[Senate Hearing 108-651]
[From the U.S. Government Publishing Office]



                                                        S. Hrg. 108-651

                     DIETARY SUPPLEMENT SAFETY ACT:
                HOW IS THE FOOD AND DRUG ADMINISTRATION
                         DOING 10 YEARS LATER?

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

                                HEARING

                               before the

                  OVERSIGHT OF GOVERNMENT MANAGEMENT,
    THE FEDERAL WORKFORCE, AND THE DISTRICT OF COLUMBIA SUBCOMMITTEE

                                 of the

                              COMMITTEE ON
                          GOVERNMENTAL AFFAIRS
                          UNITED STATES SENATE


                      ONE HUNDRED EIGHTH CONGRESS

                             SECOND SESSION

                               __________

                              JUNE 8, 2004

                               __________

      Printed for the use of the Committee on Governmental Affairs



                    U.S. GOVERNMENT PRINTING OFFICE
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                   COMMITTEE ON GOVERNMENTAL AFFAIRS

                   SUSAN M. COLLINS, Maine, Chairman
TED STEVENS, Alaska                  JOSEPH I. LIEBERMAN, Connecticut
GEORGE V. VOINOVICH, Ohio            CARL LEVIN, Michigan
NORM COLEMAN, Minnesota              DANIEL K. AKAKA, Hawaii
ARLEN SPECTER, Pennsylvania          RICHARD J. DURBIN, Illinois
ROBERT F. BENNETT, Utah              THOMAS R. CARPER, Delaware
PETER G. FITZGERALD, Illinois        MARK DAYTON, Minnesota
JOHN E. SUNUNU, New Hampshire        FRANK LAUTENBERG, New Jersey
RICHARD C. SHELBY, Alabama           MARK PRYOR, Arkansas

           Michael D. Bopp, Staff Director and Chief Counsel
      Joyce A. Rechtschaffen, Minority Staff Director and Counsel
                      Amy B. Newhouse, Chief Clerk

                                 ------                                

  OVERSIGHT OF GOVERNMENT MANAGEMENT, THE FEDERAL WORKFORCE, AND THE 
                   DISTRICT OF COLUMBIA SUBCOMMITTEE

                  GEORGE V. VOINOVICH, Ohio, Chairman
TED STEVENS, Alaska                  RICHARD J. DURBIN, Illinois
NORM COLEMAN, Minnesota              DANIEL K. AKAKA, Hawaii
ROBERT F. BENNETT, Utah              THOMAS R. CARPER, Delaware
PETER G. FITZGERALD, Illinois        FRANK LAUTENBERG, New Jersey
JOHN E. SUNUNU, New Hampshire        MARK PRYOR, Arkansas

                   Andrew Richardson, Staff Director
   Marianne Clifford Upton, Minority Staff Director and Chief Counsel
                      Kevin R. Doran, Chief Clerk


                            C O N T E N T S

                                 ------                                
Opening statements:
                                                                   Page
    Senator Voinovich............................................     1
    Senator Durbin...............................................     2

                               WITNESSES
                         Tuesday, June 8, 2004

Hon. Robert E. Brackett, Ph.D., Director, Center for Food Safety 
  and Applied Nutrition, U.S. Food and Drug Administration.......     5
Alice M. Clark, Ph.D., Vice Chancellor for Research and Sponsored 
  Programs, University of Mississippi, Oxford, Mississippi.......    18
Ronald M. Davis, M.D., Member, Board of Trustees, American 
  Medical Association (AMA)......................................    20
Charles W.F. Bell, Program Director, Consumers Union of U.S., Inc    21
Anthony L. Young, General Counsel, American Herbal Products 
  Association (AHPA).............................................    24
Bruce Silverglade, Director of Legal Affairs, Center for Science 
  in the Public Interest.........................................    25
Annette Dickinson, Ph.D., President, Council for Responsible 
  Nutrition......................................................    27

                     Alphabetical List of Witnesses

Bell, Charles W.F.:
    Testimony....................................................    21
    Prepared statement...........................................    92
Brackett, Hon. Robert E., Ph.D.:
    Testimony....................................................     5
    Prepared statement with attachments..........................    43
Clark, Alice M., Ph.D.:
    Testimony....................................................    18
    Prepared statement with attachments..........................    75
Davis, Ronald M., M.D.:
    Testimony....................................................    20
    Prepared statement...........................................    85
Dickinson, Annette, Ph.D.:
    Testimony....................................................    27
    Prepared statement with attachments..........................   123
Silverglade, Bruce:
    Testimony....................................................    25
    Prepared statement...........................................   115
Young, Anthony L.:
    Testimony....................................................    24
    Prepared statement...........................................   105

                                APPENDIX

List of Manufacturers Receiving Androstenedione Warning Letters..    66
Sample Warning Letter on Androstenedione.........................    68
Chart entitled ``Time Line of Activities To Establish Current 
  Good Manufacturing Practice Regulations (CGMPs) for Dietary 
  Supplements,'' submitted by Mr. Brackett.......................    70
Chart entitled ``CFSAN 2004 Program Priorities,'' submitted by 
  Mr. Brackett...................................................    72
American Society For Pharmacology and Experimental Therapeutics 
  (ASPET), prepared statement....................................   137

 
                 DIETARY SUPPLEMENT SAFETY ACT: HOW IS
                    THE FOOD AND DRUG ADMINISTRATION
                         DOING 10 YEARS LATER?

                              ----------                              


                         TUESDAY, JUNE 8, 2004

                                       U.S. Senate,
            Oversight of Government Management, the Federal
            Workforce, and the District of Columbia Subcommittee,  
                          of the Committee on Governmental Affairs,
                                                    Washington, DC.
    The Subcommittee met, pursuant to notice, at 2:36 p.m., in 
room SD-342 Dirksen Senate Office Building, Hon. George V. 
Voinovich, Chairman of the Subcommittee, presiding.
    Present: Senators Voinovich and Durbin.

             OPENING STATEMENT OF SENATOR VOINOVICH

    Senator Voinovich. The Subcommittee will come to order.
    Good afternoon, and thank you for coming. The Subcommittee 
is meeting this afternoon to discuss the Food and Drug 
Administration's implementation of the Dietary Supplemental 
Health Education Act of 1994, also referred to as DSHEA.
    This hearing was requested by my friend and colleague, 
Senator Durbin. In the 5\1/2\ years that I have been Chairman 
or Ranking Member on this Subcommittee, Senator Durbin and I 
have had an excellent working relationship. When I was Chairman 
of the Subcommittee during the 106th Congress, we held two 
hearings on food safety at Senator Durbin's request, and during 
the last Congress, Senator Durbin held two hearings at my 
request on one of my top issues, human capital management, and 
today, I am happy to be hosting this hearing.
    Prior to this hearing, I was not familiar with the subject 
matter of dietary supplements. After I started researching the 
issue, I began to understand why Senator Durbin wanted to hold 
a hearing. I take vitamins daily and would like to be 
guaranteed that they are labeled correctly and that they are 
safe. I also have additional concerns with people mixing 
dietary supplements and prescription drugs.
    Millions of Americans buy and use dietary supplements on a 
daily basis and believe that the products that they are taking 
are safe and beneficial to their health. Now that we have 
reached the 10th anniversary of the act, it is appropriate to 
examine whether the FDA and the dietary supplement industry 
have adhered to the intent of this law so that Congress might 
consider ways in which it could be improved and also to educate 
American consumers on the latest development in dietary 
supplement policies and practices.
    Recognizing the need for the Federal Government to address 
the American consumer's growing interest in dietary products 
and public safety, Congress overwhelmingly passed DSHEA 10 
years ago. And the purpose of the act was to provide the 
framework for ensuring that the Federal Government properly 
oversees the safety and efficacy of dietary supplements sold in 
the United States.
    Essentially, this legislation requires that all ingredients 
and supplements sold in the United States must be previously 
approved by the FDA and listed on the bottle label and that 
distributors must follow guidelines to demonstrate the veracity 
of any claims that are made in regard to the particular 
product. Additionally, an important aspect of DSHEA is the 
establishment of good manufacturing practices, GMPs, which are 
standards that could help ensure the safety of dietary 
supplements.
    In March 2003, the FDA published a proposed rule for 
dietary supplement GMPs, and the rule is currently under 
review. It is my understanding that the final rule on GMPs is 
expected by the end of the year. I applaud the Bush 
Administration and former FDA Commissioner McClellan for making 
this a priority. This is a positive step in the enforcement of 
DSHEA, and I hope these standards give American consumers of 
dietary supplements greater confidence in their safety.
    With that said, I would like to know why it took the 
regulations so long to be established. Responsible members of 
this industry have actively sought appropriate science-based 
regulations to ensure that consumers are well-educated through 
factual labeling and that dietary supplements are manufactured 
in a consistent manner to guarantee their safety and efficacy.
    Unfortunately, not all players in the market are 
responsible. It is these bad players that bring us here today. 
We need to ensure that they are held accountable and that 
Americans can depend on the existing regulatory agencies to 
protect and promote their wellbeing with regard to dietary 
supplements.
    To aid in this dialogue, the Subcommittee will be hearing 
from the U.S. Food and Drug Administration, policy researchers, 
medical professionals, consumer advocacy groups, and dietary 
supplement industry leaders, regarding the impact of the law.
    I now yield to our Ranking Member of the Subcommittee, my 
good friend, Senator Durbin, for an opening statement.

              OPENING STATEMENT OF SENATOR DURBIN

    Senator Durbin. Thank you, Mr. Chairman. And this has been 
a very cooperative bipartisan relationship, and we each have 
our interests and priorities, and Senator Voinovich has allowed 
me to pursue this, and when I chaired this same Subcommittee, I 
offered the same opportunity to him.
    And I think this is the kind of bipartisan cooperation 
people expect of us, and I am glad that we have been able to 
achieve it in this Subcommittee.
    Mr. Chairman, 1994 was an important year in the history of 
the dietary supplement industry. After an overwhelming effort 
on Capitol Hill, the dietary supplement industry won the right 
to sell their products to the American public without testing 
them in advance for safety or establishing their efficacy. The 
Dietary Supplement Health Education Act of 1994, also known as 
DSHEA, exempted the industry from informing the FDA when their 
products caused harm or injury to the people who were buying 
them.
    The law that was passed in 1994 was opposed by all public 
health, medical, and professional nutrition groups, including 
the American Cancer Society, the American Dietetic Association 
and all of the major consumer groups in America, including the 
Consumer Federation of America.
    Since then, business has been very good for the supplement 
industry. The industry has grown more than fourfold since 1994, 
from $4 billion to $18 billion in sales. According to the 
Centers for Disease Control and Prevention, more than 38 
million Americans used dietary supplements in the past 12 
months. The Internet has now grown to 143 million users, and 
there are literally thousands, hundreds of thousands of 
Websites on the Internet that sell dietary supplements.
    But meanwhile, consumers have been endangered by the FDA's 
inability to act on particular supplements, 155 people died 
after taking dietary supplements containing the stimulant 
ephedra, and thousands more suffered injury. Yet it took years, 
literally years, for the FDA to ban this substance under this 
law, DSHEA. The FDA's action, though commendable, may have been 
a classic case of closing the barn door well after the horse 
had galloped away.
    By July 2003, 6 months before FDA acted, Walgreens, CVS, 
Rite Aid, and virtually all other major drug stores and 
specialty nutrition stores in this country had already removed 
products containing ephedra from their shelves. Why? They 
believed that ephedra was too risky and exposed their stores to 
legal liability if they continued to sell dangerous ephedra 
products.
    All the major American sports organizations and the 
International Olympic Committee had already banned ephedra 
before the FDA acted. Three of the most populous States, 
Illinois, New York, and California, had done the same, and the 
nation of Canada had banned the sale of ephedra. Ephedra 
products were banned for sale on military base exchanges around 
the world, because we had literally lost soldiers who had taken 
ephedra products and died.
    Why did it take the FDA, the agency created by President 
Theodore Roosevelt to protect the American public from 
mysterious elixirs claiming to cure diseases, so long to 
finally pull the plug on ephedra? The answer? DSHEA. The law 
has to be changed to protect consumers. Millions of Americans 
take vitamins safely every day, including this Senator and the 
Chairman. Vitamins taken in recommended doses are safe.
    It is the designer supplements that are worrisome. 
Supplement makers like to say their products are safe because 
they are natural. They have been used for years. But the truth 
is that many of today's supplements contain concentrated 
extracts mixed with a myriad of other ingredients that can be 
harmful. Take the supplement Joint Ease, which was marketed as 
a natural remedy for arthritis. While the active ingredient, 
aristolochic acid, has been used for centuries in Europe and 
China, the supplement product contained the substance in 
concentrated form which was subsequently found to cause kidney 
failure and kidney cancer.
    The product was eventually recalled, but only after cases 
in the United Kingdom, Belgium, and France highlighted its 
toxicity. Until we fundamentally change the law governing how 
supplements are regulated, agencies responsible for public 
health will constantly fall short of monitoring the marketing 
practices of this industry. I do not believe that every natural 
substance needs to be subject to premarket safety testing. But 
at the very least, DSHEA should be changed so that stimulants 
are tested before marketed. When a supplement raises blood 
pressure, increases metabolism and constricts blood vessels, it 
is only prudent that we test this product before it is 
marketed. Otherwise, American consumers are going to be the 
laboratory test rats.
    Another change I would like to see made to DSHEA is making 
the adverse event reporting system mandatory for serious 
adverse events. I am not talking about someone getting dizzy 
from taking a supplement. I am talking about heart attacks, 
strokes, and death. It is absolutely necessary that we know 
when a product is seriously harming people. How can the FDA 
effectively protect the public if it does not know when the 
product is causing harm?
    Adverse event reporting is not a cumbersome process 
compared to the premarket safety and efficacy review 
prescription and over-the-counter drugs go through. Fixing 
DSHEA and keeping dietary supplements safe are challenging 
tasks. It is no assignment for the politically timid, I can 
tell you, having been on this issue for a couple years. 
Regardless, our responsibility to protect the health of the 
American consumer is clear.
    Thank you, Mr. Chairman.
    Senator Voinovich. Thank you, Senator Durbin.
    First, the Subcommittee has the pleasure of hearing 
testimony from Hon. Dr. Robert Brackett. Dr. Brackett is the 
Director of the Center for Food Safety and Applied Nutrition at 
the Food and Drug Administration. He will explain in greater 
detail the status of DSHEA's implementation.
    On the second panel, we will hear from Dr. Alice Clark, the 
Vice Chancellor for Research and Sponsored Programs at the 
University of Mississippi and a member of the National Academy 
of Sciences' Task Force for Developing a Framework for 
Evaluating the Safety of Dietary Supplements. The Subcommittee 
will also hear testimony from Dr. Ron Davis, Member of the 
Board of Trustees of the American Medical Association to 
discuss the medical society's view of DSHEA. And we will also 
hear from two consumer groups: Charles Bell, who is the Program 
Director for Consumer Reports; and Bruce Silverglade is the 
Director of Legal Affairs at the Center for Science in the 
Public Interest. And to provide insight into how DSHEA has 
affected the dietary supplementary industry, the Subcommittee 
will hear from Tony Young, General Counsel for the American 
Herbal Products Association, which represents the herbal 
supplement industry and Dr. Annette Dickinson, President of the 
Council for Responsible Nutrition, who represents many 
suppliers, manufacturers, and marketers of dietary supplements 
in the United States.
    I want to thank all of our witnesses for coming today. It 
is my sincere hope that this hearing will help point out the 
positive effects of the Dietary Supplement Health Education Act 
while at the same time providing suggestions from our witnesses 
that could further improve this law.
    Once again, we look forward to hearing from today's 
witnesses. I would appreciate it if all of you could keep your 
statements to 5 minutes and please be aware that your 
statements will be made a part of the official record of this 
Subcommittee.
    We have a custom here in this Subcommittee to swear in all 
witnesses. I would ask all of our witnesses today to stand and 
to raise your right hand, please.
    [Witnesses sworn.]
    Senator Voinovich. Let the record indicate they answered in 
the affirmative.
    Dr. Brackett, will you come forward?

 TESTIMONY OF HON. ROBERT BRACKETT, PH.D.,\1\ DIRECTOR, CENTER 
   FOR FOOD SAFETY AND APPLIED NUTRITION, U.S. FOOD AND DRUG 
                         ADMINISTRATION

    Mr. Brackett. Good afternoon, Mr. Chairman and Senator 
Durbin.
---------------------------------------------------------------------------
    \1\ The prepared statement of Mr. Brackett with attachments appears 
in the Appendix on page 43.
---------------------------------------------------------------------------
    I am Dr. Robert Brackett, Director of FDA Center for Food 
Safety and Applied Nutrition, and I am pleased today to testify 
before your Subcommittee on the Dietary Supplement Health and 
Education Act.
    Many Americans take some type of dietary supplement, and in 
many cases, there is either strong or suggestive evidence that 
many of the vitamins and minerals and other sorts of naturally-
occurring products that we take have important health benefits. 
The Dietary Supplement Health and Education Act of 1994, as you 
said, DSHEA, amended the Federal Food, Drug and Cosmetic Act to 
set up a distinct regulatory framework for these products in an 
attempt to strike the right balance between providing consumers 
access to dietary supplements that they may choose to help to 
maintain and improve their health and giving the Food and Drug 
Administration regulatory authorities to take action against 
supplements or supplement ingredients that present safety 
problems, either having false or misleading claims or otherwise 
adulterated or misbranded.
    As with foods, there is no premarket FDA approval of safety 
for most dietary supplements. However, there is a 75-day 
premarket notification requirement for manufacturers of certain 
dietary supplements that contain so-called new dietary 
ingredients that were not marketed in the United States before 
October 15, 1994. In its new dietary ingredient notification to 
FDA, the manufacturer or distributor of the supplement must 
submit information that provides the basis on which it 
concludes that the dietary supplement containing the new 
dietary ingredient will reasonably be expected to be safe.
    FDA regulates the safety of dietary supplements primarily 
through a postmarket evaluation of whether the product is 
adulterated under the provisions of the Food, Drug and Cosmetic 
Act. In developing a comprehensive postmarket safety evaluation 
of dietary supplement products, FDA collaborates with consumer 
and industry stakeholders as well as other Federal partners and 
academic centers.
    An important tool that FDA uses for developing the so-
called signal which might identify potential safety problems 
are adverse events reports. These reports are not mandatory and 
consist of voluntary reports from industry, health care 
providers and consumers.
    Under DSHEA, FDA was given authority to promulgate 
regulations for dietary supplement current good manufacturing 
practices, CGMPs, and such regulations could help ensure 
product quality and consistency. FDA published a proposed rule 
on March 13, 2003; extended the comment period; convened two 
satellite downlink outreach meetings and attended three 
outreach meetings organized by the industry.
    Publishing the final rule is a priority for FDA. The FDA 
uses three principles: direct health risk, indirect health 
risk, and economic harm to guide the development of its risk-
based enforcement strategy. Products that are not themselves 
hazardous can still present an indirect health hazard in that 
consumers may delay or forego proven medical treatments or drug 
therapies. Examples include unproven products promoted for the 
treatment of cancer, diabetes, arthritis, heart disease, and 
high blood pressure.
    This strategy provides a foundation for the agency's 
enforcement activities. However, we continually reevaluate our 
actions and emphasis in light of emerging issues or products to 
ensure that our activities achieve compliance.
    Since October 2002, FDA has conducted 224 domestic 
inspections of dietary supplement manufacturers, issued more 
than 170 warning letters and cyberletters to marketers of 
dietary supplement products, seized products worth more than $9 
million, supervised the voluntary destruction of more than $3 
million worth of supplements with promoted and unsubstantiated 
dietary supplement claims or that were unapproved drugs and 
obtained permanent injunctions against five firms distributing 
misbranded or unapproved new drugs.
    FDA enforcement has extended to our Nation's borders, where 
we have refused importation of more than 1,500 foreign 
shipments of potentially unsafe or misbranded dietary 
supplements offered for entry into the United States. The 
agency's enforcement actions send a clear message that FDA will 
not tolerate fraudulent practices that victimize or endanger 
consumers.
    In April 2004, FDA sent a warning letter to 16 dietary 
supplement manufacturers making false and misleading claims for 
weight loss products promoted over the Internet. Many of these 
products claimed to block starch, carbohydrates, fats and 
calories while maintaining that consumers would lose weight 
without any changes in their lifestyle. On March 8, 2004, the 
producers and distributors of SEA-Silver signed a consent 
decree of permanent injunction in which they agreed to stop 
manufacturing and distributing violative products and agreed to 
destroy the seized products at their expense and pay liquidated 
damages of $10,000 per day for any future violations of the 
consent decree.
    Under a settlement with the Federal Trade Commission 
entered into on March 4, 2004, the SEA-Silver defendants and 
the individual distributors agreed to pay $4.5 million in 
consumer redress, and this consent decree followed a 
coordinated effort in June 2003 that resulted in the seizure of 
$5.3 million worth of products.
    FDA will continue to use our available resources to fully 
implement DSHEA, and Mr. Chairman, I do thank you very much for 
this opportunity to testify today, and I would be very happy to 
take your questions.
    Senator Voinovich. Thank you, Dr. Brackett.
    Do you think that DSHEA gives the FDA the regulatory 
authority to supervise the dietary supplement industry?
    Mr. Brackett. It does give us the supervisory authority to 
supervise the dietary supplement industry. But what is 
important is that we take what all of the parts of DSHEA and 
implement it fully in order to get the most use out of it.
    Senator Voinovich. So it is your opinion that the law is 
adequate. Do you think that there are some improvements that 
could be made in the law that make it easier for you to get the 
job done?
    Mr. Brackett. Well, the administration has no plans at this 
time to make any changes or suggest any changes to DSHEA. There 
are a number of options that we could use that would improve 
our effectiveness, including, especially, more research that 
could be done on some of the supplements themselves so that we 
could better define what they are and what they do.
    Senator Voinovich. One issue that is of concern to this 
Subcommittee is the oversight of government management and 
restructuring, is the capacity of agencies to perform the jobs 
that they are asked to perform by Congress, in this particular 
case, DSHEA, the enforcement of it, I think in your testimony 
you said something about FDA does the job with ``available 
resources.''
    Mr. Brackett. That is right.
    Senator Voinovich. I know that FDA has numerous 
responsibilities other than enforcing DSHEA. Do you believe 
that you have the resources necessary to enforce this law?
    Mr. Brackett. Well, we have the resources we need to do and 
enforce the top priorities. Part of our strategy is to look at 
all of the different issues that we have to deal with within 
DSHEA, prioritize them based on public health risks, as I had 
mentioned earlier and then to use our resources effectively 
towards those that have the biggest public health impact.
    Senator Voinovich. What are the top priorities?
    Mr. Brackett. The top priorities are looking at those 
ingredients that might cause some sort of injury or might 
otherwise cause human health effects. As I mentioned, we can 
also have indirect effects, where people are taking dietary 
supplements in lieu of taking medical treatments, but we are 
most interested in those ingredients that might actually have a 
direct public health impact; that is, make someone ill.
    Senator Voinovich. How do you find out about those 
ingredients?
    Mr. Brackett. Well, there are several different ways, one 
of which is the label. We look to see what is on the label and 
whether the ingredients listed on the label actually have 
characteristics, known pharmacological properties that----
    Senator Voinovich. Do you have a regular policy of 
monitoring these supplements as they come onto the market? Or 
do you wait for these things to be brought to your attention by 
this adverse event reporting or from consumer groups that are 
out there monitoring new supplements?
    Mr. Brackett. Well, all of the above. We have, as I 
mentioned, the 75-day notification in which a manufacturer of a 
new dietary ingredient would send in an application for their 
product being listed as a new dietary ingredient, where they 
must show cause that they believe that this product is safe, so 
that is one way.
    Senator Voinovich. These are new ingredients. The law was 
passed 10 years ago and said that the ingredients prior to the 
passage of the law were grandfathered in.
    Mr. Brackett. That is correct.
    Senator Voinovich. So, if they come out with new 
ingredients that are different than what were grandfathered, 
they have an obligation to bring that to your attention?
    Mr. Brackett. That is correct.
    Senator Voinovich. If they do not do that, what is the 
penalty?
    Mr. Brackett. They are subject to prosecution, because they 
are marketing this product that is not an approved new dietary 
ingredient. The other things that we do in addition to looking 
at----
    Senator Voinovich. Pardon me; do you have many of those 
that do that?
    Mr. Brackett. No, there are not many who do that. We have--
probably more than half the applications that come in, we will 
object to, because they have not provided enough information, 
enough scientific information to justify that they are safe, 
and so, we are not aware of many that do that.
    Some smaller items may, when we find out about them, we do 
take action for those. And as listed in my written testimony, 
there are a number of examples of those sorts of items that we 
have taken action on.
    Senator Voinovich. About how many prosecutions have you had 
for people who failed to come in and comply with that part of 
the law?
    Mr. Brackett. I am not sure of the exact numbers. I can 
find that out, and I would be happy to get back to you with the 
exact number.

                  INFORMATION PROVIDED FOR THE RECORD

    Response: In March 2004, FDA sent 23 warning letters to 
companies asking them to cease distributing products sold as 
dietary supplements that contain androstendione (andro) and 
warning them that they could face enforcement actions if they 
do not take appropriate actions. The warning letters state that 
FDA assumes that the firm has a basis to conclude that 
androstenedione is a dietary ingredient. If androstenedione is 
a dietary ingredient, FDA believes that it is also a new 
dietary ingredient for which a premarket safety notification is 
required. Because any manufacturer or distributor who has 
received a warning letter has submitted no such notification, 
these products are adulterated and their marketing is 
prohibited under the Federal Food, Drug, and Cosmetic Act. The 
letters further state that FDA is, based on what it knows now, 
aware of no history of use or other information establishing 
that a dietary supplement containing androstenedione will 
reasonably be expected to be safe. In the absence of such 
information, these products would be adulterated even if the 
required premarket safety notification were submitted. The 
attached list has the names of the firms and the products in 
question. A sample warning letter is also attached.\1\
---------------------------------------------------------------------------
    \1\ List of Manufacturers Receiving Androstenedione Warning Letters 
and Sample Warning Letter on Androstenedione, submitted by Mr. 
Brackett, appear in the Appendix on pages 66 and 68 respectively.
---------------------------------------------------------------------------
    The Agency has never conducted a prosecution for violations 
of the notification requirements for new dietary ingredients.

    Senator Voinovich. I would like that.
    Mr. Brackett. OK.
    Senator Voinovich. As you know, under DSHEA, FDA can 
regulate dietary supplement good manufacturing practices. I 
understand that FDA will issue a final rule on GMPs possibly by 
the end of the year. Can you tell me why it has taken so long 
for these GMPs to be issued and if you feel they will bring 
about needed changes in the oversight of the dietary 
supplementary industry?
    Mr. Brackett. Well, I will answer your last part first, 
which is yes, absolutely; good manufacturing practices are 
essential to providing consistency and quality, and, as you 
mentioned earlier, to make sure that the consumers get what 
they think they are getting in an ingredient. There's a number 
of reasons why it has taken a long time. First, in 1994, when 
DSHEA was published, it took a little bit of time for FDA to, 
in making a current good manufacturing practice rule, finding 
out all of the background on the industry, what needed to be 
changed, what did not need to be changed.
    And so, we spent a lot of time meeting with the industry in 
the intervening years. From that, we were able to propose the 
rule that you had mentioned earlier.
    Senator Voinovich. When was that rule proposed again?
    Mr. Brackett. In 1993.
    Senator Voinovich. No, I am talking about the rule that----
    Mr. Brackett. Oh, in March 2003 is the current proposed 
good manufacturing practice rule. Since that time, we have 
gotten much comment from the industry. We have met with them; 
have extended the comment period; we have gotten over 1,600 
pages of comments that we very thoughtfully went through; 
hundreds of substantive comments that we will address in the 
final rule.
    Senator Voinovich. I have run out of my time, but one 
question that I have got, and then, you can save it for the 
next one is that if the law was passed 10 years ago, it seems 
to me that is a long time to consider regulation.
    Mr. Brackett. It is a long time, and that is why it is one 
of our top priorities within the Center for Foods.
    Senator Voinovich. Thank you. Senator Durbin.
    Senator Durbin. Thank you, Mr. Chairman.
    Dr. Brackett, I apologize. We are usually given biographies 
of the witnesses, and I do not have yours. Are you a medical 
doctor?
    Mr. Brackett. No, I am not. I have a Ph.D. in food 
microbiology.
    Senator Durbin. I see.
    Let me ask you a few questions, if I might. First, on the 
reporting of new ingredients, the 75-day reporting, was there a 
list published of pre-1994, pre-DSHEA ingredients so that FDA 
knows if there is a new ingredient that is being used?
    Mr. Brackett. To my knowledge, there was no specific list 
given on those ingredients.
    Senator Durbin. So how does that work?
    Mr. Brackett. What FDA does, then, is goes back to look to 
see whether certain of the dietary supplements that we know 
were sold before that time were marketed, and of course, those 
we can rule out. Otherwise, it takes research to go back and 
find out whether there is any evidence that they were, and we 
also request from the industry to show whether or not they were 
marketed before that period.
    Senator Durbin. That seems like a very unusual approach, 
that FDA did not start off with a list of pre-1994 ingredients 
so the agency would have some knowledge as to whether an 
ingredient is new. Is it possible that some ingredients were 
benign in some combinations but dangerous in other 
combinations?
    Mr. Brackett. Yes, that is true.
    Senator Durbin. So if you had an ingredient that perhaps 
was viewed as an old ingredient, had been used before 1994, now 
combined with another old ingredient, the combination itself 
could turn out to be dangerous; is that possible?
    Mr. Brackett. It would be possible. I do not know of any 
specific examples, but that goes back to one of the important 
gaps that I think we have, which is do we actually characterize 
many of these ingredients to find out individually what they do 
and what their characteristics are? And then, when you also 
have the evidence-based reviews of these compounds, see if 
there is any evidence of cross-reaction with other compounds.
    Senator Durbin. So to protect American consumers, would not 
our government and your agency want to know a lot more about 
the ingredients used before 1994, particularly in what 
combinations they were used, and whether you are not only 
seeing new ingredients but new combinations of old ingredients? 
Are not all of those important questions if your mission is to 
protect the consumers?
    Mr. Brackett. They are excellent questions, and that is 
information that we would like to have. That is true.
    Senator Durbin. And you do not have the right to establish 
that information under DSHEA, do you?
    Mr. Brackett. Well, what we are doing is working with 
academic centers such as the University of Mississippi's 
National Center for Natural Product Research, with the National 
Institutes of Health, to try to get those answers.
    Senator Durbin. We are 10 years after the fact, and I am 
glad we are still working to try to get those answers as the 
industry has grown from $4 billion in sales to $18 billion in 
sales.
    Now, let me speak about the GMPs, the manufacturing 
practices. How many years has the FDA been working on these 
regulations to establish good manufacturing practices in the 
dietary supplement industry?
    Mr. Brackett. Well, I would say at some level, we have been 
working since DSHEA was passed. It has been the most active 
probably in the last 4 or 5 years.
    Senator Durbin. So for 10 years, the FDA has been trying to 
establish basic standards of manufacture and purity of the 
products themselves, not looking into specific questions about 
whether this is a product that might be of some danger to an 
individual; is that correct?
    Mr. Brackett. That is correct. Well, as I mentioned earlier 
in the testimony, one of the things we did early on was to go 
back and check what were manufacturers doing at that time? What 
were the industry norms within the industry themselves? Which 
sorts of operations would cause products to be either 
contaminated or whether they would be reduced, or perhaps the 
amount of an ingredient might not match what was on the label.
    So we tried to learn as much about this industry as we 
could before we actually started writing.
    Senator Durbin. Are you familiar with a group called 
Consumer Lab, Dr. Cooperman and Dr. Obermeyer?
    Mr. Brackett. I have heard the name, yes.
    Senator Durbin. I believe Dr. Obermeyer was a former 
employee of the Food and Drug Administration. In Oprah 
Magazine, they just published the fact that Theragran-M, which 
is a very common multivitamin, advanced formula, high potency 
multivitamin, multimineral contained 3.65 micrograms of lead, 
which exceeded the limit for supplements used by adults. Are 
you familiar with that?
    Mr. Brackett. I have not read the article, and I have heard 
rumors about it but no personal knowledge of that issue.
    Senator Durbin. Now, going to Chairman Voinovich's 
question, Stuart Prenatal, a multivitamin, multimineral 
supplement, advertises that it has 4,000 IUs of Vitamin A. It 
turns out, after testing, it has 75 percent of the vitamin A 
that is claimed. Again, that is in the article which you are 
familiar with--or at least have heard of--but have not read. 
These are things which go to the question of good manufacturing 
practices, are they not?
    Mr. Brackett. That is exactly what good manufacturing 
practices are for, and in addition to having too little 
vitamins, it is sometimes quite dangerous to have too much as 
well, so that is also covered.
    Senator Durbin. And we are still, after 10 years, trying to 
establish basic standards on good manufacturing practices.
    Let me go to March 11, 2004, this year, where your agency 
announced a crackdown on companies selling androstenedione 
(andro), a steroid precursor. Acting FDA Commissioner Lester 
Crawford said we are using the DSHEA authority to supervise 
dietary supplements put on the market after the law was passed. 
For example, he said, we sent letters to 23 companies directing 
them to cease distributing dietary supplements containing 
andro.
    Doctor, are you familiar with a company known as GNC?
    Mr. Brackett. Yes, I am.
    Senator Durbin. Pretty widespread, large company with a lot 
of stores all over the United States.
    This morning, I asked my staff to go over to the local GNC. 
They went over and purchased this product called Skuplt. It is 
a topical fat loss product containing androstenedione. It also 
contains yohimbine, a substance the FDA announced 11 years ago 
causes serious adverse effects, including renal failure, 
seizures and deaths.
    Since the FDA has taken a specific action against this 
dietary supplement, and we still find it on the shelves of one 
of the most prominent supplement retailers in the United 
States, what does it tell us about your enforcement actions?
    Mr. Brackett. Well, with the letters that we sent out on 
androstenedione, I think all but five have withdrawn their 
products.
    Senator Durbin. Out of how many?
    Mr. Brackett. Out of, I believe, 23.
    Senator Durbin. Twenty three.
    Mr. Brackett. In this particular instance, did you say this 
was a topical?
    Senator Durbin. Yes.
    Mr. Brackett. So this may not be covered under what we were 
looking at, which were oral dietary supplements.
    Senator Durbin. All right; now, let me ask you about the 
adverse event reporting. You said one of the things that you 
feel is your responsibility is to establish the risk of a 
dietary supplement product; is that correct?
    Mr. Brackett. Yes.
    Senator Durbin. We ask the makers of prescription drugs--in 
fact, we do not ask; we require them to report adverse events 
so that the Food and Drug Administration will know if there is 
a warning sign. If someone gets seriously sick, hospitalized, 
dies from a prescription drug, the FDA is put on notice 
immediately. Did you not testify earlier that DSHEA makes this 
reporting by supplement manufacturers strictly voluntary?
    Mr. Brackett. That is correct. It is voluntary.
    Senator Durbin. So how can you protect the American 
consumer from risk if you are not even receiving from these 
companies, the dietary supplement companies, notice that their 
products are hurting, injuring or even killing American 
consumers?
    Mr. Brackett. Well, I think that the answer to that is that 
adverse event reporting, it is an important signal, but it is 
not the only thing that we use. Equally important are some of 
our knowledge of the pharmacology of some of the ingredients 
that might be in there with, even in the absence of an adverse 
event, whether we have used it against evidence-based reviews 
to see if there has been any reporting in the scientific 
literature and what the science actually points to on those 
ingredients as well as perhaps the chemical nature of the 
compounds themselves, whether they are similar to other sorts 
of ingredients that we know might cause public health problems.
    Senator Durbin. So it comes down to a basic question I will 
ask you: Either you are asking for too much information from 
the pharmaceutical companies on adverse event reporting, or you 
are not asking for enough information from the dietary 
supplement manufacturers, who have a voluntary reporting 
standard. Which is it?
    Mr. Brackett. Well, we would welcome a lot more information 
from the dietary supplement manufacturers or, I think, 
information in general from wherever, whether it be physicians 
or the public as well, as again, as one of the parts of the 
signals that we use.
    Senator Durbin. Thank you for your tolerance. Exactly how 
many people at the FDA are monitoring the dietary supplement 
industry? How many employees?
    Mr. Brackett. In total, I do not know the exact answer to 
that, because many of them in the field--again, I could be 
happy to get back with you to find the appropriate answer.
    Senator Durbin. Is it a matter of hundreds or dozens or 
fewer than 20? Just give me a rough estimate.
    Mr. Brackett. I do not want to speculate. We will find out. 
It is not probably hundreds, I do not think, but I can find out 
what the exact allocation of people to this task is for you and 
get back.

                  INFORMATION PROVIDED FOR THE RECORD

    In Fiscal Year 2003, FDA had 58 people, i.e., full-time 
equivalents (FTE), in various parts of the Agency, monitoring 
the dietary supplement industry.
    In Fiscal Year 2004, 59 people (FTE), in various parts of 
the Agency, were monitoring the dietary supplement industry.

    Senator Durbin. Thank you very much, Mr. Chairman.
    Senator Voinovich. It is my understanding that if a 
manufacturer has a defective product, they have the ability to 
recall this product. I am not sure if there is a law that 
requires manufacturers to report the defective product, or they 
are doing it because they want to protect themselves from a 
lawsuit. Would it not make sense to make it mandatory for these 
companies to submit adverse event reports?
    Mr. Brackett. Well, again, that would be one thing that 
could be done, but again, that is just a small part of the 
whole or at least an equal part of the many different factors 
that would factor in. So if we were to have adverse event 
reporting mandatory, and right now, the administration has no 
position on this, again, that would not solve the whole 
problem. We would still need to look very closely at the 
science, at our knowledge of what has been done 
pharmacologically, many other things.
    Senator Voinovich. You said that with the new ingredients, 
they have to submit it so that you can look at the product, or 
if that is mandatory, and if they do not do that, then, they 
can be prosecuted.
    Mr. Brackett. They are in violation, yes.
    Senator Voinovich. Subject to penalties, right.
    Would it not make a lot of sense to make it mandatory that 
they at least report these adverse events and provide a penalty 
that says if they do not do it, they are subject to the same 
kind of sanctions or worse or whatever that you have on not 
submitting a product for review prior to putting it on the 
market if it is new ingredients?
    Mr. Brackett. Well, that would be helpful, but again, that 
is not the whole story. And another difficult part of that is 
many of the dietary supplements today are a combination of many 
ingredients, unlike many of the pharmaceuticals. So quite 
often, when you have an adverse event reported, it may not 
necessarily be caused by the ingredient that you think it is. 
So it is complicated.
    Senator Voinovich. When ephedra came out on the market 
there were some incidents that were claimed to be as a result 
of taking ephedra that might have been due to something else. 
It seems to me that even if the event reports showed that the 
incidents were not caused by ephedra that you would investigate 
ephedra further.
    Mr. Brackett. Oh, absolutely. When we have adverse events 
reports, we do look into it. But again, standing on the pillars 
of the pharmacology, the evidence-based research, the 
scientific literature, all of that has to stand together.
    Senator Voinovich. Well, my common sense tells me that it 
would be good if we required them to do it. And I think it 
would probably be very helpful to you also. I suspect that some 
manufacturers who did have adverse event reports did not submit 
them to you.
    Additionally, I am concerned with people mixing over-the-
counter medicine or prescription drugs with dietary 
supplements. As you know this is a growing industry and 
consumption is only going to increase. In 2006, 680,000 people 
in Ohio are going to start getting prescription drug coverage 
to improve their quality of life. Is there a concern within the 
FDA that the mixing of prescription drugs and dietary 
supplements could cause adverse effects?
    Mr. Brackett. Well, certainly, Mr. Chairman, that is a 
concern, and that is one of the recommendations we always make 
is that patients discuss their medications and any other foods 
as well as dietary supplements that they may be consuming.
    Senator Voinovich. I take coumadin, and in the disclosure 
that comes along with coumadin, they talk about vegetables that 
are strong in vitamin K, and if you consume high levels of 
vitamin K, it could make the drug less effective.
    It would seem to me that a dietary supplement, should carry 
the same type of information. Individuals ought to be informed 
that if they are taking a drug like coumadin, a blood thinner, 
that these kinds of interacting could dilute the product, and 
therefore, the drug they are taking may not be as effective as 
it should be.
    Do you think the dietary supplement should be required to 
put the same kind of warnings on their labels?
    Mr. Brackett. Well, I think that would be good for them to 
do if they knew what the interactions were. Quite often, the 
manufacturers of the drugs have a better understanding of what 
interactions have been studied in much more depth.
    Senator Voinovich. You have to wonder how much real thought 
is going into labeling dietary supplements.
    One reason for such huge growth in the dietary supplement 
industry is the ability to purchase them over the Internet. 
Many of these supplements have big claims on their Websites.
    Mr. Brackett. Well, I agree. And this goes back to my 
earlier statement. We simply have to know more about the 
ingredients we are taking, and that is why we do appreciate our 
colleagues at the University of Mississippi and at the National 
Institutes of Health actually doing research on both the 
properties of these ingredients and the beneficial aspects of 
the ingredients as well.
    But again, one of the issues that we have to deal with is 
finding out exactly what the ingredient is in the first place, 
and sometimes, that is the first challenge.
    Senator Voinovich. Senator Durbin.
    Senator Durbin. Dr. Brackett, when Dr. McClellan was 
Commissioner, he promised enforcement action against some of 
the ephedra substitutes. This product here, Stacker-2, which is 
advertised on television, this is now advertised as ephedra 
free, and if you will look at the operative ingredients, they 
include cola nut and citrus aurantium, which is also known as 
bitter orange.
    Now, Dr. McClellan said that he was going to take 
enforcement action against products containing bitter orange 
and usnic acid, which are now ephedra substitutes. Can you tell 
me what has been done so far in that enforcement action?
    Mr. Brackett. Sure, actually, what Dr. McClellan's intent 
was anything, any of those stimulant products that were to be 
used in place of ephedra were to get a much closer scrutiny to 
find out, in fact, if they were of danger, and that is 
something that we have been doing. We have been looking at 
ephedra substitutes; again, to characterize them, to find out 
specifically what is in the products that are on the market; in 
some cases, you may have parts of dietary supplement come in 
from one part of the plant versus another part of the plant, 
and they may have different amounts entirely of, in this case, 
citrus aurantium. So we are trying to get all of the scientific 
data that we need, and if it looks like there is something that 
is at risk, we will take action.
    Senator Durbin. This is an unusual assignment for the FDA, 
because when it comes to other products that you monitor, for 
instance, prescription drugs, is it not true that the burden is 
on the manufacturer of the drug to establish its safety and 
efficacy, and in the case of dietary supplements, we are 
talking about the FDA scrambling to find the personnel, the 
time and the resources to do the research on the product that 
is already on the market; is not that true?
    Mr. Brackett. That is true. This is a little bit different 
than pharmaceuticals. In this case, the law is almost ahead of 
the science. In the case of pharmaceuticals, they are 
specifically developed with a chemical structure that people 
know about. In this case, people are taking common ingredients 
for which we often do not understand what the active ingredient 
in it is. And so, it is taking some basic research to just 
define and characterize what the products we are dealing with 
are.
    Senator Durbin. We are trying to take a look back at DSHEA, 
and as you take a look back, is not this an extraordinary if 
not impossible burden for the FDA to handle, to try to look at 
each new ingredient and then try to do enough research to 
determine that even on the market, it is not dangerous?
    Mr. Brackett. Well, it is impossible for FDA to do. This is 
why we partner with NIH. There are specifically in DSHEA the 
Office of Dietary Supplements that was established to help with 
this in addition to our academic partners as well. So it is a 
large-scale effort.
    Senator Durbin. Do you have the specific responsibility 
within FDA for monitoring the dietary supplement industry?
    Mr. Brackett. We have the specific authority, yes, to 
oversee the dietary supplement industry.
    Senator Durbin. And as the director of the Center for Food 
Safety and Applied Nutrition, that is your responsibility.
    Mr. Brackett. That is correct.
    Senator Durbin. I mentioned the article in Oprah Magazine 
about specific problems, and you said you were familiar with 
it. Is this the kind of thing, having been brought to your 
attention, that would result in activity by the FDA to 
establish whether or not the assertions in here are true and 
that some products currently on the shelf are dangerous?
    Mr. Brackett. Yes, and in fact, this article was brought to 
my knowledge by my staff who, in fact, is actually checking 
into those assertions.
    Senator Durbin. And let me ask the same thing about the 
Consumer Reports story. This Consumer Reports story from May of 
this year lists some 12 different supplements, starting with 
some that they have identified by testing as definitely 
hazardous to likely hazardous. Have you undertaken in the FDA 
any kind of investigation or study of these dietary supplements 
which have been identified as dangerous?
    Mr. Brackett. Yes; in fact, much of the information in the 
Consumer Reports article was not new to us. We did know about 
that. We have, in fact, done some surveillance since that time 
to look for certain ingredients that were listed in there as 
well so----
    Senator Durbin. Have any of these products been taken off 
the shelf, like ephedra?
    Mr. Brackett. Well, ephedra has been off, unless it is 
there illegally.
    Senator Durbin. Any other products on the Consumer Reports 
list?
    Mr. Brackett. We have listed or sent out warning letters, 
for instance, for aristolochic acid. In fact, that was one of 
the items for which we did surveillance and to this point have 
not found them in products marketed as dietary supplements.
    Senator Durbin. Let me just conclude, Mr. Chairman, by 
thanking you and also to say this: If the object of this law is 
to protect American consumers, I think it fails on its face. 
Take a look at the obvious here: 10 years after passing the 
law, we still have not established standards so we can even 
identify what is in these products. And I think, by the nod of 
the head, you agree with me. We do not know what is in them, to 
start with. We do not know if it is 4,000 IUs or 3,000 IUs. We 
have no idea whether there is lead contained in multivitamins 
or not.
    That is a starting point. The second thing we have not 
established is the responsibility of the industry. Ten years 
after the law is passed, we have not come up with a list of 
pre-1994 ingredients. And even if we did, you have conceded in 
your testimony it is of little value, because a combination of 
old ingredients could be dangerous, as dangerous as any new 
ingredient.
    And finally, we do not have any requirement that these 
companies selling products worth lots of money to them in 
profits even report to the Food and Drug Administration when 
people get seriously ill from having taken these products. So 
that is why I am kind of troubled by your conclusion. Having 
said these things, having heard these things, you have 
concluded by saying and therefore, we do not want to change the 
law.
    How can you possibly meet your responsibility to consumers 
to say to them if you buy a dietary supplement for yourself or 
somebody in your family, it is safe? How can you meet that 
responsibility with a law that is so weak?
    Mr. Brackett. Well, the safety and health of the consumers 
is our utmost concern. That is the thing that we most want to 
protect. What we are doing is trying to work, to maximize our 
activities under the current DSHEA before we would go out and 
sort of look for new authorities. There are many parts of DSHEA 
that we think have not been explored, that we can use to 
protect the public, and that is one of the things that we are 
going to do, which is why we do want to use DSHEA to its 
maximum, completely.
    Senator Durbin. Dr. Brackett, that approach is so timid 
that even the industry is ahead of you. We are going to have 
testimony later from someone from the dietary supplement 
industry. They have conceded that adverse event reporting is 
necessary. And yet, you are afraid to say those words. I think 
we are in trouble here. I think your watchdog responsibility 
includes being ahead of the problem and not behind it. If you 
are stuck with this 10-year-old law that is so deficient, you 
are never going to get ahead of it.
    Thanks for your testimony.
    Mr. Brackett. Thank you.
    Senator Voinovich. Thank you. I would like to make one 
point, and that is I would like to have, in writing from you, 
the chronology of going forward with this rule for these GMPs. 
I cannot believe that it has taken that long for it to happen. 
This law passed 10 years ago, and it is unacceptable.
    Mr. Brackett. We will be happy to provide that.\1\
---------------------------------------------------------------------------
    \1\ The information entitled ``Time Line of Activities To Establish 
Current Good Manufacturing Practice Regulations (CGMPs) for Dietary 
Supplements,'' submitted by Mr. Brackett appears in the Appendix on 
page 70.
---------------------------------------------------------------------------
    Senator Voinovich. Unacceptable that it takes 10 years to 
get something done. I would like to have some assurance from 
you today this is going to get done at least by the end of this 
year.
    Mr. Brackett. We will do our very best to get it done as 
soon as possible. That is our goal.
    Senator Voinovich. Is the problem that you do not have 
enough people?
    Mr. Brackett. Well, the problem has been partly going 
through many of the comments that we have to address, as you 
know, in rulemaking.
    Senator Voinovich. I would like to know how many people you 
have working on this. I also would like to know what other 
responsibilities that you have? So often, we ask agencies to do 
work, and then, we do not provide them the resources necessary 
to get the job done. So often we pass the law and forget about 
the fact that it has to be enforced.
    I am really interested in knowing, in getting a candid 
appraisal from you whether or not you have the number of people 
you need to get the job done in your agency to implement these 
laws that we have passed over the years.
    Mr. Brackett. We will be happy to get that to you.

                  INFORMATION PROVIDED FOR THE RECORD

    Approximately five full-time-equivalent employees (three 
people full-time, two people at 75 percent, one person at 50 
percent) and approximately nine others as necessary, are 
working on preparing the final rule for publication with 
dietary supplement GMP's as their first priority. We are also 
soliciting input on development of the final rule from two 
external expert consultants and one GMP expert in FDA's Center 
for Drug Evaluation and Research (CDER). In addition, when the 
final rule has been drafted, there will be additional people 
involved in the review/clearance/publication process.
    Over 400 comment letters, approximately 1,600 pages, were 
received on the proposal, most of which raised substantive 
issues that need to be addressed in the preamble to the final 
rule. Accordingly, the bulk of the effort is in reviewing and 
responding to the comments.
    CFSAN, in conjunction with the Agency's field staff, 
regulates 80 percent of the nation's food supply and is 
responsible for protecting the public's health by ensuring that 
the nation's food supply, except for meat, poultry and certain 
egg products which are the responsibility of the Department of 
Agriculture, is safe and secure, and honestly labeled. CFSAN 
has similar responsibilities for cosmetic products. Attached is 
a May 4, 2004, transmittal letter to our Colleagues in the FDA 
Foods Community forwarding our projected workload for Fiscal 
Year 2004 in accordance with the Agency's Strategic Action 
Plan. You will note that the plan includes 168 ``A-list'' 
goals, of which we anticipate at least 90 percent completion 
this year.\1\
---------------------------------------------------------------------------
    \1\ The information entitled ``CFSAN 2004 Program Priorities,'' 
appears in the Appendix on page 72.

    Senator Voinovich. Any other comments, Senator?
    Senator Durbin. No.
    Senator Voinovich. Thanks very much. We really appreciate 
your coming here today.
    Mr. Brackett. Thank you, Mr. Chairman.
    Senator Voinovich. Our next witnesses to testify are Alice 
M. Clark, Ph.D., Vice Chancellor for Research and Sponsored 
Programs, from the University of Mississippi; Ronald M. Davis, 
M.D., member of the Board of Trustees of the American Medical 
Association; Charles Bell, Program Director, Executive Office, 
Consumer Reports; Anthony L. Young, General Counsel, American 
Herbal Products Association; Bruce Silverglade, Director of 
Legal Affairs, Center for Science in the Public Interest; and 
Annette Dickinson, Ph.D., President, Council for Responsible 
Nutrition.
    This is a large second panel, so I would appreciate your 
adhering to the 5-minute rule. I appreciate you testifying 
today, and again remind you that your testimony will be made a 
part of the record along with your written statement.
    We will begin the testimony with Dr. Clark.

  TESTIMONY OF ALICE M. CLARK, PH.D.,\2\ VICE CHANCELLOR FOR 
 RESEARCH AND SPONSORED PROGRAMS, THE UNIVERSITY OF MISSISSIPPI

    Ms. Clark. Good afternoon, Mr. Chairman, and Senator 
Durbin. My name is Alice Clark. I am Vice Chancellor for 
Research and Sponsored Programs at the University of 
Mississippi and a professor of pharmacognosy. I also served as 
a member of the Committee on the Framework for Evaluating the 
Safety of Dietary Supplements at the Institute of Medicine and 
National Research Council.
---------------------------------------------------------------------------
    \2\ The prepared statement of Ms. Clark, with attachments, appears 
in the Appendix on page 75.
---------------------------------------------------------------------------
     I am here today to talk about our report, which is 
entitled ``Dietary Supplements: A Framework for Evaluating 
Safety,'' which was released in April of this year, and my 
comments today will focus on some key findings and 
recommendations of the report.
    In 1994, of course, Congress passed DSHEA in order to 
define FDA's authority to regulate dietary supplements. In the 
fall of 2000, the FDA approached the Institute of Medicine with 
a request to devise a science-based framework that it could use 
to evaluate dietary supplements under the authority of the 
current statutes.
    In short, DSHEA states that supplements are to supplement 
the diet and are therefore regulated like foods, meaning that 
they are assumed to be safe. Many of the products on the market 
are probably safe. However, to identify and take action on the 
occasional problem product, the FDA must rely on available 
evidence to evaluate whether an ingredient poses an 
unreasonable risk.
    According to DSHEA, the agency can act to protect the 
public's health when an ingredient poses a significant or 
unreasonable risk.
    In this report, we offer a science-based approach that 
allows the FDA to use available data to better identify 
supplements of concern and then evaluate the safety of those 
ingredients. This framework consists of three major steps: 
Signal detection, an initial review of that signal, and an in-
depth evaluation of the ingredient.
    In the framework's first step, the FDA becomes aware of a 
signal, a notification or an event that raises concern about a 
particular ingredient. In the framework's second step, that 
signal is reviewed to determine if the ingredient should be 
investigated further. And in the framework's third step, the 
totality of available scientific data is evaluated to determine 
if the ingredient poses an unreasonable risk.
    This approach works within the parameters of the current 
law governing how dietary supplements are regulated. One of the 
key points of this report is that the FDA does not have to find 
direct evidence of actual harm from use of a supplement 
ingredient to determine that the product poses an unreasonable 
risk. Another key point of the report is that historical use of 
an ingredient is often insufficient to demonstrate that an 
ingredient does no harm.
    The report also describes the significance of other kinds 
of data the agency can use in its safety evaluation, such as 
data from animal studies, tests done in laboratories or 
toxicity of similar or related substances. Some of these types 
of data may be sufficient by themselves for the FDA to 
determine that a supplement ingredient poses an unreasonable 
risk.
    With the approach devised by the committee, it is possible 
for the FDA to conduct effective safety evaluations within the 
current regulatory framework. However, in the process of 
devising this approach and reviewing the science, the committee 
noted that constraints imposed by aspects of DSHEA limit the 
agency's ability to conduct these evaluations as effectively 
and efficiently as possible.
    We have recommended some changes that could mitigate these 
constraints and make the law more effective in meeting the goal 
of protecting public health. I will mention just a few of those 
key recommendations now: For example, we recommend that 
supplement manufacturers and distributors be required to notify 
FDA about health problems that they discover related to the use 
of their products, and recognizing that other parties also bear 
responsibility for ensuring that health problems related to 
supplement use are brought to the FDA's attention, we recommend 
that health professionals be educated about ways to report 
health concerns and encouraged to use them.
    We also recommend that the toll-free number for FDA's 
Medwatch be printed on all supplements' packaging so that 
consumers have a clear way to relay any health concerns. And 
finally, while the committee did not do a cost analysis of 
implementing the framework, we recognize that implementing any 
framework will require additional resources. Therefore, we 
recommend that FDA be provided adequate resources to implement 
the framework and more effectively protect the public's health.
    Thank you for the opportunity to address you on this 
important topic, and I would be pleased to answer questions.
    Senator Voinovich. Thank you. Dr. Davis.

    TESTIMONY OF RONALD M. DAVIS, M.D.,\1\ MEMBER, BOARD OF 
          TRUSTEES, AMERICAN MEDICAL ASSOCIATION (AMA)

    Dr. Davis. Chairman Voinovich, Ranking Member Durbin, good 
afternoon. My name is Ron Davis. I am a preventive medicine 
physician from Detroit and a Member of the Board of Trustees of 
the American Medical Association.
---------------------------------------------------------------------------
    \1\ The prepared statement of Dr. Davis appears in the Appendix on 
page 85.
---------------------------------------------------------------------------
    On behalf of the AMA, I am pleased to be here to discuss 
the dangers of dietary supplements and whether DSHEA is 
working. The AMA has been concerned for years about the use and 
abuse of dietary supplements. These include herbal products and 
those containing anabolic steroid-like ingredients and their 
precursors. Precursors are substances that the body can convert 
into testosterone or other anabolic steroids.
    DSHEA does not provide FDA with enough authority over 
dietary supplements to adequately protect consumers. What are 
the problems with DSHEA? First, DSHEA treats a wide variety of 
so-called natural substances as foods, but the fact of the 
matter is that herbal remedies, anabolic steroids or their 
precursors are not foods, and neither are megadose vitamins.
    These supplements are biologically active compounds that 
act like drugs. They also have risks and side effects that can 
be serious and, unfortunately, sometimes fatal. Therefore, many 
dietary supplements are really drugs.
    Second, because existing law treats these products as 
foods, people think they are safe. In fact, surveys show that 
most consumers believe that these products have been approved 
by the government. But such protections do not exist for 
dietary supplements. Prescription and over-the-counter 
medications must be proved safe and effective and receive FDA 
approval before being sold. There is no such approval for 
dietary supplements.
    For the most part, supplement manufacturers do not have to 
provide premarket data to FDA: No safety data, no efficacy 
data, no quality data. They do not have to include warnings, 
precautions or side effects on their product labels, even for 
products with known serious hazards. So consumers are not told 
that many supplements can counteract their prescription 
medications or cause adverse reactions.
    Manufacturers also do not have to provide adverse event 
reports to the FDA. The bottom line? Consumers cannot be sure 
that dietary supplements work, are safe and that the bottle 
actually contains what the label says it does.
    Third, under DSHEA, the burden is on the FDA, not the 
manufacturer, to prove that a dietary supplement is unsafe or 
adulterated. This is very difficult. Ephedra is probably the 
best example of how hard it is to regulate unsafe dietary 
supplements. Ephedra causes a number of well-documented adverse 
reactions, including heart attacks, strokes, seizures, and 
death.
    For several years, the AMA asked FDA to ban ephedra 
products from the U.S. market. Yet even for a substance as 
dangerous as ephedra, it took FDA 7 years to ban the product. 
Although ephedra has been banned, we are concerned about other 
dietary supplements containing so-called natural stimulants 
that still are being sold. These products, labeled ephedra-
free, often contain bitter orange, as you mentioned, Senator 
Durbin. Bitter orange contains ephedra-like substances and may 
be associated with high blood pressure, irregular heartbeat, 
heart attack, and stroke.
    My written statement provides additional examples of the 
dangers of other supplements.
    The AMA has supported changing DSHEA for the past 6 years. 
Many dietary supplements, especially herbal products, need to 
be regulated like drugs. We urge Congress to make four changes 
in the law: (1) Require premarket approval by FDA of all 
dietary supplements for evidence of safety and efficacy. As 
with drugs, manufacturers should have the burden of proving 
their products are safe and beneficial.
    (2) Require dietary supplements to meet U.S. Pharmacopeia 
standards for identity, strength, quality, purity, packaging 
and labeling. (3) Require manufacturers to monitor their 
products for safety and to submit adverse event reports to FDA. 
And (4) reclassify dietary supplements that contain anabolic 
steroids or their precursors as drugs, subject to the 
Controlled Substances Act.
    The AMA supports pending legislation such as S. 1722, 
sponsored by you, Senator Durbin. We were pleased that last 
week, the House of Representatives passed, by an overwhelming 
margin, H.R. 3866. We encourage the Senate to pass its 
companion bill, S. 2195. These bills would make some of the 
changes that we have recommended.
    We appreciate the opportunity to present our views.
    Senator Voinovich. Thank you, Doctor. Mr. Bell.

TESTIMONY OF CHARLES W.F. BELL,\1\ PROGRAM DIRECTOR, CONSUMERS 
                       UNION OF U.S., INC

    Mr. Bell. Good afternoon, Chairman Voinovich, Ranking 
Member Durbin and other Members of the Subcommittee. I am 
Charles Bell, Programs Director for Consumer's Union, the 
nonprofit publisher of Consumer Reports and 
consumerreports.org.
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    \1\ The prepared statement of Mr. Bell appears in the Appendix on 
page 92.
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    Since 1936, our mission has been to test products, inform 
the public and protect consumers, and today, I offer this 
testimony on dietary supplements as part of our consumer 
protection function.
    The Dietary Supplement Health and Education Act of 1994 has 
opened the floodgates to thousands of untested dietary 
supplement products. While many dietary supplements including 
most vitamins and minerals taken within recommended limits are 
generally safe and can have important health benefits for 
consumers, there is a significant and growing number of highly 
questionable products that would probably not be allowed on the 
market if they were subject to premarket safety testing.
    As has been noted, under DSHEA, the burden of proof for 
removing unsafe products has been inappropriately shifted from 
manufacturers to the government. As former FDA Director David 
Kessler has stated, Congress put the FDA in the position of 
being able to act only after the fact and after substantial 
harm has already occurred.
    In the aftermath of DSHEA, new dietary supplement products 
can be introduced overnight, as can novel combinations of new 
or existing supplement ingredients. Further, unsafe dietary 
supplement products can remain on the market for many years, in 
the same stream of commerce as products approved by the FDA as 
safe and effective for their intended use.
    As an example, in 1995, Consumer Reports published this 
list of five supplements that, according to FDA, could cause 
serious harm to consumers: Ephedra, chaparral, comfrey, lobelia 
and yohimbe, and 9 years later, ephedra is the only one of 
these supplements that has finally been removed from the 
marketplace, many years after the FDA received reports of 
serious consumer health problems, including deaths and 
disabling injuries. But the other four hazardous supplements 
that we named in 1995 are all still being marketed and sold in 
retail stores and on the Internet.
    In May 2004, Consumer Reports published a major article 
called ``Dangerous Supplements Still at Large'' with a new, 
more comprehensive list but not necessarily exhaustive list, 
but this includes 12 hazardous dietary supplements including 
the four herbs earlier named that we believe are too dangerous 
to be on the market based on government warnings, adverse event 
reports and medical experts.
    These dirty dozen unsafe supplements, which we purchased in 
stores and online in February, include aristolochia, an herb 
conclusively linked to kidney failure and cancer; yohimbe, a 
sexual stimulant linked to heart and respiratory problems; 
chaparral, comfrey, germander and kava, all known or likely 
causes of liver failure; and bitter orange, its ingredients 
having effects similar to the banned weight loss supplement 
ephedra.
    The potentially dangerous effects of most of these products 
have been known for more than a decade, and at least five of 
them have been banned in Asia, Europe, and/or Canada. Now, we 
believe that consumers want additional protections to ensure 
that supplements are safe. Last month, Consumer's Union 
conducted an online survey of a random sample of over 1,200 
adults regarding dietary supplements as part of a regular 
national consumer survey that we perform.
    The survey found that more than eight in ten respondents 
agreed that poor regulation of supplements posed a personal 
risk to themselves and their families. More than nine in ten 
want the sale of supplements to be conditioned on safety and 
efficacy. Virtually everyone, 96 percent, agreed that 
supplement producers should be required to report adverse 
events, as is required for prescription drugs.
    Similarly, 96 percent want product risk information to be 
included on dietary supplement labels, and fewer than one in 
five respondents feel that supplements are already sufficiently 
regulated.
    The current serious gaps in consumer protection in DSHEA 
are not in the interests of dietary supplement consumers. 
Consumers turn to dietary supplements because they think these 
products will promote health and wellness. So it is very 
important to ensure that these products are safe and do not 
themselves pose serious health problems.
    We are pleased that the FDA finally did take action to 
remove ephedra from the marketplace in January 2004, finally 
coming off in April, but we are very concerned that the action 
came too late for many consumers, who experienced unacceptable 
health damage, including stroke, seizures, heart attacks, and 
deaths. And despite numerous warning signals, the agency failed 
to take action in a timely way to remove that product from the 
marketplace.
    Ephedra is a poster child for a failed policy. We need to 
understand why the signals of an urgent public health problem 
failed to trigger prompt action by the Federal Government.
    Many consumers are surprised to learn that the government 
does not evaluate the safety of dietary supplements before they 
are sold. Joseph Levitt, who was the Director of FDA's Center 
for Food Safety and Applied Nutrition, has testified that the 
current regulation of dietary supplements is, for the most 
part, a postmarketing program, but we cannot even run the 
postmarketing aspect of that program effectively without the 
authority to require mandatory reporting of adverse events, and 
we find this to be one of the most disturbing aspects of the 
entire ephedra debacle.
    The fact is that voluntary reporting of adverse events by 
manufacturers has failed. From 1994 to 1999, fewer than 10 of 
the 2,500 reports that the FDA received about serious consumer 
health complaints actually came from manufacturers, and we are 
very concerned that evidence has emerged that at least two 
manufacturers suppressed thousands of adverse event complaints 
relating to supplements containing ephedra: Metabolife and 
E'ola, as detailed in my written testimony.
    We wonder as we sit here today what else manufacturers may 
have known about the dangers of ephedra and other supplements, 
including those on our dietary dirty dozen list. Unless 
Congress acts now to tighten requirements from adverse event 
reporting by manufacturers, FDA will continue to lack vital 
information that is needed to ensure the safety of dietary 
supplements.
    So we would recommend that Congress make appropriate 
modifications to DSHEA to create a sensible preventive safety 
system that ensures that supplement products are reviewed for 
safety prior to marketing and sale. The safety system should 
also include effective postmarketing surveillance so the 
government can take prompt safety actions as needed, including 
recalls, warnings and import alerts. Labels of dietary 
supplements should clearly indicate what and how much is in the 
package and provide explicit warning of possible adverse 
effects, including herb-drug interactions.
    We strongly support the provisions in the Durbin bill, the 
Dietary Supplement Safety Act of 2003, S. 722, that would 
enable the FDA to take unsafe products off the market more 
quickly. We also strongly believe that dietary supplement 
makers should be required to report adverse events to the FDA. 
And in particular, on this point, I would note there is broad 
consensus among many parties that adverse event reporting is 
critical to ensuring supplement safety. As the Institute of 
Medicine in April urged Congress to amend DSHEA to require 
mandatory reporting; the AMA supports this position; the 
Inspector General of the Department of Health and Human 
Services has called for it. Even Secretary of Health and Human 
Services Tommy Thompson stated in his press conference in 
December it would be nice to have the authority to require 
mandatory adverse event reporting.
    And so, we think that is a critical step for us to take to 
learn from the experience with ephedra.
    Thank you, and I look forward to the opportunity to respond 
to questions.
    Senator Voinovich. Thank you very much. Mr. Young.

  TESTIMONY OF ANTHONY L. YOUNG,\1\ GENERAL COUNSEL, AMERICAN 
                  HERBAL PRODUCTS ASSOCIATION

    Mr. Young. Chairman Voinovich and Ranking Member Durbin, my 
name is Anthony Young. I am General Counsel to the American 
Herbal Products Association or AHPA. I appear here because 
AHPA's president, Michael McGuffin, who was here 2 years ago, 
had a preexisting commitment with the FDA's Food Advisory 
Committee.
---------------------------------------------------------------------------
    \1\ The prepared statement of Mr. Young appears in the Appendix on 
page 105.
---------------------------------------------------------------------------
    AHPA's prepared testimony addresses in some detail the 
issues you have raised with respect to the purpose of this 
hearing. With respect to FDA and DSHEA, AHPA is pleased with 
FDA's recent dietary supplement regulatory activities. Under 
the leadership of Dr. Mark McClellan, FDA began seriously to 
enforce DSHEA, and these efforts are detailed in enforcement 
reports found on FDA's Website and in Dr. Brackett's testimony 
today.
    In addition, FDA has now come to closure on how to regulate 
ephedrine alkaloid-containing dietary supplements and 
androstenedione, and they have done so. All of these 
enforcement activities were supported by the supplement 
industry's effort to assure that the funds necessary for 
dietary supplement enforcement were earmarked in FDA's budget, 
and that was a unified position of the supplement industry that 
those funds were needed.
    In addition to enforcement, FDA proposed last year current 
GMPs for dietary supplements. AHPA was one of the industry 
trade associations that presented FDA with an industry draft 
for GMPs in late 1995. While a long time coming and 
controversial in part, AHPA looks forward as you do to FDA 
making Dr. McClellan's 2004 year end deadline for the 
promulgation of GMP regulations a reality.
    It is AHPA's view that DSHEA can be strengthened in one 
important aspect, and that is with a requirement for serious 
adverse event reporting for dietary supplements. AHPA's Board 
of Trustees reached this conclusion in October 2002, and AHPA 
petitioned FDA the next year for serious AER reporting 
regulations. Both Commissioner McClellan and Deputy 
Commissioner Crawford had said FDA does not have the authority 
to do this.
    Accordingly, the time has come for Congress to provide that 
authority. Any serious adverse event reporting for dietary 
supplements should have the same protections for privacy of 
subjects and reporters and nonadmission of causation that FDA 
and the law accords to drugs, medical devices and biologics. In 
addition, FDA needs to fairly report and correct AER 
information that is demonstrably wrong. All of these 
protections are detailed in our written statement.
    As you both noted earlier, DSHEA treats new dietary 
ingredients differently than old ingredients. This is the same 
approach followed by Congress when it passed the new drug 
approval provisions of the law in 1938, the food additive 
provisions in 1958 and the medical device amendments in 1976. 
Dietary supplements with old ingredients, like old drugs, old 
food ingredients and old medical devices are to be proceeded 
against under the law's adulteration and misbranding 
provisions, and these are the tools used by FDA to regulate 
ephedrine alkaloid-containing dietary supplements.
    For new dietary ingredients, DSHEA makes FDA the 
gatekeeper. Only about 45 percent of the new dietary 
ingredients submitted to FDA go onto the market. The gate is 
narrow. The requirements for safety substantiation imposed by 
the FDA are substantial, and the FDA applies the law to those 
companies that make the required premarket notification.
    But it is clear that FDA needs to monitor the dietary 
supplement market to enforce this valuable provision with 
respect to those obviously new dietary ingredients that have 
not passed through FDA's gate. To do otherwise is unfair and 
disrespectful of the law. Not enforcing DSHEA's new dietary 
ingredient provision rewards lawbreakers at the expense of 
those who observe the law, and this is one of DSHEA's most 
important provisions.
    Let me close by saying that AHPA is committed to providing 
benefits to American consumers through our members' products. 
Thank you for the opportunity to appear before you here today.
    Senator Voinovich. Thank you, Mr. Young. Mr. Silverglade.

 TESTIMONY OF BRUCE SILVERGLADE,\1\ DIRECTOR OF LEGAL AFFAIRS, 
           CENTER FOR SCIENCE IN THE PUBLIC INTEREST

    Mr. Silverglade. Thank you very much, Mr. Chairman and 
Senator Durbin.
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    \1\ The prepared statement of Mr. Silverglade appears in the 
Appendix on page 115.
---------------------------------------------------------------------------
    I am Bruce Silverglade, Director of Legal Affairs from the 
Center for Science in the Public Interest. It is certainly 
appropriate to review the impact of DSHEA on consumers and 
discuss the need for reforms such as those included in S. 722. 
We support this legislation, and we urge that Congress enact it 
this year.
    As I will explain in a moment, however, Congress needs to 
extend additional protections to consumers that are not 
included in this legislation.
    Dietary supplements can play an important role in 
maintaining good health and can sometimes provide a valuable 
adjunct to traditional medical treatment. We certainly 
recognize that. Unfortunately, the safety and effectiveness of 
all dietary supplements has not been established, and there are 
many products which are hazardous or no more than 21st Century 
snake oil.
    The problem stems from the passage of the Dietary 
Supplement Health and Education Act of 1994, and as it has been 
said, history repeats itself, so it might be useful to look 
just for a moment at the history of this law. This is a blowup 
of the lobbying materials used by the industry in 1993 that 
urged consumers at health food stores to, ``write Congress 
today or kiss your vitamins goodbye.''
    These kinds of scare tactics were used by the industry to 
get consumers to write Congress to persuade this body to enact 
the Dietary Supplement Health and Education Act of 1994. And 
the reason I bring it up is because the same tactics are being 
used today to oppose S. 722.
    Here, we have another poster: It asks, ``Could these 
products be banned: vitamin C, multivitamins, calcium?'' This 
is a current poster at health food stores. And as the Senate 
offices on this Subcommittee and throughout this body receive 
mail from consumers, I want you to know that the mail is being 
generated by phony scare campaigns being generated not 
necessarily by these trade associations testifying here today 
but by many other segments of the dietary supplement industry.
    Now, the problems with DSHEA in the area of safety are 
rooted in that that Act changed the assumptions we make about 
the safety of products that FDA regulates. The Act changed the 
prevailing approach that the FDA takes. Food manufacturers do 
not have to demonstrate their products are safe before they are 
sold, so if you are selling lettuce, you can just sell it 
without FDA approval.
    But the manufacturers of food additives, drugs and medical 
devices must prove that their products are safe before they can 
be sold. Well, what are dietary supplements more like? Drugs 
and medical devices or lettuce? I think the answer is obvious. 
But the problem with the law is that DSHEA regulates these 
products like this kind of product--lettuce.
    Although the FDA still has the authority to take dangerous 
dietary supplements off store shelves, it must first prove that 
the product pose a significant or unreasonable risk. Well, that 
is difficult to do if there is no requirement that adverse 
event reports be submitted to the agency. Such information is 
essential to ascertaining whether a product poses a significant 
or unreasonable risk, especially in the absence of a premarket 
approval system.
    Thus, as a practical matter, the FDA has not been able to 
effectively utilize the authority granted to it by DSHEA. 
Consequently, the agency has been forced to rely on woefully 
inadequate remedies, such as issuing press releases, public 
warnings, medical alerts, voluntary recall requests, and so 
forth.
    Here is one such effort from 1993. This came from a report 
FDA issued called Unsubstantiated Claims and Documented Health 
Hazards in the Dietary Supplement Marketplace. It is out of 
print (it was issued in 1993), but it is available on the FDA 
Website as of today.
    It lists Yohimbe, for example, as a product that has, in 
the agency's own words, ``health hazards,'' many different 
types of health hazards. The supplement bottle I just held up 
before was yohimbe. We bought it today at a health food store. 
So more than 10 years later, after FDA is issuing press 
releases and alerts and warnings, this product is still 
available. Clearly, a more effective regulatory approach must 
be found if consumers are to be protected.
    Now, we all know that FDA banned ephedra, but as the 
Washington Post stated, DSHEA is truly a ``terrible law.'' The 
New York Times called the ephedra ban ``not enough'' and urged 
Congress to, ``revise the ill-conceived 1994 legislation.'' S. 
722 would help address some of these problems by requiring that 
manufacturers report serious adverse reactions to the agency. 
The legislation would also require agency approval of 
stimulants, one category of dietary supplements that pose some 
of the most severe hazards.
    These are useful steps, and we support the legislation. But 
we urge Congress to go further. Safety standards for dietary 
supplements that are used by children, pregnant women, the 
elderly, and other vulnerable groups determined by the FDA to 
be at particular risk should be raised higher than is now 
provided for in the law, and manufacturers should be required 
to submit evidence of safety before such products are sold.
    These steps, together with the provisions already 
incorporated in S. 722, would go a long way to ensuring that 
supplements in the United States are safe. Thank you.
    Senator Voinovich. Thank you. Dr. Dickinson.

 TESTIMONY OF ANNETTE DICKINSON, PH.D.,\1\ PRESIDENT, COUNCIL 
                   FOR RESPONSIBLE NUTRITION

    Ms. Dickinson. Senator Durbin, Senator Voinovich, thank you 
for giving us the opportunity to testify here today.
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    \1\ The prepared statement of Ms. Dickinson, with attachments, 
appears in the Appendix on page 123.
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    The Council for Responsible Nutrition is a trade 
association of dietary supplement manufacturers, and I am the 
president of CRN. Our members include manufacturers and 
marketers of national brands as well as store brands of dietary 
supplements available to consumers through the mass market, 
through natural product stores, direct sales and mail order.
    Our members include not only the manufacturers of finished 
products but also the suppliers of the bulk ingredients such as 
vitamins, minerals and botanicals that are contained in these 
ingredients. DSHEA was passed 10 years ago for two reasons: One 
was to ensure that consumers would continue to be able to 
choose safe and beneficial dietary supplements of a wide 
variety of products. The second was to increase the information 
available to consumers about the purposes and uses of those 
dietary supplements.
    The past 10 years have demonstrated that these purposes are 
being fulfilled, as are other goals established by the law, 
which I would like to address briefly. I think it is important 
to recognize that dietary supplements have always been 
considered as a subcategory of foods. This official 
categorization was not, as some of our witnesses would have you 
believe, created by DSHEA.
    In fact, it precedes DSHEA by about 56 years. The Food, 
Drug and Cosmetic Act of 1938 included dietary supplements 
within a category of foods called foods for special dietary 
use. In 1941, FDA established definitions for this category of 
products, and in 1976, that definition was added to the Food, 
Drug and Cosmetic Act in Section 411, the vitamin and mineral 
amendments.
    That definition is extremely broad, covering vitamins and 
minerals but also all ``other ingredients intended for use in 
supplementing the diet.'' DSHEA reconfirmed that dietary 
supplements were to continue to be regulated as foods and 
established a specific definition to clarify the categories of 
ingredients that were to be permitted in those dietary 
supplements.
    As has already been noted, it grandfathered ingredients 
that were already on the market at the time the act was passed, 
just as was done with food ingredients when the food additive 
amendments were passed and just as was done with old drugs when 
the drug amendments were passed.
    DSHEA grandfathered those ingredients in the same way that 
this was done in other food categories. At the same time, DSHEA 
established a premarket notification requirement for new 
ingredients much in the same way that new GRAS substances 
(substances generally recognized as safe) put on the market 
today for use in foods are evaluated by their manufacturers for 
safety before they are put on the market. There is no 
requirement for FDA evaluation of new GRAS ingredients.
    FDA has been seriously reviewing and evaluating these 75-
day notices that have been submitted for these new ingredients, 
and this is one of the many ways in which FDA under the recent 
Commissioner, Dr. Mark McClellan and the current acting 
Commissioner, Dr. Lester Crawford, have been vigorously 
implementing the act.
    As you all know, FDA issued a final regulation this year 
that banned ephedra in dietary supplements as of April 12, 
2004. That rule is currently undergoing judicial review and has 
survived the first phase, in which the court denied a 
preliminary injunction. This is generally viewed as an 
indication that the rule is likely to survive the entire review 
process.
    It is sometimes said that FDA took 10 years to take 
definitive action against ephedra, but this is not, in fact, an 
accurate description of the process. From the time former 
Commissioner McClellan took office and decided to resolve this 
ongoing issue, which has been a serious problem for everybody 
involved, for industry, for consumers and for FDA, from the 
time Commissioner McClellan took office, it took the agency 
less than 2 years, which, as you well know, is lightning speed 
in terms of the regulatory process, to issue a final ban on 
ephedra.
    The earlier delays that occurred in FDA enforcement were 
not due to inadequate authority but were due to false starts, 
wrong turns and a frank unwillingness to actually use the new 
provisions of DSHEA that were provided and that were ultimately 
used as Congress intended.
    Another issue that has been troubling to the industry is 
the issue of andro. CRN and other industry trade associations 
are supporting Congressional legislation that will place andro 
on a long list of similar ingredients that are to be placed 
under the Controlled Substances Act, which effectively removes 
them from the dietary supplement category. That legislation 
passed the House on June 3 and is expected to pass the Senate 
during this session.
    FDA has also taken separate action against andro, as was 
mentioned here today, sending warning letters to a number of 
manufacturers arguing that andro is an unsafe ingredient and 
is, moreover, a new dietary ingredient for which a 75-day 
notification has not been submitted. Between the Congressional 
and FDA action, andro should be off the table as an issue of 
concern by the time the next Congress convenes.
    There has been much talk about adverse event reporting. If 
there were to be an adverse event reporting requirement, it 
would be important for it to at least contain protections for 
reporting companies and for individuals that are included in 
regulations applicable to other FDA-regulated categories, 
including prescription drugs. The legislative proposals 
currently on the table tend to actually exceed the requirements 
that currently exist for pharmaceuticals and thus are not 
provisions we can support.
    We support the need for more resources for FDA to implement 
the law and are in support of the Hatch-Harkin bill, which 
would provide FDA with very substantial new resources. We also 
support----
    Senator Voinovich. Ms. Dickinson, your time is up.
    Ms. Dickinson. Yes, I am concluding.
    We also supported the provisions in DSHEA which created the 
Office of Dietary Supplements, which the Congress has very 
appropriately given significant resources.
    With all of these changes, Senators, we hope that when you 
come back in January 2005 to the next session of Congress, we 
will be able to return to hearing rooms such as this one and 
discuss the role of dietary supplements in improving the health 
of the population and ultimately in reducing health care costs.
    Senator Voinovich. Thank you very much.
    According to a recent poll, most Americans believe that 
dietary supplements are safe and are approved by the FDA before 
they can be made available to the public.
    Should this, in fact, be the case, and do you believe that 
the FDA's authority to regulate dietary supplements is 
sufficient to protect the health of the American public? I have 
heard from all of you that adverse event reports should be made 
mandatory. What else beyond that? Dr. Dickinson.
    Ms. Dickinson. I would say the primary thing that is needed 
is exactly what FDA has been doing in the past couple of years, 
which is to actively enforce and implement the law. I think 
that it is not possible to say that the law has not worked 
until FDA has actually seriously attempted to implement it, 
which they are now doing. And I think they need a little bit 
more time to demonstrate the effectiveness of that approach, as 
has been demonstrated in the case of ephedra.
    Senator Voinovich. I would like to ask the panel the same 
question I asked Dr. Brackett from the FDA. Is it your 
observation that the FDA has the resources needed to enforce 
DSHEA. Dr. Davis.
    Dr. Davis. Well, our position would be that the FDA does 
need more resources to address this issue. I think the fact 
that it took the agency so long to get the ephedra-containing 
products off the market and the fact that it has taken so long 
to finalize promulgation of standards for good manufacturing 
practices are pieces of evidence that the agency is not able to 
act as promptly and effectively as it could.
    Senator Voinovich. So even if we did require mandatory 
adverse event reporting, we have to make sure that they have 
the people necessary to follow up on the reports, correct?
    Dr. Davis. That is correct. And sometimes, the agency can 
work on a problem with in-house staff, and sometimes, it would 
need to contract out and get some expert assistance from the 
outside, like in the case of the ephedra study, where they 
brought in the RAND Corporation.
    Senator Voinovich. Mr. Silverglade.
    Mr. Silverglade. Yes, thanks very much, Mr. Chairman.
    It is our position that, of course, while all government 
agencies could use more resources, we do not like throwing good 
money after a bad law. And the way DSHEA is set up, and I think 
the witnesses attested to this, and Senator Durbin's questions 
to the witnesses illustrated this, is that the burden is on 
FDA, for example, to investigate each of these market 
notifications for these new products to determine if the 
product is safe.
    That expense should be borne by the manufacturer and then 
turned over to the FDA for a quick review by the agency. The 
whole burden should not be on the FDA. It is extremely costly, 
and the agency did say about 2 years ago that it would require 
$90 million over 5 years, I believe, from Congress to fully 
implement DSHEA. Last year, Congress gave the FDA an additional 
$1.5 million. That is not anywhere close to the $90 million the 
agency says it needs to implement DSHEA.
    So what should really happen is the law should be changed 
so that the expense of investigating the safety of these 
products is put on the manufacturers who profit from their 
sale.
    Senator Voinovich. You suggest that before the products be 
put on the market, the manufacturer has to do the same thing 
that one has to do with a prescription drug and prove that it 
is not harmful to the public?
    Mr. Silverglade. No, we do not favor an across the board 
requirement of that sort. Ordinary vitamins and minerals are 
generally recognized as safe and do not need to undergo an FDA 
review. On the other hand, a product like this, yohimbe, which 
is from tree bark, and is known by FDA to be hazardous, this 
should not be on the market until manufacturers can demonstrate 
to the agency that it is safe.
    The agency itself has said since 1993 that it is unsafe.
    Senator Voinovich. How do they know that it is unsafe. How 
does the FDA find out about unsafe products if manufacturers do 
not have to submit it to the FDA before they can put it on the 
market?
    Mr. Silverglade. Well, on this kind of product, which is an 
herb, not an ordinary vitamin or mineral, the manufacturers, 
the distributors, the sellers of this product should have to go 
to the FDA first to get approval before selling it.
    Senator Voinovich. So it is more specific?
    Mr. Silverglade. Right; dietary supplements fall into three 
major categories: There are ordinary vitamins and minerals, 
which are presumed safe for the most part. There are just one 
or two exceptions. Herbal products comprise a second category, 
and then we have a miscellaneous group of products, a third 
category. These products could be anything from shark cartilage 
to cow organs, bull testicles; believe it or not, it is all out 
for sale on the market.
    Ordinary vitamins and minerals do not now have to be 
reviewed by FDA, but products in these other two categories 
probably should be reviewed by the agency, as the American 
Medical Association has suggested, before they are sold to 
ensure that they are safe.
    Senator Voinovich. You are saying all of them should be or 
just some of them?
    Mr. Silverglade. Just certain categories that are known by 
the medical community to be more likely to pose health hazards.
    Senator Voinovich. Are you at all concerned about the 
outrageous claims that you see on the packaging and advertising 
of some of these products that lead you to believe that they 
are going to do this and that?
    Dr. Davis. Could I comment on that, Mr. Chairman?
    Senator Voinovich. Yes, Doctor.
    Dr. Davis. You are referring to structure and function 
claims, and I think that is an example of how DSHEA is not 
working. And I just found five products on the market today 
that are making some rather unbelievable claims, and just to 
read a few of those: Provides dietary support for a healthy 
nervous system. Provides dietary support for normal, healthy, 
cerebral blood vessel tone. Promotes healthy immune system by 
supporting T and B cell function, protecting against cellular 
damage and introducing beneficial enzymes. Optimal support for 
allergies and sinuses. Helps cleanse the liver from impurities 
in the diet and environment. And then, the last one is, may 
help manage hot flashes and night sweats associated with 
menopause.
    Now, these are structure and function claims. The 
manufacturers are required under DSHEA to be able to 
substantiate the truthfulness of those claims, but they are not 
required to provide data to the FDA to prove that. They are 
required to put a disclaimer on the product that says this 
statement has not been evaluated by the FDA. This product is 
not intended to treat, cure or prevent disease.
    So on the one hand, you have these claims that I just read 
for you, and then, right underneath, there is the claim that 
this is not a claim. It is not a health claim; it is a 
structure and function claim. And can the ordinary consumer 
distinguish between ``a structure and function claim and a 
health claim?'' As I read this as a physician and putting 
myself in my patients' shoes, those claims that I read sound 
awfully like health claims, which should put them under the 
authority of the FDA, and the manufacturers should be required 
to prove that those claims are correct at their own expense.
    Senator Voinovich. My time is up.
    And I will give you a chance on my next round to--I am 
sorry. Senator Durbin.
    Senator Durbin. Please let her go ahead.
    Senator Voinovich. Go ahead, Dr. Dickinson.
    Ms. Dickinson. In response to your question about the 
claims, it is our belief that false and misleading claims are 
not only a disservice to the consumer but are actually an 
unfair trade practice. We worked with the Federal Trade 
Commission and the FDA to get action taken on coral calcium 
products a year ago, which were claiming to prevent and treat 
at least 400 different diseases.
    These claims simply should not be allowed on the 
marketplace. And I think part of the answer to your previous 
question as well is that industry should be cooperating with 
FDA, responsible industry should be cooperating with FDA and 
FTC to see that these issues are taken care of, and that is one 
of the ways that the resources of FDA can be stretched and made 
more effective.
    Senator Voinovich. I will let Senator Durbin take over.
    Senator Durbin. Mr. Young, I want to make sure I understand 
what your association has decided. You agree, then, that there 
should be adverse event reporting of all dietary supplement 
products.
    Mr. Young. Reporting of serious adverse events for all 
dietary supplement products, that is correct.
    Senator Durbin. Whether they are characterized as pre-1994 
products or post-1994 products.
    Mr. Young. That is correct.
    Senator Durbin. Regardless of combinations, whether they 
are old or new.
    Mr. Young. All dietary supplements, all serious adverse 
events associated with them.
    Senator Durbin. And I assume from what you have added in 
your testimony here that you are asking for the same basic 
protection when it comes to privacy and legal admissions as 
currently exist on AERs for pharmaceuticals, for example.
    Mr. Young. That is correct, Senator.
    Senator Durbin. What is your position on premarket testing 
of your products, particularly of stimulants?
    Mr. Young. I think that our view is that stimulants can be 
regulated under the current law, and I think we have provided 
that information to your staff, but we think they can be 
regulated under current law. FDA has the authority to look into 
these various ingredients. Some of the stimulants mentioned in 
the Consumer Reports article have been known about for years.
    Our trade association has had positions with respect to the 
labeling of the yohimbe for a long time. It is set out in the 
Botanical Safety Handbook. And if these matters rise to a level 
of concern, FDA has the tools, we believe, to take the action 
they feel is necessary, whether it is to ban an ingredient, as 
they did with ephedrine alkaloid-containing supplements or 
whether it is to require labeling, which is another option FDA 
has.
    Senator Durbin. Many years ago, when we were having trouble 
with approval of medical devices, the FDA did not have the 
resources to approve devices, the industry decided to agree to 
pay a user fee to the FDA to provide them with the resources 
and staff necessary so that these approvals could take place. 
Is your association prepared to pay a user fee to the FDA to 
make certain there is adequate review and testing of your 
products before they are marketed?
    Mr. Young. I would assume that you are talking about new 
dietary ingredients, and let me clarify something that Mr. 
Silverglade said.
    Senator Durbin. No, I am talking about all.
    Mr. Young. All ingredients? No, because I think at that 
point, with respect to the older ingredients, we believe that 
they can be assessed under the law; that there is information 
available on old ingredients, and that FDA has the tools 
necessary to evaluate that.
    Senator Durbin. Mr. Young, I suspect that we are both 
doctors of the law. I know I am not a medical doctor; perhaps 
you happen to have that in your resume. But you heard Dr. 
Brackett say earlier that even new combinations of old 
ingredients could be dangerous. So how can you draw this 
distinction, as the law does, and say that we are going to make 
this apply only to new ingredients?
    Mr. Young. Well, it is a distinction that the law does 
make, and I think if we can effectively deal with new 
ingredients under the new dietary ingredient provision, which 
is a provision where the manufacturer submits the information, 
by the way, and FDA only evaluates what is submitted, FDA does 
not go out and do independent research on new ingredients.
    The manufacturer must present the data for review, and that 
data must pass muster or not. But with respect to old 
ingredients, there is information out there. It is readily 
available. The Botanical Safety Handbook where we talk about 
the safety, the cautions, etc., associated with various herbs 
was not written in a vacuum. There is a lot of information 
available to FDA and to others to evaluate the safety of these 
materials.
    Senator Durbin. So, Dr. Davis, if we are talking about old 
ingredients in the Botanical Handbook, and we are dealing with 
products that present these ingredients in new concentrations 
and new combinations, do you accept the premise that they are 
still benign?
    Dr. Davis. No, I do not. I think we may discover that there 
are harms that we did not know about before. There may be new 
interactions between an old dietary supplement and a new 
prescription medication that has just come on the market. There 
may be combinations, as you have pointed out, with an old 
dietary supplement and a newer one or new combinations. We 
talked during the ephedra hearings about ephedra being combined 
with caffeine, for example. So I would not accept that premise.
    Senator Durbin. Let me ask Dr. Dickinson a question, if I 
might, and I am going to go to your testimony here, because I 
think you were rather explicit when it came to the issue of 
ephedra, in which I can find it quickly here. I apologize. I 
had it underlined. You said delays were due to false starts, 
wrong turns, and an unwillingness to actually use the 
provisions of DSHEA as Congress intended when it came to the 
banning of ephedra, and you credited Commissioner McClellan 
with having taken control of the agency and, in less than 2 
years, as you say, lightning speed in terms of the regulatory 
process, responded to this issue.
    Did you include in your false turns the statement by the 
largest manufacturer and retailer of ephedra, Metabolife, to 
the FDA in 1999 that, ``Metabolife has never been made aware of 
any adverse health events by consumers of its products. 
Metabolife has never received a notice from a consumer that any 
serious adverse health event has occurred because of ingestion 
of Metabolife 356?''
    A statement by Metabolife in 1999, and then, after lawsuits 
were filed by the Department of Justice and individuals, here 
is what came out: Metabolife had deliberately misrepresented 
this fact to the FDA. Metabolife had 16,500 adverse event 
reports for Metabolife 356, including almost 2,000 significant 
cardiac, neurological and psychiatric reports.
    So when you are saying the problem was false starts at the 
agency, and Dr. McClellan finally straightened it out, what 
kind of responsibility do you accept as an industry for this 
kind of concealment and obfuscation of adverse event reports by 
Metabolife?
    Ms. Dickinson. I think this kind of concealment and 
obfuscation is just as outrageous as you think it is. But this 
is one company's activities.
    Senator Durbin. The largest company.
    Ms. Dickinson. A large company that is not, in my view, 
characteristic of the industry as a whole. When I spoke of 
false starts, I refer to the fact that FDA, after having first 
started begun to receive reports of adverse events on ephedra 
in 1993, held two advisory committee meetings, one in 1995, one 
in 1996, at which they failed to come to a unanimous conclusion 
about how to act; produced a rule in 1997 which overtly 
attempted to use the adverse event reports for purposes that 
FDA has always recognized and still recognizes they cannot be 
used for.
    The Government Accounting Office found that rule to be 
inadequately supported in terms of the specific actions FDA 
took. Following that event, FDA then did not take further 
action until McClellan's action in 2003. So there is a period 
of time there where FDA started off in one direction, was found 
not to be on good ground in going in that direction, and it 
really took Commissioner McClellan to put them in another 
direction.
    Senator Durbin. That was during the same time that the 
largest retailer of ephedra products in America was 
deliberately lying to the Government about adverse events.
    Ms. Dickinson. I understand that, I understand that, and I 
think it is outrageous.
    Senator Durbin. And that outrage also made it more 
complicated, did it not, for FDA to evaluate the danger of the 
product.
    Ms. Dickinson. I do not think it did, and let me explain 
why I do not think it did. As outrageous as that event was, I 
think the reality is that FDA knew everything they ever learned 
about the pattern of events associated with ephedra within the 
first couple of years that they were receiving adverse events. 
I think that from a scientific and public health point of view, 
it is a fact that one does not have to know about every event 
that occurred in order to understand what pattern is occurring.
    There were millions of people using ephedra, and FDA had a 
very extensive sample of the events that were occurring. I 
think from a scientific and public health point of view, they 
knew exactly what was happening, even if they did not know the 
actual number. And I think that is the same information that 
FDA eventually used in finalizing the rule.
    Senator Durbin. I think the fact that it took so long, and 
so many people died while we were waiting for this to occur is 
a suggestion about the inadequacy of the law.
    Mr. Chairman, I will wait and do another round of questions 
when you are finished.
    Senator Voinovich. Is there a fee that a manufacturer must 
pay when they intoroduce a new ingredient?
    Mr. Young. No, Mr. Chairman.
    Senator Voinovich. So the cost of this is all being borne 
by the FDA; is that right?
    Mr. Young. That is correct. FDA evaluates the data that is 
presented to them by the company coming to them with the new 
dietary ingredient.
    Ms. Dickinson. But the company does the work of preparing 
the data, so they help.
    Senator Voinovich. The fact is that there is no fee for the 
FDA to review the data the company prepares. How about 
prescription drugs? Is it the same situation with prescription 
drugs? Is there a fee for the FDA to review the data the 
company submits?
    Ms. Dickinson. With drugs, there is, but not with food 
additives and not with GRAS ingredients. On the food side, 
there is no fee associated with the review of a GRAS 
notification.
    Senator Voinovich. That is because the definition of a 
dietary supplement is still in the food category. I got the 
impression here that it should be defined as something other 
than a food product.
    Ms. Dickinson. No, absolutely not, not from us.
    Senator Voinovich. How about the other witnesses?
    Mr. Silverglade. Thank you, Mr. Chairman.
    I would define it a little differently than a food product. 
It does not look like food to me.
    Ms. Dickinson. Does saccharin look like food to you?
    Mr. Silverglade. It comes from tree bark. I would not eat 
it as food.
    Senator Voinovich. Mr. Young.
    Mr. Young. There are user fees for new drugs, and there are 
user fees for medical devices. I do not know the degree to 
which user fees in this industry would be appropriate. There 
have only been 188 new dietary ingredient notifications 
submitted to FDA in the 10 years that this law has been in 
effect. I think we have a lot greater concern as an industry 
with those people who are not going through the toll booth and 
paying the toll or at least gathering the information together 
and having it reviewed by FDA.
    It is like an 8-lane highway with a toll booth on one lane. 
Responsible manufacturers are going through that door. I do not 
think they ought to have to pay in order to go there and have a 
45 percent success rate of getting through until this agency is 
able to deal with those who ignore the law entirely.
    So I do not believe that it is something that would really 
facilitate the proper and timely review of these notifications.
    Senator Voinovich. You are saying 188 in a 10-year period 
have come through the door?
    Mr. Young. That is correct. We believe about 45 percent of 
those were allowed by FDA to go to market. FDA does not 
approve; they simply allow these products to go to market 
without objection.
    Senator Voinovich. Of the 188 new ingredient projects, only 
45 percent were allowed to go to the marketplace?
    Mr. Young. That is correct, Mr. Chairman.
    Senator Voinovich. What percentage of dietary supplement 
manufacturers are avoiding this requirement that the FDA review 
their product?
    Mr. Young. It is very difficult to say how many there are, 
but I have been to a lot of trade shows, and I have read trade 
magazines that can be read by FDA as well, and there are a lot 
of folks out there offering new ingredients, new, this is the 
first time ever, and in the enforcement context, my own view is 
these would be low-hanging fruit, easy targets. And this is an 
important part of the law to enforce.
    Senator Voinovich. One problem that I have, whether it is 
Enron or Global Crossings, is that you have some bad apples out 
there, and it seems to me that the industry itself, in order to 
protect itself, should become a lot more aggressive in bringing 
these matters to the attention of the Food and Drug 
Administration. How do you feel about that?
    Mr. Young. I know it has been done, that these matters have 
been brought to FDA's attention. I do not know that any of them 
have been acted upon. However, certainly, it was part of the 
decision FDA made with respect to androstenedione. FDA said on 
the one hand, it is not a dietary ingredient at all; it is 
illegal as a dietary supplement, and second of all, no 
notification has been filed if it is a dietary ingredient. So 
you are off the market. That is the only instance I am aware 
of, and industry and others urged FDA to do that, and it did 
so.
    Senator Voinovich. Does your organization, the American 
Herbal Products Association, take the initiative to police your 
own industry?
    Mr. Young. I think our association has brought matters to 
the attention of the Federal Trade Commission. I am not certain 
about the FDA. I know individual competitors in the industry 
have brought matters to the attention of FDA with respect to 
new dietary ingredients, and I think it is something that 
should be done more, because we do have a role, obviously, an 
important role in protecting the integrity of this industry.
    Senator Voinovich. Dr. Dickinson, how does your 
organization feel about acting as a watchdog and trying to 
police your own industry?
    Ms. Dickinson. I agree with Mr. Young that it is very 
important for us to be strong in taking some initiatives in 
self-regulation. CRN has just recently established a task force 
to look at some of the things that we might do more proactively 
to address some of these issues.
    Senator Voinovich. I do not know where this legislation is 
going. I can tell you one thing that if this bill comes up, I 
am certainly going to give it a great deal of thought. The fact 
of the matter is that so often the only reason why we get into 
legislation is because the industries responsible close their 
eyes to the problems facing their industry. I think that you 
all have to be a lot more aggressive in policing your own 
industry.
    Ms. Dickinson. Let me say that we have been very aggressive 
in some of these areas like GMPs. The fact that it has taken 10 
years is not because we have not been pushing it. In fact, CRN 
and the other associations took the initiative in 1995, in just 
1 year after DSHEA was passed, of going to FDA with draft 
language which we had already shared with USP that formed the 
basis of their----
    Senator Voinovich. What happened? It does not make sense. 
It is almost illogical. If you are a member of the public, and 
it is a requirement of the law, and here, it is 10 years later, 
and it has not happened? How can you explain that it did not 
happen?
    Ms. Dickinson. Well, it actually was not a requirement of 
the law. They were permitted by the law to do this. In the 
meantime, until we have unique dietary supplement GMPs, we are 
fully subject to food GMPs, so it is not that there are not 
any. It is that there is an opportunity to ratchet up the level 
of quality that would be required, and industry was fully 
supportive of that. FDA has a lot of stuff on its plate, 
including the new bioterrorism act, which we have also all had 
to be complying with and which, in fact, has brought a very 
significant amount of new resources to the agency which it can 
use for all of its regulatory activities.
    Senator Voinovich. So in this case, you would say that 
because of September 11 and the new additional money that is 
helping the agency overall, it is not a situation of where they 
have new responsibilities, but they have been given more money, 
and therefore, you think that they are better off than they 
were before.
    Ms. Dickinson. It is a mix, but they got about 700 or 800 
new inspectors as a result of the new bioterrorism law. They 
got requirements for registration. Companies had to register as 
of December 12 of last year, so they now have resources that 
they did not have before. There are also provisions related to 
advance notice of imports and the review of records which 
strengthen their overall position.
    Senator Voinovich. Mr. Silverglade.
    Mr. Silverglade. Thank you, Mr. Chairman.
    With respect to GMPs, it is really kind of a black box. We 
do not know exactly what happened, but a few things are a 
matter of record that we do know. One thing we do know is that 
the FDA sent its proposed rule for GMPs to the Office of 
Management and Budget for approval on November 8, 2000, right 
after the election.
    After President Bush took office, the proposed rule for 
GMPs was sent back from OMB to the FDA. Then Commissioner 
McClellan took charge, but now, we had several more years of 
delay. So instead of doing a very good job, I would submit that 
the Clinton Administration had finished the job. Then, the GMP 
rule was sent back by OMB after the inauguration of President 
Bush. And then, Commissioner McClellan took several more years 
dealing with it.
    Now, the FDA finally proposed a rule last year. And what is 
holding it up now? I will give you the answer: The industry. 
The industry has filed hundreds of comments claiming that this 
has to be changed, that this provision is too strong, and that 
provision is too strong, and that is why FDA has not issued a 
final rule.
    Senator Voinovich. Senator Durbin.
    Senator Durbin. And that is what Dr. Brackett said, 400 
substantive comments. So is it any wonder why this GMP is 
dragging on as long as it has?
    I would like to make sure I understand a few of the things 
that have been said. Mr. Young, are you saying that in the 10 
years of DSHEA, there have been 188 new ingredients submitted 
to the FDA of dietary supplements?
    Mr. Young. That is what is noted on their Website. That is 
correct.
    Senator Durbin. OK; is it correct that there are some 
30,000 different dietary supplement products on the market 
today?
    Mr. Young. I have no numbers, but I would not be surprised 
that is the number of what they call SKUs, the selling units.
    Senator Durbin. That may have been in Dr. Brackett's 
testimony or in one of the others, but I believe that 30,000 
was the number.
    Ms. Dickinson. But the definition----
    Senator Durbin. Excuse me a second, please.
    Does not it strike us as odd? Thirty thousand products on 
the market, and over a 10-year period of time, we average about 
19 a year that come before the FDA to test a new ingredient? 
And going back to Dr. Davis' point, combinations of old 
ingredients can also raise some concerns here as to new 
concentrations and new combinations. And I think it is proof 
positive that this current law is not giving the FDA the 
authority it needs.
    In fact, recall when Dr. Brackett was asked, well, did you 
have a listing of the old ingredients so you knew where your 
starting point was? No, it does not exist.
    Mr. Young. Well, Senator, the industry did provide lists of 
old ingredients to FDA. FDA has those lists from the industry. 
They do not give them legal significance, but I do believe they 
read those lists when they look at things. There were lists 
given by, I think, all three of the major trade associations to 
kind of record, as you suggested earlier, what was in place in 
1994.
    Senator Durbin. It also is a fact, is it not, testimony 
here that fewer than or less than 1 percent of the AERs that 
have been filed with the FDA came from the industry. Ten out of 
2,500, so the voluntary program for dietary supplements to 
self-report adverse events has generated 10 out of 2,500 
adverse event reports in the life of this act.
    Is that your understanding, too, Mr. Young?
    Mr. Young. I do not know how many have come from 
manufacturers, but I do not know that there is a voluntary 
program for manufacturers to send in adverse events other than 
that FDA would like it. There has been no organized industry 
activity that I am aware of in that regard.
    Senator Durbin. So how can we take your industry seriously 
if they do not report products on the market that are causing 
adverse health events? How can consumers take the industry as 
seriously interested in the health of America?
    Mr. Young. Well, I think the industry evaluates those 
reports. Our members evaluate those reports, and they make 
adjustments as necessary in response to those reports. They 
look at them as signals, and I think one of the reasons we 
support mandatory adverse event reporting is so that FDA, with 
all of its expertise, can aggregate that information and 
determine whether signals received by one company are similar 
to those received by other companies and begin with the process 
that the----
    Senator Durbin. Mr. Young----
    Mr. Young [continuing]. IOM has established.
    Senator Durbin [continuing]. How can they aggregate what 
they never receive?
    Mr. Young. They can if there is a mandatory reporting 
system.
    Senator Durbin. A change in the law.
    Mr. Young. That is correct.
    Senator Durbin. Dr. Dickinson, you have said that we should 
view grandfathering of old ingredients like the grandfathering 
of food.
    Ms. Dickinson. The grandfathering of GRAS ingredients, 
which are food additives ``Generally Recognized as Safe.''
    Senator Durbin. So if we had common foods that cause no 
problem, and people decided to cook them together, carrots and 
cauliflower, and that caused no problem, we should not be 
hauling in the FDA to analyze it. Is that your take on this?
    Ms. Dickinson. With regard to carrots and tomatoes, yes. 
Not necessarily with regard to the dietary supplement 
ingredients. In fact, I think it is important to recognize, and 
I am sure Mr. Young would comment on this as well, FDA, in its 
review of these new ingredient notifications is, in fact, doing 
some of the things that you suggest. FDA is determining, on the 
basis of concentration, different types of extracts, different 
types of processing, that certain ingredients that companies 
might have thought were old ingredients are, indeed, new 
ingredients.
    Senator Durbin. How many old ingredients are there? How 
many are we talking about?
    Ms. Dickinson. I think we are talking about several 
thousand. I do not think we are talking about 30,000. And the 
reason for that is that the number of 30,000 was an FDA number 
that came about when FDA was proposing nutrition labeling, and 
the cost of that they----
    Senator Durbin. But do you see that if you take several 
thousand starting old ingredients and consider just 
combinations, not concentrations, that you could be ranging 
into the millions of possibilities here?
    Ms. Dickinson. Well, one can speculate about a lot of 
things. A large number of those ingredients are essential 
nutrients or recognized nutrients. A large number of the 
additional ones are the chemicals that are reviewed in a large 
number of monographs published by organizations like USP and 
WHO.
    Senator Durbin. OK; let us start with citrus aurantium, the 
most popular, I believe, substitute for ephedra. I wrote to the 
seven largest dietary supplement companies and asked them: Did 
you test your citrus aurantium product before you marketed it? 
How many do you think tested it ahead of time?
    Ms. Dickinson. How many of them responded?
    Senator Durbin. Well, of those who responded. It is a good 
point, but how many do you think tested it?
    Ms. Dickinson. None of them may have tested it in the way 
that a drug is tested, but they certainly had information from 
their supplier of the ingredient and from other information 
that----
    Senator Durbin. Sure did. Let me read you some of the 
replies. NVE Pharmaceutical.
    Ms. Dickinson. Oh, not them; come on.
    Senator Durbin. Robert Ochifento. Are you familiar with 
him?
    Ms. Dickinson. I am.
    Senator Durbin. OK. He makes this beautiful little product, 
Stacker-2. He says: ``In my experience, it is unusual for 
companies to conduct in-house testing for nutraceutical 
compounds.'' But then, he referred me to a study involving 
Seville orange juice, a study that had been published in the 
Journal of Clinical Pharmacology, as evidence that this was not 
a dangerous product, citrus aurantium.
    And so, we contacted the people who actually authored the 
study, and here is what they said: Mr. Ochifento, president of 
NVE, making Stacker-2, who says that this study is the reason 
why he can sell this product safely, ``I do not consider our 
study using Seville orange juice even remotely sufficient to 
assess the safety of synephrine-containing dietary supplements. 
If the industry is doing that, then, in my opinion, they are 
committing an egregious error.''
    Do you understand that we are not dealing with benign 
products here?
    Ms. Dickinson. We are not dealing----
    Senator Durbin. Excuse me. I will finish, and then, you get 
your chance.
    We are dealing with products which can be in lethal 
concentration with no testing, going on the market making the 
consumer walking into that store the laboratory test rat. Now, 
is that what you want to see in the America that you live in?
    Ms. Dickinson. No, it is not.
    Senator Durbin. Is that where you think the FDA should be 
in allowing these products to be sold without testing, without 
review of adverse events? You think they should be 
grandfathered and treated like food. I do not believe that this 
is a food situation.
    Ms. Dickinson. I think that this is also not a responsible 
company and a responsible individual that we are referring to 
here. The fact that this guy does not know one end from the 
other does not necessarily mean that other companies in the 
industry do not have better information about these products.
    Senator Durbin. Would you like to give us a list of those 
companies that we should not buy products from?
    Ms. Dickinson. I would love to, but I do not think I can. I 
do not think my counsel will allow me to do that.
    Senator Durbin. Well, that sure is reassuring.
    Ms. Dickinson. I certainly can provide you a list of our 
members, and I think you can be perfectly confident buying from 
these members or from members of Mr. Young's association or 
some of the other major associations.
    Senator Durbin. Well, Mr. Young, it turns out that NVE is a 
member of your association. So what do you want to tell us 
about him?
    Mr. Young. I believe they are a member of our association, 
and I believe they are the ones that have challenged the FDA's 
ban on ephedrine alkaloid containing dietary supplements. I 
have not seen that letter before. I am surprised at his 
response.
    Senator Durbin. Would the word troubled also be included?
    Mr. Young. Troubled?
    Senator Durbin. Are you troubled by his response?
    Mr. Young. Yes, because there is a lot more information, I 
think, available about citrus aurantium, about the--there may 
be other ingredients that are in that product. I do not know 
how that product is labeled. There are various cautions that 
are recommended for these kinds of products or ingredients.
    Senator Durbin. Well it has been labeled by a lawyer for a 
cure, because it says this product is not intended to diagnose, 
treat, cure or prevent any disease.
    Mr. Young. Well, that is the statement for structure and 
function I think for the FDA that--but also, there may be 
cautions on there as well.
    Senator Durbin. It is also pictured on cable, because it is 
the world's strongest fat burner. How about that?
    Mr. Chairman, I think we have achieved what we wanted to in 
this hearing. Although it has taken awhile, I think we have 
reached the point where it is clear that DSHEA, which was 
written 10 years ago as an experiment, is an experiment that 
has failed the consumers of this country. I do not believe that 
we collect enough information about these products to say to 
any unsuspecting consumer of any age in America be safe, by 
these products.
    We have to say buy them at your risk. Your government has 
not established standards about what is included in the 
products. We have not established any standards about whether 
they are lethal, whether they are safe, whether they can 
achieve the things that they are advertised to do, and we do 
not even require the makers of the product when they are killer 
products, causing people's death, to report it to the 
government.
    We have failed miserably, and to think that the FDA's 
testimony today is that they are satisfied with this law and 
see no need for change is troubling to me. I think we have a 
greater responsibility, and I thank you for this hearing.
    Senator Voinovich. You are more than welcome, Senator 
Durbin, and I am pleased that you asked me to hold this hearing 
today. I have learned a great deal, and I am just as concerned 
about this issue as you are.
    I would like to reiterate that the responsible 
organizations that are represented here and some that are not 
should take very seriously the fact that this hearing has been 
held. They need to start doing a better job of policing their 
own industry.
    Last but not least, I do not know if this hearing is going 
to be on C-SPAN or not, but I can assure you that if it is, the 
people watching this are going to be a lot more reluctance to 
purchase any of these dietary supplements because of the 
information that has been brought out today at this hearing.
    I am personally very concerned about this, because I had a 
brother who took all kinds of dietary supplements and kept 
urging them upon me. He died from a massive stroke 2 years ago. 
I am not saying these supplements caused his stroke but there 
is reason to be concerned. I think there are a lot of Americans 
out there that for one reason or another think that these pills 
are going to be the thing that is going to keep them going, and 
they really are not.
    Thank you very much.
    Senator Durbin. Mr. Chairman, if I might say before we 
close, give thanks to the staff people who worked so hard: On 
your staff, David Cole and our clerk, Kevin Doran, and on my 
staff, Krista Donohue, Myrece Johnson and Mindy Mannlein. This 
was a very challenging issue, and they did a great job on it.
    [Whereupon, at 4:46 p.m., the Subcommittee adjourned.]


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