[House Hearing, 106 Congress]
[From the U.S. Government Publishing Office]




 
   HOW ACCURATE IS THE FDA'S MONITORING OF SUPPLEMENTS LIKE EPHEDRA?

=======================================================================

                                HEARING

                               before the

                              COMMITTEE ON
                           GOVERNMENT REFORM

                        HOUSE OF REPRESENTATIVES

                       ONE HUNDRED SIXTH CONGRESS

                             FIRST SESSION

                               __________

                              MAY 27, 1999

                               __________

                           Serial No. 106-60

                               __________

       Printed for the use of the Committee on Government Reform


     Available via the World Wide Web: http://www.house.gov/reform

                                 ______

                     U.S. GOVERNMENT PRINTING OFFICE
61-435 CC                    WASHINGTON : 2000




                     COMMITTEE ON GOVERNMENT REFORM

                     DAN BURTON, Indiana, Chairman
BENJAMIN A. GILMAN, New York         HENRY A. WAXMAN, California
CONSTANCE A. MORELLA, Maryland       TOM LANTOS, California
CHRISTOPHER SHAYS, Connecticut       ROBERT E. WISE, Jr., West Virginia
ILEANA ROS-LEHTINEN, Florida         MAJOR R. OWENS, New York
JOHN M. McHUGH, New York             EDOLPHUS TOWNS, New York
STEPHEN HORN, California             PAUL E. KANJORSKI, Pennsylvania
JOHN L. MICA, Florida                PATSY T. MINK, Hawaii
THOMAS M. DAVIS, Virginia            CAROLYN B. MALONEY, New York
DAVID M. McINTOSH, Indiana           ELEANOR HOLMES NORTON, Washington, 
MARK E. SOUDER, Indiana                  DC
JOE SCARBOROUGH, Florida             CHAKA FATTAH, Pennsylvania
STEVEN C. LaTOURETTE, Ohio           ELIJAH E. CUMMINGS, Maryland
MARSHALL ``MARK'' SANFORD, South     DENNIS J. KUCINICH, Ohio
    Carolina                         ROD R. BLAGOJEVICH, Illinois
BOB BARR, Georgia                    DANNY K. DAVIS, Illinois
DAN MILLER, Florida                  JOHN F. TIERNEY, Massachusetts
ASA HUTCHINSON, Arkansas             JIM TURNER, Texas
LEE TERRY, Nebraska                  THOMAS H. ALLEN, Maine
JUDY BIGGERT, Illinois               HAROLD E. FORD, Jr., Tennessee
GREG WALDEN, Oregon                  JANICE D. SCHAKOWSKY, Illinois
DOUG OSE, California                             ------
PAUL RYAN, Wisconsin                 BERNARD SANDERS, Vermont 
JOHN T. DOOLITTLE, California            (Independent)
HELEN CHENOWETH, Idaho


                      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

                              ----------                              
                                                                   Page
Hearing held on May 27, 1999.....................................     1
Statement of:
    Levitt, Joseph A., Director, Center for Food Safety and 
      Applied Nutrition, Food and Drug Administration............     8
    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......................................    82
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......................................   138
    Farber, Theodore M., Ph.D., principal, Toxachemica, 
      International, prepared statement of.......................    97
    Levitt, Joseph A., Director, Center for Food Safety and 
      Applied Nutrition, Food and Drug Administration, prepared 
      statement of...............................................    12
    Michal, Barbara, H.E.A.T., prepared statement of.............   151
    Mowrey, Daniel B., Ph.D., president, American Phytotherapy 
      Research Laboratory, prepared statement of.................   110
    Schlendorf, Karen, prepared statement of.....................   146
    Soller, R. William, Ph.D., senior vice president and director 
      of scientific and technical affairs, Consumer Health Care 
      Products Association, prepared statement of................    85
    Waxman, Hon. Henry A., a Representative in Congress from the 
      State of California, summaries of complaints...............    53
    Woosley, Raymond, Ph.D., professor of pharmacology and 
      medicine, Georgetown University, prepared statement of.....   183


   HOW ACCURATE IS THE FDA'S MONITORING OF SUPPLEMENTS LIKE EPHEDRA?

                              ----------                              


                         THURSDAY, MAY 27, 1999

                          House of Representatives,
                            Committee on Government Reform,
                                                    Washington, DC.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.''
    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.
    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.
    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.
    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. 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.
    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.
    [Witness sworn.]
    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.
    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 signal--and we 
will be hearing that word a lot today--to 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.
    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.
    Finally, it is not just dedication to anything; it is a 
dedication to excellence--excellence 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.
    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.
    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:]

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    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 staff--we 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 add--to 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.
    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.
    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 me--
and I mentioned it in my opening statement--is 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 me--I 
take Slim Fast. I know I look thin, strong, healthy and 
everything--why 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.
    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. Waxman.
    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.
    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.
    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.
    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.
    Mr. Burton. Very well.
    [The information referred to follows:]
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    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 the--we have received overall about, I 
believe the number is about 1,000 reports altogether. The 
number, total number that is serious, I am going--I 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 talking--it is a large enough number 
that it is--that 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.
    Mr. Levitt. I think--I 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 heard--and 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.
    So it would--both 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 event--these reports are 
not required--that 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.
    In that setting, it was clear, I think, that--to 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.
    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 reacting--
questioning 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?
    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.
    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.
    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.
    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 drugs--and 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.
    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 be--let 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?
    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 could--just 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.
    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 that--that 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 resources--I 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.
    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.
    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 was--you did not understand exactly what 
I meant to say anyway. What I meant to say was what we need to 
do--and 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.
    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 indicate--we put out warning, first of all, so there 
was public warning, and then we transferred authority--or 
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.
    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?
    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?
    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.
    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.
    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.
    [Witnesses sworn.]
    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

    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.
    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.
    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.
    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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    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.
    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.
    FDA's system does not take into account whether or how 
publicity affects the reporting rate and I have with me--and it 
is in my written testimony--charts 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.
    Mr. Burton. Thank you, Dr. Farber.
    [The prepared statement of Mr. Farber follows:]
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    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.
    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.
    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 the--throw the baby out with the bath water, as it were.
    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:]
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    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.
    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.
    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:]
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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.
    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.
    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.
    Mr. Burton. Thank you very much. That was a very touching 
statement.
    [The prepared statement of Ms. Schlendorf follows:]
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    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.
    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.
    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.
    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:]
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    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 of--as 
they described, young children unknowingly taking poisons.
    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.
    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 process--perhaps 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.
    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:]
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    Mr. Burton. I have a granddaughter and a grandson, and I 
share your concern about their exposure to things that could 
harm them.
    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.
    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.
    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 is--is 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.
    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 day--and at one time 
several years ago it was as high as 300--taking 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 are--and 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.
    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.
    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.
    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 is--that 
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 say--I am not saying that abuse 
potential doesn't exist with ephedra. It does.
    But I know--and it has been recently established--I 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.
    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.
    Mr. Farber. Clearly the products that you have discussed--
and I can go on and name many, many more like Brain Wash, Cloud 
9, Ultimate Xphoria, Love Potion 69 and so on and so forth--
they 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 label--and the labeling 
on these products are almost identical to the labeling on 
Primatine--they 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.
    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 meth--a 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?
    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 is--Medical 
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.
    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.
    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 either--either 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.
    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 
they--is that illegal to purchase them and to offer them for 
sale?
    Mr. Levitt. OK. The rule on that is that if these products 
are--contain 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 there--by 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.
    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 how--if 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 over--excessive 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. I--you 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.
    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.
    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 was--so 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.
    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?
    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.
    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 
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