mrs. Schlendorf's and Ms. Michal's children lost their lives because of the over use or overexcessive consumption of these pills.
They have been taken off the market by the FDA, have they not?
Mr. LEVITT. You mean those particular ones?
Mr. BURTON. Yes.
Mr. LEVITT. My staff are telling me yes.
Mr. BURTON. What I would like to know, and followup to what Ms. Schakowsky just asked, is were the advertisements fairly consistent with what she just read for these other things that are on the Internet?
Mr. LEVITT. Iyou don't know? Are they fairly consistent with what
Mrs. SCHLENDORF. Yes, they are, and I also know that the exact product Ultimate Xphoria that my son took, it was recommended to take four and he only took four to maybe eight. That particular product is no longer manufactured. The company is still in business and they are manufacturing other similar things.
Page 85 PREV PAGE TOP OF DOC Mr. BURTON. OK.
Mrs. SCHLENDORF. There are lots of other things on the Internet very similar that any 10-year-old can buy. Those have not been taken off the market.
Mr. BURTON. OK. Thank you.
I would like to ask, Mr. Levitt, can't the Federal Trade Commission work with you to get these products that are being advertised on the Internet, that are using similar advertising techniques, can't they followup and try to run these people down?
I know that there are some ''Internet police'' now that are out there trying to get unscrupulous people off the Internet. It seems to me that the same thing could be done for these products that are endangering young people with excessive amounts of ephedrine.
Mr. LEVITT. Well, there are mechanisms that we are using.
Mr. BURTON. OK.
Mr. LEVITT. And shall continue to use for those.
But may I just say I think it is a mistake, and at least a number of the testimony in the previous panel suggested that the evidence and the adverse events that we have found are not limited to those that are viewed as ''high abuse levels.'' The questions that were basically asked were five.
No. 1, are there consistent patterns of signs and symptoms associated with the use of these different ephedra alkaloid containing products? And the answer to that was yes.
Two was, are the patterns consistent with the available scientific evidence and known physiologic and pharmacologic effects of ephedrine alkaloids? The answer was yes. The answer I am giving here was the answer from our Foods Advisory Committee.
Three, does exposure occur temporarily before the onset of the observed scientific symptoms, meaning did they take the product first? The answer was yes.
Is there other evidence of causality, meaning dechallenge, rechallenge? Dr. Woosley referred to that also, and the answer was yes.
Page 86 PREV PAGE TOP OF DOC And then the question was, considering the totality of the available information, is there a biologically plausible explanation for the adverse events? And the committee concluded, I believe unanimously, that the answer was so.
Mr. BURTON. Was there any indication from that about the amount?
Mr. LEVITT. There was a number of views expressed about the amount. Some expressed Dr. Woosley's view that it would not be possible to establish a safe amount. Others on the committee suggested that FDA try and establish a safe level. That's what FDA tried to do in the proposed rule and so forth.
If I may, just one other point that is related to this. Appended to my written testimony is a chart that I would just like to put up briefly because it wasso much of this was addressed by the previous panel, because I think, again, a point that is often misunderstood. There are a lot of adverse events, some of them more serious than others, some less serious, obviously, than others, and we have talked about that. But what FDA did, and what is important to understand about the system in general, is that the point of those reports is not to give you a definitive answer. The point of those reports is to signal, is there a potential problem here? If they do, what else can we look at?
And the chart here shows, you start really at the bottom. What is in the literature that we know about it? Are there any controlled clinical trials? In this case, there were some trials dealing with weight loss. What do we know about the OTC drug experience? What do the experts say?
We take all of that together and say, is this supporting a global finding that there is a public health problem with these products? And they unanimously said, yes.
And so I was appreciative of some of the prior testimony about the FDA process. Before, we talked mostly about the process in general, but this is a case where the system did identify a real public health issue.
Page 87 PREV PAGE TOP OF DOC People are struggling on exactly what is the right remedy. You referenced that. Is there a safe dose or not a safe dose? How many different products are out there? Is it some products and not other products?
There is a lot of complexities to the issue, but I think that should not take away from the underlying finding. And the Timothy Johnson segments, I think, underscored that, that there is something going on here that we need to try and remedy and do the right thing about that.
We are trying to do that, but I think, as you have also seen, it is a challenging labyrinth to get all the way through.
Mr. BURTON. Obviously there are some strong differences of opinion.
Mr. LEVITT. Right.
Mr. BURTON. The thing on the Internet, though, and we are going to review all of this information that has been submitted by everybody, the thing on the Internet is really important and you are going to put these disclaimers on there, you say, to try to make sure that people don't
Mr. LEVITT. Yes. You mean the webpage, yes.
Mr. BURTON. On the webpage, right.
I would like to ask Dr. Yetley one last question. Is she still here?
This is on a different subject, but since we have you here I would like to ask you about it. We have received hundreds of letters from the public regarding the Codex Committee on Nutrition and Food for Special Dietary Use. There are a lot of consumers that are concerned that through an international governing body, upper limits will be set on the dosage of their vitamins.
Can you give me an outline of what the controversy is on that real quickly?
Page 88 PREV PAGE TOP OF DOC Mr. LEVITT. Could I just say, thank you for asking that question because again there is a lot of misinformation out there about that. I am sure Dr. Yetley can explain.
Mr. BURTON. Thank you for prefacing her comment with that. I appreciate that.
Ms. YETLEY. Thank you. The Codex Committee is an international standard setting committee. It is part of the WTO agreements, or at least it feeds into those.
There is a proposal on the table that was forwarded by the German government, which is proposing to set standards for vitamin and mineral supplements that would include both minimum and maximum levels.
First of all, let me make it very clear that even if the Codex Committee were to adopt these standards, it would not affect the products in the United States. The products under DSHEA would still have jurisdiction here. So it would not affect availability of these products in the United States.
This issue has come up before the Codex Committee on Nutrition and Foods for Special Dietary Use for the last two meetings. The U.S. position has been to oppose this particular standard because it is not consistent with our laws. However, the rest of the delegates have, as a majority, wanted to move forward.
We are now in the process of offering to work with other governments to write a background paper that would lay out the pros and cons of the various perspectives of different governments and different delegations. So it will give us a chance to lay forth our philosophies and concerns as well as other governments'.
Mr. BURTON. We would like to, if it would be possible, Doctor, to have you meet with our staff for a full briefing.
Ms. YETLEY. I would be glad to.
Page 89 PREV PAGE TOP OF DOC Mr. BURTON. We would really appreciate it.
Mr. LEVITT. I think that it is just indicative of the fact that these products are regulated differently in different countries, and when you get into different international fora, everybody tries to move it.
Mr. BURTON. Sure. We would like to have a briefing just so we can understand that better.
Mr. LEVITT. Sure.
Mr. BURTON. Mr. Levitt, thank you very much. Doctor, thank you very much.
We I want to thank all of our witnesses. It has been a long day. We really appreciate it, and we hope this has shed some light on this whole problem. The meeting stands adjourned.
[Whereupon, at 4:45 p.m., the committee was adjourned.]
[Additional information submitted for the hearing record follows:]
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[The official committee record contains additional material here.]