<DOC>
[106th Congress House Hearings]
[From the U.S. Government Printing Office via GPO Access]
[DOCID: f:61435.wais]
HOW ACCURATE IS THE FDA'S MONITORING OF SUPPLEMENTS LIKE EPHEDRA?
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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?
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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.
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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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