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DEPARTMENT OF HEALTH AND HUMAN SERVICES

PUBLIC HEALTH SERVICE

FOOD AND DRUG ADMINISTRATION

CENTER FOR FOOD SAFETY AND APPLIED NUTRITION

DIETARY SUPPLEMENTS PUBLIC MEETING

PRE-MARKET NOTIFICATION PROGRAM FOR

NEW DIETARY INGREDIENTS

Monday, November 15, 2004

9:04 a.m.

Harvey W. Wiley Building

5100 Paint Branch Parkway

College Park, Maryland 20740
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C O N T E N T S

AGENDA ITEM PAGE

Welcome - Barbara Schneeman, Ph.D., Director,

Office of Nutritional Products, Labeling and

Dietary Supplements 3

Opening Remarks - Michael Landa, Deputy Director of

Regulatory Affairs, CFSAN 4

Meeting Introduction - Susan Walker, M.D.,

Director, Division of Dietary Supplement Programs 7

Moderator - Vasilios Frankos, Ph.D., Special

Assistant to Division Director, Division of Dietary

Supplement Programs 15

Facilitator - Kelly Williams-Randolph, D.V.M.,,

M.P.M., Consumer Safety Officer, Division of

Dietary Supplement Programs 17

Speaker Group 1

Michael McGuffin, President, American Herbal

Products Association 19

Annette Dickinson, Ph.D., President, Council for

Responsible Nutrition 39

David Seckman, Executive Director and CEO, National

Nutritional Foods Association 56

Speaker Group 2

Alan Feldstein, Counsel, and Richard Collins,

Principal, Collins, McDonald & Gann, P.C. 69

George A. Burdock, Ph.D., President, Burdock Group 81

A. Wes Siegner, Jr., Director, Hyman, Phelps &

McNamara, P.C. 96

Speaker Group 3

John L. Zenk, M.D., Chief Medical Officer,

Humanetics Corporation 116

Paul Bolar, Vice President, Regulatory and Legal

Affairs, Pharmavite 121

Willi Hunziker, D.V.M., MBA, CEO, Hunziker

Consulting 132

Closing Remarks - Vasilios Frankos, Ph.D. 143

P R O C E E D I N G S

DR. SCHNEEMAN: Good morning. If I could

get everyone to please take their seats, I think

we'd like to get started. We know we have a full

program, and we want to give as much time as

possible for our presenters and commenters so that

FDA has an opportunity to hear what it is you have

to say.

My name is Barbara Schneeman. I'm the

Director of the Office of Nutritional Products,

Labeling and Dietary Supplements. That is one of

the offices in the Center for Food Safety and

Applied Nutrition, and we are definitely pleased to

welcome you out here to College Park for this

meeting on new dietary ingredients.

As the meeting has been set up, FDA is

here to listen. We'll be gathering comments and

analyzing those over the next few weeks, and we

know that many of you also plan to submit written

comments, and we're looking forward to those

written comments as well.

Without further, I want to introduce

someone from the Center Director's office, who is

also relatively new to our office, Mike Landa, who

has been with FDA for quite a number of years but

has just recently taken the position of Deputy

Director for Regulatory Affairs in the Center for

Food Safety and Applied Nutrition. And so I'd like

to ask Mike to make a few opening comments.

Thank you.

MR. LANDA: Thank you. Thanks, Barbara.

First, let me welcome everyone. Thank you

for coming today to share your views with us. We

hope and expect this meeting will be instructive

for us, but let me add we don't anticipate that it

will be interactive; that is, what we expect it to

be is in what's called listening mode. The "we,"

as you will learn later this morning, will consist

of sort of a listening panel, including myself, Dr.

Schneeman, and several others.

With respect to the NDI notice itself, let

me just say we know there have been requests for an

extension of the comment period. We know it's a

long-ish notice, at least in terms of the number of

questions we've asked and areas we've asked for

comment on. We will be making a decision shortly

on the request for extension, and we'll let you

know once the decision has been made.

The purpose of the meeting today, as

Barbara mentioned, is for us to hear presentations

on the Pre-Market Notification Program for NDIs.

We're soliciting comments from all interested

persons, from consumers, from industry, from

others, concerning the content and requirements,

format requirements for notifications made under

the statute and in the agency's regulations. The

Federal Register notice announcing this meeting

sets out the questions we're most interested in

hearing your comments on in great detail. Copies

of the notice, by the way, are on the registration

table outside the auditorium.

We'll consider the presentations we hear

today and any comments we get to the docket in

deciding what our next step or steps will be. That

makes it, of course, extremely important that you

make sure to get your comments to the

docket--closer? Okay. Is that better? Is that

worse?

[Laughter.]

MR. LANDA: To briefly recap what I was

saying, but apparently no one heard, a couple of

points. One, we're going to be--"we" meaning the

agency folks here--we'll be in listening mode

today. We may ask clarifying questions of the

speakers, but we are here primarily to listen. In

that sense, we don't expect the meeting to be

interactive.

The second point I made was that we know

we have requests for extension of the comment

period in-house. The agency has not yet decided

whether to grant that request. We'll let you know

as soon as a decision is made.

The third point was that there are copies

of the notice available at the registration desk.

For those of you who don't have a copy with you,

perhaps during a break you can grab one out there.

We will, of course, take into accounts presentations we hear

today and any comments we received

on the docket in deciding what the next step or

steps will be in relation to new dietary ingredient

notifications. It makes it all the more important

that people make sure to get comments to the

docket. If they are sent elsewhere in the agency,

they may or may not work themselves to the docket,

so please send them there.

In just a minute, I'll turn the program

over to Dr. Susan Walker, who is in what we call

ONPLDS, with affection. Susan is Director of the

Division of Dietary Supplement Programs in ONPLDS.

But just before I turn the meeting over to her, I'd

like to publicly acknowledge the work of the

division in making this meeting happen. I think

ONPLDS certainly in general but the division in

particular really drove this meeting. I'd also

like to acknowledge the work of a couple of lawyers

in the Office of Chief Counsel who do foods work

for us: Irene Chen and Louisa Nickerson.

I think with that I'll just turn the

meeting over to Susan.

DR. WALKER: Thank you, Mike, and thank

you all very much for coming. We're truly glad

that you're all here today, and we've been looking

forward to this meeting. Let me see if I can

actually remember how to do this audiovisual piece.

Well, maybe we need an AV person. Oh,

there we go.

What I'm going to do is very briefly just

introduce the members of our panel today, and then

I'll give a very short background about how we got

to where we are today and why we're having this

meeting. And I'd actually like these folks to

stand up because they've done so much work in

getting us to this point. As Mike said, the

division is within the Office of Nutritional

Products, Labeling and Dietary Supplements. Our

Office Director, Dr. Barbara Schneeman, has been

extremely supportive and completely behind our

efforts, and we really thank her for that.

There are three branches in the division,

and we've got Dr. Bob Moore, Compliance. I think

you're all pretty familiar with Bob. And then Dr.

Linda Pellicore, Regulations and Review, and Linda

is really the person you have to get through if

you're going to get through the NDI program. So

I'd like to introduce Linda especially. And then

Dr. Jason Woo, who's our Clinical Team Leader.

Also we have Dr. Bill Frankos, Special Assistant

for Science Review, and Bill has recently come to

the agency, about a year ago, and he will be

moderating our session. And we'll talk more about

that in a bit.

Now, I'd like to acknowledge Dr. Kelly

Williams-Randolph, who was very instrumental in

setting up our meeting and making sure this

happened today.

Other members of our panel I'd like to

introduce: Mike Landa, who you just met; Barbara

Schneeman; and then Dr. Jeanne Rader, who is

Division Director for the Research and Applied

Technology Division; and then Dr. Alan Rulis, who

I'm sure you all know, who is currently the Senior

Advisor for Special Projects.

Now, in our new dietary ingredient

program, basically we have a variety of ingredients

that are notified to us, but this is our recent

history, which is predominantly botanicals and

botanically derived substances. So as we move

forward, it's important to remember this is a very

large part of what we're receiving in our

notification process, and this probably reflects

the fact that the complexity of this area really

drives some of the complexity of this entire

process. And we really have to be aware of these

substances as we move forward.

Now, in looking at our notification

program over the past few years, we've noticed that

there have been many more notifications and that

FDA has been objecting to a larger percentage of

these notifications. And looking at these, we

wanted to determine why is this happening, and

we've identified several factors. These are not

all the factors, but basically they're issues about

describing the new dietary ingredient. We need to

know what it is, and that actually sounds like a

very simple question, but it's a very complex

issue, particularly with botanicals.

We need to understand how and why it's

eligible to be a new dietary ingredient. We need

to understand what's an adequate amount of safety

information for the statutory bar in the law which

is establishing reasonable expectation of safety.

And then we've noticed there's other necessary

information that's frequently not there, just

general identifying information.

All of these are in dockets and they're

publicly available. Anybody can go in there, can

see all the notifications and see all the responses

from FDA.

So this is the history in the past ten

years. The notifications, obviously we're getting

more and more, and there's a higher and higher

objection rate. Some folks have pointed out that

it's likely that there are notifications in here

that may not be new dietary ingredients.

So what's really the key to the issue

today? It can be summarized in two slides that I'm

going to put up here. And this is the discussion

we really need to have over the next few weeks and

months.

The first piece is when is a substance an

eligible dietary ingredient under the statute,

under 201(ff), which has three sections, so it's

going to be very important to look at the basic

eligibility of a substance to be a dietary

ingredient.

So once this gate has been opened and gone

through, the next question is: Was the dietary

ingredient marketed in the U.S. prior to October

15, 1994? Because this is the actual statutory

definition of a new dietary ingredient in DSHEA,

and there are really only two answers. It's yes or

no. If it was not, then that substance is a new

dietary ingredient. If it was, then it's not a new

dietary ingredient.

The ramifications of this are large

because if you're a new dietary ingredient, not all

new dietary ingredients have to notify. A subset

of new dietary ingredients has to notify. So the

next question that's going to be very important is:

What is the group of substances that does not have

to notify? The third important question is: For

those that do have to notify, how do we fulfill

both parts of the notification requirement such

that we don't reach a status where that product is

adulterated? Because if there exists a history of

use or other evidence of safety, basically

establishing this reasonable expectation of safety

and FDA has been notified, then that's a lawfully

marketed product. If either of these is not met,

that product on its face is adulterated.

So the scope of this meeting clearly is to

discuss and receive comments on the status of

substances as new dietary ingredients; questions

about the chemical identity of a new dietary

ingredient; when and under what circumstances does

an ingredient that may have been available prior to

1994, is there a point at which it becomes new

because it's been transformed, there's been a

chemical alteration, there's been a different

extraction process? We've really got to develop an

understanding of what "marketed prior to 1994"

really means in terms of safety because we really

have to bring this all back to safety. The intent

of that section of DSHEA I would imagine--this is

me speaking personally, but it's the safety

gatekeeper. And if we look at 201(ff), the

identity section, and we look at 413, the new

dietary ingredients section, those two pieces taken

together are a very powerful safety tool.

So we need to look at the standard for

establishing a reasonable expectation of safety,

what type of information should be provided. We

need to look at some of the definitions for new

dietary ingredients. And when we look at all this,

as we said in the notice, we'll determine if

there's a need for guidance or amending the

regulations.

So in order to proceed with this actually

complicated task, we're having this public meeting

today to get started. We'll receive the comments

to the docket. We'll look at those and then

determine next steps. And for today's meeting, I'd

like to actually introduce Dr. Bill Frankos, who's

going to serve as our moderator. Bill is a Special

Assistant for Science Review within the division,

and he received his Ph.D. in pharmacology and

toxicology from the University of Maryland Pharmacy

School. He has over 30 years' experience in the

toxicological and pharmacological evaluation of

data used to assess the safety of nutritional

supplements, foods and food additives, drugs,

medical devices, cosmetics, pesticides, and

environmental and occupational exposures. And

prior to joining FDA, Bill was a principal in

Environ Corporation and Associate Director, Life

Sciences Division, at Clement Associates.

Previous to joining the private sector, he

was with us in FDA in the Office of the Commissioner as a

senior toxicologist, and previous to

that at the Office of Food Additive Safety, I

believe. So Bill obviously has a lot of

experience. He's going to be very helpful in

moving this process along, and I'd like to

introduce him today as moderator for our session.

Thank you.

DR. FRANKOS: Thank you. I'm quite

excited at the prospect of starting to deal with

some of the issues that have been presented in the

Federal Register notice. The list of questions

that you've all seen is a list that was developed

after the whole division went back and carefully

looked at the process of NDI review and the

problems that occurred. We felt that there were so

many issues that we needed to deal with that we

needed to open this up to the public, get input,