1

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
2

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,

and start a process that is certainly going to take

several months, and we feel that it needs to be a

public process. This meeting is the first of what

I think will be other meetings that may have to

occur in order to bring this together.

The panel that Susan introduced is here to

really listen, but if clarification is needed, they

certainly will ask questions. The ground rules for

the questioning is that we will only be asking

questions that are clarifying questions.

Now, if any members of the audience have a

specific question, a clarifying question they would

like to ask, if you come to one of these mikes here

and introduce yourselves, we can recognize you.

But I would like those questions to be clarifying

questions, not going into areas that have not been

addressed by the speakers.

I'd like to introduce Kelly

Williams-Randolph. She's been doing a great job

coordinating this notice, and she wants to go

through a little bit of the housekeeping, and then

after that we'll start with the speakers. Thank

you.

DR. WILLIAMS-RANDOLPH: Thanks, Bill.

Good morning. I'd like to start off with a welcome

to the members of the FDA panel, the folks from

industry, consumers, health professionals, and

everybody that's here in the audience. I'd like to

go over some meeting logistics with you, starting

with today's agenda.

This morning we will spend with

introductory remarks and one speaker group session.

There will be a morning break at 10:30 a.m. for 15

minutes, and then another speaker group session.

After the second speaker group session, we will

have another 15-minute break, scheduled for 11:45

a.m., and then have our final speaker group

session. Bill Frankos will then give closing

remarks.

In addition, I would also like to go over

the speaker group session presentation time limits

and time limits for clarification questions from

FDA panel and audience members. Each speaker will

have 15 minutes to present, with a five-minute

follow-up period for clarification questions

regarding the presentation. We will be using a

color card timing formula for keeping speaker

presentations on schedule. A green card will

signal the speaker that they have five remaining

minutes. A yellow card will indicate the speaker

has one remaining minute. And the red card will

indicate that the speaker should finish his or her

sentence.

In closing, you can find bathrooms located

midway between the front entrance of the building

and the registration tables. Signs are also posted

indicating the location of the restrooms, and on

the back of your agendas you'll find a floor plan.

Thank you, and I hope you will find today

useful. Now I'll give the floor back to Bill.

DR. FRANKOS: Thank you.

Our first speaker will be Michael

McGuffin, who is president of the American Herbal

Products Association. Michael, can you come up?

MR. McGUFFIN: Thanks, Bill. How do I get

to my presentation here?

[Pause.]

MR. McGUFFIN: Good morning. It's a

pleasure to be here, and I appreciate the

opportunity to address you all. I really

appreciate the people from FDA inviting me.

I already tried to negotiate an extra five

minutes from Bill, so I hope we can tolerate. I've

got a pretty packed presentation here.

AHPA represents about 200 companies that

sell herbal products, almost exclusively as dietary

supplements, and my primary comments are going to

be the impact of this rule on herbal products.

AHPA will submit substantive comments to the

docket, and just for the record, we would really

appreciate those extra 60 days. This is a knotty

issue, as you all know, and anything you can do to

give us the time extension will be appreciated.

I'm going to just move into this in the

interest of trying to get through this in 15 or

maybe 18 minutes, and I want to start with the

definition if a dietary ingredient, specifically as

that applies to botanicals, and I'm emphasizing

here with these bold lines that there are really

two different classes of botanical ingredients:

the 321(ff)(1)(C), which is an herb or other

botanical, it's an unprocessed herbal ingredient;

and then (F) can be a concentrate, a metabolite, a

constituent, an extract, or a combination of any of

the above. And I think it's important to think of

these separately. Although much of the information

that's required for a new raw material herb or a

new constituent or concentrate or extract are the

same, there are some differences that I'm going to

point out that I think are important to keep in

mind.

I'll get back to this a little later, but

I want to look, too, at just an overview of what's

required in a new dietary ingredient notification.

If you go to 21 CFR 190.6, that's where the reg is

written, and I class five different pieces of

information that are required there if you break

down the various subparagraphs. And I don't need

to say much about the first or the last. Almost

everybody knows their name and address and

remembers to sign it. But each of these other

things needs some attention: the name of the

ingredient, which with an herb must include the

Latin name; a description of the supplement that

contains the ingredient, including, of course, the

level of use and conditions of use; and the big

deal, the thing that we're really after, the

evidence on which a reasonable expectation of

safety is based.

I want to point out something that's not

here. It does not specifically state in 190.6 that

you need to identify the dietary ingredient.

There's a requirement for a description of the

supplement. There is not a specified requirement

for a description of the ingredient. I'm going to

again come back to that later because it's

something that we need to pay attention to.

A quick review. As of last week, there

are 249 notices on the docket. Fifteen of these

are for dietary supplements. They don't belong

here. There should not be submissions for new

dietary supplements. It's not required. It

confuses the system. But where we end up was 194

unique dietary ingredient submissions. There are

also a number of duplicates, a few withdrawn, but

this 249 comes down to 194. And of those 194, I

get slightly different numbers than Susan did, I

think. I count 83 non-herbal dietary ingredients

and 111 herbal. And then the herbal breakdown into

that subparagraph (C), the unprocessed herbs, there

are 33 of those; herbal constituents, which is one

of the words used in subparagraph (F), there are 26

of those, and then there are 52 herbal extracts, or

concentrates or oils or things that aren't just the

herb but neither are they constituents.

I don't do as good a job of drawing these

pretty pictures as Susan also, but here's just a

pie graph of--again, you can see over half of these

are botanicals, and they're kind of split between

these three subclasses of botanicals.

Then here's the outcome, here's what

happens if you look at these different subclasses

with regard to the number of notifications, the

number that are filed. And "filed" is as close as

FDA gets to "accepted." It means they didn't

object to. It means they didn't send you back a

letter with the word "adulterated" in the letter.

So of the non-herbal ingredients, you can see 63

percent of those are being filed; 65 percent of the

herbal constituents; but the unprocessed herbs,

only one out of five is making it through the

process. And the extracts, it's a little greater

than one out of three. So there's clearly the

herbal constituents, things like sesamin from

sesame seed, vinpocetine, those are getting

through; whereas, the herbs themselves tend not to.

Now, my interest is herbs, so I'm, of

course, concerned about what is it that's making it

so that the herbs don't get through, and so I've

looked at why FDA refuses to file so many of these.

Some of the issues are very specific to

herbs: plant part not named. Again, though, 190.6

does not specify tell us the part of the plant.

One of the suggestions that AHPA will make, 190.6

should specify name the part of the plant if your

ingredient is a botanical. It's obvious. You

don't have an ingredient that's a botanical without

also naming the part. But it's not stated. Some

companies miss that, and we'd like to help them

address that. This No. 247, that's a mushroom, and

FDA said we don't know what part of the mushroom.

So those were both objected to or rejected.

There's confused nomenclature in the last one

filed, this plum extract, where the filing company

said we're not sure if it's Terminalia ferdinandiana or

lapides. FDA said, well, if you don't

know, then we don't know. It turns out those are

two different names for the same plant. They

should have called me and I could have helped them

with that. But, nonetheless, that kind of

confusion gets an objection notice. Or in the case

of freeze-dried kimchi--I love it. Somebody wants

to sell us freeze-dried kimchi, but they didn't

tell us that it was Brassica, so FDA said we don't

know what to do with that.

Many of the other reasons that FDA objects

to herbal filings, though, are the same that they

object to the non-herbal filings, and Susan pointed

out some of these. I've quoted from some specific

notices. "It is unclear...whether the test

substances used in the referenced studies are

qualitatively or quantitatively similar to" to your

new dietary ingredient. So somebody says I want my

ganiderma product to come to market, and here's a

whole lot of information about ganiderma extract,

but they don't clarify that it's, in fact, their

ganiderma extract. FDA says we don't have any

information that's a basis for knowing that your

ingredient is safe. I've seen that one over and

over and over. And then as Susan also mentioned,

inadequate information to clearly identify the

ingredient.

There have been other issues. Things have

been rejected just because they're frank toxins,

things like extract of oleander--thank you for

rejecting that one--pokeweed lectins, illegal

substances like GBL, and then sometimes because the

described dietary supplement is in a form that

doesn't fit the definition. My favorite one is an

herbal eyepatch which FDA wisely chose to reject.

With regard to this second point here,

though, the inadequate information presented to

identify the ingredient, I want to repeat, 190.6

does not specifically state identify the

ingredient. Again, it's an obvious recommendation

that AHPA will make that 190.6 should, in fact,

state that the identification of the ingredient

must be included.

The next two slides are looking at the

requirements set in 190.6 and breaking it down into

the identity, the description of the supplement in

which the product goes, and the evidence of safety.

And I have two slides here. This one is for

subparagraph (C), which is herb or other botanical.

And my position is that all you need to identify an

herb is the name of the herb and the part. You

don't need chemistry. You don't need anything that

goes further than that because peppermint leaf is

peppermint leaf if that's what I'm selling. Now,

that's an old ingredient, but just to make the

impression. Whereas, if it's anything in (F), if

it's an extract, if it's a concentrate, clearly you

need a lot more information, and all of these

points are actually from a document that AHPA

produced a couple of years ago, a guidance on

manufacturing of extracts that I will leave a copy

into the record here.

You have to disclose the solvents, the

ratios, all other ingredients. You need to

describe the process. Is it a liquid product or a

solid product? And then these bracketed items--the

markers, characterization, and purity--are often

but not always relevant. It's a much more dense

process once it moves from an unprocessed herb.

Whereas the dietary supplement description, it's

not any different for the subclass (F), which are

the extracts and concentrates, than it is for the

raw herbs. And the only difference that I have on

evidence is that the evidence of the herb would be

history of use and other evidence, whereas the

extract you can argue that the history of use of

similar dietary ingredients, like the raw herb, has

relevance.

I also want to point out that in the

description I've made a pointed statement that

there is not a requirement to identify the other

dietary ingredients. Most companies want to say,

"My new dietary ingredient is this ingredient, and

the use is 50 milligrams in a dietary supplement."

Most of those submissions have gone through. Most

recently, FDA in one letter said, well, we don't

know what the other ingredients are, so how would

we know that the supplement is safe? We want to

argue against FDA taking that any further.

Old versus new, again, the class (C) and

the class (F) are different. With regard to just

herbs--roots and leaves and seeds and things that

are just parts of plants--AHPA in 1995 sent out a

call to industry to identify old herbal dietary

ingredients. The next year we submitted a list of

over 1,600 herbs to FDA, identified those as

believed to be in commerce prior to the date, and

in 2000 we published "Herbs of Commerce," 2nd

edition. We added about 400 other plants in the

meantime, numerous Chinese plants, numerous

Ayurvedic plants, fungi, algaes. It's a very

thorough document.

We also disclaimed it in two different

ways. The first disclaimer says just because it's

here doesn't mean it was marketed prior to the

date. And the second one says just because it's

not doesn't mean it wasn't.

Our thinking here was we accepted

submissions honorably. We believed that they were

submitted honorably. But we didn't go out and

double-check or prove that chamomile had, in fact,

been marketed prior to the date. Nonetheless, it

is AHPA's position that even though "Herbs of

Commerce" may not be authoritative, this disclaimer

should not be read as a reason to abandon our text.

It should not be seen as assuming that there is no

relationship whatsoever between the listing of an

herb in "Herbs of Commerce" and its marketing prior

to the date. That is what we asked people to tell

us. We think it has relevance. We think it does

create a presumption of presence in the

marketplace.

If the agency wants to take it further and

get to something like an authoritative reference,

AHPA is uniquely positioned. We would be happy to

discuss being actively involved in a process or

being contracted for a process to do an old dietary

ingredient substantiation for botanicals. We know

a lot about this issue.

Then with regard to old herb extracts--and

by extracts I mean everything in (F)--we didn't go

out and say tell us all of the extracts. We didn't

ask that kind of thing a decade ago. But there are

standard accepted extract forms: decoctions,

liquid extracts, dry extracts, tinctures. There

are long accepted food-grade solvents, and I've

listed numerous of those here; established

extraction processes. And there is a reason to

think that all of the common herbs were

manufactured by all of these common processes with

all of these common solvents. And if I've got a

32-percent ethanol chamomile, I shouldn't have to

prove that a 32-percent ethanolic extract of

chamomile was marketed because it's in the range of

reasonableness that it was marketed.

I also want to point out there are other

solvents that I didn't list here and other

extraction processes that had come into the

marketplace, not as extensively, things like hexane

and acetone, super-critical gases and

super-critical extraction.

Let me move then to suggestions, and the

first few here I'm just repeating, modifications to

190.6, and an assumption that "Herbs of Commerce"

herbs are "old," as are extracts by common

processes. I'm repeating, we'd really like to see

the agency just not accept filings for new dietary

supplements. Those are wrong. They create a

bizarre record where now there's a document that

says that licorice root and ginseng aren't allowed

to be sold because somebody submitted--actually,

they don't say that. They say your product may be

adulterated which contains this ingredient. There

are these lawyers in California that will make lots

out of that. We'd really like to see that stop.

We'd also like to see the agency refuse

filings for obvious old dietary ingredients, and

I've listed a number of them here.

With regard to enforcement, I think it's

obvious that enforcement needs to be prioritized

based on safety concerns, and one point in passing,

Susan mentioned the food exemption if it's present

in the food supply and not chemically altered, and

we want to make sure that the agency thinks what we

think, that international food supply counts

against that clause.

We'd like to see restraint from overly

broad or maybe I mean overly narrow interpretations, but

I've given some examples. For an

herb, for the agency to say you didn't give us

specifications on purity, that's a GMP issue, not a

new dietary ingredient issue. Compositional

analysis, I've made my pitch that I don't believe

compositional analysis of chamomile flowers is

warranted; whereas, chamomile extract in a new

solvent and a new extraction method may be. And,

also, this issue about I really strongly argue

against any requirement that the only way I can get

my new dietary ingredient approved is to disclose

every other ingredient that it may ever be marketed

with. That puts an unfair burden on every product

that has a single new dietary ingredient versus the

whole world of products that have only old dietary

ingredients. And we would oppose that.

There's a tendency for companies to

resubmit when they change the dose and that I think

is wise, but we'd like some guidance on that.

There ought to be minimum criteria for FDA to

review a submission. I'm not sure what those are,

but I'm sure that they do include all of the

administrative parts of 190.6, if it's not in

triplicate, if it's not signed, if it didn't

disclose the plant part, those kinds of what I

called here administrative or technical issues.

And then, of course, the identity of the new

dietary ingredient, if it's not identified I don't

think the agency should go through that whole

process of sending it back saying your ingredient

is adulterated. I think the agency ought to not

accept it, and I know that the record shows the

agency does go back and ask for more information.

We encourage that. We'd love to see more timely

access at FDA's docket. I notice today it's really

up to date. We appreciate that. But I also know

that you pushed a bunch of stuff through in the

last few weeks. We appreciate that.

In closing, AHPA and another organization,

NPI, we're in the middle of creating a searchable

database. We're going to make it so that you can

go in and search for astaxanthin or licorice or

whatever and find every submission that mentioned

that. We'll also search--we'll provide a summary

outcome statement of what happened, was it filed or

was it objected to.

A couple things that I didn't get on here,

we'd love to see an opportunity to withdraw that's

very similar to what happens in a GRAS notice.

There have been three or four withdrawals, one of

which the agency refused to allow. We think that

it ought to have rules that are a very similar to

the GRAS withdrawal process.

We need to see consistency. I know that

FDA intends to be consistent, but I can find

examples. Astaxanthin, there have been five

submissions--the three that were submitted prior to

2002, those were accepted; the two that were

submitted this summer were not. I don't know that

they were markedly different, those ingredients.

If they were not, we'd need to understand did

something change in the policy, because it needs to

be very consistent, and I think you understand

that.

I know that there's a new emphasis now on

the agency saying exactly which subparagraph of a

dietary ingredient is it in. I think that's a good

question. But I also don't think that when

the--that's not a reason to object to a filing just

because somebody didn't tell you that they believe

that deer antler is in subparagraph (E) or that

carnitine is also in subparagraph (E).

Maybe my last statement. The industry

needs to see the whole process of the new dietary

ingredient notification as a gate through which new

ingredients can come, not as a barrier that refuses

to allow new ingredients into the marketplace. And

we really look forward to working with the agency.

Guidance is definitely needed.

One point I forgot to make, some of these

submissions are just a mess, and that needs to be

acknowledged. Some of them don't deserve to be

filed. They're embarrassingly narrow in the

information that's submitted, and I think I can

close it there.

DR. FRANKOS: Thank you, Mike.

Any questions? Linda.

PARTICIPANT: Mike, I wonder if you could

tell us what NPI stands for on that last slide.

MR. McGUFFIN: You know, on the Metro on

the way in, I thought--I'm fairly certain it's the

Natural Products Institute. I think that's what it

is. They're a publication company in our trade who

does a lot of work in communication, and we're

partnering with them to put this thing together.

DR. FRANKOS: Mike?

PARTICIPANT: When you compiled "Herbs for

Commerce," did you ask for documentation?

MR. McGUFFIN: We did not. We just asked

for people to tell us, some companies provided--oh,

sorry. Yes, the question was, when we compiled the

information for "Herbs of Commerce," did we ask for

documentation? No, we did not. We simply asked

for people to inform us what they were selling.

Some companies provided us with notarized

statements. Some companies provided us with copies

of their catalogues or advertising. And, also, I'm

kind of a pack rat. I've got a whole box of

catalogues from '93 and prior.

DR. FRANKOS: I have one question. When

you said that whole herbs history of use is

relevant for evaluating the safety of extracts, I

was curious how you would use that data when there

are so many forms of extracts.

MR. McGUFFIN: I'll tell you what. The

question is: How would I use information about

whole herbs to evaluate the safety of an extract of

that whole herb? What I have done, Bill, is I've

looked at all 249 of these. What I haven't done is

file one. So I'm not sure. I think some of the

toxicologists that are going to talk to us might

have more relevant responses to that because I

think the way that you would use it, though, is the

more that you could show that your extract had a

chemical characteristic that was similar to the raw

botanical, then I think you're going to be able to

use that as information that suggests that we've

been using that for some number of years or

generations.

DR. FRANKOS: Thank you.

Yes, Jason?

PARTICIPANT: [inaudible, off microphone]

you're specifying international use as a food, not

as a medicine or--

MR. McGUFFIN: Correct. Yes, the question

is with regard to my call for international use,

there's that one--I forget. What is it? I forget.

The one that says that you're not required to

submit a new dietary ingredient that is present in

the food supply in a form that's not chemically

altered. That's exactly the part I'm saying. If

it's present in the food supply in South Africa,

that's okay; it doesn't have to have been present

in the food supply in South Dakota.

DR. FRANKOS: Okay. Thank you.

MR. McGUFFIN: Thank you.

Our next speaker is Annette Dickinson.

She's president of the Council for Responsible

Nutrition. Annette?

DR. DICKINSON: Good morning, and thanks

to FDA for the opportunity to be here and for

beginning this initiative.

The Council for Responsible Nutrition is

one of the leading trade associations for the

dietary supplement industry. Our members include

mainstream manufacturers of dietary ingredients

themselves, as well as manufacturers of both

national brand names and private label dietary

supplements. And we also have a number of members

whose interest is international in scope.

We want to congratulate FDA for the three

documents that were issued in the last few months,

all of which are intended to move the agency and

the industry toward full implementation of DSHEA.

We don't believe anything is more important to

solidifying the confidence in dietary supplements

and the confidence both on the part of the

regulators and on the part of Congress as well as

consumers than moving to full implementation, and

we congratulate the agency over the past couple of

years for a number of initiatives toward full

implementation and enforcement, which we believe is

necessary.

At the same time, we are concerned that

that enforcement and implementation be consistent

with the intent of DSHEA, and I know that the staff

at FDA is determined to make that happen. The

purpose of DSHEA was to ensure consumer access to a

wide variety of products and also to provide

consumers with more information about the uses of

those products. The intent of DSHEA was to affirm

the safety of a broad array, a very broad array of

existing dietary ingredients and establish a

notification process for new ingredients that was

distinct from, deliberately distinct from and

intended to be less burdensome than the food

additive approach that the agency was using at the

time.

We have also submitted in conjunction with

this meeting a statement prepared by our legal

counsel, Peter Barton Hutt, which was prepared at

the request of both CRN and one of our sister

associations, CHPA, the Consumer Healthcare

Products Association, which presents his legal view

of the status of dietary ingredients and new

dietary ingredients.

The definition of dietary ingredients in

the act is extremely broad and was meant to be

broad, and any discussion of new dietary

ingredients we believe must begin with a discussion

of what fits within the rubric of dietary

ingredients in the first place.

While we agree that safety is an important

factor in determining whether an ingredient may be

marketed and also an important factor in

determining whether an NDI notification is adequate

for its purpose, safety is not necessarily a factor

in defining the category per se, that is, the

category of dietary ingredients. And I'll offer a

couple of examples of why that must be the case.

One of the categories of dietary

ingredients is minerals. Minerals is an extremely

broad category. Minerals typically occur

naturally, not as elements but as various

compounds. Calcium, for example, is an essential

nutrient, an essential mineral which occurs

naturally as calcium carbonate and some other

forms. However, it has been used for many years in

dietary supplements and is grandfathered in other

forms that actually do not occur naturally, such as

calcium citrate. This illustrates a point, which

is that we do not believe the inclusion of a

mineral in this category depends on it being in a

naturally occurring form. In addition, we do not

believe that inclusion in the mineral category is

limited to nutrients that are essential. Calcium

is certainly an essential mineral. But there are

many others, such as tin, vanadium, silicon, and

boron, that have for many years been present in

very popular national and private brands of

multivitamin/multimineral formulations, and we

consider all of these to be grandfathered

ingredients.

Likewise, the area of botanicals is an

extremely broad category. It includes common and

generally safe ingredients such as ginseng, garlic,

and ginkgo. It also includes ingredients about

which some safety concerns have been raised, such

as comfrey, chapparal, and kava. The fact that

there may be safety concerns that need to be

addressed does not mean that the ingredient doesn't

fall definitionally into the category. It is an

issue that needs to be dealt with separately, and

we urge FDA in its proceedings to keep these two

sides of the issue separate, that is, what falls

within the category of the definition and where

safety issues may arise.

Another category of ingredients in DSHEA

is dietary substances. We believe dietary

substances is an extraordinarily broad category and

must be accepted as broad. There is a colloquy

that we refer FDA to in our written comments that

occurred during the passage of NLEA, not DSHEA,

back in 1990 and that focuses on what might qualify

as a nutritional substance. We believe that all of

the substances mentioned in that colloquy, which

include enzymes, coenzyme Q-10, evening primrose

oil, and various other substances, certainly fall

within this category of dietary substances.

The next question has to do with if

something is an ingredient, is it a grandfathered

ingredient? In order to be grandfathered, there

are three criteria that must be met: the

ingredient must have been on the market in a

dietary supplement; it must have been on the market

in the U.S.; and it must have been on the market

prior to October 15, 1994.

The vast majority of dietary supplements

on the market currently contain grandfathered

ingredients, and there is no suggestion in the law

itself that there are any circumstances under which

an old ingredient would become a new ingredient.

This is something that is going to require

considerable discussion within FDA, within our

various associations, and among us all during this

period of comment that we have available to us. We

have discovered in our various conference calls

leading up to this meeting that we don't

necessarily have agreement within our association

about the breadth of what might be grandfathered

and whether there are conditions under which an old

ingredient might become a new ingredient. So this

will be, I am sure, a fertile field for further

discussion as we move forward here, and it's

another reason why we did join with AHPA and NNFA

and other associations in requesting an extension

of the comment period.

Another issue I'd like to raise is that in

some of FDA's recent enforcement actions, warning

letters, FDA has taken the position that certain

ingredients were not grandfathered because they

were not legally marketed before 1994. The term

"legally marketed" does not appear in DSHEA, and we

do not believe that necessarily legal marketing is

a criteria for what is grandfathered, and I want to

give you three examples of why that might be the

case.

The first two involve the essential trace

minerals selenium and chromium. On several

occasions during the decades prior to the passage

of DSHEA, FDA took the position that selenium and

chromium were not formally recognized as food

additives and were not formally approved as GRAS

substances and, therefore, were not, technically

speaking, legally marketed as dietary supplement

ingredients. Nevertheless, as we know, these

ingredients were commonly marketed in dietary

supplements prior to DSHEA and are still commonly

marketed in dietary supplements. And, in fact, FDA

has now established an RDI for both of these

minerals. Therefore, it cannot be a criterion

chromium and selenium being legitimate ingredients

of dietary supplements and being grandfathered that

FDA should have viewed them to be legally marketed

prior to DSHEA.

Another example is amino acids. Under FDA

food additive regulations, there were very limited

conditions under which amino acids could be added

to conventional foods, and technically FDA viewed

them as not being legal ingredients in dietary

supplements. Nevertheless, they were widely

markets as dietary supplements and still are and,

in fact, now have their own subcategory in the

definition of dietary supplements. Therefore, we

believe this is another illustration that

grandfathering cannot be denied based on a narrow

interpretation of whether an ingredient was legally

marketed prior to DSHEA.

In these comments today, CRN is going to

focus really on some very broad issues and not

delve into most of the detailed questions that FDA

presented in the Federal Register notice, although

we will certainly do that before the end of this

process.

In describing the information that should

be provided in a new ingredient notification, we're

going to skip over most of those questions, but we

are going to indicate that one of the concerns that

has come through loud and clear from our members is

that FDA should be aware that much of the information they

have requested, particularly regarding

processing, may be proprietary information. And as

we move forward, there will be a need to assure

that proprietary information can be protected.

In addition to requesting information

about the dietary ingredient, FDA requests certain

information regarding the dietary supplement, and

we believe this is entirely appropriate. DSHEA

refers to the new ingredient notification needing

to provide information on the basis of which the

dietary supplement itself can be expected to be

safe. However, as one small part of this section,

FDA asks the question whether a label should be

required to be submitted at this point. We would

simply note that in many cases the dietary

ingredient notification is filed by the ingredient

supplier or by a manufacturer during a pre-launch

phase of development of the product, and a label

simply may not be available at that point, so we do

not believe submission of a label should be a

critical part of that process.

Really the core question facing all of us

here and the core question that will need to be

resolved before the end of this process is: What

type of information should be included in an NDI

notification in order to establish a reasonable

expectation of safety? FDA has outlined a number

of questions that are very good questions that

should be considered by every company submitting an

NDI notification. However, we do not believe that

the questions posed should be viewed as an absolute

requirement or an outline for the information that

must be submitted in a notification. We believe it

really goes beyond what we see as the intent of

DSHEA in establishing this notification process.

In particular, members of our association

who are very familiar with food additive petitions

look at this list of questions and they see

something very similar to a "Red Book" list of what

must be submitted for a food additive. Members of

our association who are on the pharmaceutical side

look at this list and they see great similarity to

what might be required for an NDA filing. And we

do not believe either the food additive model or

the NDA model was intended to be the basis for

describing what needs to be included in a new

ingredient notification.

We would request, as we move forward with

defining what does need to be included, that FDA

express its openness to consultation with companies

who are considering an NDI notification in order to

help them direct their information in such a way

that the NDI notification will include the

information FDA expects to see and that the company

can improve its chances of having the NDI

notification accepted.

Some FDA personnel in the last little

while here, the last month or so, have made

presentations in which they have indicated that

they really see no difference in the standard of

safety that is described in DSHEA and the standard

of safety that is expressed for food additives. We

cannot agree with this assumption because we

believe that when Congress wrote DSHEA, it

certainly was aware of the standards of safety that

are set for food additives, and it chose to

establish a different statement. It indicated that

new ingredients should be reasonably expected to be

safe. Furthermore, in terms of the process, it did

not permit or require FDA to actually approve an

NDI; that is, there is no formal approval of the

NDI from FDA once the document is submitted.

What is required is that the manufacturer

or distributor should have in its holdings and

should submit to FDA sufficient information to

support the manufacturer's determination that the

ingredient and the product are reasonably expected

to be safe. We believe those are significant

differences from the food additive model and that

FDA should clearly incorporate those aspects into

their consideration.

There are other models than the classic

food additive model that we believe bear

consideration here as FDA looks for a model on

which to base the new ingredient notifications. In

particular, the GRAS self-determination process we

believe is an extremely effective and flexible

process. I don't know what's happening to my--it

looks fine right here on this screen. I don't know

what's happening up there. We believe the GRAS

self-determination process is an example of a

highly effective and flexible process which allows

manufacturers to make a determination of safety,

relying heavily on the input of experts or

committees of experts to help them make that

determination and to help respond to any questions

FDA may have.

There are other programs that might be

considered. For example, the EPA has a program

that it puts new chemicals through when it approves

new chemicals for introduction into the

environment, which involves a functional analysis,

a functional safety analysis--a structure activity

analysis, is what I'm trying to say, of the

compound as it relates to other compounds in the

same class. And we think this might have some

relevance to FDA's review as it pertains to new

ingredients that are single chemicals.

Likewise, Canada's Natural Health Products

Directorate has recently--is just this year

implementing a whole new program of review,

including protocols for safety evaluation of

natural health products, and we believe there may

be some elements of this that would be relevant to

this program.

FDA itself has adopted on occasion other

methods than the food additive method for looking

at safety of various ingredients in evaluating

health claims for psyllium and stanol and sterol

esters. FDA found that those ingredients did not

have official regulatory status at the time the

health claim was evaluated and required the

companies to submit certain additional information

on the safety of those ingredients, and we think

the nature of those submissions may be relevant to

this process.

Finally, FDA's guidance on new plant

varieties produced through biotechnology also

relies heavily on manufacturer determination of

safety and on comparability to existing plant

varieties with a minimal or no reliance on actual

clinical testing to go along with that.

FDA addresses the need for definition of

certain other terms that appear in DSHEA, and we

will reiterate here the same point that we made

with regard to dietary ingredients. All of the

terms should be understood broadly and literally,

terms such as extract, constituent, metabolite, and

the issues having to do with safety or other

considerations that arise because of the breadth of

some of those definitions we believe should be

dealt with directly and separately and not used as

reasons for restricting the definition itself.

We do endorse the seven recommendations

FDA made in the Federal Register notice for

improving the format and content of notifications,

and we will be addressing those in more detail in

further iterations of our comments on this issue.

Finally, we congratulate FDA for

undertaking this initiative and also for fully

involving all stakeholders, which we believe is

critical to the successful outcome of this

discussion. And we look forward to future

opportunities to work with FDA to improve the

confidence with which consumers, regulators, and

legislators can view this product category.

Thank you very much for this opportunity.

[Applause.]

DR. FRANKOS: Any questions?

[No response.]

DR. FRANKOS: Annette, I have one

question. With respect to using a GRAS

self-determination process, how would you see that

fitting into the NDI notification process?

DR. DICKINSON: I would see that fitting

in in a way similar to the current GRAS

self-determination process where a company may

submit their determination to FDA and request

listing of that GRAS notification. In that process

also, FDA does not formally approve the GRAS

ingredient, but simply arrives at a point where it

has no further questions. But the company would

ahead of time do its analysis of the safety,

including relevant involvement of experts.

DR. FRANKOS: Thank you.

Okay. Our next speaker is David Seckman,

and he is Executive Director and CEO of the

National Nutritional Foods Association.

MR. SECKMAN: I'm David Seckman, Executive

Director and CEO of the National Nutritional Foods

Association. NNFA was founded in 1936 and is the

oldest and largest trade association in the natural

products industry. We represent the interests of

more than 8,000 retailers, manufacturers,

suppliers, and distributors of health foods,

dietary supplements, and related items. I

appreciate being able to submit this testimony in

response to the FDA's request for input on

pre-market notification for new dietary

ingredients. And I think I'm glad I didn't have

slides today.

[Laughter.]

MR. SECKMAN: Just kidding.

NNFA has consistently supported FDA's

ability and efforts to enforce the Dietary

Supplement Health and Education Act of 1994 and to

ensure that dietary supplements continue to be

safe. In fact, in May of 2002, we submitted

comments to FDA suggesting ways for FDA to enhance

the quality, utility, and clarity of the pre-market

notification requirements for a new dietary

ingredient under Section 413. We continue to

believe that FDA could use public comments on

Section 413 to provide the industry with much

needed guidance on NDI submissions. Of course, any

guidance will apply to any company putting dietary

ingredients on the market, whether they be the

manufacturers of finished products or raw

ingredient suppliers who need to guarantee safety

to their customers.

What everyone in the industry needs is

clear guidance. Specifically, NNFA believes that,

as written, Section 413 is unclear both as to when

a new dietary ingredient notification is required

and the type of information to be included if a

pre-market notification is filed. In light of

FDA's November 4th publication of its major

initiatives for dietary supplements, NNFA

specifically urges FDA to use caution in enforcing

on NDI issues before it offers clarification to

industry as to when a pre-market submission is

required. Although NNFA will be commenting in more

detail later, the following are a couple of key

issues and comments that we think that need to be

addressed in the guidance.

Our first issue concerns the not

chemically altered exemption. According to Section

413, a dietary supplement containing an NDI is not

adulterated if the dietary supplement contains only

dietary ingredients which have been presented in

the food supply as an article used for food in the

form in which the food has not been chemically

altered. Thus, the chemically unaltered

ingredients from the food supply does not require

NDI filings to be made before being used in a

dietary supplement.

The legislative history of DSHEA offers a

small bit of clarification of what is meant by

chemically altered, and I quote: "The term

`chemically altered' does not include the following

physical modifications: minor loss of volatile

components, dehydration, lyophilization, milling,

tincture or solution in water, slurry powder, or

solid in suspension." Clearly, many forms of

processing have been left off this list, and FDA

has not offered industry guidance of how to

determine whether a process would or would not be

considered chemically altered.

NNFA takes the position that a dietary

ingredient should fall within its not chemically

altered exemption as long as the resulting dietary

ingredient is found in nature. Supplements are a

subset of food. They need to be regulated

accordingly. If it can be shown that an ingredient

either is a single entity or complex, can be found

in our diets, and there is no evidence of ill

effects, that ingredient should be allowed for

sale. Moreover, FDA should not assume that changes

in the processing or formulation always result in a

change in the chemical structure that would require

an NDA filing. Such an interpretation is

consistent with the intent of Section 413 in that

it would require exempt entities which known safety

records based on food usage from the NDA pre-market

submission requirement.

Our next concern in regard to Section 413

is the lack of clarification as to whether

components of food, such as the lycopene found in

tomatoes are subject to the pre-market notification

requirement. NNFA takes the position that

components would also be subject to the not

chemically altered exemption in Section 413(a)(1);

thus, if the extraction method used to isolate

components does not results in the chemical

alteration of the component, the component should

be exempt from the NDA filing requirement.

Moreover, the 413 exemption should extend to the

components to the components that are chemically

altered during the extraction process but are in a

form that is found in nature. Such components,

again, have been proven safe within the food

supply.

NNFA's next concern is in regard to how

the NDI substance should be chemically identified,

an issue FDA raised in numerous questions about it

in the Federal Register notice. NNFA takes the

position that chemical identifications of a

substance must reflect the level of variation of

the substance that is found in nature. For

example, botanical ingredients vary in composition

depending on where in the world they are grown.

Certainly the agency would not require an NDI

notification for each region unless there are

significant differences that result in a safety

issue. In addition, other ingredients may vary as

percentage of certain confirmations. Again,

however, this level of differences should not

trigger the new NDI requirements as long as the

variation reflects that which is found in nature.

Next I would like to comment on the type

of information about a dietary supplement product

that should be included in the NDI notification.

NNFA has some specific concerns about conditions of

use and labeling as put forth by the FDA in its

notice. NNFA would like to point out that when the

agency raises such questions, it blurs the line

between an NDI and a dietary supplement product as

a whole. FDA should not be concerned with how an

ingredient was used unless it was previously used

as a drug, which raises other sections of DSHEA or

how it was labeled. This information does not go

to the safety of the dietary ingredient and should

not alter the review process as to whether a

specific dietary ingredient is safe for use.

My final comments have to do with

establishing a reasonable expectation of safety.

FDA raises the question of what quality and

quantity of data and information are needed to

establish a reasonable expectation of safety based

upon the history of use. NNFA takes the position

that FDA should establish clear parameters

regarding what kinds of evidence would sufficiently

demonstrate reasonable evidence of safety.

However, NNFA cautions that FDA's guidelines should

not be so rigid so as to establish inflexible

requirements. The kinds of data available for

dietary ingredients vary widely, from very long

documented history of use to clinical studies to

observational reviews. The kinds of data available

may also change over time. NNFA is concerned that

the NDA process, along with the FDA's recently

issued initiatives, does not become a mechanism to

stifle or halt NDI submissions by presenting an

almost insurmountable barrier for acceptance. To

adequately reflect this reality, FDA should

continuously exercise flexibility in the types of

evidence required, for example, where an NDI does

not have a long history of consumption by human,

such as novel extractions of grandfathered

botanicals. Moreover, an NDI that is an extract

from an old dietary ingredient and is significantly

similar to the old dietary ingredient might require

less safety data than a new one. To respond

otherwise would result in the stifling of research

and development for the use ingredients.

FDA also raises questions about what

quality and quantity of data and information are

needed and to establish a reasonable expectation of

safety based upon information other than a history

of use. Here, NNFA would simply like to point out

that while a certain amount of scientific evidence

is certainly necessary to establish safety, the

burden should not be so high as to mirror a drug

safety review. NNFA submits that information to

establish a reasonable expectation of safety should

suffice. This may include animal and in vitro

studies conducted in an appropriate model or other

test.

Finally, the FDA specifically questioned

what types of documentations are necessary to

establish that an ingredient was marketed in the

U.S. before October 15, 1994, and thus

grandfathered. NNFA and other industry groups in

1994 took the lead in developing lists that

reflected products marketed prior to that year.

Those lists have been relied on by industry, by

industry lawyers, consultants, and presumably even

the FDA. NNFA submits that they have achieved

authoritative status and should continue to be

available to be relied upon for confirming

grandfather status. I'd also like to point out

that if an ingredient does not appear on one of

these lists, it may also be grandfathered if there

is evidence of marketability prior to October 1994.

Examples of such evidence may include human

studies, product advertisement, product catalogues,

order forms, and invoices.

Again, in closing, I'd like to thank the

FDA for the opportunity to comment on the NDI

process.

DR. FRANKOS: Thank you.

Any questions? Jason?

PARTICIPANT: [inaudible, off microphone]

variation in nature. Does that mean just in one

species or parts or portions of the plant or

[inaudible]?

DR. FRANKOS: Can you repeat the question,

please? Or go to a mike, yes.

MR. SECKMAN: You want clarification of

what--

PARTICIPANT: Clarification to variation

in nature, extending to just the different growing

conditions you might find in botanicals, or

different portions of the plants being used?

MR. SECKMAN: Both.

DR. FRANKOS: Any other questions?

PARTICIPANT: How did you postulate human

studies that may have been done on an ingredient

prior to October of '94 would constitute reason for

those ingredients to be grandfathered in?

[inaudible] on ingredients never led to or related

to those ingredients being sold in the marketplace?

MR. SECKMAN: Did everybody hear the

question?

DR. FRANKOS: No. I think paraphrase it.

MR. SECKMAN: Studies done on humans

before 1994, is what your question really was, how

does it relate to the new dietary ingredients for

the new dietary ingredient requirements?

PARTICIPANT: Right. I asked [inaudible].

DR. FRANKOS: Mike, please.

PARTICIPANT: Okay. I asked you how is it

that you could postulate that human studies or

studies--you know, clinical trials perhaps, done

prior to October of '94 on certain dietary

supplements or ingredients should be equivalent to

those ingredients being grandfathered in if those

ingredients were never sold on the marketplace?

MR. SECKMAN: I mean, there are valid

studies that were done prior to. They just haven't

been used in the filing of the new dietary

ingredient. I think you can make a fair argument

to that sense and be able to file it based on that

information. I think that should be able to be

used.

PARTICIPANT: Will the person who just

asked the question identify himself, please?

MR. KALMAN: The person that asked the

question was Douglas Kalman from Miami Research

Associates.

DR. FRANKOS: Any other questions?

[No response.]

DR. FRANKOS: Okay. We're on time,

actually a little early. I think we could just go

right into a 15-minute break and then start again.

I would like to point out that the next speakers

can go to a breakout room during the break and

prepare their slides. There's a room set up. I

don't know what room it is, but it's next door to

the auditorium.

PARTICIPANT: 1A-001.

DR. FRANKOS: 1A-001.

[Recess.]

DR. FRANKOS: We're having some

audiovisual problems, so I'd like it if everybody

could come back together, we'll have Alan Feldstein

give an oral presentation, so he is the slides, and

so we can start, and hopefully they'll get the

audiovisual stuff together shortly.

And one other thing: There is overflow in

Room 1A-001, if there are not enough seats or if

anybody is feeling hot, there is a room that has

been set up, and there is an audiovisual connection

in that room as well. So there are also chairs

that are open down here at the bottom, up front.

I think we will start then with Alan

Feldstein. He is counsel with Collins, McDonald &

Gann. Alan, I think they're working there. Maybe

you could sit here.

MR. FELDSTEIN: Sure, that would be fine.

Good morning. Can everybody hear me okay?

Great. Collins, McDonald & Gann is a law firm

located in the State of New York that represents

manufacturers, distributors, marketers, and

individuals in the sports and fitness supplement

industry. Again, my name is Alan Feldstein, and I

am your slides today. And with me is my colleague

Richard Collins, principal of the firm; I'm of

counsel of the firm.

Again, as everyone has said, we appreciate

the opportunity to share our thoughts, and we

welcome the opportunity to present our comments on

this matter, which is of great importance not only

to our clients but to the segment of the industry

we represent as a whole.

We have reviewed the Federal Register