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DEPARTMENT OF HEALTH AND HUMAN SERVICES

FOOD AND DRUG ADMINISTRATION

CENTER FOR FOOD SAFETY AND APPLIED NUTRITION

FOOD ADVISORY COMMITTEE MEETING

Advice on CFSAN'S Draft Report:

Approaches to Establish Thresholds for Major Food Allergens and for Gluten in Food

Wednesday, July 13, 2005

8:30 A.M. to 5:50 P.M.

Greenbelt Marriott

6400 Ivy Lane

Grand Ballroom

Greenbelt, Maryland 20770

P A R T I C I P A N T S

FOOD ADVISORY COMMITTEE STANDING MEMBERS:

Richard A. Durst, Ph.D. - Acting Chairman

Jeffrey A. Barach, Ph.D. (Industry Representative)

Patrick S. Callery, Ph.D.

Dennis Gonsalves, Ph.D., M.S.

Jean M. Halloran (Consumer Representative)

Douglas C. Heimburger, M.D., M.S.

Margaret C. McBride, M.D.

Mark Nelson, Ph.D. (Industry Representative)

Carol I. Waslien Ghazaii, Ph.D., R.D.

TEMPORARY VOTING MEMBERS:

Petr Bocek, M.D., Ph.D.

Margaret Briley, Ph.D., R.D.

Erica Brittain, Ph.D.

Ciaran P. Kelly, M.D.

Soheila June Maleki, Ph.D.

David O. Oryang

Marc D. Silverstein, M.D.

Suzanne Teuber, M.D.

FOOD AND DRUG ADMINISTRATION:

Catherine Copp, J.D. - Senior Policy Advisor

Food and Drug Administration, CFSAN

Steven M. Gendel, Ph.D. - Senior Scientist

Food and Drug Administration

National Center for Food Safety and Technology

Rhonda Kane, M.S., R.D. - Consumer Officer

Food and Drug Administration, CFSAN

Michael M. Landa, J.D. - Deputy Director for Regulatory Affairs

Food and Drug Administration, CFSAN

Stefano Luccioli, M.D. - Senior Medical Advisor

Food and Drug Administration, CFSAN

Marcia Moore, Food Advisory Committee, Executive Secretary

Jenny Slaughter - Director

Food and Drug Administration Integrity and Ethics Staff

P A R T I C I P A N T S (Continued)

GUEST SPEAKERS:

Rene Crevel, Ph.D. - Senior Scientist

Unilever, Safety and Environmental Assurance Centre, United Kingdom

Susan Hefle, Ph.D. - Associate Professor and Co-Director

Food Allergy Research and Resource Program, University of Nebraska

Stefano Luccioli, M.D., - Senior Medical Advisor

CFSAN, FDA Assistant Professor, Georgetown University

Anne Munoz-Furlong

Director, Food Allergy & Anaphylaxis Network

Steve Taylor, Ph.D. - Maxcy Distinguished Professor & Director

Food Allergy Research and Resource Program, University of Nebraska

Robert Wood, M.D. - Professor

Johns Hopkins University School of Medicine

C O N T E N T S

PAGE

Call to Order, Welcome and Introductions

Charge to the Food Advisory Committee

Richard Durst, Ph.D., Acting Chairman 6

Conflict of Interest Statement & Other

Instructions

Jenny Slaughter, FDA 10

Welcome and Opening Statement

Michael M. Landa, Esq., CSAN, FDA 14

Use of Food allergen Thresholds

Catherine L. Copp, Esq., CFSAN, FDA 18

Introduction to Food Allergens

Robert Wood, M.D. 23

Patient Perspectives on Food Allergies

Anne Munoz-Furlong 72

Allergenicity: Analytical Methods

Susan Hefle, Ph.D. 99

Question and Answer Session 126

Oral Challenge Studies: Purpose, Design,

and Evaluation

Stefano Luccioli, M.D.

Senior Medical Advisor, CFSAN, FDA 133

Question and Answer Session 161

Threshold Modeling Approach

Rene Crevel, Ph.D. 170

Food Allergen Thresholds

Steve Taylor, Ph.D. 189

Overview of Approaches to Establishing

Thresholds: Allergens

Steven M. Gendel, Ph.D., FDA 218

C O N T E N T S (Continued)

PAGE

Public Comments:

Tracy Atagi 228

John Carroll 232

Diane Castiglione 242

Will Duensing 247

Martin J. Hahn, Esq. 250

Peggy Mockett 254

Kim Mudd 257

Kim Mulherin 260

Linda Webb 264

Jupiter Yeung 268

Committee Discussion:

Panel Discussion with Guest Speakers

Thresholds for Food Allergens - Questions 272

Adjournment

Richard Durst, Ph.D., Acting Chairman 414

P R O C E E D I N G S

CALL TO ORDER, WELCOME, AND INTRODUCTIONS

CHARGE TO THE FOOD ADVISORY COMMITTEE

CHAIRMAN DURST: I would like to call the

meeting to order.

Good morning. I am Dick Durst, professor

of chemistry in the Food Science and Technology

Department at Cornell University. I was asked to

chair this meeting over the next two and a half

days. I would like to make a few announcements

before we begin our meeting this morning.

I would appreciate it if everyone would

turn off their cell phones, unless they are

expecting a call of a super emergency nature. I

would also like to ask if the guest speakers could

make themselves available for the discussion this

afternoon, I would really appreciate it. We may

have some additional questions.

We have received a charge from the FDA to

give our evaluation of the draft report prepared by

the Threshold Working Group. I assume all of the

members have read that thoroughly. In my opinion,

I it was fascinating.

It was an excellent article and I commend

the Committee for coming up with it. It was very

educational. Not being an expert on food allergens

myself, it was extremely educational, and I was

able to follow it quite clearly.

Our charge is to evaluate this report to

determine whether the approaches that are presented

in there are the only ones or the better ones,

which of the ones that are in there might be the

most appropriate. This is the focus of our meeting

today, both on the food allergens and on gluten.

Let me also begin by asking the committee

members to introduce themselves. We will start

with Dr. Silverstein.

Marc, would you start it off?

DR. SILVERSTEIN: Good morning. My name

is Marc Silverstein, and I'm a general internist

and geriatrician at Baylor Health Care System in

Dallas.

DR. TEUBER: Good morning. My name is

Suzanne Teuber, I am an allergist at UC-Davis.

MR. ORYANG: Good morning. I am

David Oryang. I am a risk analyst and agricultural

engineer at the United States Department of

Agriculture, Animal and Plant Health Inspection

Service.

DR. KELLY: I am Ciaran Kelly, and I am a

gastroenterologist at the Harvard Medical School in

Boston.

DR. MALEKI: I am Soheila Maleki. I am a

scientist with the USDA.

DR. BRITTAIN: Erica Brittain, I am a

statistician at the National Institute of Allergy

and Infectious Disease.

DR. BRILEY: Margaret Briley, University

of Texas at Austin, nutritionist.

DR. BOCEK: Good morning. I am

Petr Bocek, medical officer in NIH's National

Institute of Allergy and Infectious Diseases.

MRS. MOORE: I am Marcia Moore. I am with

the FDA as the executive secretary of the Food

Advisory Committee.

DR. WASLIEN: I am Carol Waslien. I am a

nutritional epidemiologist at the University of

Hawaii.

DR. McBRIDE: I am Margaret McBride. I am

a child neurologist at Akron Children's Hospital.

DR. CALLERY: I am Patrick Callery, a

pharmaceutical scientist from West Virginia

University.

DR. GONSALVES: I am Dennis Gonsalves, a

scientist with USDA in Hawaii.

DR. HEIMBURGER: I am Doug Heimburger, a

physician and nutrition specialist at the

University of Alabama at Birmingham.

DR. BARACH: Jeff Barach with Food

Products Association, vice president for special

projects and regulatory affairs.

DR. NELSON: Mark Nelson with the Grocery

Manufacturers Association responsible for

regulatory and scientific policy.

MS. HALLORAN: Jean Halloran from the

Consumers Union where I am director of food policy

initiatives.

CHAIRMAN DURST: Thank you very much.

One other item is that we may have some of

our members leave early on Friday, depending on the

amount of time we can spend. What I propose is

that today and tomorrow that we anticipate having

to go perhaps till 6 o'clock so that we can be sure

that we have enough time for all of our

discussions.

Okay. Let me introduce our first speaker.

This will be Jenny Slaughter, director of Ethics

and Integrity Staff at the FDA, to describe the

"Conflict of Interest Statement" and other

instructions.

CONFLICT OF INTEREST STATEMENT

AND OTHER INSTRUCTIONS

MS. SLAUGHTER: Well, good morning and

welcome. The Food and Drug Administration is

convening today's meeting of the Food Advisory

Committee under the authority of the Federal

Advisory Committee Act of 1972.

With the exception of the industry

representatives, all members of the Committee are

special government employees or regular Federal

employees from other agencies subject to Federal

conflict of interest laws and regulations.

FDA has determined that members of this

Advisory Committee are in compliance with Federal

ethics and conflict of interest laws including, but

not limited to, 18 U.S.C. 208 and 21 U.S.C. 355 and

354.

Under 18 U.S.C., Section 208, applicable

to all government agencies, and 21 U.S.C. 355,

applicable to only FDA, Congress has authorized FDA

to grant waivers to special government employees

who have financial conflicts when it is determined

that the Agency's need for particular

interventional services outweighs the potential

conflict of interest.

Members who are special government

employees at today's meeting including special

government employees appointed as temporary voting

members, have been screened for potential financial

conflicts of interest of their own as well as those

of their spouse, minor child, and employer, which

are related to the discussions of today's and

tomorrow's and Friday's meeting regarding the "FDA

Draft Report: Approaches to Establish Thresholds

for Major Food Allergens and for Gluten in Foods."

These interests may include investments,

consulting, expert witness testimony, contracts,

grants, research and development agreements, public

speaking, writing, patents, royalties, and primary

employment.

In accordance with 18 U.S.C. 208(b)(3),

full waivers have been granted to the following

participants, Dr. Suzanne Teuber and Dr. Soheila

Maleki, please note that all of the interests in

the firms that could potentially be affected by the

Committee's decisions.

A copy of the written waiver statements

may be obtained by submitting a written request to

the Agency's Freedom of Information Office, Room

12A-30 of the Parklawn Building.

In addition, the following individuals are

participating as FDA's invited guest speakers,

July 13th: Dr. Rene Crevel, Dr. Susan Hefle,

Anne Mun [MLM1] oz-Furlong, Dr. Steve Taylor, and

Dr. Robert Wood.

The following individuals will be

participating as FDA invited guest speakers

tomorrow, July 14th: Dr. Pekka Collin,

Dr. Alessio Fasano, Dr. Donald Kasarda,

Dr. Cynthia Kupper, and Dr. Joseph Murray.

Lastly, I would like to report that

Dr. Jeffrey Barach and Dr. Mark Nelson are serving

as the industry representatives on the Committee at

today's meeting. They are acting on behalf of all

regulated industry.

Dr. Jeffrey Barach is employed by the

National Food Processors Association and

Dr. Mark Nelson is employed by the Grocery

Manufacturers of America.

A copy of this document will be placed on

the back table, if anybody wishes to take a look at

it. I thank you.

CHAIRMAN DURST: Thank you very much.

We will now go on to the welcome and opening

statement by Dr. Michael Landa, the deputy director

for Regulatory Affairs at CFSAN, the FDA.

Mike.

WELCOME AND OPENING STATEMENT

MR. LANDA: Thank you, Dr. Durst. You

will be pleased to learn that I don't have a

doctorate or an M.D. I'm just a plain, old J.D.

(General laughter.)

MR. LANDA: Thanks again. Good morning to

everyone. Welcome to the members of the committee,

to the guest speakers, to members of the public who

have joined us today, and to my fellow FDA

employees.

I would like to give a special thanks to

the Committee members for your willingness to take

time from busy schedules to help us with your

expertise for a meeting that will be several days

long. We are all here today, tomorrow and a fair

chunk of Friday.

Let me just add that Dr. Brackett had

hoped to be here this morning, but he wasn't able

to make it. I am hopeful that he will be here for

some portion of the meeting. He was called

downtown for a meeting this morning.

I am going to refer to a couple of points

on the food allergens, but the points I'm making

apply to celiac disease as well. It is just less

cumbersome to start with the food allergens. The

agenda has been making, I think, an opening

statement, of course I'm really not going to do

that.

There are just a few points I want to make

as you go into your inquiry today. The first is

virtually every FDA speaker makes at this kind of

proceeding which is what we do really is based on

science.

We talk about being a science-based

agency. It is the bedrock; it is the foundation.

In that context, I am going to paraphrase what may

be a rather obscure 19th century Senator, Karl

Shrews from Pennsylvania.

The paraphrase essentially is, Our science

correct or incorrect, when it is correct, help us

keep it correct; when it is incorrect, help us to

correct it. That is as much as anything else what

we want from you here in terms of your expertise in

the science.

If with respect to the threshold in the

Draft Report, we have gotten it right, we want to

know from you that we have gotten it right. We

want your help in keeping it right. If we have

gotten it wrong, we want your help in getting it

right. That includes, as you will hear, if we have

not considered an approach that we should have

considered, we want to know that from you.

The third point I will make is that

Americans suffer from food allergies, particularly

children. There is some evidence that the number

is increasing. If you add to that family members,

you really have tens of millions of folks who are

involved. At the moment their principle means of

protection really is exquisite attention to the

food label. That is their pathway to safety I

suppose.

We are hoping that eventually thresholds

will provide another path to safety. This is the

beginning of the inquiry into thresholds, that is,

the approaches that are outlined in the report. It

is the first step in a very important process.

The last point I will make is just that

this is as much as anything else for members of the

public, the docket is going to remain open until

about the middle of August.

If people have comments, based on what

they have heard today, for example, they should

feel free to submit those comments to the docket.

Again, it is until about, I don't remember the

precise date, but it is the middle of August.

In that connection, I should say we are

especially interested, as I think is always the

case, in data. In this case, data of the type

outlined in the report.

Thank you.

CHAIRMAN DURST: Thank you, Mike. Since

Mr. Landa didn't want me conferring a doctorate

degree on him, I will not do it with Catherine

Copp, who is the policy advisor at CFSAN, also the

FDA, who will discuss the use of food allergens

thresholds.

USE OF FOOD ALLERGENS THRESHOLDS

MS. COPP: I was hoping. Oh, well.

(General laughter.)

MS. COPP: Thank you, Dr. Durst.

Good morning. As you know, the focus of

this meeting today and tomorrow and the discussion

on Friday is the Draft Report of CFSAN's Threshold

Working Group: Approaches to Establish Thresholds

for Major Food Allergens and For Gluten in Food.

I have been asked to provide a context for

the Draft Report in terms of CFSAN's programmatic

efforts. This is one thing that if I were a real

doctor I could do. Lawyer's don't do this.

(Slide.)

MS. COPP: Last August, Congress enacted

the Food Allergen Labeling and Consumer Protection

Act, which we refer to in-house by the somewhat

awkward acronym "FALCPA."

This new law amends the Federal Food, Drug

and Cosmetic Act, the principle statute

administered by FDA by requiring that the label of

a food product that is or contains an ingredient

that bears or contains a major food allergen

declare the presence of the allergen as specified

in the law. In shorthand, the declaration is to be

in "consumer friendly" terms.

FALCPA defines a "major food allergen" as

one of the eight foods or food groups or a food

ingredient that contains protein derived from one

of these foods. Those are listed on the bottom of

this slide. By "food groups," I mean fish, tree

nuts and crustacean shellfish, which were

identified by Congress in the law.

(Slide.)

MS. COPP: The possible existence of

threshold levels for food allergens is an important

scientific issue, as Mr. Landa has pointed out,

associated with our implementation of FALCPA.

Although the law does not require FDA to

establish thresholds for any food allergen, there

are three possible ways, which are listed on this

slide, that such thresholds could be used to

implement the new law, these are: administering the

petition process provided for in FALCPA,

administering its notification process, and

addressing the issue or the occurrence of

cross-contact.

(Slide.)

MS. COPP: FALCPA provides two processes

by which an ingredient may be exempt from the

FALCPA labeling requirements, a petition process

and a notification process. I'm trying to read my

own slides (laughter). No, okay.

Under the petition process, an ingredient

may be exempt, if the petitioner demonstrates that

the ingredient does not cause an allergenic

response that poses a risk to human health.

Given this language for the petition

exemption standard, we believe it will be very

important for us to both understand food allergen

thresholds and to have a sound scientific framework

for evaluating the existence of such thresholds.

Under the notification process, an

ingredient may be exempt, if the notification

contains scientific evidence that demonstrates that

the ingredient does not contain allergenic protein,

or, if FDA has previously determined under the food

additive approval process that the food ingredient

does not cause an allergenic response that poses a

risk to human health.

(Slide.)

MS. COPP: Given this language for the

notification exemption standard, we also believe

that it will be very important for us to understand

food allergen thresholds and to have a sound

scientific framework for evaluating the existence

of such thresholds.

(Slide.)

Finally, the FALCPA directs FDA to prepare

and submit a report to Congress. This report will

focus principally on the issue of cross-contact of

foods with food allergens and is to describe the

types, current use of, and consumer preferences

with respect to so-called "advisory labeling."

Processed in a facility that also processes tree

nuts is an example of such labeling.

Cross-contact may occur during food

production when residues of an allergenic food are

present in the manufacturing environment and are

unintentionally incorporated into a food. Because

the food is not intended to contain the allergen,

it is not declared as an ingredient on the food's

label. In some cases, however, the potential

presence of the food allergen is declared by a

voluntary advisory statement.

We also believe that understanding food

allergen thresholds and developing a sound

scientific framework for evaluating the existence

of such thresholds may also be useful to us in

evaluating and addressing food allergen

cross-contact and the use of advisory labeling.

Thank you.

CHAIRMAN DURST: Thank you very much.

Does the Committee have any questions or

discussion of this presentation?

(No verbal response.)

CHAIRMAN DURST: If not, I think we will

proceed.

The next speaker is Dr. Robert Wood,

professor at Johns Hopkins University School of

Medicine, who will give us an introduction to food

allergens.

INTRODUCTION TO FOOD ALLERGENS

DR. WOOD: Thank you very much. It is a

pleasure to be here. What I was asked to do is to

provide an overview of food allergens and food

allergy leading into the discussion that is going

to go on over these next couple of days.

(Slide.)

DR. WOOD: The beginning of this, any talk

about food allergy really requires that we have

some common definition that we can all agree on.

This is something that is not as easy as it might

sound and often generates a lot of confusion. The

reality is that a lot of what is called food

allergy is really not food allergy and may fall

under more of a food intolerance category.

When we are talking about food allergy,

there are a couple of key ingredients. One of them

is that there is an immunologic component to the

reaction. The reaction is typically to the protein

component of the food as opposed to a food

intolerance that is more often related to the

carbohydrate component of the food. Importantly to

this meeting, exquisitely small amounts may cause a

reaction and that these reactions can be severe and

even life threatening.

(Slide.)

DR. WOOD: The pathophysiology of the

allergic response is sort of very schematically

diagramed here. What we are thinking about is a

process that begins with exposure and with most

allergy, probably all allergy, you have to have

some prior exposure to develop your sensitivity.

(Slide.)

DR. WOOD: There is a genetic

predisposition that makes some people particularly

more prone to develop allergy in general, whether

it be food allergy or respiratory allergy, than

others. There are some people who no

matter what, how, when and where they are exposed

they will never develop an allergy, and others who

with very trivial exposure may develop a severe

allergy.

If you are in this group who is

genetically predisposed, your immune system then